A Genome-wide Analysis of Admixture in Uyghurs and a High-Density Admixture Map for Disease-Gene Discovery

PubMed Central

Xu, Shuhua; Jin, Li

2008-01-01

Following up on our previous study, we conducted a genome-wide analysis of admixture for two Uyghur population samples (HGDP-UG and PanAsia-UG), collected from the northern and southern regions of Xinjiang in China, respectively. Both HGDP-UG and PanAsia-UG showed a substantial admixture of East-Asian (EAS) and European (EUR) ancestries, with an empirical estimation of ancestry contribution of 53:47 (EAS:EUR) and 48:52 for HGDP-UG and PanAsia-UG, respectively. The effective admixture time under a model with a single pulse of admixture was estimated as 110 generations and 129 generations, or admixture events occurred about 2200 and 2580 years ago for HGDP-UG and PanAsia-UG, respectively, assuming an average of 20 yr per generation. Despite Uyghurs' earlier history compared to other admixture populations, admixture mapping, holds promise for this population, because of its large size and its mixture of ancestry from different continents. We screened multiple databases and identified a genome-wide single-nucleotide polymorphism panel that can distinguish EAS and EUR ancestry of chromosomal segments in Uyghurs. The panel contains 8150 ancestry-informative markers (AIMs) showing large frequency differences between EAS and EUR populations (FST > 0.25, mean FST = 0.43) but small frequency differences (7999 AIMs validated) within both populations (FST < 0.05, mean FST < 0.01). We evaluated the effectiveness of this admixture map for localizing disease genes in two Uyghur populations. To our knowledge, our map constitutes the first practical resource for admixture mapping in Uyghurs, and it will enable studies of diseases showing differences in genetic risk between EUR and EAS populations. PMID:18760393

The potential of volatile organic compounds for the detection of active disease in patients with ulcerative colitis.

PubMed

Smolinska, A; Bodelier, A G L; Dallinga, J W; Masclee, A A M; Jonkers, D M; van Schooten, F-J; Pierik, M J

2017-05-01

To optimise treatment of ulcerative colitis (UC), patients need repeated assessment of mucosal inflammation. Current non-invasive biomarkers and clinical activity indices do not accurately reflect disease activity in all patients and cannot discriminate UC from non-UC colitis. Volatile organic compounds (VOCs) in exhaled air could be predictive of active disease or remission in Crohn's disease. To investigate whether VOCs are able to differentiate between active UC, UC in remission and non-UC colitis. UC patients participated in a 1-year study. Clinical activity index, blood, faecal and breath samples were collected at each out-patient visit. Patients with clear defined active faecal calprotectin >250 μg/g and inactive disease (Simple Clinical Colitis Activity Index <3, C-reactive protein <5 mg/L and faecal calprotectin <100 μg/g) were included for cross-sectional analysis. Non-UC colitis was confirmed by stool culture or radiological evaluation. Breath samples were analysed by gas chromatography time-of-flight mass spectrometry and kernel-based method to identify discriminating VOCs. In total, 72 UC (132 breath samples; 62 active; 70 remission) and 22 non-UC-colitis patients (22 samples) were included. Eleven VOCs predicted active vs. inactive UC in an independent internal validation set with 92% sensitivity and 77% specificity (AUC 0.94). Non-UC colitis patients could be clearly separated from active and inactive UC patients with principal component analysis. Volatile organic compounds can accurately distinguish active disease from remission in UC and profiles in UC are clearly different from profiles in non-UC colitis patients. VOCs have demonstrated potential as new non-invasive biomarker to monitor inflammation in UC. © 2017 John Wiley & Sons Ltd.

Ethnic stratification amid China's economic transition: evidence from the Xinjiang Uyghur Autonomous Region.

PubMed

Wu, Xiaogang; Song, Xi

2014-03-01

This paper analyzes a sample from the 2005 mini-census of Xinjiang to examine ethnic stratification in China's labor markets, with a special focus on how ethnic earnings inequality varies by employment sector. We show that Han and Uyghur Chinese dominated different economic sectors. Excluding those in agriculture, Uyghurs were more likely to work in government or institutions than either Han locals or migrants, and also more likely to become self-employed. The Han-Uyghur earnings gap was negligible within government/public institutions, but increased with the marketization of the employment sector. It was the largest among the self-employed, followed by employees in private enterprises and then employees in public enterprises. Han migrants in economic sectors enjoyed particular earnings advantages and hukou registration status had no impact on earnings attainment except in government/public institutions. These findings have important implications for understanding social and economic sources of increasing ethnic conflicts in Xinjiang in recent years. Copyright © 2013 Elsevier Inc. All rights reserved.

Prevalence of visual impairment and refractive errors among different ethnic groups in schoolchildren in Turpan, China.

PubMed

Chin, Man Pan; Siong, Kar Ho; Chan, Ka Ho; Do, Chi Wai; Chan, Henry Ho Lung; Cheong, Allen Ming Yan

2015-05-01

There is currently limited information about ethnic differences in myopia prevalence within mainland China, especially in rural or semi-rural areas. We examined the prevalence of refractive errors, visual impairment and spectacle coverage in school children of varying ethnicity in Turpan, Xinjiang province. A community eye care service was provided for five schools. Presenting monocular distance and near visual acuity (VA), and ocular alignment were assessed. Retinoscopy and cycloplegic subjective refraction were performed for participants with presenting visual impairment (distance VA worse than 0.3 logMAR; Snellen 6/12 or 20/40) or abnormal binocular vision. Questionnaires administered prior to the eye examinations were used to collect information regarding personal lifestyle and parental myopia. A total of 646 out of 690 (94%) subjects aged four to 19 years (11.9 ± 2.6; mean ± S.D.) completed the eye examination. Three hundred and eighty-two (59%) of participants were of Uyghur ethnicity, followed by Han, 176 (27%) and Hui, 74 (12%). The mean age of Uyghur, Han and Hui students was 12.3 ± 2.7, 11.4 ± 2.6 and 11.4 ± 2.3 years respectively, in which the Uyghur students were significantly older than the Han and Hui students (F(3,631) = 5.58 p < 0.001). In total, 170 (27%) and 85 (13%) subjects failed the screening examination for one eye or both eyes, respectively. The prevalence of presenting visual impairment was not significantly different among the ethnic groups (p = 0.26). After cycloplegic refraction, most subjects' VA (98%) improved to better than 0.3 logMAR (Snellen 6/12 or 20/40). The prevalence of "clinically-significant myopia" (≤-0.50 dioptres) was 27%, 18% and 13% in Han, Hui and Uyghur children, respectively (p < 0.001). In contrast, Uyghur students had the highest prevalence of astigmatism (Uyghur 12%, Han 5%, Hui 4%). The overall spectacle coverage was 36%, while spectacle coverage among ethnic groups were similar (Han, 41%; Uyghur, 32%; Hui, 41%; χ(2) = 2.23, df = 2, p = 0.33). The prevalence of clinically significant myopia varied markedly with ethnicity in school children sampled from a semi-rural region of mainland China (Han > Hui > Uyghur). As reported previously, uncorrected/under-corrected refractive error was the main cause of presenting visual impairment. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Exploring Uyghur University Students' Identities Constructed through Multilingual Practices in China

ERIC Educational Resources Information Center

Guo, Xiaoyan; Gu, Mingyue

2018-01-01

This article explores how a cohort of tertiary-level Uyghur students contested and negotiated their identities through multilingual practices in the receiving community. Drawing upon interview data from fieldwork, this study indicates that these students experienced essentialist understandings and negative views in the host society. Participants…

Gene Polymorphism Association with Type 2 Diabetes and Related Gene-Gene and Gene-Environment Interactions in a Uyghur Population

PubMed Central

Xiao, Shan; Zeng, Xiaoyun; Fan, Yong; Su, Yinxia; Ma, Qi; Zhu, Jun; Yao, Hua

2016-01-01

Background We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. Material/Methods A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY®SNP genotyping. Factors associated with T2D were assessed by logistic regression analyses. Gene-gene and gene-environment interactions were analyzed by generalized multifactor dimensionality reduction. Results Genotype distributions of rs10811661 (CDKN2A/2B), rs7195539, rs8050136, and rs9939609 (FTO) and allele frequencies of rs8050136 and rs9939609 differed significantly between diabetes and control groups (all P<0.05). While rs10811661, rs8050136, and rs9939609 were eliminated after adjusting for covariates (P>0.05), rs7195539 distribution differed significantly in co-dominant and dominant models (P<0.05). In gene-gene interaction analysis, after adjusting for covariates the two-locus rs10811661-rs7195539 interaction model had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.5483 (P=0.014). In gene-environment interaction analysis, the 3-locus interaction model TG-HDL-family history of diabetes had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.7072 (P<0.001). The 4-locus interaction model, rs7195539-TG-HDL-family history of diabetes had a cross-validation consistency of 8/10 (P<0.001). Conclusions Polymorphisms in CDKN2A/2B and FTO, but not CDKAL1, may be associated with T2D, and alleles rs8050136 and rs9939609 are likely risk alleles for T2D in this population. There were potential interactions among CDKN2A/2B (rs10811661) – FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population. PMID:26873362

[Determination of rutin, quercetin and kaempferol in Althaea rosea (L) Gavan for Uyghur medicine by high performance liquid chromatography].

PubMed

Muhetaer, Tu'erhong; Resalat, Yimin; Chu, Ganghui; Yin, Xuebo; Munira, Abudukeremu

2015-12-01

Uyghur medicine is one important part of the national medicine system. Uyghur medicine modernization, namely the study of effective components with modern technologies, is the only way for the scientification, standardization, and industrialization of Uyghur medicine. Here we developed a selective extraction method for rutin, quercetin and kaempferol in Althaea rosea (L) Gavan. The three active species were determined by high performance liquid chromatography (HPLC) with HC-C18 column (250 mm x 4.6 mm, 5 μm) and the mobile phase of CH3OH-0.4% H3PO4 (50 :50, v/v). Rutin, quercetin and kaempferol were baseline separated with each other and the interference species with flow rate of 1.0 mL/min and column temperature of 30 degrees C. Under the optimal conditions, linear correlation were obtained in the mass concentration range of 12.5-150 μg/mL (r = 0.999 8) for rutin, 12.5-125 μg/mL (r = 0.999 9) for quercetin, and 12.5-125 μg/mL (r = 0.998 8) for kaempferol. The recoveries (n = 5) of rutin, quercetin and kaempferol were 100.25% ( RSD = 1.1%), 97.60% ( RSD = 0.47%) and 97.75% (RSD = 0.71%), respectively. The method can be used to determine the contents of rutin, quercetin and kaempferol in Althaea rosea (L) Gavan and provide the guidance for the analysis of the flavonoids in other Uyghur medicines.

Analysis of Genomic Admixture in Uyghur and Its Implication in Mapping Strategy

PubMed Central

Xu, Shuhua; Huang, Wei; Qian, Ji; Jin, Li

2008-01-01

The Uyghur (UIG) population, settled in Xinjiang, China, is a population presenting a typical admixture of Eastern and Western anthropometric traits. We dissected its genomic structure at population level, individual level, and chromosome level by using 20,177 SNPs spanning nearly the entire chromosome 21. Our results showed that UIG was formed by two-way admixture, with 60% European ancestry and 40% East Asian ancestry. Overall linkage disequilibrium (LD) in UIG was similar to that in its parental populations represented in East Asia and Europe with regard to common alleles, and UIG manifested elevation of LD only within 500 kb and at a level of 0.1 < r2 < 0.8 when ancestry-informative markers (AIMs) were used. The size of chromosomal segments that were derived from East Asian and European ancestries averaged 2.4 cM and 4.1 cM, respectively. Both the magnitude of LD and fragmentary ancestral chromosome segments indicated a long history of Uyghur. Under the assumption of a hybrid isolation (HI) model, we estimated that the admixture event of UIG occurred about 126 [107∼146] generations ago, or 2520 [2140∼2920] years ago assuming 20 years per generation. In spite of the long history and short LD of Uyghur compared with recent admixture populations such as the African-American population, we suggest that mapping by admixture LD (MALD) is still applicable in the Uyghur population but ∼10-fold AIMs are necessary for a whole-genome scan. PMID:18355773

Long-term outcome of patients with distal ulcerative colitis and inflammation of the appendiceal orifice.

PubMed

Naves, Juan E; Lorenzo-Zúñiga, Vicente; Marín, Laura; Mañosa, Míriam; Oller, Blanca; Moreno, Vicente; Zabana, Yamile; Boix, Jaume; Cabré, Eduard; Domènech, Eugeni

2011-12-01

Skip inflammation of the appendiceal orifice has been described in distal UC (UC-IAO) but long-term clinical outcomes are poorly established. Our aim was to evaluate the long-term clinical outcomes of UC-IAO as compared to classic distal UC. Patients with UC-IAO were identified from the local IBD database. Disease outcome and therapeutic requirements during follow-up were accurately collected, and compared with a control group of patients with distal UC without peri-appendiceal involvement matched by disease extent (proctitis/distal), smoking habit, and date and age at diagnosis. Fourteen UC patients were found to have UC-IAO, most of them with initial extent of UC limited to the rectum. All patients were initially managed with mesalazine administered orally (28.5%), topically (28.5%), or in combination (43%). After a median follow-up of 78 months (interquartile range--IQR 45-123) most UC-IAO patients were successfully managed with oral and/or topical aminosalicylates. Only one of them developed proximal disease progression. As compared to controls, no differences in clinical outcomes or therapeutic requirements were found. Patients with UC-IAO tend to present a mild course, with a low probability to develop proximal progression of disease extent or to require immunosuppressive therapy or colectomy.

Investigation of novel biomarkers for predicting the clinical course in patients with ulcerative colitis.

PubMed

Hamanaka, Shinsaku; Nakagawa, Tomoo; Hiwasa, Takaki; Ohta, Yuki; Kasamatsu, Shingo; Ishigami, Hideaki; Taida, Takashi; Okimoto, Kenichiro; Saito, Keiko; Maruoka, Daisuke; Matsumura, Tomoaki; Takizawa, Hirotaka; Kashiwado, Koichi; Kobayashi, Sohei; Matsushita, Kazuyuki; Matsubara, Hisahiro; Katsuno, Tatsuro; Arai, Makoto; Kato, Naoya

2018-06-05

The clinical course of ulcerative colitis (UC) is characterized by repeated episodes of relapse and remission. We hypothesized that biomarkers that help distinguish refractory UC patients who are in remission using strong anti-immunotherapy could contribute in preventing the overuse of corticosteroids for treatment. Here we clarified novel autoantibodies for UC patients in remission as clinical indicators to distinguish between refractory and non-refractory UC. Antigen proteins recognized by serum antibodies of patients with UC in remission were screened using the protein array method. To validate the results, AlphaLISA was used to analyze the serum antibody titers with candidate protein antigens. Serum samples from 101 healthy controls, 121 patients with UC, and 39 patients with Crohn's disease were analyzed. Of 66 candidate protein antigens screened by ProtoArray™, 6 were selected for this study. The serum titers of anti-poly ADP-ribose glycohydrolase (PARG), anti-transcription elongation factor A protein-like 1 (TCEAL1), and anti-proline-rich 13 (PRR13) antibodies were significantly higher in patients with UC than in healthy controls. Anti-PARG and anti-PRR13 antibody titers were significantly higher in patients with refractory UC than in patients with non-refractory UC. There were no significant differences in any antibody titer between the active and remission phases. The serum titers of anti-PARG, anti-TCEAL1, and anti-PRR13 antibodies were elevated in patients with UC. Anti-PARG and anti-PRR13 antibody titers may be novel clinical indicators for detecting refractory UC in patients in remission. This article is protected by copyright. All rights reserved.

Prevention of urinary tract infections in palliative radiation for vertebral metastasis and spinal compression: A pilot study in 71 patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manas, Ana; Glaria, Luis; Pena, Carmen

2006-03-01

Purpose: To assess the impact of bladder instillations of hyaluronic acid (HA) on the prevalence of urinary tract infection (UTI) in patients receiving emergency radiotherapy for metastatic spinal cord compression. Methods and Materials: Patients were recruited consecutively at one center and assigned to usual care (UC) (n = 34, mean age 62.2 years) or UC with once-weekly HA instillation (UC + HA) (Cystistat: 40 mg in 50 mL phosphate-buffered saline) (n = 37; mean age, 63.1 years). All patients had an indwelling catheter and received radiotherapy. UTI status was assessed at baseline and during hospitalization. Results: At baseline, patient groupsmore » were comparable, except for the prevalence of UTI at baseline, which was 11.8% and 0% in the UC and UC + HA patients, respectively (p = 0.0477). During hospitalization, 76.5% (vs. 11.8% at baseline, p < 0.0001) of the UC patients had a UTI compared with 13.5% (vs. 0% at baseline, p = 0.0541) of the UC + HA patients (p < 0.0001). Both groups were hospitalized for similar periods (19.8 days [UC] vs. 18.5 days, p = 0.4769) and received equivalent radiotherapy sessions (4.6 [UC] vs. 5.8 sessions, p = 0.2368). Conclusions: Patients receiving UC + HA had a 5.7-fold decrease in UTI prevalence over the hospitalization period compared to UC patients, suggesting that bladder instillations of HA effectively prevent UTI in patients with indwelling catheters receiving radiotherapy for nerve compression.« less

Genetic polymorphisms of the drug-metabolizing enzyme cytochrome P450 3A5 in a Uyghur Chinese population.

PubMed

Chen, Zhengshuai; Li, Jingjie; Chen, Peng; Wang, Fengjiao; Zhang, Ning; Yang, Min; Jin, Tianbo; Chen, Chao

2016-09-01

1.  Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in Uyghur ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. 2. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP3A5 gene in 96 unrelated healthy Uyghur individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP3A5 coding regions. 3. We found 24 different CYP3A5 polymorphisms in the Uyghur population, three of which were novel: the synonymous mutation 43C > T in exon 1, two mutations 32120C > G and 32245T > C in 3'-untranslated region, and we detected the allele frequencies of CYP3A5*1 and *3 as 64.58% and 35.42%, respectively. While no subjects with CYP3A5*6 were identified. Other identified genotypes included the heterozygous genotype 1A/3A (59.38%) and 1A/3E (11.46%), which lead to decreased enzyme activity. In addition, the frequency of haplotype "TTAGGT" was the most prevalent with 0.781. 4. Our data provide new information regarding CYP3A5 genetic polymorphisms in Uyghur individuals, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs.

Serology of Patients with Ulcerative Colitis After Pouch Surgery Is More Comparable with that of Patients with Crohn's Disease.

PubMed

Goren, Idan; Yahav, Lior; Tulchinsky, Hagit; Dotan, Iris

2015-10-01

The serologic status of patients with ulcerative colitis (UC) who develop postoperative pouchitis was compared with that of patients with Crohn's disease (CD) and unoperated patients with UC. Pouch patients were stratified into normal pouch, acute/recurrent acute pouchitis, and chronic pouchitis/Crohn's-like disease of the pouch groups. Antibodies against glycans associated with CD (anti-Saccharomyces cerevisiae, anti-laminaribioside, anti-chitobioside, and anti-mannobioside carbohydrate antibodies [ASCA, ALCA, ACCA, and AMCA, respectively]) were detected and correlated with type of inflammatory bowel disease and pouch behavior. A total of 501 patients with inflammatory bowel diseases were recruited: 250 (50%) CD, 124 (24.7%) unoperated UC, and 127 (25.3%) UC-pouch. At least 1 positive antibody was detected in 77.6% CD, 52.0% UC-pouch and 33.1% unoperated UC (P < 0.0001 for all). ACCA and AMCA prevalence in CD, UC-pouch and unoperated patients with UC were 33.2%, 24.4%, and 16.9% (P = 0.003 for all) and 35.2%, 26.8%, and 7.3%, respectively (P < 0.0001 for all). ALCA and ASCA were more prevalent in patients with CD than unoperated UC and UC-pouch patients. A longer interval since pouch surgery was associated with inflammatory pouch behavior: 12.45, 11.39, and 8.5 years for acute/recurrent acute pouchitis, chronic pouchitis/Crohn's-like disease of the pouch, and normal pouch, respectively, P = 0.01 for all. The prevalence of the CD-associated anti-glycan antibodies ACCA and AMCA is significantly increased in UC-pouch patients, suggesting that pouch surgery may trigger differential immune responses to glycans. The finding that the serology of UC-pouch patients shares similarities with that of patients with CD supports the notion that those 2 inflammatory bowel diseases share a common pathogenic pathway.

Gender and Ethnic Variation in Arranged Marriages in a Chinese City

ERIC Educational Resources Information Center

Zang, Xiaowei

2008-01-01

Using a data set (N = 1,600) collected in the city of Urumchi in 2005, this article examines ethnic differences in arranged marriages in urban China. Data analysis shows a rapid decline in parental arrangement for both Uyghur Muslims and Han Chinese in Urumchi. Han Chinese are less likely than Uyghur Muslims to report arranged marriages, with main…

They Are What You Hear in Media Reports: The Racial Stereotypes toward Uyghurs Activated by Media

PubMed Central

Jin, Jia; Pei, Guanxiong; Ma, Qingguo

2017-01-01

Stereotypes from the major nationality toward minorities constitute a widely concerning problem in many countries. As reported by previous studies, stereotypes can be activated by media information that portrays the negative aspects of the target group. The current study focused on the neural basis of the modulation of negative media information on Han Chinese stereotypes toward Uyghurs by using event-related potentials. We employed the lexical decision task, in which participants were asked to categorize the presented word as positive or negative. Behavioral result showed that participants had a shorter reaction time to positive adjectives than to negative adjectives. The data of brain activity showed that compared with the Han condition, the Uyghurs condition elicited smaller N400 differences in the media priming group, whereas there was no significant N400 deflection difference between Han Chinese and Uyghurs in the control group. The current results suggested that the negative media information might influence their judgments toward other groups reflected in the deflection of N400 amplitude. Therefore, in order to mitigate or even eliminate stereotypes about national minorities, the effort of the media is important. PMID:29270104

They Are What You Hear in Media Reports: The Racial Stereotypes toward Uyghurs Activated by Media.

PubMed

Jin, Jia; Pei, Guanxiong; Ma, Qingguo

2017-01-01

Stereotypes from the major nationality toward minorities constitute a widely concerning problem in many countries. As reported by previous studies, stereotypes can be activated by media information that portrays the negative aspects of the target group. The current study focused on the neural basis of the modulation of negative media information on Han Chinese stereotypes toward Uyghurs by using event-related potentials. We employed the lexical decision task, in which participants were asked to categorize the presented word as positive or negative. Behavioral result showed that participants had a shorter reaction time to positive adjectives than to negative adjectives. The data of brain activity showed that compared with the Han condition, the Uyghurs condition elicited smaller N400 differences in the media priming group, whereas there was no significant N400 deflection difference between Han Chinese and Uyghurs in the control group. The current results suggested that the negative media information might influence their judgments toward other groups reflected in the deflection of N400 amplitude. Therefore, in order to mitigate or even eliminate stereotypes about national minorities, the effort of the media is important.

Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease

PubMed Central

Wettermark, Björn; Löfberg, Robert; Eriksson, Irene; Sundström, Johan; Lördal, Mikael

2016-01-01

Background and Aims: Crohn’s disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. Methods: This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. Results: A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. Conclusions: This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients. PMID:26733406

Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.

PubMed

Kevans, D; Tyler, A D; Holm, K; Jørgensen, K K; Vatn, M H; Karlsen, T H; Kaplan, G G; Eksteen, B; Gevers, D; Hov, J R; Silverberg, M S

2016-03-01

There is an unexplained association between ulcerative colitis [UC] and primary sclerosing cholangitis [PSC], with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC. UC patients with PSC [PSC-UC] and without PSC [UC] were identified from biobanks at Oslo University Hospital, Foothills Hospital Calgary and Mount Sinai Hospital Toronto. Microbial DNA was extracted from colonic tissue and sequencing performed of the V4 region of the 16S rRNA gene on Illumina MiSeq. Sequences were assigned to operational taxonomic units [OTUs] using Quantitative Insights Into Microbial Ecology [QIIME]. Microbial alpha diversity, beta diversity, and relative abundance were compared between PSC-UC and UC phenotypes. In all, 31 PSC-UC patients and 56 UC patients were included. Principal coordinate analysis [PCoA] demonstrated that city of sample collection was the strongest determinant of taxonomic profile. In the Oslo cohort, Chao 1 index was modestly decreased in PSC-UC compared with UC [p = 0.04] but did not differ significantly in the Calgary cohort. No clustering by PSC phenotype was observed using beta diversity measures. For multiple microbial genera there were nominally significant differences between UC and PSC-UC, but results were not robust to false-discovery rate correction. No strong PSC-specific microbial associations in UC patients consistent across different cohorts were identified. Recruitment centre had a strong effect on microbial composition. Future studies should include larger cohorts to increase power and the ability to control for confounding factors. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients.

PubMed

Cranenburg, Ellen C M; Brandenburg, Vincent M; Vermeer, Cees; Stenger, Melanie; Mühlenbruch, Georg; Mahnken, Andreas H; Gladziwa, Ulrich; Ketteler, Markus; Schurgers, Leon J

2009-02-01

Matrix gamma-carboxyglutamate (Gla) protein (MGP) is a potent local inhibitor of cardiovascular calcification and accumulates at areas of calcification in its uncarboxylated form (ucMGP). We previously found significantly lower circulating ucMGP levels in patients with a high vascular calcification burden. Here we report on the potential of circulating ucMGP to serve as a biomarker for vascular calcification in haemodialysis (HD) patients. Circulating ucMGP levels were measured with an ELISA-based assay in 40 HD patients who underwent multi-slice computed tomography (MSCT) scanning to quantify the extent of coronary artery calcification (CAC). The mean ucMGP level in HD patients (193 +/- 65 nM) was significantly lower as compared to apparently healthy subjects of the same age (441 +/- 97 nM; p < 0.001) and patients with rheumatoid arthritis (RA) without CAC (560 +/- 140 nM; p < 0.001). Additionally, ucMGP levels correlated inversely with CAC scores (r = -0.41; p = 0.009), and this correlation persisted after adjustment for age, dialysis vintage and high-sensitivity C-reactive protein (hs-CRP). Since circulating ucMGP levels are significantly and inversely correlated with the extent of CAC in HD patients, ucMGP may become a tool for identifying HD patients with a high probability of cardiovascular calcification.

Evaluation of a multiplex PCR assay for detection of cytomegalovirus in stool samples from patients with ulcerative colitis

PubMed Central

Nahar, Saifun; Iraha, Atsushi; Hokama, Akira; Uehara, Ayako; Parrott, Gretchen; Ohira, Tetsuya; Kaida, Masatoshi; Kinjo, Tetsu; Kinjo, Takeshi; Hirata, Tetsuo; Kinjo, Nagisa; Fujita, Jiro

2015-01-01

AIM: To evaluate a multiplex PCR assay for the detection of bacterial and viral enteropathogens in stool samples from patients with ulcerative colitis (UC). METHODS: We prospectively analyzed 300 individuals, including immunocompetent patients, immunocompromised patients, and patients with UC. Stool samples were collected from the recto-sigmoid region of the colon by endoscopy. The samples were qualitatively analyzed for bacterial and viral enteropathogens with a multiplex PCR assay using a Seeplex® Kit. Additional clinical and laboratory data were collected from the medical records. RESULTS: A multiplex PCR assay detected 397 pathogens (191 bacteria and 206 viruses) in 215 samples (71.7%). The most frequently detected bacteria were Escherichia coli H7, 85 (28.3%); followed by Aeromonas spp., 43 (14.3%); and Clostridium perfringens, 36 (12.0%) samples. The most prevalent viruses were Epstein-Barr virus (EBV), 90 (30.0%); followed by human herpes virus-6 (HHV-6), 53 (17.7%); and cytomegalovirus (CMV), 37 (12.3%) samples. The prevalence rate of CMV infection was significantly higher in the immunocompromised group than in the immunocompetent group (P < 0.01). CMV infection was more common in patients with UC (26/71; 36.6%) than in the immunocompetent patients excluding UC (6/188; 3.2%) (P < 0.01). CMV infection was more prevalent in UC active patients (25/58; 43.1%) than in UC inactive patients (1/13; 7.7%) (P < 0.05). Among 4 groups which defined by the UC activity and immunosuppressive drugs, the prevalence rate of CMV infection was highest in the UC active patients with immunosuppressive drugs (19/34; 55.8%). Epstein-Barr virus (EBV) infection was more common in the immunocompromised patients excluding UC (18/41; 43.9%) than in the immunocompetent patients excluding UC (47/188; 25.0%) (P < 0.05). The simultaneous presence of CMV and EBV and/or HHV6 in UC active patients (14/58; 24.1%) was greater than in immunocompromised patients excluding UC (5/41; 12.2%) (P < 0.05). CONCLUSION: The multiplex PCR assay that was used to analyze the stool samples in this study may serve as a non-invasive approach that can be used to exclude the possibility of CMV infection in patients with active UC who are treated with immunosuppressive therapy. PMID:26640344

Increased small intestinal permeability in ulcerative colitis: rather genetic than environmental and a risk factor for extensive disease?

PubMed

Büning, Carsten; Geissler, Nora; Prager, Matthias; Sturm, Andreas; Baumgart, Daniel C; Büttner, Janine; Bühner, Sabine; Haas, Verena; Lochs, Herbert

2012-10-01

A disturbed epithelial barrier could play a pivotal role in ulcerative colitis (UC). We performed a family-based study analyzing in vivo gastrointestinal permeability in patients with UC, their healthy relatives, spouses, and controls. In total, 89 patients with UC in remission, 35 first-degree relatives (UC-R), 24 nonrelated spouses (UC-NR), and 99 healthy controls (HC) were studied. Permeability was assessed by a sugar-drink test using sucrose (gastroduodenal permeability), lactulose/mannitol (intestinal permeability), and sucralose (colonic permeability). Data were correlated with clinical characteristics including medical treatment. Increased intestinal permeability was detected significantly more often in UC patients in remission (25/89, 28.1%) compared with HC (6/99, 6.1%; P < 0.001). Similar results were obtained in UC-R (7/35, 20.0%; P = 0.01 compared with HC) regardless of sharing the same household with the patients or not. No difference was found between UC-NR (3/24, 12.5%) and HC. Notably, in UC patients increased intestinal permeability was found in 12/28 patients (42.9%) with pancolitis, 7/30 (23.3%) patients with left-sided colitis, and in 2/19 (10.5%) patients with proctitis (P = 0.04). Gastroduodenal and colonic permeability were similar in all groups. Among patients on azathioprine, increased intestinal permeability was only seen in 1/18 (5.6%) patients. In contrast, in 24/70 (34.3%) patients without azathioprine, an increased intestinal permeability was found (P = 0.005). An increased intestinal but not colonic permeability was found in UC patients in clinical remission that could mark a new risk factor for extensive disease location. Similar findings in healthy relatives but not spouses suggest that this barrier defect is genetically determined. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Interleukin 27 is up-regulated in patients with active inflammatory bowel disease.

PubMed

Furuzawa Carballeda, Janette; Fonseca Camarillo, Gabriela; Yamamoto-Furusho, Jesús K

2016-08-01

The aim of the study was to characterize and quantify tissue gene and protein expression of IL-27 in ulcerative colitis (UC) and Crohn's disease (CD) patients. This is an observational and cross-sectional study. Fifty-four patients with IBD were studied: 27 active UC, 12 inactive UC, 10 active CD, and 5 inactive CD. All patients belonged to the Inflammatory Bowel Disease Clinic at the Instituto Nacional de Ciencias Médicas y Nutrición. We found that IL-27 gene expression was significantly higher in active UC versus inactive UC group (P = 0.015). The IL-27 mRNA expression was increased in patients with active CD compared with inactive CD disease (P = 0.035). The percentage of IL-27 immunoreactive cells was higher in active UC versus active CD patients and non-inflamed tissue controls. The IL-27 was significantly elevated in active UC and CD patients, and it was associated with disease severity.

Prognosis and related factors of HPV infections in postmenopausal Uyghur women.

PubMed

Sui, Shuang; Zhu, Mingyue; Jiao, Zhen; Han, Lili; Wang, Lin; Niyazi, Mayineur; Zhu, Kaichun

2018-03-25

With the aim to explore the characteristics of persistent HPV infections in postmenopausal Uyghur women and analyse the possible related risk factors, from September 2012 to September 2013; postmenopausal Uyghur women with HPV positive and pathologically diagnosed as non-cervical intraepithelial neoplasia (CIN) lesions and non-cervical cancer were recruited. Their clinical course was closely followed up for 24-36 months, and the risk factors were analysed by a logistic regression model. One hundred and sixteen positive women were followed for 36 months. The total persistent HPV infection rate was 67.9%, and the type-specific persistent infection rate was 73.7% at 36 months. Nine (32.1%) women were naturally cleared of their HPV infection at 36 months. We found that an HPV16 infection and an HPV58 infection, and time since menopause over 2 years were closely related with a persistent HPV infection. More attention should be paid to the women above 2 years of menopause who were infected with HPV16 and HPV58 in their further cervical carcinoma screening. Impact statement What is already known on this subject? Previous study revealed that menopause was a risk factor for a persistent HPV infection in Uyghur women. What do the results of this study add? The present study presented the characteristics of HPV persistent infection and the risk factors in Uyghur postmenopausal women. More attention should be paid to the women above 2 of years of menopause who are infected with HPV16 and HPV58. What are the implications of these findings for clinical practice and/or further research? This study would offer a theoretical basis for a better screening design, especially the women above 2 years' menopause who have been infected with HPV16 and HPV58 in the Xinjiang region.

p53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis.

PubMed

Lu, Xiaohong; Yu, Yuanjie; Tan, Shiyun

2017-10-25

Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study. Final 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians. p53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

Association of Clinical Features with Human Leukocyte Antigen in Japanese Patients with Ulcerative Colitis.

PubMed

Iwamoto, Taku; Yashima, Kazuo; Morio, Keiko; Ueda, Naoki; Ikebuchi, Yuichiro; Kawaguchi, Koichiro; Harada, Kenichi; Isomoto, Hajime

2018-03-01

The human leukocyte antigen (HLA) region has been found to be involved in the pathogenesis of inflammatory bowel disease (IBD), which is classified into ulcerative colitis (UC) and Crohn's disease (CD), by genome-wide association studies. The aim of this study was to confirm whether HLA-alleles confer susceptibility to UC and to determine whether HLA-allel1es are associated with the clinical phenotypes in Japanese patients with UC. In this study, HLA typing was performed by PCR-sequence-specific oligonucleotides (PCR-SSO) to confirm the correlation between UC and HLA alleles (for HLA-A, B, DRB1) in 45 Japanese UC patients. In addition, whether the HLA alleles are related to patient and clinical background characteristics was examined. Overall, 62.2%, and 66.7% of the 45 UC patients had HLA-B*52 and HLA-DRB1*15, respectively. These allele frequencies were significantly higher than in previously reported Japanese control persons ( P < 0.0001). The frequencies of extraintestinal manifestations [odds ratio (OR) = 0.12, P = 0.039] and a history of colectomy (OR = 0.18, P = 0.046) were lower in HLA-B*52-positive UC patients than in HLA-B*52 negative UC patients. The white blood cell (WBC) count was significantly higher in HLA-DRB1*15-positive patients (9430 ± 4592/μL) than in HLA-DRB1*15-negative patients (6729 ± 2160/μL). Thus, HLA-B*52 and DRB1*15 appear to be associated with disease features and severity in Japanese UC patients. These results indicate that HLA-B*52 and DRB1*15 are not only associated with overall UC susceptibility, but also with the clinical phenotypes in Japanese patients.

Approach to cytomegalovirus infections in patients with ulcerative colitis

PubMed Central

Park, Sung Chul; Jeen, Yoon Mi; Jeen, Yoon Tae

2017-01-01

Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or ‘an innocent bystander’ in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC. PMID:28490715

KIAA0319 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

PubMed Central

Zhao, Hua; Chen, Yun; Zhang, Bao-ping; Zuo, Peng-xiang

2016-01-01

The gene KIAA0319 has been reported to be associated with developmental dyslexia (DD) in previous studies, although the results have not always been consistent. However, few studies have been conducted in Uyghur populations. In the present study, we aimed to investigate the association of KIAA0319 polymorphisms and DD in individuals of Uyghurian descent. We used a custom-by-design 48-Plex SNPscan Kit to genotype 18 single-nucleotide polymorphisms (SNPs) of KIAA0319 in a group of 196 children with dyslexia and 196 controls of Uyghur descent aged 8–12 years. As a result, 7 SNPs (Pmin=0.001) of KIAA0319 had nominal significant differences between the cases and controls under specific genotypic models. The two SNPs rs6935076 (P=0.020 under dominant model; P=0.028 under additive model) and rs3756821 (P=0.021 under additive model) remained significantly associated with dyslexia after Bonferroni correction. Linkage disequilibrium analysis showed three blocks within KIAA0319, and only a 10-SNP haplotype in block 3 was present at significantly different frequencies in the dyslexic children and controls. This study indicated that genetic polymorphisms of KIAA0319 are associated with an increased risk of DD in the Uyghur population. PMID:27098879

Early Transcriptomic Changes in the Ileal Pouch Provide Insight into the Molecular Pathogenesis of Pouchitis and Ulcerative Colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Yong; Dalal, Sushila; Antonopoulos, Dionysios

Background: Ulcerative colitis (UC) only involves the colonic mucosa. Yet, nearly 50% of patients with UC who undergo total proctocolectomy with ileal pouch anal anastomosis develop UC-like inflammation of the ileal pouch (pouchitis). By contrast, patients with familial adenomatous polyposis (FAP) with ileal pouch anal anastomosis develop pouchitis far less frequently. We hypothesized that pathogenic events associated with the development of UC are recapitulated by colonic-metaplastic transcriptomic reprogramming of the UC pouch. Methods: We prospectively sampled pouch and prepouch ileum mucosal biopsies in patients with UC with ileal pouch anal anastomosis 4, 8, and 12 months after their pouch wasmore » in continuity. Mucosal samples were also obtained from patients with FAP. Transcriptional profiles of the UC and FAP pouch and prepouch ileum were investigated via RNA sequencing and compared with data from a previously published microarray study. Results: Unlike patients with FAP, subjects with UC exhibited a large set of differentially expressed genes between the pouch and prepouch ileum as early as 4 months after pouch functionalization. Functional pathway analysis of differentially expressed genes in the UC pouch revealed an enhanced state of immune/inflammatory response and extracellular matrix remodeling. Moreover, >70% of differentially expressed genes mapped to published inflammatory bowel diseases microarray data sets displayed directional changes consistent with active UC but not with Crohn's disease. Conclusions: The UC pouch, well before histologic inflammation, already displays a systems-level gain of colon-associated genes and loss of ileum-associated genes. Patients with UC exhibit a unique transcriptomic response to ileal pouch creation that can be observed well before disease and may in part explain their susceptibility to the development of pouchitis.« less

Individual health discount rate in patients with ulcerative colitis.

PubMed

Waljee, Akbar K; Morris, Arden M; Waljee, Jennifer F; Higgins, Peter D R

2011-06-01

In cost-effectiveness analysis, discount rates are used in calculating the value of future costs and benefits. However, standard discount rates may not accurately describe the decision-making of patients with ulcerative colitis (UC). These patients often choose the long-term risks of immunosuppressive therapy over the short-term risks of colectomy, demonstrating very high discount rates for future health. In this study we aimed to measure the discount rate in UC patients and identify variables associated with the discount rate. We surveyed patients with UC and patients who were postcolectomy for UC to measure their valuations of UC and colectomy health states. We used Standard Gamble (SG) and Time-Trade-Off (TTO) methods to assess current and future health state valuations and calculated the discount rate. Participants included 150 subjects with UC and 150 subjects who were postcolectomy for UC. Adjusted discount rates varied widely (0%-100%), with an overall median rate of 55.0% (interquartile range [IQR] 20.6-100), which was significantly higher than the standard rate of 5%. Within the normal range of discount rates, patients' expected discount rate increased by 0.80% for each additional year of age, and female patients had discount rates that averaged ≈ 8% less than their age-matched counterparts and approached statistical significance. The accepted discount rate of 5% grossly underestimates UC patients' preference for long-term over short-term risk. This might explain UC patients' frequent choice of the long-term risks of immunosuppressive medical therapy over the short-term risks of colectomy. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

[Clinical analysis of cutaneous manifestations and related factors in patients with ulcerative colitis].

PubMed

Tian, Y; Li, J X; Wang, H H; Li, R Y; Liu, X G

2016-07-01

To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors. Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study. Skin disorders were confirmed by the dermatologists. Clinical data were collected and compared between patients with and without cutaneous manifestations. Among the total 373 UC patients, there were 34 cases (9.1%) with cutaneous manifestations, including 11 pyoderma gangrenosum, 8 erythema nodosum, 6 eczema, 3 psoriasis, 2 pemphigus, 1 granulomatous cheilitis, 1 ichthyosis, 1 acne rosacea, and 1 impetigo. The skin manifestations may occur after the diagnosis, simultaneously or even before the diagnosis of UC, which were 24, 7 and 3 patients respectively. The mean age in patients with skin lesions was (47.2±12.1) years, male to female ratio 0.79∶1. More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0%(17/34) vs 25.1%(85/339), P=0.01]. In addition, the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5%(26/34) vs 54.6%(185/339), P=0.04]. The cutaneous manifestations associated with UC are polymorphic, erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients. Skin lesions occur concurrently, pre or post the diagnosis of UC. Skin lesions in UC patients suggest more severe disease activity. Clinicians need to pay more attention to this group.

Golimumab in unresponsive ulcerative colitis.

PubMed

Lippert, Elisabeth; Müller, Martina; Ott, Claudia

2014-01-01

Ulcerative colitis (UC) is a chronic inflammation mainly affecting the colon mucosa. It predominantly occurs in younger patients. Until recently, the main goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain, and weight loss, by using mesalazine and steroids. With newer medications, such as immunomodulators (thiopurines) and the biologics providing blockade of tumor necrosis factor (TNF), the goals of the therapy in UC have changed to long-term remission and mucosal healing. The first available anti-TNF therapy in UC included infusion therapy with infliximab every few weeks. In 2012, subcutaneously administered adalimumab gained approval for the treatment of UC in Germany. In patients with a mild disease, therapy with mesalazine, orally or topically, can be sufficient. In patients with moderate to severe disease, therapy with azathioprine or anti-TNF is often required to reach disease control; however, this is only efficient in about two-thirds of patients. Some patients either show no response or a lost response while on treatment. So, further medical options are warranted in the treatment of UC. With golimumab, a new approach in the treatment of mild to moderate UC recently became available in Germany and is a promising new option in the therapy regimen for patients with UC.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry.

PubMed

Gordillo, Jordi; Cabré, Eduard; Garcia-Planella, Esther; Ricart, Elena; Ber-Nieto, Yolanda; Márquez, Lucía; Rodríguez-Moranta, Francisco; Ponferrada, Ángel; Vera, Isabel; Gisbert, Javier P; Barrio, Jesús; Esteve, Maria; Merino, Olga; Muñoz, Fernando; Domènech, Eugeni

2015-12-01

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

THE RELATIONSHIP BETWEEN CULTURAL IDENTITY AND SELF-ESTEEM AMONG CHINESE UYGHUR COLLEGE STUDENTS: THE MEDIATING ROLE OF ACCULTURATION ATTITUDES.

PubMed

Dong, Li; Lin, Chongde; Li, Tsingan; Dou, Donghui; Zhou, Liqing

2015-08-01

Most acculturation research throughout the world has been conducted in immigrant settings. In order to examine the generalizability of the previous conclusions in immigrant settings, the present study tried to explore the relationship between cultural identity and self-esteem and the mediating role of acculturation attitudes in China. Using the cross-sectional design, a total number of 342 Uyghur college students were asked to complete a survey comprising the Multi-Group Ethnic/National Identity Measure-Revised Scale, the Acculturation Attitudes Scale, and the Rosenberg Self-Esteem Scale. Using hierarchical multiple regression, the results indicated that cultural identity was positively correlated with self-esteem. A significant mediation of acculturation was observed between cultural identity and self-esteem. These findings demonstrated the significance of cultural identity and acculturation attitudes in the adaptation of Chinese Uyghur college students, in which integration is an optimal acculturation attitude.

Development and Validation of an Inflammatory Bowel Diseases Monitoring Index for Use With Mobile Health Technologies.

PubMed

Van Deen, Welmoed K; van der Meulen-de Jong, Andrea E; Parekh, Nimisha K; Kane, Ellen; Zand, Aria; DiNicola, Courtney A; Hall, Laurin; Inserra, Elizabeth K; Choi, Jennifer M; Ha, Christina Y; Esrailian, Eric; van Oijen, Martijn G H; Hommes, Daniel W

2016-12-01

Mobile health technologies are advancing rapidly as smartphone use increases. Patients with inflammatory bowel disease (IBD) might be managed remotely through smartphone applications, but no tools are yet available. We tested the ability of an IBD monitoring tool, which can be used with mobile technologies, to assess disease activity in patients with Crohn's disease (CD) or ulcerative colitis (UC). We performed a prospective observational study to develop and validate a mobile health index for CD and UC, which monitors IBD disease activity using patient-reported outcomes. We collected data from disease-specific questionnaires completed by 110 patients with CD and 109 with UC who visited the University of California, Los Angeles, Center for IBD from May 2013 through January 2014. Patient-reported outcomes were compared with clinical disease activity index scores to identify factors associated with disease activity. Index scores were validated in 301 patients with CD and 265 with UC who visited 3 tertiary IBD referral centers (in California or Europe) from April 2014 through March 2015. We assessed activity of CD based on liquid stool frequency, abdominal pain, patient well-being, and patient-assessed disease control, and activity of UC based on stool frequency, abdominal pain, rectal bleeding, and patient-assessed disease control. The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.90 in patients with CD and 0.91 in patients with UC. They identified endoscopic activity with area under the receiver operating characteristic values of 0.63 in patients with CD and 0.82 in patients with UC. Both scoring systems responded to changes in disease activity (P < .003). The intraclass correlation coefficient for test-retest reliability was 0.94 for CD and for UC. We developed and validated a scoring system to monitor disease activity in patients with CD and UC that can be used with mobile technologies. The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.9 or higher in patients with CD or UC, and endoscopic activity in patients with UC but not CD. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis.

PubMed

Sargın, Zeynep Gök; Erin, Nuray; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients' demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC.

Appendectomy does not decrease the risk of future colectomy in UC: results from a large cohort and meta-analysis.

PubMed

Parian, Alyssa; Limketkai, Berkeley; Koh, Joyce; Brant, Steven R; Bitton, Alain; Cho, Judy H; Duerr, Richard H; McGovern, Dermot P; Proctor, Deborah D; Regueiro, Miguel D; Rioux, John D; Schumm, Phil; Taylor, Kent D; Silverberg, Mark S; Steinhart, A Hillary; Hernaez, Ruben; Lazarev, Mark

2017-08-01

Early appendectomy is inversely associated with the development of UC. However, the impact of appendectomy on the clinical course of UC is controversial, generally favouring a milder disease course. We aim to describe the effect appendectomy has on the disease course of UC with focus on the timing of appendectomy in relation to UC diagnosis. Using the National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Disease Genetics Consortium database of patients with UC, the risk of colectomy was compared between patients who did and did not undergo appendectomy. In addition, we performed a meta-analysis of studies that examined the association between appendectomy and colectomy. 2980 patients with UC were initially included. 111 (4.4%) patients with UC had an appendectomy; of which 63 were performed prior to UC diagnosis and 48 after diagnosis. In multivariable analysis, appendectomy performed at any time was an independent risk factor for colectomy (OR 1.9, 95% CI 1.1 to 3.1), with appendectomy performed after UC diagnosis most strongly associated with colectomy (OR 2.2, 95% CI 1.1 to 4.5). An updated meta-analysis showed appendectomy performed either prior to or after UC diagnosis had no effect on colectomy rates. Appendectomy performed at any time in relation to UC diagnosis was not associated with a decrease in severity of disease. In fact, appendectomy after UC diagnosis may be associated with a higher risk of colectomy. These findings question the proposed use of appendectomy as treatment for UC. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Golimumab in unresponsive ulcerative colitis

PubMed Central

Lippert, Elisabeth; Müller, Martina; Ott, Claudia

2014-01-01

Ulcerative colitis (UC) is a chronic inflammation mainly affecting the colon mucosa. It predominantly occurs in younger patients. Until recently, the main goals in the treatment of UC were to temper the symptoms, such as diarrhea, pain, and weight loss, by using mesalazine and steroids. With newer medications, such as immunomodulators (thiopurines) and the biologics providing blockade of tumor necrosis factor (TNF), the goals of the therapy in UC have changed to long-term remission and mucosal healing. The first available anti-TNF therapy in UC included infusion therapy with infliximab every few weeks. In 2012, subcutaneously administered adalimumab gained approval for the treatment of UC in Germany. In patients with a mild disease, therapy with mesalazine, orally or topically, can be sufficient. In patients with moderate to severe disease, therapy with azathioprine or anti-TNF is often required to reach disease control; however, this is only efficient in about two-thirds of patients. Some patients either show no response or a lost response while on treatment. So, further medical options are warranted in the treatment of UC. With golimumab, a new approach in the treatment of mild to moderate UC recently became available in Germany and is a promising new option in the therapy regimen for patients with UC. PMID:24904202

Are HLA-DR or TAP genes genetic markers of severity in ulcerative colitis?

PubMed

Heresbach, D; Alizadeh, M; Reumaux, D; Colombel, J F; Delamaire, M; Danze, P M; Gosselin, M; Genetet, B; Bretagne, J F; Semana, G

1996-12-01

The pathogeny of ulcerative colitis (UC) is not yet elucidated, but some arguments suggest the implication of genetic factors. Among the candidate genes, those encoding for HLA class II genotypes have been extensively studied in UC; however, discordant data may be imputable to heterogeneity, characterized by immunological markers such as atypical ANCA (p-ANCA), or to inclusion of more or less intractable UC. The aim of our study is to evaluate the interest of HLA class II and TAP genetic markers to identify different clinical forms of UC, according to p-ANCA status. Unrelated patients with a history of UC (n = 91) and healthy control subjects with no personal or family history of inflammatory bowel diseases (IBD) (n = 200) were included. HLA-DRB1*03 was less frequent in UC patients than in healthy controls (8% vs 28%, PC < 0.03). No association was found with any TAP genotypes. Moreover, there was no association with the HLA-DR2 specificity, either in the entire group of UC patients (38% vs 28%) or in the p-ANCA-positive subgroup of patients (30%). The most consistent finding in the present study is that some genetic markers may characterize intractability in UC patients. HLA-DR2 was associated with poor prognosis, regardless of p-ANCA status. In HLA-DR2 and non-HLA-DR2 groups, colectomy was done in 55% and 27% of patients, respectively, (PC < 0.05). Furthermore, in non-HLA-DR2 patients, p-ANCA could be of interest to characterize those with more severe prognosis. Our results confirm the interest of genetic studies to define UC genetic susceptibility, taking into account intractability of the disease. They do not support the hypothesis that p-ANCA is a subclinical marker of genetic susceptibility to UC.

An ethnopharmacological study of aromatic Uyghur medicinal plants in Xinjiang, China.

PubMed

Zhao, Lu; Tian, Shuge; Wen, E; Upur, Halmuart

2017-12-01

An ethnobotanical survey was completed in a remote village and surrounding country of Xinjiang, where most Uyghur medicinal plants could be collected. This work clarifies and increases ethnobotanical data. We surveyed and organized aromatic medicinal plants that are commonly used in clinical settings to provide a significant reference for studying new medical activities. In the survey, informants who have traditional knowledge on aromatic Uyghur medicinal plants were interviewed between March 2014 and September 2014. Aromatic medicinal plant species and pertinent information were collected. Some therapeutic methods and modes of preparation of traditional aromatic medicinal plants were found. A total of 86 aromatic medicinal plant species belonging to 36 families were included in our study. We identified 34 plant species introduced from different regions such as Europe, India and Mediterranean areas. Fruits and whole plants were the most commonly used parts of plant, and most aromatic medicinal plants could be applied as medicine and food. We assigned the medicinal plants a use value (UV). Knowing the UV of species is useful in determining the use reliability and pharmacological features of related plants. Xinjiang is an area in which indigenous aromatic medicinal plants are diversely used and has therefore established a sound dimensional medical healthcare treatment system. Some aromatic Uyghur medicinal plants are on the verge of extinction. Hence, further strategies for the conservation of these aromatic medicinal plants should be prioritized.

Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy

PubMed Central

Farkas, Klaudia; Lakatos, Péter László; Szűcs, Mónika; Pallagi-Kunstár, Éva; Bálint, Anita; Nagy, Ferenc; Szepes, Zoltán; Vass, Noémi; Kiss, Lajos S; Wittmann, Tibor; Molnár, Tamás

2014-01-01

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC. RESULTS: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC. CONCLUSION: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped. PMID:24659890

Clinical and economic outcomes in a population-based European cohort of 948 ulcerative colitis and Crohn's disease patients by Markov analysis.

PubMed

Odes, S; Vardi, H; Friger, M; Esser, D; Wolters, F; Moum, B; Waters, H; Elkjaer, M; Bernklev, T; Tsianos, E; O'Morain, C; Stockbrügger, R; Munkholm, P; Langholz, E

2010-04-01

Forecasting clinical and economic outcomes in ulcerative colitis (UC) and Crohn's disease (CD) patients is complex, but necessary. To determine: the frequency of treatment-classified clinical states; the probability of transition between states; and the economic outcomes. Newly diagnosed UC and CD patients, allocated into seven clinical states by medical and surgical treatments recorded in serial 3-month cycles, underwent Markov analysis. Over 10 years, 630 UC and 318 CD patients had 22,823 and 11,871 cycles. The most frequent clinical outcomes were medical/surgical remission (medication-free) and mild disease (on 5-aminosalicylates, antibiotics, topical corticosteroids), comprising 28% and 62% of UC cycles and 24% and 51% of CD cycles respectively. The probability of drug-response in patients receiving systemic corticosteroids/immunomodulators was 0.74 in UC, 0.66 in CD. Both diseases had similar likelihood of persistent drug-dependency or drug-refractoriness. Surgery was more probable in CD, 0.20, than UC, 0.08. In terms of economic outcomes, surgery was costlier in UC per cycle, but the outlay over 10 years was greater in CD. Drug-refractory UC and CD cases engendered high costs in the cohort. Most patients on 5-aminosalicylates, corticosteroids and immunomodulators had favourable clinical and economic outcomes over 10 years. Drug-refractory and surgical patients exhibited greater long-term expenses.

Profound loss of neprilysin accompanied by decreased levels of neuropeptides and increased CRP in ulcerative colitis

PubMed Central

Sargın, Zeynep Gök; Tazegul, Gokhan; Elpek, Gülsüm Özlem; Yıldırım, Bülent

2017-01-01

Neprilysin (NEP, CD10) acts to limit excessive inflammation partly by hydrolyzing neuropeptides. Although deletion of NEP exacerbates intestinal inflammation in animal models, its role in ulcerative colitis (UC) is not well explored. Herein, we aimed to demonstrate changes in NEP and associated neuropeptides at the same time in colonic tissue. 72 patients with UC and 27 control patients were included. Patients’ demographic data and laboratory findings, five biopsy samples from active colitis sites and five samples from uninvolved mucosa were collected. Substance P (SP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) were extracted from freshly frozen tissues and measured using ELISA. Levels of NEP expression were determined using immunohistochemistry and immunoreactivity scores were calculated. GEBOES grading system was also used. We demonstrated a profound loss (69.4%) of NEP expression in UC, whereas all healthy controls had NEP expression. Patients with UC had lower neuronal SP; however non-neuronal SP remained similar. UC patients had also lower neuronal and non-neuronal VIP levels. CGRP were low in general and no significant changes were observed. Additionally, CRP positive patients with UC had higher rates of NEP loss (80% vs 51.9%) and lower SP levels when compared with CRP negative patients with UC. Concurrent decreases in SP and VIP with profound loss of NEP expression observed in UC is likely to be one of the factors in pathogenesis. Further studies are required to define the role of neuropeptides and NEP in UC. PMID:29232715

Immunosuppressive function of mesenchymal stem cells from human umbilical cord matrix in immune thrombocytopenia patients.

PubMed

Ma, Li; Zhou, Zeping; Zhang, Donglei; Yang, Shaoguang; Wang, Jinhong; Xue, Feng; Yang, Yanhui; Yang, Renchi

2012-05-01

Human umbilical cord matrix/Wharton's jelly (hUC)-derived mesenchymal stem cells (MSC) have been shown to have marked therapeutic effects in a number of inflammatory diseases and autoimmune diseases in humans based on their potential for immunosuppression and their low immunogenicity. Currently, no data are available on the effectiveness of UC-MSC transplantation in immune thrombocytopenia (ITP) patients. It was the objective of this study to assess the effect of allogeneic UC-MSCs on ITP patients in vitro and in vivo. Peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BM-MNCs) from ITP patients and healthy controls were co-cultured with UC-MSCs for three days and seven days, respectively. Flow cytometry and ELISA were applied to assess the various parameters. In PBMCs from ITP patients, the proliferation of autoreactive T, B lymphocytes and destruction of autologous platelets were dramatically suppressed by UC-MSCs. UC-MSCs not only suppressed co-stimulatory molecules CD80, CD40L and FasL expression but also in shifting Th1/Th2/Treg cytokines profile in ITP patients. UC-MSCs obviously reversed the dysfunctions of megakaryocytes by promoting platelet production and decreasing the number of living megakaryocytes as well as early apoptosis. In addition, the level of thrombopoietin was increased significantly. Our clinical study showed that UC-MSCs play a role in alleviating refractory ITP by increasing platelet numbers. These findings suggested that UC-MSCs transplantation might be a potential therapy for ITP.

Ulcerative colitis with acute pleurisy

PubMed Central

Lu, Shuming; Wang, Lihua; Zhang, Weisheng; Zhang, Zhuqing; Liu, Lina; Wang, Yingde; Meng, Hua

2017-01-01

Abstract Rationale: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease, are associated with a large number of extraintestinal manifestations. Pulmonary manifestations are infrequently seen in patients with IBD. Moreover, serositis including pleural and pericardial manifestations in UC is rare. Patient concerns: We report a case of UC with acute pleurisy in a 43-year-old man; review literature; and discuss the diagnosis, differential diagnosis, and treatment. Diagnoses: Active duodenal ulcer was found using gastroscopy. Multiple ulcers in segmented pattern were noticed in the left hemi-colon using colonoscopy. An UC in active stage was confirmed subsequently by histology. Intervention: The patient was treated with bifidobacterium tetravaccine tablets, oral mesalazine and mesalazine enemas. The omeprazole and mucosal protective agents were given to treat the duodenal ulcer. Outcomes: As follow-up, the therapy including oral mesalazine and infliximab regularly was continued and the patient condition was stabilized. Main lesson: Pulmonary involvement should be considered in patients who develop pleurisy in UC. Infliximab is considered the better available treatment for patients presenting with pleurisy in UC. PMID:28746225

Takayasu arteritis and ulcerative colitis: high rate of co-occurrence and genetic overlap.

PubMed

Terao, Chikashi; Matsumura, Takayoshi; Yoshifuji, Hajime; Kirino, Yohei; Maejima, Yasuhiro; Nakaoka, Yoshikazu; Takahashi, Meiko; Amiya, Eisuke; Tamura, Natsuko; Nakajima, Toshiki; Origuchi, Tomoki; Horita, Tetsuya; Matsukura, Mitsuru; Kochi, Yuta; Ogimoto, Akiyoshi; Yamamoto, Motohisa; Takahashi, Hiroki; Nakayamada, Shingo; Saito, Kazuyoshi; Wada, Yoko; Narita, Ichiei; Kawaguchi, Yasushi; Yamanaka, Hisashi; Ohmura, Koichiro; Atsumi, Tatsuya; Tanemoto, Kazuo; Miyata, Tetsuro; Kuwana, Masataka; Komuro, Issei; Tabara, Yasuharu; Ueda, Atsuhisa; Isobe, Mitsuaki; Mimori, Tsuneyo; Matsuda, Fumihiko

2015-05-01

Takayasu arteritis (TAK) is a systemic vasculitis affecting large arteries and large branches of the aorta. Ulcerative colitis (UC) is a prevalent autoimmune colitis. Since TAK and UC share HLA-B*52:01 and IL12B as genetic determinants, and since there are case reports of the co-occurrence of these diseases, we hypothesized that UC is a common complication of TAK. We undertook this study to perform a large-scale analysis of TAK, both to evaluate the prevalence of concurrent cases of TAK and UC and to identify and estimate susceptibility genes shared between the 2 diseases. We analyzed a total of 470 consecutive patients with TAK from 14 institutions. We characterized patients with TAK and UC by analyzing clinical manifestations and genetic components. Genetic overlapping of TAK and UC was evaluated with the use of UC susceptibility single-nucleotide polymorphisms by comparing risk directions and effect sizes between susceptibility to the 2 diseases. Thirty of 470 patients with TAK had UC (6.4% [95% confidence interval 4.3-9.0]). This percentage was strikingly higher than that expected from the prevalence of UC in Japan. Patients with TAK complicated with UC developed TAK at an earlier stage of life (P = 0.0070) and showed significant enrichment of HLA-B*52:01 compared to TAK patients without UC (P = 1.0 × 10(-5) ) (odds ratio 12.14 [95% confidence interval 2.96-107.23]). The 110 non-HLA markers of susceptibility to UC significantly displayed common risk directions with susceptibility to TAK (P = 0.0054) and showed significant departure of permutation P values from expected P values (P < 1.0 × 10(-10) ). UC is a major complication of TAK. These 2 diseases share a significant proportion of their genetic background, and HLA-B*52:01 may play a central role in their co-occurrence. © 2015, American College of Rheumatology.

Clinical epidemiology of ulcerative colitis in Arabs based on the Montréal classification.

PubMed

Alharbi, Othman R; Azzam, Nahla A; Almalki, Ahmed S; Almadi, Majid A; Alswat, Khalid A; Sadaf, Nazia; Aljebreen, Abdulrahman M

2014-12-14

To determine the clinical, epidemiological and phenotypic characteristics of ulcerative colitis (UC) in Saudi Arabia by studying the largest cohort of Arab UC patients. Data from UC patients attending gastroenterology clinics in four tertiary care centers in three cities between September 2009 and September 2013 were entered into a validated web-based registry, inflammatory bowel disease information system (IBDIS). The IBDIS database covers numerous aspects of inflammatory bowel disease. Patient characteristics, disease phenotype and behavior, age at diagnosis, course of the disease, and extraintestinal manifestations were recorded. Among 394 UC patients, males comprised 51.0% and females 49.0%. According to the Montréal classification of age, the major chunk of our patients belonged to the A2 category for age of diagnosis at 17-40 years (68.4%), while 24.2% belonged to the A3 category for age of diagnosis at > 40 years. According to the same classification, a majority of patients had extensive UC (42.7%), 35.3% had left-sided colitis and 29.2% had only proctitis. Moreover, 51.3% were in remission, 16.6% had mild UC, 23.4% had moderate UC and 8.6% had severe UC. Frequent relapse occurred in 17.4% patients, infrequent relapse in 77% and 4.8% had chronic disease. A majority (85.2%) of patients was steroid responsive. With regard to extraintestinal manifestations, arthritis was present in 16.4%, osteopenia in 31.4%, osteoporosis in 17.1% and cutaneous involvement in 7.0%. The majority of UC cases were young people (17-40 years), with a male preponderance. While the disease course was found to be similar to that reported in Western countries, more similarities were found with Asian countries with regards to the extent of the disease and response to steroid therapy.

Long-Term Benefit of Mesalamine Granules for Patients Who Achieved Corticosteroid-Induced Ulcerative Colitis Remission.

PubMed

Lichtenstein, Gary R; Gordon, Glenn L; Zakko, Salam; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ron; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2016-01-01

Patients with ulcerative colitis (UC) who achieve remission with corticosteroids often relapse after tapering or discontinuation; alternative treatments limiting steroid exposure and UC relapse would be beneficial. It remains uncertain whether patients with corticosteroid-induced remission experience benefit with mesalamine granules (MG), a locally acting aminosalicylate extended-release capsule formulation for maintenance of UC remission in adults. Efficacy and safety of MG 1.5 g once daily was evaluated in patients with UC in corticosteroid-induced remission. Data from patients with previous corticosteroid use to achieve baseline UC remission were analyzed from two 6-month randomized, double-blind, placebo-controlled trials and a 24-month open-label extension (OLE). Six-month relapse-free rates were assessed using the revised Sutherland Disease Activity Index. UC-related adverse events (AEs) were recorded during the 30 months. Included were 158 steroid-treated patients in UC remission (MG, n = 105; placebo, n = 53) and 74/105 MG-treated patients who continued MG in the OLE. A significantly larger percentage of patients remained relapse-free at 6 months with MG (77.1 %) versus placebo (54.7 %; P = 0.006), with a 55 % reduction in relapse risk (hazard ratio [HR] 0.45; 95 % CI 0.25-0.79). There was a similar (49.2 %) reduction in risk of UC-related AEs at 6 months (HR 0.51; 95 % CI 0.31-0.84; P = 0.009) that was sustained during the OLE. MG 1.5 g once daily administered for maintenance of corticosteroid-induced remission was associated with low risk of relapse and UC-related AEs. CLINICALTRIALS.GOV: NCT00744016, NCT00767728, and NCT00326209.

Determination of Cytomegalovirus Prevalence and Glycoprotein B Genotypes Among Ulcerative Colitis Patients in Ahvaz, Iran

PubMed Central

Taherkhani, Reza; Farshadpour, Fatemeh; Makvandi, Manoochehr; Hamidifard, Mojtaba; Esmailizadeh, Mahdi; Ahmadi, Bijan; Heidari, Hamid

2015-01-01

Background: The human cytomegalovirus (HCMV) is a common pathogen which usually remains asymptomatic in the healthy adults; however, it can cause a symptomatic disease in the immunocompromised patients. The risk of infection with HCMV increases in ulcerative colitis (UC) patients as a result of receiving immunosuppressive agents. Objectives: This study aimed to determine the prevalence and the glycoprotein B genotypes of HCMV among the patients with HCMV disease superimposed on an UC flare that required hospitalization in Imam Khomeini Hospital in Ahvaz, Iran, during 2010- 2012. Patients and Methods: In this case-control study, formalin-fixed paraffin-embedded intestinal tissue samples were taken from 98 patients with UC disease including 53 males and 45 females (mean age ± standard deviation, 38.95 ± 17.93) and 67 control patients with noninflammatory disease who were referred to Imam Khomeini Hospital during 2010-2012. Detection of HCMV genome in intestinal samples was carried out by seminested polymerase chain reaction. Glycoprotein B genotypes were determined by sequencing. Results: Among 98 patients with UC, only 12 (12.2%) patients were positive for HCMV genome, while the HCMV genome was not detected in any of the controls. (P = 0.002). The distribution of HCMV gB genotypes in 12 CMV-positive UC patients was as follow: gB1, 11 (91.7%) and gB3, 1 (8.3%). The most prevalent genotype in CMV-positive UC patients was gB1. Conclusions: In this study, high prevalence of 91.7% HCMV gB1 genotype was predominant among HCMV-positive UC patients, which suggests that there might be an association between HCMV gB genotype 1 and UC disease. PMID:25793098

Prevalence of inflammatory bowel disease in two districts of Sri Lanka: a hospital based survey

PubMed Central

2010-01-01

Background Inflammatory bowel disease (IBD) is being increasingly diagnosed in Asia. However there are few epidemiological data from the region. Methods To determine prevalence and clinical characteristics of IBD, a hospital-based survey was performed in the Colombo and Gampaha districts (combined population 4.5 million) in Sri Lanka. Patients with established ulcerative colitis (UC) and Crohn's disease (CD), who were permanent residents of these adjoining districts, were recruited from hospital registries and out-patient clinics. Clinical information was obtained from medical records and patient interviews. Results There were 295 cases of IBD (UC = 240, CD = 55), of which 34 (UC = 30, CD = 4) were newly diagnosed during the study year. The prevalence rate for UC was 5.3/100,000 (95% CI 5.0-5.6/100,000), and CD was 1.2/100,000 (95% CI 1.0-1.4/100,000). The incidence rates were 0.69/100,000 (95% CI 0.44-0.94/100,000) for UC and 0.09/100,000 (95% CI 0.002-0.18/100,000) for CD. Female:male ratios were 1.5 for UC and 1.0 for CD. Mean age at diagnosis was (males and females) 36.6 and 38.1y for UC and 33.4 and 36.2y for CD. Among UC patients, 51.1% had proctitis and at presentation 58.4% had mild disease. 80% of CD patients had only large bowel involvement. Few patients had undergone surgery. Conclusions The prevalence of IBD in this population was low compared to Western populations, but similar to some in Asia. There was a female preponderance for UC. UC was mainly mild, distal or left-sided, while CD mainly involved the large bowel. PMID:20302651

High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial.

PubMed

Aoun, Mabel; Makki, Maha; Azar, Hiba; Matta, Hiam; Chelala, Dania Nehme

2017-06-07

Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K 2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K 2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score. This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 μg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks. At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman's rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046). The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01). Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 μg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess the changes in vascular calcifications in hemodialysis patients treated with vitamin K 2 over a longer follow-up period. The clinical trial was registered on clinicaltrials.gov (Identification number NCT02876354 , on August 11, 2016).

Determination of cytomegalovirus prevalence and glycoprotein B genotypes among ulcerative colitis patients in ahvaz, iran.

PubMed

Taherkhani, Reza; Farshadpour, Fatemeh; Makvandi, Manoochehr; Hamidifard, Mojtaba; Esmailizadeh, Mahdi; Ahmadi, Bijan; Heidari, Hamid

2015-02-01

The human cytomegalovirus (HCMV) is a common pathogen which usually remains asymptomatic in the healthy adults; however, it can cause a symptomatic disease in the immunocompromised patients. The risk of infection with HCMV increases in ulcerative colitis (UC) patients as a result of receiving immunosuppressive agents. This study aimed to determine the prevalence and the glycoprotein B genotypes of HCMV among the patients with HCMV disease superimposed on an UC flare that required hospitalization in Imam Khomeini Hospital in Ahvaz, Iran, during 2010- 2012. In this case-control study, formalin-fixed paraffin-embedded intestinal tissue samples were taken from 98 patients with UC disease including 53 males and 45 females (mean age ± standard deviation, 38.95 ± 17.93) and 67 control patients with noninflammatory disease who were referred to Imam Khomeini Hospital during 2010-2012. Detection of HCMV genome in intestinal samples was carried out by seminested polymerase chain reaction. Glycoprotein B genotypes were determined by sequencing. Among 98 patients with UC, only 12 (12.2%) patients were positive for HCMV genome, while the HCMV genome was not detected in any of the controls. (P = 0.002). The distribution of HCMV gB genotypes in 12 CMV-positive UC patients was as follow: gB1, 11 (91.7%) and gB3, 1 (8.3%). The most prevalent genotype in CMV-positive UC patients was gB1. In this study, high prevalence of 91.7% HCMV gB1 genotype was predominant among HCMV-positive UC patients, which suggests that there might be an association between HCMV gB genotype 1 and UC disease.

Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?

PubMed

Balci, Ugur; Ozer, Kutan; Gorgel, Sacit Nuri; Sefik, Ertugrul; Girgin, Cengiz; Dincel, Cetin

2013-10-01

The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.

Appendectomy, smoking habits and the risk of developing ulcerative colitis: a case control study in private practice setting.

PubMed

de Saussure, Philippe; Clerson, Pierre; Prost, Pierre-Louis; Truong Tan, Nghiep; Bouhnik, Yoram; Gil-Rch

2007-05-01

The strongest environmental factors identified for ulcerative colitis (UC) are cigarette smoking and appendectomy. However, most studies have been performed using case-controls from hospital-based populations. The purpose of this study was to compare the history of previous appendectomy and smoking habits in a group of patients with UC and a control group, followed by gastroenterologists in private practice. We performed a case control study in which 100 physicians recruited UC-patients and age and sex matched controls. Data were collected during a single visit. Based on a standardized questionnaire, UC patients and controls were divided into never, former or current smokers, and into subjects with or without a previous history of appendectomy. One hundred and ninety eight age- and sex-matched pairs of UC patients and controls were included. The prevalence of appendectomy in the UC-patients and control group was 12% and 46%, respectively. The pairwise-matched OR of ulcerative colitis for previous appendectomy was 0.10 (95% CI, 0.05-0.21) (P<0.0001). The OR for former and never smokers versus current smokers was 2.40 (95% CI 1.31-4.38) (P=0.004). In UC-patients, the OR of family history of UC compared with controls was 2.80 (95% CI, 1.01-7.77) (P=0.048). This case-control study confirmed a strong negative correlation between both appendectomy and tobacco smoking, and ulcerative colitis in patients followed-up by gastroenterological practitioners.

Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.

PubMed

Kadivar, Khadijeh; Ruchelli, Eduardo D; Markowitz, Jonathan E; Defelice, Magee L; Strogatz, Melissa L; Kanzaria, Mitul M; Reddy, Krishna P; Baldassano, Robert N; von Allmen, Daniel; Brown, Kurt A

2004-09-01

Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesis; however, they fail to accurately reflect in vivo intestinal IL-13 production. We evaluate IL-13, IL-6, and IL-1beta elaborations from colonic organ cultures of pediatric IBD patients Endoscopic lamina propria biopsies or surgical specimens from pediatric patients with IBD were organ cultured and supernatants evaluated by enzyme-linked immunosorbent assay for IL-1beta, IL-6, and IL-13. IL-13 concentrations were significantly reduced in ulcerative colitis (UC) patients when compared with normal controls (P = 0.002) and Crohn disease (CD) patients (P = 0.001). End-stage UC patients at colectomy had lower intestinal IL-13 production than all other UC patients (P = 0.002). No significant correlation was found between IL-13 concentration and histologic disease severity (P = 0.134). Diminished intestinal IL-13 production is present in UC patients and wanes further with clinical disease progression. These findings suggest that UC patients may be differentiated from CD patients by intestinal IL-13 quantitation, and UC patients may benefit from IL-13 enhancing therapies. Copyright 2004 Lippincott Williams & Wilkins

Internet-orientated Assessment of QOL and Actual Treatment Status in Japanese Patients with Inflammatory Bowel Disease: The 3I survey.

PubMed

Matsumoto, Takayuki; Yanai, Shunichi; Toya, Yosuke; Ueno, Masato; Nakamura, Shotaro

2015-06-01

This survey aimed to compare actual lifestyle factors and QOL between Japanese IBD patients and healthy Japanese controls, by questionnaire using an internet-web system. Through the internet-web system, we asked 464 patients with Crohn's disease [CD], 360 patients with ulcerative colitis [UC], and 4100 healthy controls to answer a questionnaire including an eight-item short-form health survey [SF-8]. The survey was conducted until data had been accumulated from the predetermined numbers of patients [120 patients each with CD and UC] and healthy controls [240 subjects]. QOL assessment by SF-8 revealed scores for six of the eight subscale items and the summary score for the mental component to be significantly lower in the CD and UC groups than in controls. There was a significant negative correlation between each SF-8 score and the degree of CD and UC symptoms. The marriage rate in adult patients was significantly lower in the CD than in the UC group or the controls. The mean annual income and the employment rate were significantly lower in the CD than in the UC group or the controls. CD patients receiving biologicals were more frequently satisfied with the efficacy of treatment than UC patients were with their treatment regimens [56% vs 29%]. Actual lifestyle factors and QOL appear to be impaired in Japanese patients with IBD, especially those with CD. The subjective efficacy of biologicals might be greater in CD than in UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Albumin as a prognostic marker for ulcerative colitis

PubMed Central

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Trivedi, Chinmay; Yang, Yu-Xiao

2017-01-01

AIM To evaluate the role of albumin at the time of ulcerative colitis (UC) diagnosis in predicting the clinical course of disease. METHODS Nationwide cohort of patients with newly diagnosed UC in the Veterans Affairs health care system was identified and divided into two categories: hypoalbuminemia (i.e., ≤ 3.5 gm/dL) or normal albumin levels (i.e., > 3.5 gm/dL) at the time of UC diagnosis. The exposure of interest was presence of hypoalbuminemia defined as albumin level ≤ 3.5 g/dL at the time of UC diagnosis. Patients were then followed over time to identify the use of ≥ 2 courses of corticosteroids (CS), thiopurines, anti-TNF medications and requirement of colectomy for UC management. RESULTS The eligible study cohort included 802 patients, but 92 (11.4%) patients did not have their albumin levels checked at the time of UC diagnosis, and they were excluded. A total of 710 patients, who had albumin levels checked at time of UC diagnosis, were included in our study. Amongst them, 536 patients had a normal albumin level and 174 patients had hypoalbuminemia. Patients with hypoalbuminemia at diagnosis had a higher likelihood of ≥ 2 courses of CS use (adjusted HR = 1.7, 95%CI: 1.3-2.3), higher likelihood of thiopurine or anti- TNF use (adjusted HR = 1.72, 95%CI: 1.23-2.40) than patients with normal albumin level at diagnosis. There was a trend of higher likelihood of colectomy in hypoalbuminemic patients, but it was not statistically significant (Adjusted HR = 1.7, 95%CI: 0.90-3.25). CONCLUSION Hypoalbuminemia at disease diagnosis can serve as a prognostic marker to predict the clinical course of UC at the time of diagnosis. PMID:29259376

Systematic review with meta-analysis: real-world effectiveness and safety of vedolizumab in patients with inflammatory bowel disease.

PubMed

Schreiber, Stefan; Dignass, Axel; Peyrin-Biroulet, Laurent; Hather, Greg; Demuth, Dirk; Mosli, Mahmoud; Curtis, Rebecca; Khalid, Javaria Mona; Loftus, Edward Vincent

2018-06-04

Selective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness. A systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn's disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014-June 22, 2017. Response and remission rates were combined in random-effects meta-analyses. At treatment week 14, 32% of UC patients [95% confidence interval (CI) 27-39%] and 30% of CD patients (95% CI 25-34%) were in remission; and at month 12, 46% for UC (95% CI 37-56%) and 30% for CD (95% CI 20-42%). For UC, the rates of corticosteroid-free remission were 26% at week 14 (95% CI 20-34%) and 42% at month 12 (95% CI 31-53%); for CD they were 25% at week 14 (95%, CI 20-31%) and 31% at month 12 (95%, CI 20-45%). At month 12, 33-77% of UC and 6-63% of CD patients had mucosal healing. Nine percent of patients reported serious adverse events. Vedolizumab demonstrated real-world effectiveness in patients with moderate-to-severely active UC or CD, with approximately one-half and one-third of patients, respectively, in remission at treatment month 12. These findings are consistent with clinical trial data and support the long-term benefit-risk profile of vedolizumab.

Clinical course of ulcerative colitis patients who develop acute pancreatitis

PubMed Central

Kim, Jong Wook; Hwang, Sung Wook; Park, Sang Hyoung; Song, Tae Jun; Kim, Myung-Hwan; Lee, Ho-Su; Ye, Byong Duk; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun

2017-01-01

AIM To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. METHODS We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. RESULTS Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent. CONCLUSION Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent. PMID:28596686

Clinical course of ulcerative colitis patients who develop acute pancreatitis.

PubMed

Kim, Jong Wook; Hwang, Sung Wook; Park, Sang Hyoung; Song, Tae Jun; Kim, Myung-Hwan; Lee, Ho-Su; Ye, Byong Duk; Yang, Dong-Hoon; Kim, Kyung-Jo; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun

2017-05-21

To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0.30%) had aminosalicylate-induced, and 13 (1.73%) had thiopurine-induced pancreatitis. All 13 patients with autoimmune pancreatitis (AIP) had type 2 AIP. Two (15.4%) patients had pre-existing AIP, and three (23.1%) patients developed AIP and UC simultaneously. Compared to non-pancreatitis patients, AIP patients had UC diagnosed at a significantly younger age (median, 22.9 years vs 36.4 years; P = 0.001). AIP and aminosalicylate-induced pancreatitis patients had more extensive UC compared to non-pancreatitis patients. All patients with pancreatitis recovered uneventfully, and there were no recurrences. Biologics were used more frequently in aminosalicylate- and thiopurine-induced pancreatitis patients compared to non-pancreatitis patients [adjusted OR (95%CI), 5.16 (1.42-18.67) and 6.90 (1.83-25.98), respectively]. Biologic utilization rate was similar among AIP and non-pancreatitis patients [OR (95%CI), 0.84 (0.11-6.66)]. Colectomy rates for autoimmune, aminosalicylate-induced, and thiopurine-induced pancreatitis, and for non-pancreatitis patients were 15.4% (2/13), 20% (2/10), 15.4% (2/13), and 7.3% (239/3256), respectively; the rates were not significantly different after adjusting for baseline disease extent. Pancreatitis patients show a non-significant increase in colectomy, after adjusting for baseline disease extent.

Efficacy of vedolizumab for induction of clinical response and remission in patients with moderate to severe inflammatory bowel disease who failed at least two TNF antagonists.

PubMed

De Vos, Martine; Dhooghe, Barbara; Vermeire, Severine; Louis, Edouard; Mana, Fazia; Elewaut, Ann; Bossuyt, Peter; Baert, Filip; Reenaers, Catherine; Van Gossum, Marc; Macken, Elisabeth; Ferrante, Marc; Hindryckx, Pieter; Dewit, Olivier; Holvoet, Tom; Franchimont, Denis

2018-04-01

Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015). Rates of clinical response and remission were retrospectively evaluated at Week 10 for UC and Week 14 for CD using the physician's global assessment (PGA), Mayo score and Harvey Bradshaw index (HBI) or Crohn's disease activity score (CDAI) scores. Eighty-four patients (29 UC, 55 CD) had sufficient data for analysis. For UC patients, clinical response was observed in 76% based on PGA and 59% based on the Mayo score. The corresponding percentages for CD patients were 80% for PGA and 65% for HBI/CDAI. Clinical remission rates were 10% and 40% for UC and CD, respectively. Steroid-free remission was observed in respectively 10% and 35%. Globally, corticosteroids were stopped in 14 out of 48 patients (29%). No new safety signals were reported. Up to 70% TNF-refractory/intolerant UC and CD patients achieved a clinical response after 10 to 14 weeks of vedolizumab treatment in this real-life cohort.

Decreased levels of serum omentin-1 in patients with inflammatory bowel disease.

PubMed

Yin, Jian; Hou, Peng; Wu, Zhiqiang; Nie, Yanxiao

2015-01-10

Inflammation is involved in the mechanism of inflammatory bowel disease (IBD). Omentin, a newly discovered adipokine, is thought to play an anti-inflammatory role. This study aimed to determine whether serum levels of omentin-1 are associated with the presence and disease activity of IBD. This study consisted of 192 patients with IBD: 100 with Crohn's disease [CD], 92 with ulcerative colitis [UC], and 104 healthy subjects. Serum levels of omentin-1 were measured using enzyme-linked immunosorbent assay (ELISA). Serum omentin-1 levels were significantly decreased in CD and UC patients compared with healthy controls. Multivariable logistic regression analysis revealed that serum omentin-1 levels were inversely associated with the presence of CD and UC. Active CD and UC patients both had significantly decreased levels of serum omentin-1 compared with inactive CD and UC patients. In both CD and UC patients, serum omentin-1 levels were significantly associated with decreased levels of body mass index (BMI) and C-reactive protein (CRP). Decreased serum omentin-1 levels could be considered as an independent predicting marker of the presence and disease activity of IBD.

Prevalence of Dry Eye in Uyghur and Han Ethnic Groups in Western China.

PubMed

Gong, Ying-Ying; Zhang, Fan; Zhou, Jin; Li, Jing; Zhang, Guang-Hui; Wang, Jun-Liang; Gu, Zhen-Sheng

2017-06-01

To describe and compare the prevalence and characteristics of dry eye among Han and Uyghur persons living in Kashi, the most inland city of China. A total of 1015 residents of Kashi participated in this 2013 cross-sectional study. To evaluate clinical characteristics, each subject completed (1) a dry-eye questionnaire detailing symptoms of dry eye, (2) Schirmer's I-test (SIT), (3) tear-film break-up time (BUT) test, and fluorescein staining of the cornea. Dry eye was defined as the existence of dry eye symptoms and at least two positive clinical signs. Data were analyzed using SPSS software. The prevalence and risk factors of dry eye were evaluated using a multivariate model. Overall, 282 (27.8%) of the 1015 participants were diagnosed with dry eye (95% confidence interval (CI): range, 25.5-30.1). The prevalence of dry eye among Han persons (37.9 %) (95% CI: range, 35.8-40.0) was higher than that among Uyghurs (21.8%) (95% CI: 19.6-24.0) (p < 0.05). The prevalence of dry eye was 25.6% (95% CI: range, 23.3-27.8) among men and 28.7% (95% CI: 26.5-30.9) among women (p > 0.05). Risk factors for dry eye included ethnicity, age, occupation, arthritis, and dry mouth. Our study revealed a higher prevalence of dry eye among Han than Uyghur persons in Kashi. Dry eye was significantly associated with environment and ethnicity.

Polymorphisms of the IL-1beta and IL-1beta-inducible genes in ulcerative colitis.

PubMed

Nohara, Hiroaki; Saito, Yuki; Higaki, Singo; Okayama, Naoko; Hamanaka, Yuichiro; Okita, Kiwamu; Hinoda, Yuji

2002-11-01

Ulcerative colitis (UC) is a chronic disorder of undetermined etiology, but a genetic predisposition to UC is well recognized. Among cytokines induced in UC, interleukin 1 (IL-1) appears to have a central role because of its immunological upregulatory and proinflammatory activities. The aim of this study was to assess whether UC is associated with polymorphisms of the IL-1beta gene and three additional genes inducible with IL-1beta in Japanese subjects. A total of 96 patients with UC and 106 ethnically matched controls were genotyped at polymorphic sites in IL-1beta, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and inducible nitric oxide synthase (iNOS) genes, using polymerase chain reaction (PCR)-based methods. There was no significant difference in genotype distributions of IL-1beta, MMP-1, MMP-3, and iNOS genes between controls and UC patients in a Japanese population. Also, no significant association of those polymorphisms with various clinical parameters of the patients was found. However, concerning association of age at onset with clinical factors in UC, the frequency of pancolitis was significantly higher in UC patients with age at onset being less than 30 years than in those more than 30 years of age (P = 0.049). No association of the IL-1beta and three IL-1beta-inducible gene polymorphisms with UC was observed in a Japanese population.

Balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes is vital for patients with ulcerative colitis.

PubMed

Dai, Shi-Xue; Wu, Gang; Zou, Ying; Feng, Yan-Ling; Liu, Hong-Bo; Feng, Jin-Shan; Chi, Hong-Gang; Lv, Ru-Xi; Zheng, Xue-Bao

2013-01-01

Immune balances are important for many diseases including ulcerative colitis (UC). This study aimed to explore the role of the balance between CD8+ CD28+ and CD8+ CD28- T lymphocytes for the immunological pathogenesis of UC. Sixteen patients with UC, 16 patients with irritable bowel syndrome (IBS) and 15 healthy volunteers were enrolled. The frequencies of CD8+ CD28+ and CD8+CD28- T lymphocytes in peripheral blood and colon tissue were tested using flow cytometry and immunofluorescent, respectively. The cytokines of the two lymphocytes were detected by protein chips and ELISA. The expression of the signal transducers, the JAK3 and STAT6, as well the transcription factors, the NFATc2 and GATA3, was all detected by both western blot and immunohistochemistry. For UC patients, the frequencies of CD8+ CD28+ T lymphocytes, together with the ratios of CD8+ CD28+ / CD8+ CD28- T lymphocytes in blood and colon tissue, were significantly lower than those in both IBS patients and healthy volunteers. But the frequencies of CD8+ CD28- T lymphocytes in blood and colon tissue of the UC patients were significantly higher than the other two groups. The concentration of IL-7 and -13, and the expression of JAK3 and STAT6 in UC patients, were significantly lower when compared with the other two groups. Conversely, the concentration of IL-12p40 and -15, and the expression of GATA3 and NFATc2 in UC patients, were significantly higher than both IBS and control group. The balance of CD8+ CD28+ / CD8+ CD28- T lymphocytes plays a vital role in UC, while the balance tilt towards CD8+ CD28+ T lymphocytes is beneficial for patients with UC.

Patients' diets and preferences in a pediatric population with inflammatory bowel disease.

PubMed

Green, T J; Issenman, R M; Jacobson, K

1998-01-01

To determine the dietary practices of the pediatric inflammatory bowel disease population at the Children's Hospital of the Hamilton Health Sciences Corporation and the reported effectiveness of those diets. A questionnaire mailed to 153 pediatric patients was returned by 125 patients (76 Crohn's disease [CD] and 49 ulcerative colitis [UC] patients)--an 82% response rate. The median age of respondents was 13 years, and 62% were male. Ninety per cent and 71% of CD and UC patients, respectively, had changed their diets since diagnosis. Caloric supplements (eg, BOOST [Mead Johnson Nutritionals]), sole source nutrition, low fibre and lactose-free diets were used by more than 15% of CD patients, whereas lactose-free, nonspicy, low acid, additive-free, caloric supplement and low fibre diets were used by more than 15% of UC patients. A diet supplement was more commonly used in CD patients (P < 0.05) and an additive-free diet in UC patients. Corn and corn products, nuts, milk and bran were avoided by more than 20% of CD and UC patients; however, more CD than UC patients avoided corn and corn products. In addition, UC patients (more than 20%) also avoided tomato, other dairy (nonfluid milk-based products and foods containing milk products), chocolate, cheese, wheat, tomato sauces and fruit juice. A benefit was reported for 103 of 141 reported diets, with the most commonly alleviated symptoms being abdominal pain, diarrhea and flatulence. Many children with inflammatory bowel disease have altered their diets to manage their disease and have attributed symptomatic relief to these diets.

Update on the management of ulcerative colitis.

PubMed

Taba Taba Vakili, Sahar; Taher, Mohammad; Ebrahimi Daryani, Nasser

2012-01-01

The present treatment goals for inflammatory bowel diseases (IBD) especially ulcerative colitis (UC) include rapid induction of clinical remission, steroid-free maintenance of clinical remission, mucosal healing and improvement of quality of life in UC patients. Immunomodulators have been reserved for steroid- dependent or steroid- refractory UC patients. Among these agents, azathioprine/6-mercaptopurine should be used for maintenance of remission in quiescent UC. Calcineurin inhibitors can be prescribed as a short-term rescue therapy in steroid- refractory UC patients, but the long term efficacy of these agents remains unclear. According to retrospective studies, methotraxate is not recommended for inducing and maintaining remission in UC. Novel biological therapies targeting different specific immunological pathways continue to be developed and introduced for a variety of clinical scenarios in IBD. Infliximab is currently used for induction and maintenance therapy in patients who have moderately to severely active UC with an inadequate response to conventional agents such as aminosalicylates, corticosteroids, or immunomodulators. Other anti-TNF agents and biologic therapies are undergoing evaluation in clinical trials for their efficacy in IBD. Most patients who start biologics should continue treatment for the foreseeable future and potential consequences of discontinuation should be discussed with individual patients. Currently, data do not exist to administer biologics as first-line therapy in UC. Emerging data suggest that biologics may have the potential to prevent complications and limit disease progression. If such benefits are proven, biologics may be used in the future to modulate subclinical inflammation and to prevent the development of clinical disease.

Molecular profiling of mucosal tissue associated microbiota in patients manifesting acute exacerbations and remission stage of ulcerative colitis.

PubMed

Walujkar, Sandeep A; Kumbhare, Shreyas V; Marathe, Nachiket P; Patangia, Dhrati V; Lawate, Parimal S; Bharadwaj, Renu S; Shouche, Yogesh S

2018-05-23

Dysbiosis of intestinal microflora has been postulated in ulcerative colitis (UC), which is characterized by imbalance of mucosal tissue associated bacterial communities. However, the specific changes in mucosal microflora during different stages of UC are still unknown. The aim of the current study was to investigate the changes in mucosal tissue associated microbiota during acute exacerbations and remission stages of UC. The mucosal microbiota associated with colon biopsy of 12 patients suffering from UC (exacerbated stage) and the follow-up samples from the same patients (remission stage) as well as non-IBD subjects was studied using 16S rRNA gene-based sequencing and quantitative PCR. The total bacterial count in patients suffering from exacerbated phase of UC was observed to be two fold lower compared to that of the non-IBD subjects (p = 0.0049, Wilcox on matched-pairs signed rank tests). Bacterial genera including Stenotrophomonas, Parabacteroides, Elizabethkingia, Pseudomonas, Micrococcus, Ochrobactrum and Achromobacter were significantly higher in abundance during exacerbated phase of UC as compared to remission phase. The alterations in bacterial diversity with an increase in the abnormal microbial communities signify the extent of dysbiosis in mucosal microbiota in patients suffering from UC. Our study helps in identifying the specific genera dominating the microbiota during the disease and thus lays a basis for further investigation of the possible role of these bacteria in pathogenesis of UC.

Recent trends and future directions for the medical treatment of ulcerative colitis.

PubMed

Naganuma, Makoto; Mizuno, Shinta; Nanki, Kosaku; Sugimoto, Shinya; Kanai, Takanori

2016-12-01

Recently, several medical treatments for ulcerative colitis (UC) have been developed, including 5-aminosalicylic acids (5-ASAs), corticosteroids, thiopurine, calcineurin inhibitors, and anti-tumor necrosis factor (TNF) α treatments. Treatment options including calcineurin inhibitors and anti-TNF treatment for refractory UC are discussed in this article. Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib. Budesonide foamwill be used as one treatment option in patients with distal colitis. Herbal medicine, such as Qing-Dai is also effective for active UC and may be useful for patients who are refractory to anti-TNFα treatments. In the near future, physicians will able to use many different treatments for UC patients. However, we should not forget 5-ASA and corticosteroids as the fundamental treatments for UC patients.

Analysis of fat and muscle mass in patients with inflammatory bowel disease during remission and active phase.

PubMed

Rocha, Raquel; Santana, Genoile Oliveira; Almeida, Neogélia; Lyra, Andre Castro

2009-03-01

Inflammatory bowel disease (IBD) is often associated with malnutrition. The aim of this study was to compare the body composition of outpatients with IBD during remission and active phase. In order to evaluate disease activity we used Crohn's Disease Activity Index for Crohn's disease (CD) patients and Lichtiger's Index for ulcerative colitis (UC) patients. All patients underwent the analysis of BMI, arm muscle area (AMA) and triceps plus subscapula skinfold thickness (TST+SST) to identify total, muscle and fat mass, respectively. In total 102 patients were evaluated (CD, n 50; UC, n 52) and the majority was young women. Malnutrition according to BMI was found in 14.0 % of patients with CD and 5.7 % of UC patients. Muscle mass depletion was detected in more than half of the CD and UC patients. The BMI, TST+SST and AMA values were lower in the active phase only in CD patients (P < 0.05). Fat mass depletion was associated with active phase in both CD and UC patients. Body composition parameters obtained using BMI, TST+SST and AMA were not correlated with the presence of fistula in CD patients (P>0.05). In conclusion, patients without signs of malnutrition had fat mass depletion especially in the active phase and muscle mass depletion occurred both in CD and UC patients.

IBS-like symptoms in patients with ulcerative colitis

PubMed Central

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain–gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain–gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted. PMID:25733921

IBS-like symptoms in patients with ulcerative colitis.

PubMed

Gracie, David J; Ford, Alexander C

2015-01-01

Ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal disorders that, until recently, have been considered dichotomous conditions falling on either side of a functional-organic divide. However, persistent gastrointestinal symptoms, akin to those of IBS, are observed in up to one in three patients with quiescent UC. Whether these lower gastrointestinal symptoms are secondary to coexistent IBS or occult UC disease activity is uncertain, but when objective evidence of disease activity is lacking, escalation of conventional pharmacotherapy in such patients is often ineffective. The etiologies of both UC and IBS remain unclear, but dysregulation of the enteric nervous system, an altered microbiome, low-grade mucosal inflammation, and activation of the brain-gut axis is common to both; this suggests that some overlap between the two conditions is plausible. How best to investigate and manage IBS-type symptoms in UC patients remains unclear. Studies that have assessed patients with UC who meet criteria for IBS for subclinical inflammation have been conflicting in their results. Although evidence-based treatments for IBS exist, their efficacy in UC patients reporting these types of symptoms remains unclear. Given the disturbances in gut microbiota in UC, and the possible role of the brain-gut axis in the generation of such symptoms, treatments such as probiotics, fecal transfer, antidepressants, or psychological therapies would seem logical approaches to use in this group of patients. However, there are only limited data for all of these therapies; this suggests that randomized controlled trials to investigate their efficacy in this setting may be warranted.

Ethnic variations in ulcerative colitis: Experience of an international hospital in Thailand.

PubMed

Permpoon, Vibhakorn; Pongpirul, Krit; Anuras, Sinn

2016-08-06

To investigate the clinical characteristics, treatment, medication use, and treatment response in patients with ulcerative colitis (UC) across ethnic groups. This study retrospectively analyzed medical records of all 268465 patients who visited the Bumrungrad International Digestive Disease Center during 2005-2010. The demographics, clinical characteristics, medication use, results of investigations, and medical and surgical management for patients with UC were evaluated. Evaluation included sigmoidoscopy and colonoscopy performed in compliance with the American Society of Gastrointestinal Endoscopy practice guidelines. Patient ethnicities were categorized into seven groups: Thai, Oriental, South Asian (SA), Middle Eastern (ME), Caucasian, African, and Hispanic. UC pathological severity was classified into inactive, mild, moderate, and severe. Associations between categorical variables were analyzed using the χ(2) or Fischer's exact test. Associations between categorical and interval variables were analyzed using Student's t-test and/or analysis of covariance. UC was diagnosed in 371 of the 268465 patients: male 56.33%; ME 42%, Caucasian 23%, and Thai 19%. Annual incidence of UC was 82 cases per 100000 with wide ethnic variation, ranging from 29 to 206 cases per 100000 in Oriental and ME patients, respectively. Of the patients with UC, 16.71% had severe UC with highest incidence among the patients from ME (20.39%) and lowest among the Caucasian population (11.90%). ME had highest proportion of pancolitis (52.90%), followed by Caucasian (45.35%) and Asian (34.40%). Only 20.93% of Caucasian patients received steroid, compared with 26.40% and 27.10% of Asian and Middle Eastern, respectively (P = 0.732). Overall, 13.72% of UC patients did not respond to steroid therapy, with non-significantly higher proportions of non-responders among Asian and Middle Eastern patients (15.22% and 15.04%, respectively) (P = 0.781). On average, 5.93% underwent surgical management with ethnic variation, ranging from 0% in African to 18% in SA. Cancer was found in three (Thai, ME, and African) cases (0.82 institution-specific incidence). Incidence, symptom duration, pathological severity, clinical manifestations, medication use, treatment response, need for surgical consultation, and cancer incidence of patients with UC potentially vary by ethnicity.

DNA methylation of ESR-1 and N-33 in colorectal mucosa of patients with ulcerative colitis (UC).

PubMed

Arasaradnam, Ramesh P; Khoo, Kevin; Bradburn, Mike; Mathers, John C; Kelly, Seamus B

2010-07-01

Epigenetic marking such as DNA methylation influence gene transcription and chromosomal stability and may also be affected by environmental exposures. Few studies exist on alteration in DNA methylation profiles (genomic and gene specific methylation) in patients with Ulcerative Colitis (UC) and no studies exist that assess its relationship with lifestyle exposures. The methylation level of both ESR-1 and N-33 genes were significantly higher in UC subjects compared with controls (7.9% vs. 5.9%; p = 0.015 and 66% vs. 9.3%; p < 0.001 respectively). There was no detectable difference in global DNA methylation between patients with UC and age and sex matched controls. No associations between indices of DNA methylation and anthropometric measures or smoking patterns were detected. To assess genomic methylation and promoter methylation of the ESR-1 (oestrogen receptor-1) and N-33 (tumor suppressor candidate-3) genes in the macroscopically normal mucosa of UC patients as well as to investigate effects of anthropometric and lifestyle exposures on DNA methylation. Sixty eight subjects were recruited (24 UC and 44 age and sex matched controls). Colorectal mucosal biopsies were obtained and DNA was extracted. Genomic DNA methylation was quantified using the tritium-labelled cytosine extension assay (3[H] dCTP) while gene specific methylation was quantified using the COBRA method. For the first time, we have shown increased methylation in the promoter regions of the putative tumor suppressor gene N-33 in macroscopically normal mucosa of patients with UC. In addition, we have confirmed that methylation of ESR-1 promoter is higher in UC patients compared with age and sex matched controls. These findings suggest that inactivation through methylation of the putative tumor suppressor genes N-33 and ESR-1 may not be associated with colorectal carcinogenesis in UC.

The Individual Health Discount Rate in Patients with Ulcerative Colitis

PubMed Central

Waljee, Akbar K.; Morris, Arden M.; Waljee, Jennifer F.; Higgins, Peter D.R.

2015-01-01

Background In cost-effectiveness analysis, discount rates are used in calculating the value of future costs and benefits. However, standard discount rates may not accurately describe the decision-making of patients with Ulcerative Colitis (UC). These patients often choose the long-term risks of immunosuppressive therapy over the short-term risks of colectomy, demonstrating very high discount rates for future health. In this study, we aimed to measure the discount rate in UC patients and identify variables associated with the discount rate. Methods We surveyed patients with UC and patients who were post-colectomy for UC to measure their valuations of UC and colectomy health states. We used Standard Gamble(SG) and Time-Trade-Off(TTO) methods to assess current and future health state valuations, and calculated the discount rate. Results Participants included 150 subjects with UC and 150 subjects who were post-colectomy for UC. Discount rates varied widely (20.6%–100%) with an overall median rate of 55.0%, which was significantly higher than the standard rate of 5%. Older age and male gender and predicted high discount rates (aversion to immediate risk in favor of distant future risk). For each additional decade of age, patients’ expected discount rate increased by 0.77%. Female gender was the only predictor of very low discount rates. Female patients’ discount rates averaged 8.1% less than age-matched males. Conclusions The accepted discount rate of 5% grossly underestimates UC patients’ preference for long-term over short-term risk. This might explain UC patients’ frequent choice of the long-term risks of immunosuppressive medical therapy over the short-term risks of colectomy. PMID:21560195

Comparison of clinicopathologic characteristics of urothelial carcinoma between patients after renal transplantation and on dialysis.

PubMed

Zhang, Bo; Shen, Cheng; Han, Wen-ke; Yu, Wei

2014-09-15

Urothelial carcinoma (UC) is a common complication after renal replacement therapy (RRT) among Chinese end-stage renal disease (ESRD) patients. It is unclear whether there are any differences in the clinicopathologic characteristics of UC between renal transplantation (RT) and dialysis patients; such differences could impact RRT modality selection. We retrospectively reviewed clinicopathologic data for 27 RT patients and 40 dialysis patients who were diagnosed with UC in our center to explore differences in the clinicopathologic characteristics of UC and prognoses between the two groups. The median follow-up period was 92 months (2-137) for the RT group and 71 months (18-155) for the dialysis group. The demographic and baseline data showed no significant differences between the two groups. Upper urinary tract UC (UUC) occurred more frequently in the RT group (22 UUCs in 39 UCs), whereas bladder UC (BUC) predominated in the dialysis group (33 BUCs in 49 UCs) (P=0.025). The pathologic grading in the RT group was significantly higher than that in the dialysis group (P=0.046 for WHO1973 grading, P=0.026 for WHO2004 grading), whereas the difference in tumor stage was not significant (P=0.089). The RT group manifested a higher recurrence rate than the dialysis group (P=0.024). However, the overall and cancer-specific survival rates between the two groups were not significantly different (P=0.239 and P=0.818, respectively). Certain traits of UC, including tumor site, pathologic grading, and recurrence-free survival, were notably different between RT and dialysis patients, but the overall and cancer-specific survival rates were similar.

Avoiding restorative proctocolectomy for colorectal cancer in patients with ulcerative colitis based on preoperative diagnosis involving p53 immunostaining: report of a case.

PubMed

Sada, Haruki; Shimomura, Manabu; Hinoi, Takao; Egi, Hiroyuki; Kawaguchi, Koji; Yano, Takuya; Niitsu, Hiroaki; Saitou, Yasufumi; Sawada, Hiroyuki; Miguchi, Masashi; Adachi, Tomohiro; Ohdan, Hideki

2015-03-26

The standard operation for colitic cancer in ulcerative colitis (UC) is restorative proctocolectomy; however, sporadic colorectal cancer (CRC) can coincidentally arise in patients with UC and the optimal procedure remains controversial. Therefore, it is crucial to preoperatively determine whether the CRC in UC is a sporadic or colitic cancer. We report a case of avoiding proctocolectomy for sporadic CRC in a patient with UC based on preoperative diagnosis involving p53 immunostaining. A 73-year-old man with CRC in UC had undergone sigmoid colectomy with lymphadenectomy because of the submucosal deep invasion pathologically after endoscopic mucosal resection. The cancer was diagnosed sporadic cancer preoperatively not only based on the endoscopic, clinical, and histological patterns but also that the colon epithelium was unlikely to develop dysplasia as the circumference and unaffected UC mucosa did not detect p53 protein overexpression. Recent reports have shown that the immunohistochemical detection of p53 protein overexpression can be useful for a differential diagnosis and as a predictor of dysplasia and colitic cancer. The analysis of p53 mutation status based on immunostaining of p53 protein expression in the unaffected UC mucosa can be useful for the decision regarding a surgical procedure for CRC in patients with UC.

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis

PubMed Central

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-01-01

Background Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. Objective The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Methods Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. Results A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. Conclusions The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population. PMID:29511562

Prevalence and risk factors for colorectal adenomas in patients with ulcerative colitis.

PubMed

Gordillo, Jordi; Zabana, Yamile; Garcia-Planella, Esther; Mañosa, Míriam; Llaó, Jordina; Gich, Ignasi; Marín, Laura; Szafranska, Justyna; Sáinz, Sergio; Bessa, Xavier; Cabré, Eduard; Domènech, Eugeni

2018-03-01

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa. The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC. Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed. A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development. The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

Ulcerative colitis-associated colorectal cancer

PubMed Central

Yashiro, Masakazu

2014-01-01

The association between ulcerative colitis (UC) and colorectal cancer (CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC (UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, low-grade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC. PMID:25469007

Readressing the role of Toll-like receptor-4 alleles in inflammatory bowel disease: colitis, smoking, and seroreactivity.

PubMed

Manolakis, Anastassios C; Kapsoritakis, Andreas N; Kapsoritaki, Anastasia; Tiaka, Elisavet K; Oikonomou, Konstantinos A; Lotis, Vassilis; Vamvakopoulou, Dimitra; Davidi, Ioanna; Vamvakopoulos, Nikolaos; Potamianos, Spyros P

2013-02-01

Toll-like receptor (TLR) polymorphisms, and especially TLR-4 Asp299Gly and TLR-4 Thr399Ile, have been linked with Crohn's disease (CD) and to a lesser extent with ulcerative colitis (UC), CD behavior, and compromised seroreactivity to microbial antigens. Available data, however, are conflicting. To address these issues, the distribution of TLR-4 polymorphic alleles was assessed in patients with UC, CD, and healthy controls (HC), considering patient and disease characteristics as well as related serological markers. TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms were determined in 187 UC and 163 CD patients and 274 randomly selected HC. C reactive protein, anti-Saccharomyces cerevisiae mannan antibodies, anti-mannobioside carbohydrate antibodies, anti-laminariobioside carbohydrate antibodies IgG, and anti-chitobioside carbohydrate antibodies (ACCA) IgA levels were also assessed. UC and especially pancolitis patients carried the mutant alleles more frequently compared to CD patients and HC or UC patients with different disease extents (P = 0.002 and P < 0.0001, respectively). Involvement of the colon was more frequent in CD patients with mutant TLR-4 compared to those with wild-type alleles (P = 0.004). Levels and positivity rates of ACCA IgA were lower in inflammatory bowel disease (IBD) patients carrying the mutant compared to those with wild-type alleles (0.075 < P < 0.05). Despite the mutant TLR-4 predisposition for UC pancolitis, smoking was associated with more limited disease (P < 0.001). The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

Lack of association between two key SNPs on chromosome 12p13 and ischemic stroke in Chinese Uyghur population.

PubMed

Tong, Yeqing; Zhan, Faxian; Han, Jinjun; Zhang, Yanwei; Yin, Xiaoxu; Geng, Yijie; Hou, Shuangyi; Ye, Jianjun; Guan, Xuhua; Han, Shenhong; Wang, Yunxia; Mason, Katherine A; Lu, Zuxun; Liu, Jiafa; Cheng, Jinquan

2012-12-15

Recent genome-wide association studies (GWAS) have identified two key SNPs (rs11833579 and rs12425791) on chromosome 12p13 that were significantly associated with stroke in Caucasians. However, the validity of the association has remained controversial. We performed genetic association analyses in a very unique population which has 60% European ancestry and 40% East Asian ancestry. No significant association between these two SNPs and ischemic stroke was detected in this Chinese Uyghur population. Copyright © 2012 Elsevier B.V. All rights reserved.

Direct comparison of two different mesalamine formulations for the induction of remission in patients with ulcerative colitis: A double-blind, randomized study

PubMed Central

Ito, Hiroaki; Iida, Mitsuo; Matsumoto, Takayuki; Suzuki, Yasuo; Sasaki, Hidetaka; Yoshida, Toyomitsu; Takano, Yuichi; Hibi, Toshifumi

2010-01-01

Background: Mesalamine is the first-line drug for the treatment of ulcerative colitis (UC). We directly compared the efficacy and safety of two mesalamine formulations for the induction of remission in patients with UC. Methods: In a multicenter, double-blind, randomized study, 229 patients with mild-to-moderate active UC were assigned to 4 groups: 66 and 65 received a pH-dependent release formulation of 2.4 g/day (pH-2.4 g) or 3.6 g/day (pH-3.6 g), respectively; 65 received a time-dependent release formulation of 2.25 g/day (Time-2.25 g), and 33 received placebo (Placebo). The drugs were administered three times daily for eight weeks. The primary endpoint was a decrease in the UC disease activity index (UC-DAI). Results: In the full analysis set (n = 225) the decrease in UC-DAI in each group was 1.5 in pH-2.4 g, 2.9 in pH-3.6 g, 1.3 in Time-2.25 g and 0.3 in Placebo, respectively. These results demonstrate the superiority of pH-3.6 g over Time-2.25 g (P = 0.003) and the noninferiority of pH-2.4 g to Time-2.25 g. Among the patients with proctitis-type UC, a significant decrease in UC-DAI was observed in pH-2.4 g and pH-3.6 g as compared to Placebo, but not in Time-2.25 g. No differences were observed in the safety profiles. Conclusions: Higher dose of the pH-dependent release formulation was more effective for induction of remission in patients with mild-to-moderate active UC. Additionally, the pH-dependent release formulation was preferable to the time-dependent release formulation for patients with proctitis-type UC (UMIN Clinical Trials Registry, no. C000000288). (Inflamm Bowel Dis 2010) PMID:20049950

“Mucosal healing” in ulcerative colitis: Between clinical evidence and market suggestion

PubMed Central

Pagnini, Cristiano; Menasci, Francesca; Festa, Stefano; Rizzatti, Gianenrico; Fave, Gianfranco Delle

2014-01-01

In recent decades, the prominent role of endoscopy in the management of ulcerative colitis (UC) has been translated into the concept of mucosal healing (MH) as a fundamental therapeutic end-point. This is partially the consequence of growing evidence of a positive prognostic role of MH on the disease course and partially due to market cues indicating a higher rate of MH in patients treated by novel potent biologic agents. The aim of the present review is to clarify the current knowledge of MH in UC, analyzing the definition, the putative prognostic role and the association of MH with the current drugs used to treat UC patients. Because solid data about the management of UC patients based solely on the healing of the mucosa are not yet available, a tailored approach for individual patients thatconsiders the natural history of UC and the presence of prognostic indicators of aggressive disease is desirable. Consequently, unnecessary examinations and treatment would be avoided and restricted to UC patients who require the maximum amount of effort to affect the disease course in the short and long term. PMID:24891976

One-year effectiveness and safety of vedolizumab therapy for inflammatory bowel disease: a prospective multicentre cohort study.

PubMed

Amiot, A; Serrero, M; Peyrin-Biroulet, L; Filippi, J; Pariente, B; Roblin, X; Buisson, A; Stefanescu, C; Trang-Poisson, C; Altwegg, R; Marteau, P; Vaysse, T; Bourrier, A; Nancey, S; Laharie, D; Allez, M; Savoye, G; Moreau, J; Vuitton, L; Viennot, S; Aubourg, A; Pelletier, A-L; Bouguen, G; Abitbol, V; Gagniere, C; Bouhnik, Y

2017-08-01

We recently showed that vedolizumab is effective in patients with Crohn's disease (CD) and ulcerative colitis (UC) with prior anti-TNF failure in a multicentre compassionate early-access programme before marketing authorisation was granted to vedolizumab. To assess effectiveness and safety of vedolizumab at week 54 in patients UC and CD. Between June and December 2014, 173 patients with Crohn's disease (CD) and 121 with ulcerative colitis (UC) were treated with vedolizumab induction therapy. Among those 294 patients, 272 completed the induction period and were evaluated at the week 14 visit (161 patients with CD and 111 with UC). Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. The primary outcome was steroid-free clinical remission at week 54. At week 54, steroid-free clinical remission rates at week 54 were 27.2% and 40.5% in patients with CD and UC respectively. In addition, the sustained steroid-free clinical remission (from week 14 to week 54) rates were 8.1% and 19.0% respectively. No deaths were observed. Severe adverse events occurred in 17 (7.2%) patients, including six (2.5%) leading to vedolizumab discontinuation. Vedolizumab is able to maintain steroid-free clinical remission in up to one-third of patients with UC and CD at week 54 with a reasonable safety profile. A significant number of patients experienced loss of response during the first year of treatment, particularly in patients with CD. © 2017 John Wiley & Sons Ltd.

High frequency of parasitic and viral stool pathogens in patients with active ulcerative colitis: report from a tropical country.

PubMed

Banerjee, Debabrata; Deb, Rachana; Dar, Lalit; Mirdha, Bijay R; Pati, Sunil K; Thareja, Sandeep; Falodia, Sushil; Ahuja, Vineet

2009-01-01

Diarrhoeal relapses in patients with ulcerative colitis (UC) may be associated with enteric infections and its diagnosis may lessen avoidable exposure to corticosteroids and/or immunosuppressants. The purpose of this study was to assess the frequency of stool pathogens (parasitic and viral) in patients with active UC. This prospective cross-sectional study included 49 consecutive patients (32 M, 17 F, mean age 35.8+/-12 years) with active UC. Three stool samples were collected from each patient and examined for parasitic infection. Rectal biopsies were obtained during sigmoidoscopy to demonstrate cytomegalovirus (CMV) inclusion bodies and to conduct qualitative polymerase chain reaction (PCR) for CMV and herpes simplex virus (HSV) DNA detection. Median duration of illness was 3.9+/-3.7 years and 83.7% of the patients had moderate to severe disease. The prevalence of parasitic infections in UC was 12%. The organisms isolated were Strongyloides stercoralis in 4%, Ankylostoma duodenale in 4%, Cryptosporidium in 2% and Entamoeba histolytica in 2% of the patients. The prevalence of CMV and HSV in rectal biopsies using qualitative PCR was 8% and 10%, respectively. No predictive factor was identified with CMV superinfection in patients with active UC. In India there is a high prevalence of parasitic and viral infections in patients with active UC. The results of the study suggest that, in tropical countries with a known high prevalence of parasitic diseases, aggressive evaluation for parasitic and viral infections should be carried out, as early identification and prompt treatment of such infections can improve the clinical course of patients with active UC.

Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn’s Colitides

PubMed Central

Korolkova, Olga Y; Myers, Jeremy N; Pellom, Samuel T; Wang, Li; M’Koma, Amosy E

2015-01-01

BACKGROUND As accessible diagnostic approaches fail to differentiate between ulcerative colitis (UC) and Crohn’s colitis (CC) in one-third of patients with predominantly colonic inflammatory bowel disease (IBD), leading to inappropriate therapy, we aim to investigate the serum cytokine levels in these patients in search of molecular biometric markers delineating UC from CC. METHODS We measured 38 cytokines, chemokines, and growth factors using magnetic-bead-based multiplex immunoassay in 25 UC patients, 28 CC patients, and 30 controls. Our results are compared with those from a review of current literature regarding advances in serum cytokine profiles and associated challenges preventing their use for diagnostic/prognostic purposes. RESULTS Univariate analysis showed statistically significant increases of eotaxin, GRO, and TNF-α in UC patients compared to controls (Ctrl); interferon γ, interleukin (IL)-6, and IL-7 in CC group compared to Ctrl; and IL-8 in both UC and CC versus Ctrl. No cytokines were found to be different between UC and CC. A generalized linear model identified combinations of cytokines, allowing the identification of UC and CC patients, with area under the curve (AUC) = 0.936, as determined with receiver operating characteristic (ROC) analysis. CONCLUSIONS The current knowledge available about circulating cytokines in IBD is often contradictory. The development of an evidence-based tool using cytokines for diagnostic accuracy is still preliminary. PMID:26078592

Decreased Plasma Histidine Level Predicts Risk of Relapse in Patients with Ulcerative Colitis in Remission

PubMed Central

Hisamatsu, Tadakazu; Ono, Nobukazu; Imaizumi, Akira; Mori, Maiko; Suzuki, Hiroaki; Uo, Michihide; Hashimoto, Masaki; Naganuma, Makoto; Matsuoka, Katsuyoshi; Mizuno, Shinta; Kitazume, Mina T.; Yajima, Tomoharu; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi; Kanai, Takanori

2015-01-01

Ulcerative colitis (UC) is characterized by chronic intestinal inflammation. Patients with UC have repeated remission and relapse. Clinical biomarkers that can predict relapse in UC patients in remission have not been identified. To facilitate the prediction of relapse of UC, we investigated the potential of novel multivariate indexes using statistical modeling of plasma free amino acid (PFAA) concentrations. We measured fasting PFAA concentrations in 369 UC patients in clinical remission, and 355 were observed prospectively for up to 1 year. Relapse rate within 1 year was 23% (82 of 355 patients). The age- and gender-adjusted hazard ratio for the lowest quartile compared with the highest quartile of plasma histidine concentration was 2.55 (95% confidence interval: 1.41–4.62; p = 0.0020 (log-rank), p for trend = 0.0005). We demonstrated that plasma amino acid profiles in UC patients in clinical remission can predict the risk of relapse within 1 year. Decreased histidine level in PFAAs was associated with increased risk of relapse. Metabolomics could be promising for the establishment of a non-invasive predictive marker in inflammatory bowel disease. PMID:26474176

Difference in Ulex europaeus agglutinin I-binding activity of decay-accelerating factor detected in the stools of patients with colorectal cancer and ulcerative colitis.

PubMed

Okazaki, Hiroaki; Mizuno, Motowo; Nasu, Junichirou; Makidono, Chiho; Hiraoka, Sakiko; Yamamoto, Kazuhide; Okada, Hiroyuki; Fujita, Teizo; Tsuji, Takao; Shiratori, Yasushi

2004-03-01

Expression of decay-accelerating factor (DAF, CD55), a complement-regulatory glycoprotein, is enhanced in colorectal-cancer (CC) cells and colonic epithelium in ulcerative colitis (UC), and stools from these patients contain increased amounts of DAF. Carbohydrate chains of glycoproteins are often altered during malignant transformation or inflammation. In this study, we investigated whether DAF molecules in patients with CC and those with UC differ with respect to oligosaccharide side chains. We analyzed DAF in stools and homogenates of colonic-tissue specimens obtained from patients with CC or UC using solid-phase enzyme-linked assay and Western blotting for reactivity with the lectins Ulex europaeus agglutinin I (UEA-I), wheat-germ agglutinin, peanut agglutinin, and concanavalin A. UEA-I bound to DAF in stools from patients with UC but not in that from the stools of CC patients, as demonstrated on the solid-phase enzyme-linked assay (P <.05, Mann-Whitney U test) and Western blotting. Binding of UEA-I was specifically inhibited by the addition of fucose. The difference in UEA-I reactivity with DAF was observed also in colonic-tissue homogenates from patients with UC and those with CC. DAF expressed in the mucosa and excreted into the stools of UC patients is different from that expressed in CC with regard to UEA-I reactivity. Future studies should be directed toward determining whether a qualitatively unique isoform of DAF is present, of which sugar chains are specific to CC in UC patients.

Analysis of endoscopic brush samples identified mucosa-associated dysbiosis in inflammatory bowel disease.

PubMed

Nishino, Kyohei; Nishida, Atsushi; Inoue, Ryo; Kawada, Yuki; Ohno, Masashi; Sakai, Shigeki; Inatomi, Osamu; Bamba, Shigeki; Sugimoto, Mitsushige; Kawahara, Masahiro; Naito, Yuji; Andoh, Akira

2018-01-01

The mucosa-associated gut microbiota directly modulates epithelial and mucosal function. In this study, we investigated the mucosa-associated microbial community in patients with inflammatory bowel disease (IBD), using endoscopic brush samples. A total of 174 mucus samples from 43 patients with ulcerative colitis (UC), 26 with Crohn's disease (CD) and 14 non-IBD controls were obtained by gentle brushing of mucosal surfaces using endoscopic cytology brushes. The gut microbiome was analyzed using 16S rRNA gene sequencing. There were no significant differences in microbial structure among different anatomical sites (the ileum, cecum and sigmoid colon) within individuals. There was, however, a significant difference in microbial structure between CD, UC and non-IBD controls. The difference between CD and non-IBD controls was more marked than that between UC patients and non-IBD controls. α-Diversity was significantly lower in UC and CD patients than non-IBD controls. When comparing CD patients with non-IBD controls, the phylum Proteobacteria was significantly increased and the phyla Firmicutes and Bacteroidetes were significantly reduced. These included a significant increase in the genera Escherichia, Ruminococcus (R. gnavus), Cetobacterium, Actinobacillus and Enterococcus, and a significant decrease in the genera Faecalibacterium, Coprococcus, Prevotella and Roseburia. Comparisons between CD and UC patients revealed a greater abundance of the genera Escherichia, Ruminococcus (R. gnavus), Clostridium, Cetobacterium, Peptostreptococcus in CD patients, and the genera Faecalibacterium, Blautia, Bifidobacterium, Roseburia and Citrobacter in UC patients. Mucosa-associated dysbiosis was identified in IBD patients. CD and UC may be distinguishable from the mucosa-associated microbial community structure.

What do patients with urothelial cancer know about the association of their tumor disease with smoking habits? Results of a German survey study

PubMed Central

Fritsche, Hans-Martin; Gilfrich, Christian; Dombrowski, Mirja; Maurer, Odilo; Spachmann, Philipp; Kumar, Manju Ganesh; Bjurlin, Marc; Burger, Maximilian; Brookman-May, Sabine

2018-01-01

Purpose Smoking represents a primary risk factor for the development of urothelial carcinoma (UC) and a relevant factor impacting UC-specific prognosis. Data on the accordant knowledge of UC-patients in this regard and the significance of physicians in the education of UC-patients is limited. Materials and Methods Eighty-eight UC-patients were enrolled in a 23-items-survey-study aimed to analyse patient knowledge and awareness of their tumor disease with smoking along with physician smoking cessation counselling. Results The median age of the study patients was 69 years; 26.1% (n=23), 46.6% (n=41), and 27.3% (n=24), respectively, were non-smokers, previous, and active smokers. Exactly 50% of active smokers reported a previous communication with a physician about the association of smoking and their tumor disease; however, only 25.0% were aware of smoking as main risk factor for UC development. Merely 33% of the active smokers had been prompted directly by their physicians to quit smoking. About 42% of active smokers had received the information that maintaining smoking could result in a tumor-specific impairment of their prognosis. Closely 29% of active and about 5% of previous smokers (during the time-period of active smoking) had been offered support from physicians for smoking cessation. No association was found between smoking anamnesis (p=0.574) and pack-years (p=0.912), respectively, and tumor stage of UC. Conclusions The results of this study suggest that the medical conversation of physicians with UC-patients about the adverse significance of smoking is limited. Implementation of structured educational programs for smoking cessation may be an opportunity to further enhance comprehensive cancer care. PMID:29520384

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis.

PubMed

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-10-27

Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. © European Crohn’s and Colitis Organisation (ECCO) 2017.

Usefulness of Transcriptional Blood Biomarkers as a Non-invasive Surrogate Marker of Mucosal Healing and Endoscopic Response in Ulcerative Colitis

PubMed Central

Planell, Núria; Masamunt, M Carme; Leal, Raquel Franco; Rodríguez, Lorena; Esteller, Miriam; Lozano, Juan J; Ramírez, Anna; Ayrizono, Maria de Lourdes Setsuko; Coy, Claudio Saddy Rodrigues; Alfaro, Ignacio; Ordás, Ingrid; Visvanathan, Sudha; Ricart, Elena; Guardiola, Jordi; Panés, Julián; Salas, Azucena

2017-01-01

Abstract Background and Aims Ulcerative colitis [UC] is a chronic inflammatory disease of the colon. Colonoscopy remains the gold standard for evaluating disease activity, as clinical symptoms are not sufficiently accurate. The aim of this study is to identify new accurate non-invasive biomarkers based on whole-blood transcriptomics that can predict mucosal lesions and response to treatment in UC patients. Methods Whole-blood samples were collected for a total of 152 UC patients at endoscopy. Blood RNA from 25 UC individuals and 20 controls was analysed using microarrays. Genes that correlated with endoscopic activity were validated using real-time polymerase chain reaction in an independent group of 111 UC patients, and a prediction model for mucosal lesions was evaluated. Responsiveness to treatment was assessed in a longitudinal cohort of 16 UC patients who started anti-tumour necrosis factor [TNF] therapy and were followed up for 14 weeks. Results Microarray analysis identified 122 genes significantly altered in the blood of endoscopically active UC patients. A significant correlation with the degree of endoscopic activity was observed in several genes, including HP, CD177, GPR84, and S100A12. Using HP as a predictor of endoscopic disease activity, an accuracy of 67.3% was observed, compared with 52.4%, 45.2%, and 30.3% for C-reactive protein, erythrocyte sedimentation rate, and platelet count, respectively. Finally, at 14 weeks of treatment, response to anti-TNF therapy induced alterations in blood HP, CD177, GPR84, and S100A12 transcripts that correlated with changes in endoscopic activity. Conclusions Transcriptional changes in UC patients are sensitive to endoscopic improvement and appear to be an effective tool to monitor patients over time. PMID:28981629

Medical resource utilization and associated costs in patients with ulcerative colitis in the UK: a chart review analysis.

PubMed

Bodger, Keith; Yen, Linnette; Szende, Agota; Sharma, Gunjan; Chen, Yaozhu J; McDermott, John; Hodgkins, Paul

2014-02-01

Limited evidence is available on the economic burden of ulcerative colitis (UC) in the UK, particularly relating to the impact of relapse frequency on direct medical costs. This study identifies and assesses medical resource utilization (MRU) and associated direct costs in mild and moderate UC patients in the UK. A retrospective chart review of patients with mild-to-moderate UC diagnosed at least 1 year before the study was performed. From 33 general practitioner (GP) and 34 gastroenterologist sites, charts of the last three UC patients fulfilling the inclusion criteria were reviewed. Descriptive statistics were calculated for MRU and 2011 costs (GB£) by number of relapses. The study population included 201 patients with a mean age of 39.9 years; 44% were women and the mean disease duration was 7.4 years. UC-related costs of each MRU category increased with the number of relapses. Comparing patients without relapse with those with more than two relapses, the mean annual UC-related costs were £14 versus £2556 for hospitalizations; £218 versus £988 for visits (including nurse, GP, specialist, and other visits); £21 versus £1303 for procedures; £17 versus £188 for diagnostics; and £1168 versus £6660 for all-cause total costs. Age, sex, and site of data reporting (GP vs. gastroenterologist) were not associated with MRU or costs. Patients with mild-to-moderate UC incurred considerable costs that increased markedly with the number of relapses. These findings support the importance of maintenance therapies in UC that reduce or prevent relapses. Quantifying the relationship between relapse rate and costs will inform future health economic studies.

High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

PubMed Central

Liu, Yanhou; Zhao, Zhongfang; Li, Tianyi; Liao, Qi; Kushner, Nicholas; Touzjian, Neal Y.; Shao, Yiming; Sun, Yongtao; Strong, Amie J.; Lu, Yichen

2012-01-01

Background Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort. Methodology/Principal Findings Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group. Conclusions At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates. PMID:23251376

Influences of APOA5 Variants on Plasma Triglyceride Levels in Uyghur Population

PubMed Central

Wang, Yi; Wu, Di; Jin, Li; Wang, Xiaofeng

2014-01-01

Objective Single nucleotide polymorphisms (SNPs) in apolipoprotein A5 (APOA5) gene are associated with triglyceride (TG) levels. However, the minor allele frequencies and linkage disequilibriums (LDs) of the SNPs in addition to their effects on TG levels vary greatly between Caucasians and East Asians. The distributions of the SNPs/haplotypes and their associations with TG levels in Uyghur population, an admixture population of Caucasians and East Asians, have not been reported to date. Here, we performed a cross-sectional study to address these. Methods Genotyping of four SNPs in APOA5 (rs662799, rs3135506, rs2075291, and rs2266788) was performed in 1174 unrelated Uyghur subjects. SNP/haplotype and TG association analyses were conducted. Results The frequencies of the SNPs in Uyghurs were in between those in Caucasians and East Asians. The LD between rs662799 and rs2266788 in Uyghurs was stronger than that in East Asians but weaker than that in Caucasians, and the four SNPs resulted in four haplotypes (TGGT, CGGC, TCGT, and CGTT arranged in the order of rs662799, rs3135506, rs2075291, and rs2266788) representing 99.2% of the population. All the four SNPs were significantly associated with TG levels. Compared with non-carriers, carriers of rs662799-C, rs3135506-C, rs2075291-T, and rs2266788-C alleles had 16.0%, 15.1%, 17.1%, and 12.4% higher TG levels, respectively. When haplotype TGGT was defined as the reference, the haplotypes CGGC, TCGT, and CGTT resulted in 16.1%, 19.0%, and 19.8% higher TG levels, respectively. The proportions of variance in TG explained by APOA5 locus were 2.5%, 0.3%, 0.4%, and 1.9% for single SNP rs662799, rs3135506, rs2075291, and rs2266788, respectively, and 3.0% for the haplotypes constructed by them. Conclusions The association profiles between the SNPs and haplotypes at APOA5 locus and TG levels in this admixture population differed from those in Caucasians and East Asians. The functions of these SNPs and haplotypes need to be elucidated comprehensively. PMID:25313938

Umbilical cord-derived mesenchymal stem cells reversed the suppressive deficiency of T regulatory cells from peripheral blood of patients with multiple sclerosis in a co-culture – a preliminary study

PubMed Central

Yang, Hongna; Sun, Jinhua; Wang, Feng; Li, Yan; Bi, Jianzhong; Qu, Tingyu

2016-01-01

The immunoregulatory function of T regulatory cells (Tregs) is impaired in multiple sclerosis (MS). Recent studies have shown that umbilical cord-derived mesenchymal stem cells (UC-MSCs) exert regulatory effect on the functions of immune cells. Thus, we investigated whether UC-MSCs could improve the impaired function of Tregs from MS patients. Co-cultures of UC-MSCs with PBMCs of MS patients were performed for 3 days. Flow cytometry was used to determine the frequency of Tregs. A cell proliferation assay was used to evaluate the suppressive capacity of Tregs. ELISA was conducted for cytokine analysis in the co-cultures. Our results showed that UC-MSCs significantly increased the frequency of CD4+CD25+CD127low/− Tregs in resting CD4+ T cells (p<0.01) from MS, accompanied by the significantly augmented production of cytokine prostaglandin E2, transforming growth factor (−β1, and interleukin-10, along with a reduced interferon-γ production in these co-cultures (p<0.05 - 0.01). More importantly, UC-MSC-primed Tregs of MS patients significantly inhibited the proliferation of PHA-stimulated autologous and allogeneic CD4+CD25− T effector cells (Teffs) from MS patients and healthy individuals compared to non-UC-MSC-primed (naïve) Tregs from the same MS patients (p<0.01). Furthermore, no remarkable differences in suppressing the proliferation of PHA-stimulated CD4+CD25− Teffs was observed in UC-MSC-primed Tregs from MS patients and naïve Tregs from healthy subjects. The impaired suppressive function of Tregs from MS can be completely reversed in a co-culture by UC-MSC modulation. This report is the first to demonstrate that functional defects of Tregs in MS can be repaired in vitro using a simple UC-MSC priming approach. PMID:27705922

Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Santiago-Hernández, Jean J; Pérez-Hernández, Nonanzit; Ramírez-Fuentes, Silvestre; Fragoso, José Manuel; Vargas-Alarcón, Gilberto

2011-07-01

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown etiology. Among cytokines induced in UC, interleukin 1 antagonist (IL-1ra) and interleukin 1 β (IL-1β) seems to have a central role because of its immunoregulatory and proinflammatory activities. To determine the association between IL-1RA and IL-1B gene polymorphisms and the clinical features of UC in the Mexican Mestizo population. Five polymorphisms in the IL-1 gene cluster members IL-1B (rs16944), IL1F10 (rs3811058), and IL-1RN (rs419598, rs315952, and rs315951) were genotyped by 5' exonuclease TaqMan genotyping assays in a group of 200 Mexican patients with UC and 248 ethnically matched unrelated healthy controls. We found a significant increased frequencies of IL-1RN6/1 TC (rs315952) and RN6/2 CC (rs315951) and decreased frequency of IL-1B-511 TC (rs16944) genotypes in UC patients as compared with healthy controls. In the subgroup analysis, we found a significant association between the RN6/2 GG (rs315951) and IL-1B-511 CC (rs16944) genotypes and the presence of steroid-dependence in UC patients (pC=00001, OR=15.6 and pC=0.008, OR=4.09, respectively). Patients with UC showed increased frequencies of IL-1RN "CTC" and "TCG" haplotypes when compared with healthy controls (P=0.019, OR=1.43 and P<10(-7), OR=2.63, respectively). Two haplotypes (TTG and CTG) showed decreased frequency in patients when compared with healthy controls (P=9×10(-7), OR=0.11 and P=8×10(-6), OR=0.11, respectively). IL-1 RN and IL-1B polymorphisms were associated with the genetic susceptibility to develop UC and might be associated with the presence of steroid-dependence in UC patients.

Long-term safety and tolerability of once-daily mesalamine granules in the maintenance of remission of ulcerative colitis.

PubMed

Lichtenstein, Gary R; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P

2014-08-01

Ulcerative colitis (UC), a chronic, relapsing, and remitting inflammatory bowel disease, requires long-term treatment to maintain remission. In this study, the long-term safety and tolerability of mesalamine granules (MG) therapy was evaluated in the maintenance of UC remission. Previous prospective studies evaluating different oral mesalamine formulations have not exceeded a duration of 14 months. A phase 3, multicenter, 24-month, open-label extension study evaluating MG 1.5 g once daily in patients who achieved previous remission from mild to moderate UC was performed. Eligible patients had successfully participated in 1 of 2 previous 6-month double-blind, placebo-controlled trials or were new patients in remission. Safety assessments included monitoring of adverse events (AEs) and clinical laboratory tests. Risk of UC recurrence was assessed by the occurrence of UC-related AEs. Of the 393 patients enrolled (280 from the double-blind studies; 113 new patients), 388 were included in the safety population. The most common AEs included nasopharyngitis (13.9%), headache (11.6%), and diarrhea (10.8%), and the incidence of these events was generally lower in the MG group versus historical placebo group from the double-blind studies. Pancreatic, renal, and hepatic AEs occurred in 23 patients (5.9%). The risk of UC-related AEs was low and was maintained for 24 months during the open-label study. Once-daily MG has a favorable safety profile for the maintenance of remission for up to 2 years in patients with UC.

EDARV370A associated facial characteristics in Uyghur population revealing further pleiotropic effects.

PubMed

Peng, Qianqian; Li, Jinxi; Tan, Jingze; Yang, Yajun; Zhang, Manfei; Wu, Sijie; Liu, Yu; Zhang, Juan; Qin, Pengfei; Guan, Yaqun; Jiao, Yi; Zhang, Zhaoxia; Sabeti, Pardis C; Tang, Kun; Xu, Shuhua; Jin, Li; Wang, Sijia

2016-01-01

An adaptive variant of human Ectodysplasin receptor, EDARV370A, had undergone strong positive selection in East Asia. In mice and humans, EDARV370A was found to affect ectodermal-derived characteristics, including hair thickness, hair shape, active sweat gland density and teeth formation. Facial characteristics are also largely ectodermal derived. In this study, taking advantage of an admixed population of East Asian and European ancestry-the Uyghur, we aim to test whether EDARV370A is affecting facial characteristics and to investigate its pleiotropic nature and genetic model. In a sample of 1027 Uyghurs, we discover that EDARV370A is significantly associated with several facial characteristics, in particular shape of earlobe (P = 3.64 × 10 (-6) ) and type of chin (P = 9.23 × 10 (-5) ), with successful replication in other East Asian populations. Additionally, in this Uyghur population, we replicate previous association findings of incisors shoveling (P = 1.02 × 10 (-7) ), double incisors shoveling (P = 1.86 × 10 (-12) ) and hair straightness (P = 3.99 × 10 (-16) ), providing strong evidence supporting an additive model for the EDARV370A associations. Partial least square path model confirms EDARV370A systematically affect these weakly related ectodermal-derived characteristics, suggesting the pleiotropic effect of EDARV370A mainly plays roles in early embryo development. This study extends our knowledge about the pleiotropic nature of EDARV370A and provides potential clues to its adaptation fitness in human evolution.

Text Messaging to Improve Disease Management in Patients With Painful Diabetic Peripheral Neuropathy.

PubMed

Bauer, Victoria; Goodman, Nancy; Lapin, Brittany; Cooley, Camille; Wang, Ed; Craig, Terri L; Glosner, Scott E; Juhn, Mark S; Cappelleri, Joseph C; Sadosky, Alesia B; Masi, Christopher

2018-06-01

Purpose The purpose of the study was to determine the impact of educational text messages on diabetes self-management activities and outcomes in patients with painful diabetic peripheral neuropathy (pDPN). Methods Patients with pDPN identified from a large integrated health system who agreed to participate were randomized to 6 months of usual care (UC) or UC plus twice-daily diabetes self-management text messages (UC+TxtM). Outcomes included the Pain Numerical Rating Scale, Summary of Diabetes Self-Care Activities (SDSCA), questions on diabetes health beliefs, and glycated hemoglobin (A1C). Changes from baseline were evaluated at 6 months and compared between groups. Results Demographic characteristics were balanced between groups (N = 62; 53% female, mean age = 63 years, 94% type 2 diabetes), as were baseline measures. After 6 months, pain decreased with UC+TxtM from 6.3 to 5.5 and with UC from 6.5 to 6.0, with no difference between groups. UC+TxtM but not UC was associated with significant improvements from baseline on all SDSCA subscales. On diabetes health beliefs, UC+TxtM patients reported significantly increased benefits and reduced barriers and susceptibility relative to UC at 6 months. A1C declined in both groups, but neither change was significant relative to baseline. Conclusions Patients with pDPN who receive twice-daily text messages regarding diabetes management reported reduced pain relative to baseline, although this change was not significant compared with usual care. In addition, text messaging was associated with increased self-management activities and improved diabetes health beliefs and total self-care. These results warrant further investigation.

High-Dose Ursodeoxycholic Acid Is Associated With the Development of Colorectal Neoplasia in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis

PubMed Central

Eaton, John E.; Silveira, Marina G.; Pardi, Darrell S.; Sinakos, Emmanouil; Kowdley, Kris V.; Luketic, Velimir A.C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Lindor, Keith D.

2011-01-01

OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28–30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30–20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC. PMID:21556038

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

PubMed

Bartolucci, Jorge; Verdugo, Fernando J; González, Paz L; Larrea, Ricardo E; Abarzua, Ema; Goset, Carlos; Rojo, Pamela; Palma, Ivan; Lamich, Ruben; Pedreros, Pablo A; Valdivia, Gloria; Lopez, Valentina M; Nazzal, Carolina; Alcayaga-Miranda, Francisca; Cuenca, Jimena; Brobeck, Matthew J; Patel, Amit N; Figueroa, Fernando E; Khoury, Maroun

2017-10-27

Umbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients. Evaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic stable heart failure and reduced ejection fraction. Patients with heart failure and reduced ejection fraction under optimal medical treatment were randomized to intravenous infusion of allogenic UC-MSCs (Cellistem, Cells for Cells S.A., Santiago, Chile; 1×10 6 cells/kg) or placebo (n=15 per group). UC-MSCs in vitro, compared with bone marrow-derived mesenchymal stem cells, displayed a 55-fold increase in the expression of hepatocyte growth factor, known to be involved in myogenesis, cell migration, and immunoregulation. UC-MSC-treated patients presented no adverse events related to the cell infusion, and none of the patients tested at 0, 15, and 90 days presented alloantibodies to the UC-MSCs (n=7). Only the UC-MSC-treated group exhibited significant improvements in left ventricular ejection fraction at 3, 6, and 12 months of follow-up assessed both through transthoracic echocardiography ( P =0.0167 versus baseline) and cardiac MRI ( P =0.025 versus baseline). Echocardiographic left ventricular ejection fraction change from baseline to month 12 differed significantly between groups (+7.07±6.22% versus +1.85±5.60%; P =0.028). In addition, at all follow-up time points, UC-MSC-treated patients displayed improvements of New York Heart Association functional class ( P =0.0167 versus baseline) and Minnesota Living with Heart Failure Questionnaire ( P <0.05 versus baseline). At study completion, groups did not differ in mortality, heart failure admissions, arrhythmias, or incident malignancy. Intravenous infusion of UC-MSC was safe in this group of patients with stable heart failure and reduced ejection fraction under optimal medical treatment. Improvements in left ventricular function, functional status, and quality of life were observed in patients treated with UC-MSCs. URL: https://www.clinicaltrials.gov/ct2/show/NCT01739777. Unique identifier: NCT01739777. © 2017 The Authors.

Influence of culture on tripartite self-concept development in adolescence: a comparison between Han and Uyghur cultures.

PubMed

Abdukeram, Ziwida; Mamat, Marhaba; Luo, Wei; Wu, Yanhong

2015-02-01

This study investigated the development of cultural variability in interdependent self-construal by comparing the differences in the tripartite self-concept of adolescent samples from the Han and Uyghur cultures. Participants (460 males, 522 females; M age = 16.3 yr., SD = 4.8) in the sub-phases of pre-, early-, mid-, late- and post-adolescence were asked to completed the revised Twenty Statements Test, and the items generated by the participants were coded into private, relational, and collective self-statements. The private self-statements were further differentiated by personal and social orientation, and the relational self-statements were further coded into family and friend focus. The relational aspect of an individual's self, or personal relationship, became increasingly important with age in the Han cultural groups, whereas the collective aspect of an individual's self, or social identity, became increasingly important with age in the Uyghur cultural groups. These findings seem to show the development of differences between relational and collective interdependent self-construals. Furthermore, these findings emphasize the need for further research into the development of within-cultural differences in self-construal.

IBS-like Symptoms in Patients with Ulcerative Colitis in Deep Remission Are Associated with Increased Levels of Serum Cytokines and Poor Psychological Well-being.

PubMed

Jonefjäll, Börje; Öhman, Lena; Simrén, Magnus; Strid, Hans

2016-11-01

Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission. We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined. The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03). IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

The risk of bladder cancer in patients with urinary calculi: a meta-analysis.

PubMed

Yu, Zhang; Yue, Wu; Jiuzhi, Li; Youtao, Jiang; Guofei, Zhang; Wenbin, Guo

2018-01-05

The objective of this meta-analysis was to evaluate the association between a history of urinary calculi (UC) and the risk of bladder cancer (BC). A literature search was performed from inception until July 2017. Studies that reported odds ratios (OR), relative risks or hazard ratios comparing the risk of BC in patients with the history of UC vs those without the history of UC were included. Pooled odds ratios and 95% confidence interval (CI) were calculated using a random-effect or fixed-effect method. Thirteen studies were included in our analysis to assess the association between a history of UC and risk of BC. The pooled OR of BC in patients with UC was 1.87 (95% CI, 1.45-2.41). Bladder calculi [OR, 2.17 (95% CI, 1.52-3.08)] had a higher risk of BC than kidney calculi [OR, 1.39 (95% CI, 1.06-1.82)]. The subjects had a history of UC that was associated with increased BC risk both in males [OR, 2.04 (95% CI, 1.41-2.96)] and in females [OR, 2.99 (95% CI, 2.37-3.76)]. The subgroup analysis demonstrated that UC increasing risk of BC both in case-control studies [OR, 1.75 (95% CI, 1.25-2.45)] and cohort studies [OR, 2.27 (95% CI, 1.55-3.32)]. The pooled OR of BC risk in patients with UC were 1.60 (95% CI, 1.15-2.24) in America, 1.36 (95% CI, 1.14-1.64) in Europe and 3.05 (95% CI, 2.21-4.21) in Asia, respectively. Our study demonstrates a significant increased risk of BC in patients with prior UC. This finding suggests that a history of UC is associated with BC and may impact clinical management and cancer surveillance. Further studies still needed to confirm the findings.

Urothelial carcinoma involving the distal penis.

PubMed

Dason, Shawn; Sheikh, Adeel; Wang, Jing Gennie; Tauqir, Syeda; Davies, Timothy O; Shayegan, Bobby

2012-04-01

Urothelial carcinoma (UC) rarely metastasizes to the penis and skin. We report the case of a 73-year-old man with UC metastases to the corpus spongiosum and dermis of the distal penis. We also review the clinicopathologic characteristics and management options for UC metastasizing to the penis. The patient presented with priapism and edema of the genital region. This follows a 5-year history of urothelial carcinoma in situ that progressed to invasive cancer despite intravesical immunotherapy. Seventeen months prior to presentation, the patient underwent a radical cystectomy with adjuvant chemotherapy. The cystectomy specimen demonstrated a pT4a N2 M0 G3 UC and margins were positive for carcinoma in situ. Follow-up had been negative for recurrence until his presentation with priapism. Incisional biopsy of the glans revealed UC and radical penectomy was performed with negative margins. The penile specimen demonstrated extensive involvement of the corpus spongiosum by UC with lymphovascular invasion and subepidermal involvement. Three months after penectomy, the patient presented with inguinal nodal recurrence. Palliative radiotherapy was administered and the patient passed away eight months after surgery.

Validation of the "German Inflammatory Bowel Disease Activity Index (GIBDI)": An Instrument for Patient-Based Disease Activity Assessment in Crohn's Disease and Ulcerative Colitis.

PubMed

Hüppe, Angelika; Langbrandtner, Jana; Häuser, Winfried; Raspe, Heiner; Bokemeyer, Bernd

2018-05-09

 Assessment of disease activity in Crohn's disease (CD) and ulcerative colitis (UC) is usually based on the physician's evaluation of clinical symptoms, endoscopic findings, and biomarker analysis. The German Inflammatory Bowel Disease Activity Index for CD (GIBDI CD ) and UC (GIBDI UC ) uses data from patient-reported questionnaires. It is unclear to what extent the GIBDI agrees with the physicians' documented activity indices.  Data from 2 studies were reanalyzed. In both, gastroenterologists had documented disease activity in UC with the partial Mayo Score (pMS) and in CD with the Harvey Bradshaw Index (HBI). Patient-completed GIBDI questionnaires had also been assessed. The analysis sample consisted of 151 UC and 150 CD patients. Kappa coefficients were determined as agreement measurements.  Rank correlations were 0.56 (pMS, GIBDI UC ) and 0.57 (HBI, GIBDI CD ), with p < 0.001. The absolute agreement for 2 categories of disease activity (remission yes/no) was 74.2 % (UC) and 76.6 % (CD), and for 4 categories (none/mild/moderate/severe) 60.3 % (UC) and 61.9 % (CD). The kappa values ranged between 0.47 for UC (2 categories) and 0.58 for CD (4 categories).  There is satisfactory agreement of GIBDI with the physician-documented disease activity indices. GIBDI can be used in health care research without access to assessments of medical practitioners. In clinical practice, the index offers a supplementary source of information. © Georg Thieme Verlag KG Stuttgart · New York.

Takayasu's Disease in a Patient with Ulcerative Colitis.

PubMed

Chae, Myung Joon; Yu, Cheol Woong; Lee, Soo Yeon; Jang, Duck Hyun; Hyun, Joo Yong; Jeong, Su Jin; Kim, Myoung Hwan

2013-02-01

A 35-year-old Korean man with a 10-year history of ulcerative colitis (UC) presented with pain and swelling of the right neck. The patient was diagnosed with Takayasu's arteritis (TA) and had human leukocyte antigen (HLA) B-52, which is frequently found in patients having both UC and Takayasu's disease concurrently on HLA analysis. This case is the first report of a patient with both TA and UC in Korea, to the best of our knowledge.

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

PubMed Central

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

Prevalence and factors associated with the presence of abnormal function liver tests in patients with ulcerative colitis.

PubMed

Yamamoto-Furusho, Jesús K; Sánchez-Osorio, Magdalena; Uribe, Misael

2010-01-01

To investigate the prevalence of abnormal function liver tests and risk factors associated with their development in Mexican patients with UC. A total of 200 patients with confirmed diagnosis of UC were evaluated prospectively during a one year period from January 1, 2007 to December 31, 2008. A total of 94 females and 106 males patients with UC were analyzed. The age at diagnosis was 31.4 ± 13.2 years and the mean of disease duration was 6.7 ± 5.2 years. We found a high prevalence of abnormal function livers tests in 40% of UC patients. The pattern of abnormal function liver test was hepatitis in 70%, cholestatic (20%) and mixed (10%). The most common cause of abnormal function liver test was transient elevation in 50 patients (63%) followed by fatty liver disease (11.2%), primary sclerosing cholangitis (6.3%), drug-toxicity (6%) and others (13.5%) including chronic hepatitis C, total parenteral nutrition, granulomatous and ischemic hepatitis. In the multivariate logistic regression model, active disease, colectomy and abdominal sepsis were factors that persisted associated with the development of abnormal liver tests in UC patients. A high prevalence of abnormal function liver tests (40%) was found in Mexican UC patients is likely to be related to active disease, colectomy and the presence of sepsis.

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

PubMed

Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

Ulcerative colitis patients with an inflammatory response upon mesalazine cannot be desensitized: a randomized study.

PubMed

Buurman, Dorien J; De Monchy, Jan G R; Schellekens, Reinout C A; van der Waaij, Laurens A; Kleibeuker, Jan H; Dijkstra, Gerard

2015-04-01

Mesalazine is a key drug in the treatment of ulcerative colitis (UC). Intolerance to mesalazine has been described, including fever and gastrointestinal symptoms. Several case reports reported successful desensitization of patients with mesalazine intolerance. The aim was to assess the number of UC patients who are persistently intolerant to mesalazine after single-blinded rechallenge and to test the effectiveness of a rapid desensitization protocol in UC patients demonstrated mesalazine intolerance. This is a prospective, single-blind randomized study in UC patients who discontinued mesalazine because of intolerance. Patients with severe reactions were excluded. Eligible patients underwent a skin patch test with mesalazine followed by a single-blinded randomized crossover rechallenge with 500 mg mesalazine or placebo. Patients with symptoms upon rechallenge were admitted to the hospital for 3 days oral desensitization. Nine of the 37 identified UC patients who discontinued mesalazine because of intolerance were included. All nine patients had negative patch tests, seven patients had symptoms (fever, nausea, vomiting and diarrhea) within 2 h upon rechallenge. Four of these seven patients participated in the desensitization protocol and in none a successful desensitization could be performed. All four had an inflammatory intolerance reaction with rise in C-reactive protein. There were no elevations in serum tryptase or urinary-methylhistamine levels observed and no signs of immediate type allergic reactions, like urticaria, bronchial obstruction or anaphylaxis. We recommend not to rechallenge UC patients with an inflammatory response upon mesalazine and these patients will not benefit from a rapid desensitization protocol.

The severity of inflammation at onset of ulcerative colitis is not associated with IBS-like symptoms during clinical remission.

PubMed

Jonefjäll, Börje; Simrén, Magnus; Öhman, Lena; Lasson, Anders; Svedlund, Jan; Strid, Hans

2015-09-01

Symptoms compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in clinical remission. It has been suggested that these symptoms might arise due to post-inflammatory changes comparable with post-infectious IBS. The aim was to study factors at new onset of UC that predict development of IBS-like symptoms during clinical remission. In total, 98 patients with new onset of UC were followed prospectively for 3 years with yearly follow-up visits. Data from the first visit at the onset of UC were compared between a group of patients who fulfilled the criteria for IBS while in remission (UCR+IBS) during follow-up and a group who did not (UCR-IBS). Among the UC patients, 87 met the criteria for clinical remission and 25 (29%) of these reported IBS-like symptoms in remission during follow-up. There was no difference in inflammatory disease activity at the initial flare or in the prevalence of previous IBS symptoms when comparing UCR+IBS and UCR-IBS patients. The UCR+IBS patients reported more severe gastrointestinal symptoms, including abdominal pain, during their primary flare. The severity and extent of inflammation at onset of UC do not seem to affect the development of IBS-like symptoms in UC patients during clinical remission. The high prevalence of IBS-like symptoms is not explained by pre-existing IBS. UCR+IBS patients reported more severe gastrointestinal symptoms at disease onset, which might indicate a more sensitive gastrointestinal tract in this category of patients. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Costs of ulcerative colitis from a societal perspective in a regional health care area in Spain: A database study.

PubMed

Aldeguer, Xavier; Sicras-Mainar, Antoni

2016-01-01

To estimate the management of UC associated costs from the societal perspective in Spain. Observational, longitudinal study with retrospective data collection based on reviews of outpatient health records. Socio-demographic, clinical and sick leave information was gathered. Patients diagnosed of UC between 2002 and 2012, older than 18 years, followed-up by a minimum of 12 months post diagnosis, with at least two clinical and use of resources data recorded, were included. 285 UC patients [51.2% men; 44.5 (SD: 15.6) years old; 88.4% without family history of UC; 39.3% proctitis; 5.6 (2.5) years disease follow-up] participated. More than half (65.6%) were active workers, 75.9% were on sick leave for reasons different from UC [mean 0.66 (0.70) times per year] during (mean) 28.43 (34.45) days. Only 64 patients were on UC-related sick-leaves, lasting (mean) 26.17 (37.43) days. Absenteeism due to medical visits caused loss of 29.55 (21.38) working hours per year. Mean direct and indirect annual cost per UC patient were €1754.10 (95%CI: 1473.37-2034.83) and €399.32 (282.31-422.69), respectively. Absenteeism was estimated at €88.21(32.72-50.06) per patient per year, in which sick-leaves were the main component of indirect costs (88.2%). Age, UC family history, diarrhea at diagnosis, blood and blood-forming organs diseases and psychological disorders were the main predictors of indirect costs. UC is a costly disease for the society and the Spanish National Healthcare System. Indirect costs imply a major burden by affecting the most productive years of patients. Further research is needed considering all components of productivity loss, including presenteeism-associated costs. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Assessing the Impact of Surgeon Experience on Urinary Continence Recovery After Robot-Assisted Radical Prostatectomy: Results of Four High-Volume Surgeons.

PubMed

Fossati, Nicola; Di Trapani, Ettore; Gandaglia, Giorgio; Dell'Oglio, Paolo; Umari, Paolo; Buffi, Nicolò Maria; Guazzoni, Giorgio; Mottrie, Alexander; Gaboardi, Franco; Montorsi, Francesco; Briganti, Alberto; Suardi, Nazareno

2017-09-01

To test the impact of surgeon experience on urinary continence (UC) recovery after robot-assisted radical prostatectomy (RARP). The study included 1477 consecutive patients treated with RARP by four surgeons between 2006 and 2014. UC recovery was defined as being completely dry over a 24-hour period at follow-up. Surgeon experience was coded as the total number of RARP performed by the surgeon before the patient's operation. Multivariable analysis tested the association between surgeon experience and UC recovery. Covariates consisted of patient age, Charlson comorbidity index, preoperative International Index of Erectile Function-Erectile Function domain (IIEF-EF), nerve-sparing surgery (none vs unilateral vs bilateral), and preoperative risk groups (low- vs intermediate- vs high risk). The number of cases performed by each surgeon was 541, 413, 411, and 112, respectively. Median follow-up was 24 months (inter-quartile range: 18, 40). The UC recovery rate at 1 year after surgery was 82%. At multivariable analyses, surgeon experience represented an independent predictor of UC recovery (hazard ratio: 1.02, p < 0.001). The surgical learning curve was similar among surgeons, moving linearly from ∼60% of UC rate at the initial cases to almost 90% after more than 400 procedures. In patients undergoing RARP, surgeon experience is a significant predictor of UC recovery. The surgical learning curve of UC recovery does not reach a plateau even after more than 100 cases, suggesting a continuous improvement of the surgical technique. These findings deserve attention for patient counseling and future comparative studies evaluating functional outcomes after RARP.

Low prevalence of Blastocystis sp. in active ulcerative colitis patients.

PubMed

Rossen, N G; Bart, A; Verhaar, N; van Nood, E; Kootte, R; de Groot, P F; D'Haens, G R; Ponsioen, C Y; van Gool, T

2015-05-01

Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5-49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0-37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls.

Evidence to Support Monitoring of Vedolizumab Trough Concentrations in Patients With Inflammatory Bowel Diseases.

PubMed

Dreesen, Erwin; Verstockt, Bram; Bian, Sumin; de Bruyn, Magali; Compernolle, Griet; Tops, Sophie; Noman, Maja; Van Assche, Gert; Ferrante, Marc; Gils, Ann; Vermeire, Séverine

2018-04-25

Trough concentrations of vedolizumab were found to correlate with clinical response in phase 3 studies of patients with ulcerative colitis (UC) or Crohn's disease (CD). Nevertheless, there are no solid data to support monitoring of vedolizumab trough concentrations in treated patients. We investigated the correlation between vedolizumab exposure and response in a real-world population and aimed to identify patient factors that affect exposure and response. We performed a retrospective cohort study of 179 consecutive patients (66 with UC and 113 with CD) who began vedolizumab therapy from September 1, 2015, through October 1, 2016, at University Hospitals Leuven, Belgium. Serum concentrations of vedolizumab were measured before all infusions up to week 30. Effectiveness endpoints included endoscopic healing (UC, Mayo endoscopic sub-score ≤1; CD, absence of ulcers), clinical response (physicians' global assessment), and biologic response or remission (based on level of C-reactive protein) and were assessed at week 14 (for patients with UC) and week 22 (for patients with CD). A stepwise forward addition-backward elimination modeling approach was performed to identify factors independently associated with vedolizumab exposure and response. Vedolizumab trough concentrations >30.0 μg/mL at week 2, >24.0 μg/mL at week 6, and >14.0 μg/mL during maintenance therapy associated with a higher probability of attaining the effectiveness endpoints for patients with UC or CD (P < .05). Higher body mass and more severe disease (based on high level of C-reactive protein and low level of albumin and/or hemoglobin) at the start of vedolizumab therapy associated with lower trough concentrations of vedolizumab over the 30-week period and a lower probability of achieving mucosal healing (P < .05). Mucosal healing was achieved in significantly more patients with UC than patients with CD, even though a diagnosis of UC was not an independent predictor of higher vedolizumab trough concentrations. In a retrospective study of 179 patients with CD or UC, we observed a correlation between vedolizumab exposure and response. These findings support monitoring of vedolizumab trough concentrations to predict patients' outcome. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Extraintestinal manifestations in Crohn's disease and ulcerative colitis: results from a prospective, population-based European inception cohort.

PubMed

Isene, Rune; Bernklev, Tomm; Høie, Ole; Munkholm, Pia; Tsianos, Epameonondas; Stockbrügger, Reinhold; Odes, Selwyn; Palm, Øyvind; Småstuen, Milada; Moum, Bjørn

2015-03-01

In chronic inflammatory bowel disease (IBD) (Crohn's disease [CD] and ulcerative colitis [UC]), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations [EIM]). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.

Collaborative care for depression symptoms in an outpatient cardiology setting: A randomized clinical trial.

PubMed

Carney, Robert M; Freedland, Kenneth E; Steinmeyer, Brian C; Rubin, Eugene H; Ewald, Gregory

2016-09-15

Depression is a risk factor for morbidity and mortality in patients with coronary heart disease. Finding effective methods for identifying and treating depression in these patients is a high priority. The purpose of this study was to determine whether collaborative care (CC) for patients who screen positive for depression during an outpatient cardiology visit results in greater improvement in depression symptoms and better medical outcomes than seen in patients who screen positive for depression but receive only usual care (UC). Two hundred-one patients seen in an outpatient cardiology clinic who screened positive for depression during an outpatient visit were randomized to receive either CC or UC. Recommendations for depression treatment and ongoing support and monitoring of depression symptoms were provided to CC patients and their primary care physicians (PCPs) for up to 6months. There were no differences between the arms in mean Beck Depression Inventory-II scores(CC, 15.9; UC, 17.4; p=.45) or in depression remission rates(CC, 32.5%; UC, 26.2%; p=0.34) after 6months, or in the number of hospitalizations after 12months (p=0.73). There were fewer deaths among the CC (1/100) than UC patients (8/101) (p=0.03). This trial did not show that CC produces better depression outcomes than UC. Screening led to a higher rate of depression treatment than was expected in the UC group, and delays in obtaining depression treatment from PCPs may have reduced treatment effectiveness for the CC patients. A different strategy for depression treatment following screening in outpatient cardiology services is needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Predictors of Outcome in Ulcerative Colitis.

PubMed

Waterman, Matti; Knight, Jo; Dinani, Amreen; Xu, Wei; Stempak, Joanne M; Croitoru, Kenneth; Nguyen, Geoffrey C; Cohen, Zane; McLeod, Robin S; Greenberg, Gordon R; Steinhart, A Hillary; Silverberg, Mark S

2015-09-01

Approximately 80% of patients with ulcerative colitis (UC) have intermittently active disease and up to 20% will require a colectomy, but little data available on predictors of poor disease course. The aim of this study was to identify clinical and genetic markers that can predict prognosis. Medical records of patients with UC with ≥5 years of follow-up and available DNA and serum were retrospectively assessed. Immunochip was used to genotype loci associated with immune mediated inflammatory disorders (IMIDs), inflammatory bowel diseases, and other single nucleotide polypmorphisms previously associated with disease severity. Serum levels of pANCA, ASCA, CBir1, and OmpC were also evaluated. Requirement for colectomy, medication, and hospitalization were used to group patients into 3 prognostic groups. Six hundred one patients with UC were classified as mild (n = 78), moderate (n = 273), or severe disease (n = 250). Proximal disease location frequencies at diagnosis were 13%, 21%, and 30% for mild, moderate, and severe UC, respectively (P = 0.001). Disease severity was associated with greater proximal extension rates on follow-up (P < 0.0001) and with shorter time to extension (P = 0.03) and to prednisone initiation (P = 0.0004). When comparing severe UC with mild and moderate UC together, diagnosis age >40 and proximal disease location were associated with severe UC (odds ratios = 1.94 and 2.12, respectively). None of the single nucleotide polypmorphisms or serum markers tested was associated with severe UC, proximal disease extension or colectomy. Older age and proximal disease location at diagnosis, but not genetic and serum markers, were associated with a more severe course. Further work is required to identify biomarkers that will predict outcomes in UC.

MtDNA genomes reveal a relaxation of selective constraints in low-BMI individuals in a Uyghur population.

PubMed

Zheng, Hong-Xiang; Li, Lei; Jiang, Xiao-Yan; Yan, Shi; Qin, Zhendong; Wang, Xiaofeng; Jin, Li

2017-10-01

Considerable attention has been focused on the effect of deleterious mutations caused by the recent relaxation of selective constraints on human health, including the prevalence of obesity, which might represent an adaptive response of energy-conserving metabolism under the conditions of modern society. Mitochondrial DNA (mtDNA) encoding 13 core subunits of oxidative phosphorylation plays an important role in metabolism. Therefore, we hypothesized that a relaxation of selection constraints on mtDNA and an increase in the proportion of deleterious mutations have played a role in obesity prevalence. In this study, we collected and sequenced the mtDNA genomes of 722 Uyghurs, a typical population with a high prevalence of obesity. We identified the variants that occurred in the Uyghur population for each sample and found that the number of nonsynonymous mutations carried by Uyghur individuals declined with elevation of their BMI (P = 0.015). We further calculated the nonsynonymous and synonymous ratio (N/S) of the high-BMI and low-BMI haplogroups, and the results showed that a significantly higher N/S occurred in the whole mtDNA genomes of the low-BMI haplogroups (0.64) than in that of the high-BMI haplogroups (0.35, P = 0.030) and ancestor haplotypes (0.41, P = 0.032); these findings indicated that low-BMI individuals showed a recent relaxation of selective constraints. In addition, we investigated six clinical characteristics and found that fasting plasma glucose might be correlated with the N/S and selective pressures. We hypothesized that a higher proportion of deleterious mutations led to mild mitochondrial dysfunction, which helps to drive glucose consumption and thereby prevents obesity. Our results provide new insights into the relationship between obesity predisposition and mitochondrial genome evolution.

[Psycho-social factors of sexual failure among newly married Uyghur young males].

PubMed

Erkin, Ashim; Hamrajan, Memtili; Kadirjan, Mijit; Adil, Eli; Elijan, Abdureshit; Ibrahim, Ubul; Abdulla, Tursun; Hasanjan, Abdurehim; Turgun, Hekim; Eli, Ablet; Eset, Metmusa

2016-08-01

To study the psycho-social risk factors of sexual failure among newly married young males in the Uyghur population. We conducted a paired case control study of 186 newly married Uyghur young males (aged 17－30 ［23.4±2.9］ yr) with sexual failure and another 186 (aged 18－34 ［24.0±3.1］ yr) with no such problem as controls. We performed a logistic regression analysis on the possible psycho-social risk factors of this condition. Logistic regression analysis showed that the risk factors of sexual failure among the newly married men included personality (OR=0.271, 95% CI 0.176－0.420), income (OR=0.391, 95% CI 0.264－0.580), history of masturbation (OR=0.824, 95% CI 0.710－0.956), premarital sex (OR=0.757, 95% CI 0.677－0.847), sense of obligation (OR=1.756, 95% CI 1.157－2.693), equality of the social status (OR=0.574, 95% CI 0.435－0.756), degree of mutual care (OR=1.605, 95% CI 1.268－2.032), female's psychological obstacle (OR=2.832, 95% CI 1.221－6.569), and religion (OR=0.643, 95% CI 0.472－0.967). There was a statistical significance in the correlation between these factors and sexual failure in the newly married males (all P<0.05). Sexual failure of newly married Uyghur young males are associated with many psycho-social factors, which necessitates sexual education among young males and particularly pre-marriage sexual education and psychological guide among both males and females.

Genome-wide scans reveal variants at EDAR predominantly affecting hair straightness in Han Chinese and Uyghur populations.

PubMed

Wu, Sijie; Tan, Jingze; Yang, Yajun; Peng, Qianqian; Zhang, Manfei; Li, Jinxi; Lu, Dongsheng; Liu, Yu; Lou, Haiyi; Feng, Qidi; Lu, Yan; Guan, Yaqun; Zhang, Zhaoxia; Jiao, Yi; Sabeti, Pardis; Krutmann, Jean; Tang, Kun; Jin, Li; Xu, Shuhua; Wang, Sijia

2016-11-01

Hair straightness/curliness is one of the most conspicuous features of human variation and is particularly diverse among populations. A recent genome-wide scan found common variants in the Trichohyalin (TCHH) gene that are associated with hair straightness in Europeans, but different genes might affect this phenotype in other populations. By sampling 2899 Han Chinese, we performed the first genome-wide scan of hair straightness in East Asians, and found EDAR (rs3827760) as the predominant gene (P = 4.67 × 10 -16 ), accounting for 3.66 % of the total variance. The candidate gene approach did not find further significant associations, suggesting that hair straightness may be affected by a large number of genes with subtle effects. Notably, genetic variants associated with hair straightness in Europeans are generally low in frequency in Han Chinese, and vice versa. To evaluate the relative contribution of these variants, we performed a second genome-wide scan in 709 samples from the Uyghur, an admixed population with both eastern and western Eurasian ancestries. In Uyghurs, both EDAR (rs3827760: P = 1.92 × 10 -12 ) and TCHH (rs11803731: P = 1.46 × 10 -3 ) are associated with hair straightness, but EDAR (OR 0.415) has a greater effect than TCHH (OR 0.575). We found no significant interaction between EDAR and TCHH (P = 0.645), suggesting that these two genes affect hair straightness through different mechanisms. Furthermore, haplotype analysis indicates that TCHH is not subject to selection. While EDAR is under strong selection in East Asia, it does not appear to be subject to selection after the admixture in Uyghurs. These suggest that hair straightness is unlikely a trait under selection.

Risk of colectomy in patients with ulcerative colitis under thiopurine treatment.

PubMed

Cañas-Ventura, Alex; Márquez, Lucia; Ricart, Elena; Domènech, Eugeni; Gisbert, Javier P; García-Sanchez, Valle; Marín-Jiménez, Ignacio; Rodriguez-Moranta, Francisco; Gomollón, Fernando; Calvet, Xavier; Merino, Olga; Garcia-Planella, Esther; Vázquez-Romero, Narcis; Esteve, Maria; Iborra, Marisa; Gutiérrez, Ana; Vera, Maribel; Andreu, Montserrat

2014-10-01

Little is known about the risk factors of colectomy in patients with ulcerative colitis (UC) under thiopurine treatment. The aim of the study was to determine the prevalence and the predictive risk factors of colectomy in an extensive cohort of patients with UC treated with thiopurines in Spain. Among 5753 UC patients, we identified those diagnosed between 1980 and 2009 and treated with azathioprine or mercaptopurine (AZA/MP). We analyzed the age at diagnosis, familial history of IBD, extraintestinal manifestations (EIMs), disease extent, smoking status and treatment requirements (AZA/MP, cyclosporine (CsA) or anti-TNFα). Colectomies for dysplasia or cancer were excluded. Survival analysis and Cox proportional hazard regression were performed. Results were reported as hazard ratios (HR) with 95% CI. Among the 1334 cases included, 119 patients (8.9%) required colectomy after a median time of 26 months (IQR 12-42) after AZA/MP initiation. Independent predictors of colectomy were: Extensive UC (HR 1.7, 95% CI: 1.1-2.6), EIMs (HR 1.5, 95% CI: 1.0-2.4), need for antiTNFα (HR 2.3, 95% CI: 1.5-3.4) and need for CsA (HR 2.4, 95% CI: 1.6-3.7). Patients requiring early introduction of AZA/MP had an increased risk of colectomy with a HR of 4.9 (95% CI: 3.2-7.8) when AZA/MP started in the first 33 months after UC diagnosis. Nearly one-tenth of patients with UC under thiopurines require colectomy. Extensive UC, EIMs, need for CsA or anti-TNFα ever and an early need for AZA/MP treatment were associated with a higher risk of colectomy. These risk factors of colectomy could help to stratify risk in further controlled studies in UC. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Decreased colonization of fecal Clostridium coccoides/Eubacterium rectale species from ulcerative colitis patients in an in vitro dynamic gut model with mucin environment.

PubMed

Vermeiren, Joan; Van den Abbeele, Pieter; Laukens, Debby; Vigsnaes, Louise Kristine; De Vos, Martine; Boon, Nico; Van de Wiele, Tom

2012-03-01

The mucus layer in the colon, acting as a barrier to prevent invasion of pathogens, is thinner and discontinuous in patients with ulcerative colitis (UC). A recent developed in vitro dynamic gut model, the M-SHIME, was used to compare long-term colonization of the mucin layer by the microbiota from six healthy volunteers (HV) and six UC patients and thus distinguish the mucin adhered from the luminal microbiota. Although under the same nutritional conditions, short-chain fatty acid production by the luminal communities from UC patients showed a tendency toward a lower butyrate production. A more in-depth community analysis of those microbial groups known to produce butyrate revealed that the diversity of the Clostridium coccoides/Eubacterium rectale and Clostridium leptum group, and counts of Faecalibacterium prausnitzii were lower in the luminal fractions of the UC samples. Counts of Roseburia spp. were lower in the mucosal fractions of the UC samples. qPCR analysis for butyryl-CoA:acetate CoA transferase, responsible for butyrate production, displayed a lower abundance in both the luminal and mucosal fractions of the UC samples. The M-SHIME model revealed depletion in butyrate producing microbial communities not restricted to the luminal but also in the mucosal samples from UC patients compared to HV. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

High intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitis.

PubMed

Bamias, Giorgos; Kaltsa, Garyfallia; Siakavellas, Spyros I; Papaxoinis, Kostis; Zampeli, Evanthia; Michopoulos, Spyros; Zouboulis-Vafiadis, Irene; Ladas, Spiros D

2010-11-01

Decoy receptor-3 (DcR3) is a member of the TNF receptor superfamily of proteins, which has been implicated in anti-apoptotic and anti-inflammatory pathways, via binding to TL1A, LIGHT and Fas-L. The role of the TL1A/DcR3 ligand/receptor pair in ulcerative colitis (UC) has not been studied. We investigated the systemic (peripheral blood) and local (large intestine) expression of DcR3 and TL1A in 64 patients with UC and 56 healthy controls. DcR3 serum concentrations were highly elevated in patients with active UC (P<0.0001 vs. healthy controls). This elevation was clearly related to the presence of intestinal inflammation as it was less frequently observed in patients in remission (P=0.003 vs. active UC) whereas effective treatment resulted in disappearance or significant decrease of serum DcR3 (P=0.006 vs. pre-treatment). Furthermore, DcR3 mRNA transcripts were significantly elevated in inflamed areas of the colon (P=0.002 vs. non-affected of the same patient). In addition to DcR3 elevation, we found increased circulating levels of TL1A in patients with either active or inactive UC in comparison to healthy controls (P<0.001 for both). We conclude that elevated serum DcR3 may serve as an indicator of active colonic inflammation in patients with UC. TL1A/DcR3-mediated pathways may participate in the pathogenesis of UC. Copyright © 2010 Elsevier Inc. All rights reserved.

Epidemiological and clinical characteristics of inflammatory bowel diseases in Cairo, Egypt.

PubMed

Esmat, Serag; El Nady, Mohamed; Elfekki, Mohamed; Elsherif, Yehia; Naga, Mazen

2014-01-21

To study the natural history, patterns and clinical characteristics of inflammatory bowel diseases (IBD) in Egypt. We designed a case-series study in the gastroenterology centre of the Internal Medicine department of Cairo University, which is a tertiary care referral centre in Egypt. We included all patients in whom the diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) was confirmed by clinical, laboratory, endoscopic, histological and/or radiological criteria over the 15 year period from 1995 to 2009, and we studied their sociodemographic and clinical characteristics. Endoscopic examinations were performed by 2 senior experts. This hospital centre serves patients from Cairo, as well as patients referred from all other parts of Egypt. Our centre received 24156 patients over the described time period for gastro-intestinal consultations and/or interventions. A total of 157 patients with established IBD were included in this study. Of these, 135 patients were diagnosed with UC (86% of the total), and 22 patients, with CD (14% of the total). The mean ages at diagnosis were 27.3 and 29.7, respectively. Strikingly, we noticed a marked increase in the frequency of both UC and CD diagnoses during the most recent 10 years of the 15 year period studied. Regarding the gender distribution, the male:female ratio was 1:1.15 for UC and 2.6:1 for CD. The mean duration of follow up for patients with UC was 6.2 ± 5.18 years, while the mean duration of follow up for patients with CD was 5.52 ± 2.83 years. For patients with UC we found no correlation between the severity of the disease and the presence of extraintestinal manifestations. Eleven patients had surgical interventions during the studied years: 4 cases of total colectomy and 7 cases of anal surgery. We observed a ratio of 6:1 for UC to CD in our series. The incidence of IBD seems to be rising in Egypt.

Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease

PubMed Central

De Cassan, Chiara; Savarino, Edoardo; Marson, Piero; Tison, Tiziana; Hatem, Giorgia; Sturniolo, Giacomo Carlo; D’Incà, Renata

2014-01-01

AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity. METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients’ charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points. RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively). CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics. PMID:25493030

Epidemiological and clinical characteristics of inflammatory bowel diseases in Cairo, Egypt

PubMed Central

Esmat, Serag; El Nady, Mohamed; Elfekki, Mohamed; Elsherif, Yehia; Naga, Mazen

2014-01-01

AIM: To study the natural history, patterns and clinical characteristics of inflammatory bowel diseases (IBD) in Egypt. METHODS: We designed a case-series study in the gastroenterology centre of the Internal Medicine department of Cairo University, which is a tertiary care referral centre in Egypt. We included all patients in whom the diagnosis of ulcerative colitis (UC) or Crohn’s disease (CD) was confirmed by clinical, laboratory, endoscopic, histological and/or radiological criteria over the 15 year period from 1995 to 2009, and we studied their sociodemographic and clinical characteristics. Endoscopic examinations were performed by 2 senior experts. This hospital centre serves patients from Cairo, as well as patients referred from all other parts of Egypt. Our centre received 24156 patients over the described time period for gastro-intestinal consultations and/or interventions. RESULTS: A total of 157 patients with established IBD were included in this study. Of these, 135 patients were diagnosed with UC (86% of the total), and 22 patients, with CD (14% of the total). The mean ages at diagnosis were 27.3 and 29.7, respectively. Strikingly, we noticed a marked increase in the frequency of both UC and CD diagnoses during the most recent 10 years of the 15 year period studied. Regarding the gender distribution, the male:female ratio was 1:1.15 for UC and 2.6:1 for CD. The mean duration of follow up for patients with UC was 6.2 ± 5.18 years, while the mean duration of follow up for patients with CD was 5.52 ± 2.83 years. For patients with UC we found no correlation between the severity of the disease and the presence of extraintestinal manifestations. Eleven patients had surgical interventions during the studied years: 4 cases of total colectomy and 7 cases of anal surgery. CONCLUSION: We observed a ratio of 6:1 for UC to CD in our series. The incidence of IBD seems to be rising in Egypt. PMID:24574754

Usefulness of rectally administering [1-(13)C]-butyrate for breath test in patients with active and quiescent ulcerative colitis.

PubMed

Kato, Kimitoshi; Ishii, Yukimoto; Mizuno, Shigeaki; Sugitani, Masahiko; Asai, Satoshi; Kohno, Tadashi; Takahashi, Katsuyuki; Komuro, Sachiko; Iwamoto, Maho; Miyamoto, Shunpachi; Takayama, Tadatoshi; Arakawa, Yasuyuki

2007-02-01

Impaired butyrate metabolism plays a part in ulcerative colitis (UC). To assess the usefulness of measuring butyrate metabolism as an indication of inflammatory activity, we investigated the rate of butyrate metabolism by breath test after administering [1-(13)C]-butyrate rectally to patients with UC. Thirty-eight UC patients (22 active, 16 quiescent) and 15 healthy controls were given [1-(13)C]-butyrate enemas. The (13)CO2 production rate was measured by breath test using an infrared spectrometric analyzer. The quantity of expired (13)CO2 was significantly lower in the active than in the quiescent UC and control groups. Cumulative (13)CO2 production at 240 min showed significant negative correlations with the clinical activity index (r=-0.65, p<0.0001), endoscopic activity index (r=-0.63, p=0.0001) and histology (r=-0.71, p<0.0001) in the active UC group. The (13)CO2 production rate was significantly increased in the quiescent stage as compared with the active stage in six UC patients, in whom clinical remission was achieved, in accordance with improvements in the clinical activity index, the endoscopic activity index, histology and fecal butyrate concentrations. Significant inverse correlations between the cumulative (13)CO2 production rate and these three parameters were seen in these six UC patients assessed in both the active and quiescent stages. Measurement of expired (13)CO2 after rectally administering [1-(13)C]-butyrate in active and quiescent UC appears to be a promising and reliable method for evaluating disease activity and metabolic changes associated with amelioration of inflammation.

Ulcerative colitis in a multiracial Asian country: Racial differences and clinical presentation among Malaysian patients

PubMed Central

Tan, Yan-Mei; Goh, Khean-Lee

2005-01-01

AIM: TO determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. METHODS: Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. RESULTS: There were 45 confirmed cases of UC, of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0 ± 10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; c2 = 15.45,P < 0.001) and 3.06 (CI = 1.24-7.78; c2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; c2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%). CONCLUSION: UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease. PMID:16270398

Meta-analysis: the efficacy of rectal beclomethasone dipropionate vs. 5-aminosalicylic acid in mild to moderate distal ulcerative colitis.

PubMed

Manguso, F; Balzano, A

2007-07-01

Beclomethasone dipropionate (BDP) is a second-generation steroid with topical effects and minimal systemic activity for patients with ulcerative colitis (UC). To review all available literature to assess the efficacy of enema/foam BDP compared with enema/foam 5-aminosalicylic acid (5-ASA) in the control of left-sided mild-moderate UC. We selected randomized controlled trials of enema/foam BDP compared with enema/foam 5-ASA treatment in patients with UC. Two reviewers assessed trial quality and extracted data independently. Four trials involving 428 UC patients, 209 treated with 5-ASA (1-4 g o.d.) and 219 with BDP (3 mg o.d.), were included. Intention-to-treat analysis showed that 5-ASA induced improvement/remission of UC in 146 (69.9%) patients, while BDP in 143 (65.3%). The test for heterogeneity (Cochran Q) was not significant and Mantel-Haenszel pooled estimate of odds ratio was 1.23 (95% CI = 0.82-1.85). The results did not change when analysis was performed on a per-protocol basis. The randomized controlled trials identified in this review showed that rectal BDP has equal effect as 5-ASA to control symptoms in UC.

{sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Ying; Lin, Lianjie; Xu, Yanbin

2013-04-19

Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected tomore » multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.« less

Postoperative Mortality Among Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis of Population-Based Studies.

PubMed

Singh, Sunny; Al-Darmaki, Ahmed; Frolkis, Alexandra D; Seow, Cynthia H; Leung, Yvette; Novak, Kerri L; Ghosh, Subrata; Eksteen, Bertus; Panaccione, Remo; Kaplan, Gilaad G

2015-10-01

There have been varying reports of mortality after intestinal resection for the inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis of population-based studies to determine postoperative mortality after intestinal resection in patients with IBD. We searched Medline, EMBASE, and PubMed, from 1990 through 2015, to identify 18 articles and 3 abstracts reporting postoperative mortality among patients with IBD. The studies included 67,057 patients with ulcerative colitis (UC) and 75,971 patients with Crohn's disease (CD), from 15 countries. Mortality estimates stratified by emergent and elective surgeries were pooled separately for CD and UC using a random-effects model. To assess changes over time, the start year of the study was included as a continuous variable in a meta-regression model. In patients with UC, postoperative mortality was significantly lower among patients who underwent elective (0.7%; 95% confidence interval [CI], 0.6%-0.9%) vs emergent surgery (5.3%; 95% CI, 3.8%-7.4%). In patients with CD, postoperative mortality was significantly lower among patients who underwent elective (0.6%; 95% CI, 0.2%-1.7%) vs emergent surgery (3.6%; 95% CI, 1.8%-6.9%). Postoperative mortality did not differ for elective (P = .78) or emergent (P = .31) surgeries when patients with UC were compared with patients with CD. Postoperative mortality decreased significantly over time for patients with CD (P < .05) but not UC (P = .21). Based on a systematic review and meta-analysis, postoperative mortality was high after emergent, but not elective, intestinal resection in patients with UC or CD. Optimization of management strategies and more effective therapies are necessary to avoid emergent surgeries. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Umbilical cord mesenchymal stem cell (UC-MSC) transplantations for cerebral palsy

PubMed Central

Dong, Huajiang; Li, Gang; Shang, Chongzhi; Yin, Huijuan; Luo, Yuechen; Meng, Huipeng; Li, Xiaohong; Wang, Yali; Lin, Ling; Zhao, Mingliang

2018-01-01

This study reports a case of a 4-year-old boy patient with abnormalities of muscle tone, movement and motor skills, as well as unstable gait leading to frequent falls. The results of the electroencephalogram (EEG) indicate moderately abnormal EEG, accompanied by irregular seizures. Based on these clinical characteristics, the patient was diagnosed with cerebral palsy (CP) in our hospital. In this study, the patient was treated with umbilical cord mesenchymal stem cell (UC-MSC) transplantation therapy. This patient received UC-MSC transplantation 3 times (5.3*107) in total. After three successive cell transplantations, the patient recovered well and showed obvious improvements in EEG and limb strength, motor function, and language expression. However, the improvement in intelligence quotient (IQ) was less obvious. These results indicate that UC-MSC transplantation is a promising treatment for cerebral palsy. PMID:29636880

Effect of a Food Supplement Containing L-Methionine on Urinary Tract Infections in Pregnancy: A Prospective, Multicenter Observational Study.

PubMed

Passaro, Mario; Mainini, Giampaolo; Ambrosio, Francesco; Sgambato, Raimondo; Balbi, Giancarlo

2017-06-01

Adjuvants or alternatives to antibiotics in urinary tract infections (UTIs) during pregnancy seem advisable because of possible fetal stress. The present study assessed the effectiveness of a food supplement containing L-methionine and Hibiscus sabdariffa L. and Boswellia serrata Roxb. extracts as a treatment for symptomatic UTIs in pregnancy. Pregnant patients with symptomatic cystitis were screened for UTIs in three different clinical centers. Those unwilling to take antibiotics were offered two alternative treatments: (A) a 1-week treatment with the food supplement or (B) a week in which they were advised to increase their fluid consumption to more than 1.5 L daily. After 1 week, group B patients who still had positive urine cultures (UCs) or had no UC performed took the food supplement for an additional week. UCs were performed on all patients at the first visit (w0) and on most of them at 7 days (w1). Patients who were still positive at w1 or had no UC performed at w1 had UC performed 14 days (w2) thereafter. Of 264 pregnant women enrolled, 216 joined group A, while 48 joined group B. At w1, 70.0% of group A patients and 43.2% of those in group B had negative UCs (p = 0.003). The reduction of bacterial load was 42.2% ± 8.0% and 4.5% ± 9.2%, respectively (p < 0.0001). At w1, symptoms disappeared in 135 patients (62.5%) in group A and 22 patients (45.8%) in group B (p = 0.03). At w2, 30 of 32 group B patients who switched to taking the supplement for the second week had negative UCs, including 20 who had been positive at w1. At w2, all group A patients had negative UCs. No side effects were reported. The food supplement provided effective treatment and might be an adjuvant or alternative to antibiotic therapy of symptomatic UTI in pregnancy.

Long-term Efficacy, Safety, and Immunogenicity of Biosimilar Infliximab After One Year in a Prospective Nationwide Cohort.

PubMed

Gonczi, Lorant; Gecse, Krisztina B; Vegh, Zsuzsanna; Kurti, Zsuzsanna; Rutka, Mariann; Farkas, Klaudia; Golovics, Petra A; Lovasz, Barbara D; Banai, Janos; Bene, Laszlo; Gasztonyi, Bea; Kristof, Tunde; Lakatos, Laszlo; Miheller, Pal; Nagy, Ferenc; Palatka, Karoly; Papp, Maria; Patai, Arpad; Salamon, Agnes; Szamosi, Tamas; Szepes, Zoltan; Toth, Gabor T; Vincze, Aron; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

2017-11-01

It has been previously shown that biosimilar infliximab CT-P13 is effective and safe in inducing remission in inflammatory bowel diseases. We report here the 1-year outcomes from a prospective nationwide inflammatory bowel disease cohort. A prospective, nationwide, multicenter, observational cohort was designed to examine the efficacy and safety of CT-P13 in the induction and maintenance treatment of Crohn's disease (CD) and ulcerative colitis (UC). Demographic data were collected and a harmonized monitoring strategy was applied. Clinical remission, response, and biochemical response were evaluated at weeks 14, 30, and 54, respectively. Safety data were registered. Three hundred fifty-three consecutive inflammatory bowel disease (209 CD and 144 UC) patients were included, of which 229 patients reached the week 54 endpoint at final evaluation. Age at disease onset: 24/28 years (median, interquartile range: 19-34/22-39) in patients with CD/UC. Forty-nine, 53, 48% and 86, 81 and 65% of patients with CD reached clinical remission and response by weeks 14, 30, and 54, respectively. Clinical remission and response rates were 56, 41, 43% and 74, 66, 50% in patients with UC. Clinical efficacy was influenced by previous anti-tumor necrosis factor (TNF) exposure in patients with a drug holiday beyond 1 year. The mean C-reactive protein level decreased significantly in both CD and UC by week 14 and was maintained throughout the 1-year follow-up (both UC/CD: P < 0.001). Thirty-one (8.8%) patients had infusion reactions and 32 (9%) patients had infections. Antidrug antibody positivity rates were significantly higher throughout patients with previous anti-TNF exposure; concomitant azathioprine prevented antidrug antibody formation in anti-TNF-naive patients with CD. Results from this prospective nationwide cohort confirm that CT-P13 is effective and safe in inducing and maintaining long-term remission in both CD and UC. Efficacy was influenced by previous anti-TNF exposure; no new safety signals were detected.

Surgical Outcomes in Vedolizumab-Treated Patients with Ulcerative Colitis.

PubMed

Lightner, Amy L; McKenna, Nicholas P; Moncrief, Sara; Pemberton, John H; Raffals, Laura E; Mathis, Kellie L

2017-12-01

Surgical outcomes and pouch outcomes in the setting of vedolizumab remains poorly understood. We sought to determine the rate of 30-day postoperative surgical infectious complications and pouch-specific complications among patients with ulcerative colitis (UC) who received vedolizumab within 12 weeks of surgery. A retrospective chart review between 5/1/2014 and 12/31/2016 of all adult patients with UC who underwent an abdominal operation was performed. Patients with UC who received vedolizumab within 12 weeks of their abdominal operation were compared with patients with UC on anti-TNFα treatment. Eighty-eight patients received vedolizumab and 62 received anti-TNFα within 12 weeks of surgery. More vedolizumab-treated patients had superficial surgical site infections (P = 0.047) and mucocutaneous separation at the ileostomy (P = 0.047), but there was no difference in the overall surgical infectious complication rate, deep space SSI, 30-day hospital readmission or return to the operating room. On univariate analysis of SSI among patients with UC, exposure to vedolizumab was not a significant predictor of SSI (P = 0.27), but steroids were predictive of SSI on univariate (P = 0.02) and multivariable analysis (P = 0.02). After ileal pouch anal anastomosis, there was a higher rate of intra-abdominal abscesses (31.3% versus 5.9%) and mucocutaneous separation (18.8% versus 0%) in the vedolizumab group compared with the anti-TNFα group, but statistical significance was not reached. Vedolizumab patients had significantly increased rates of superficial SSI, but not overall infectious complications. Among ileal pouch anal anastomosis patients, peripouch abscess rates were increased among vedolizumab-treated patients, but this did not reach statistical significance. Vedolizumab seems safe in the perioperative period for patients with UC.

Enteric microbiota leads to new therapeutic strategies for ulcerative colitis.

PubMed

Chen, Wei-Xu; Ren, Li-Hua; Shi, Rui-Hua

2014-11-14

Ulcerative colitis (UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition (termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrate-producing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractive approach for UC therapy. Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC. Such therapies include fecal microbiota transplantation, probiotics, prebiotics, antibiotics, helminth therapy, and dietary polyphenols, all of which can alter the abundance and composition of the enteric microbiota. Although there have been many large, randomized controlled clinical trials assessing these treatments, the effectiveness and safety of these bacteria-driven therapies need further evaluation. This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.

Ulcerative colitis in smokers, non-smokers and ex-smokers

PubMed Central

Bastida, Guillermo; Beltrán, Belén

2011-01-01

Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit. PMID:21734782

Systematic Review: Rectal Therapies for the Treatment of Distal Forms of Ulcerative Colitis.

PubMed

Cohen, Russell D; Dalal, Sushila R

2015-07-01

Many therapeutic options are available for patients with distal forms of ulcerative colitis (UC). Rectal therapies (e.g., suppositories, foams, gels, and enemas) may be recommended either alone or in combination with oral treatment. Compared with oral therapies, rectal therapies are underused in patients with distal forms of UC, although rectal therapies have favorable efficacy and safety profiles. This systematic review identified 48 articles for inclusion after a comprehensive PubMed search and the identification of additional relevant articles through other sources. Inclusion criteria were clinical studies examining efficacy and safety of 5-aminosalicylic acid, corticosteroid, and non-5-aminosalicylic acid rectal therapies (suppositories, foams, gels, and enemas) that induce or maintain remission in patients with ulcerative proctitis, ulcerative proctosigmoiditis, or left-sided colitis (i.e., distal forms of UC). The quality of the evidence presented was evaluated using the GRADE system. Overall, a greater percentage of patients with distal forms of UC receiving 5-aminosalicylic acids or corticosteroid rectal formulations derived greater therapeutic benefit after treatment compared with patients receiving placebo. Furthermore, most uncontrolled studies of rectal therapies reported that patients with distal forms of UC had marked improvement from baseline after treatment. The overall safety profile of rectal therapies was favorable. Treatment with second-generation corticosteroids, such as budesonide and beclomethasone dipropionate, did not increase the incidence of steroid-related adverse effects. The current literature supports the use of rectal therapies for both induction and maintenance of remission in patients with distal forms of UC.

Relationship between serum interleukin-17 level and inflammatory bowel disease.

PubMed

Liu, Q L; Huang, L; Zhao, Q J; Li, Q; He, Z

2016-01-01

By detecting expression of interleukin (IL)-17A, IL-10 and interferon-γ (IFN-γ) in serum of inflammatory bowel disease (IBD) patients, this study aims to analyze the effects of these factors on the pathogenesis of IBD. According to illness status, selected patients were divided into Crohn’s disease (CD) group (28 patients), ulcerative colitis (UC) group (74 patients) and normal control group (36 patients); enzymelinked immunosorbent assay (ELISA) was used to detect IL-17A, IL-10 and IFN-γ levels in serum; immunohistochemical assay was used to detect local IL-17A expression in the colonic mucosa of each group. Clinical results showed that IL-17A content of the UC group and CD group was significantly higher than that of the normal control group (p less than 0.05); IL-17A content of the CD group was higher than that of the UC group (p>0.05). The UC group had the highest IL-10 content, and the difference between the UC group and other two groups had statistical significance (p less than 0.05); the difference of IL-10 content between UC group and normal control group had no statistical significance (p>0.05). There was no significant difference of IFN-γ level between the CD group and the UC group and normal control group (p>0.05), and no significant difference of IFN-γ level was shown between the CD group and the UC group (p>0.05). Both the CD and UC groups showed IL-17A positive staining in cytoplasm of lymphocyte, however no positive staining was found in any layer of intestinal mucosa of the normal control group. IL-17A was locally expressed in the colon of IBD patients in remission; furthermore, it also had high expression in serum; thus, there still existed high expression of pro-inflammatory factor, which might be related to relapse of IBD. Therefore, prevention of IL-17A may become a feasible therapy for IBD in the future.

High treatment persistence rate and significant endoscopic healing among real-life patients treated with vedolizumab - a Finnish Nationwide Inflammatory Bowel Disease Cohort Study (FINVEDO).

PubMed

Ylisaukko-Oja, Tero; Aaltonen, Jaakko; Nuutinen, Heikki; Blomster, Timo; Jussila, Airi; Pajala, Markku; Salminen, Kimmo; Moilanen, Veikko; Hakala, Kalle; Kellokumpu, Mikko; Toljamo, Kari; Rautiainen, Henna; Kuisma, Juha; Peräaho, Markku; Molander, Pauliina; Silvennoinen, Jouni; Liukkonen, Ville; Henricson, Hans; Tillonen, Jyrki; Esterinen, Mirva; Nielsen, Christian; Hirsi, Eija; Lääne, Margus; Suhonen, Ulla-Maija; Vihriälä, Ilkka; Mäkelä, Petri; Puhto, Mika; Punkkinen, Jari; Sulonen, Hannu; Herrala, Sauli; Jokelainen, Jari; Tamminen, Klaus; Sipponen, Taina

2018-02-01

The efficacy and tolerability of vedolizumab in the treatment of inflammatory bowel diseases (IBD) has been demonstrated in an extensive GEMINI clinical trial programme. Clinical trials represent highly selected patient populations and, therefore, it is important to demonstrate effectiveness in real-life clinical practice. We set out to assess real-world treatment outcomes of vedolizumab in a nationwide cohort of treatment refractory Finnish Crohn's disease (CD) and ulcerative colitis (UC) patients. This was a nationwide, retrospective, non-interventional, multi-centre chart review study. All adult patients from 27 Finnish gastroenterology centers with a diagnosis of UC or CD who had at least one vedolizumab infusion since the availability of the product in Finland, were included in the study. Data were collected retrospectively from medical charts at baseline, week 14, and month 6. The primary outcome measure was treatment persistence 24 weeks post-vedolizumab initiation. A total of 247 patients were included (108 CD, 139 UC). A total of 75.0% (n = 81) of all CD patients and 66.2% (n = 92) of all UC patients, were persistent on vedolizumab therapy for 6 months post treatment initiation. At month 6, 41.8% (28/67) of the treatment persistent CD patients and 73.3% (63/86) of the treatment persistent UC patients achieved clinical remission. Significant improvement in endoscopic scores were observed among treatment persistent patients (CD, n = 17, ΔSES-CD=-5.5, p = .008; UC, n = 26, ΔMayo endoscopic score =-0.5, p = .003) at month 6. Vedolizumab provides an effective and well-tolerated treatment option in real-world clinical practice even among treatment refractory IBD patients.

The impact of Clostridum difficile on surgical rate among ulcerative colitis patients: A systemic review and meta-analysis.

PubMed

Peng, Jiang-Chen; Shen, Jun; Zhu, Qi; Ran, Zhi-Hua

2015-01-01

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case-control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36-2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.

Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: consider primary biliary cholangitis not always primary sclerosing cholangitis.

PubMed

Polychronopoulou, Erietta; Lygoura, Vasiliki; Gatselis, Nikolaos K; Dalekos, George N

2017-09-25

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Effectiveness and Cost-Effectiveness of Spinal Cord Stimulation for Refractory Angina (RASCAL Study): A Pilot Randomized Controlled Trial.

PubMed

Eldabe, Sam; Thomson, Simon; Duarte, Rui; Brookes, Morag; deBelder, Mark; Raphael, Jon; Davies, Ed; Taylor, Rod

2016-01-01

Patients with "refractory angina" (RA) unsuitable for coronary revascularization experience high levels of hospitalization and poor health-related quality of life. Randomized trials have shown spinal cord stimulation (SCS) to be a promising treatment for chronic stable angina and RA; however, none has compared SCS with usual care (UC). The aim of this pilot study was to address the key uncertainties of conducting a definitive multicenter trial to assess the clinical and cost-effectiveness of SCS in RA patients, i.e., recruitment and retention of patients, burden of outcome measures, our ability to standardize UC in a UK NHS setting. RA patients deemed suitable were randomized in a 1:1 ratio to SCS plus UC (SCS group) or UC alone (UC group). We sought to assess: recruitment, uptake, and retention of patients; feasibility and acceptability of SCS treatment; the feasibility and acceptability of standardizing UC; and the feasibility and acceptability of the proposed trial outcome measures. Patient outcomes were assessed at baseline (prerandomization) and three and six months postrandomization. We failed to meet our planned recruitment target (45 patients) and randomized 29 patients (15 SCS group, 14 UC group) over a 42-month period across four sites. None of the study participants chose to withdraw following consent and randomization. With exception of two deaths, all completed evaluation at baseline and follow-up. Although the study was not formally powered to compare outcomes between groups, we saw a trend toward larger improvements in both primary and secondary outcomes in the SCS group. While patient recruitment was found to be challenging, levels of participant retention, outcome completion, and acceptability of SCS therapy were high. A number of lessons are presented in order to take forward a future definitive pragmatic randomized trial. © 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

Assessment of selected psychological factors in patients with inflammatory bowel disease

PubMed Central

Kaczówka, Anna; Jeżewska, Maria

2015-01-01

Introduction In the majority of patients with inflammatory bowel diseases (IBD) mental health problems are demonstrated in the form of excessive anxiety and unstable emotional reactions. Emotional instability affects the wellbeing of these patients, and also their attitude towards the disease and the course of treatment. Aim The objective of the study is to evaluate psychological factors in patients with IBD, and to compare patients with ulcerative colitis (UC) and patients suffering from Crohn's disease (CD) with respect to intensity of these factors. Material and methods The study included 108 patients with IBD. NEO-FFI and type-D Scale were used to evaluate personality traits. Anxiety level was measured with STAI. CECS was used to measure the patients’ tendency to suppress negative emotions. Results In the patients with CD 45% of subjects presented type D personality. In the group of patients with UC, type D personality was found in 38%. The higher levels of neuroticism and extraversion were observed in patients with UC, whereas the patients with CD exhibited a higher level of openness to experience and agreeableness. In patients with CD the levels of state anxiety were elevated, whereas in patients with UC higher scores were both for state and trait anxiety. Conclusions There were no statistically significant differences in terms of personality factors in a group of patients with CD and UC. It was found that the majority of patients with IBD suffer elevated or high sense of anxiety. PMID:27110311

Mucosal Transcriptomics Implicates Under Expression of BRINP3 in the Pathogenesis of Ulcerative Colitis

PubMed Central

Smith, Philip J.; Levine, Adam P.; Dunne, Jenny; Guilhamon, Paul; Turmaine, Mark; Sewell, Gavin W.; O'Shea, Nuala R.; Vega, Roser; Paterson, Jennifer C.; Oukrif, Dahmane; Beck, Stephan; Bloom, Stuart L.; Novelli, Marco; Rodriguez-Justo, Manuel; Smith, Andrew M.

2014-01-01

Background: Mucosal abnormalities are potentially important in the primary pathogenesis of ulcerative colitis (UC). We investigated the mucosal transcriptomic expression profiles of biopsies from patients with UC and healthy controls, taken from macroscopically noninflamed tissue from the terminal ileum and 3 colonic locations with the objective of identifying abnormal molecules that might be involved in disease development. Methods: Whole-genome transcriptional analysis was performed on intestinal biopsies taken from 24 patients with UC, 26 healthy controls, and 14 patients with Crohn's disease. Differential gene expression analysis was performed at each tissue location separately, and results were then meta-analyzed. Significantly, differentially expressed genes were validated using quantitative polymerase chain reaction. The location of gene expression within the colon was determined using immunohistochemistry, subcellular fractionation, electron and confocal microscopy. DNA methylation was quantified by pyrosequencing. Results: Only 4 probes were abnormally expressed throughout the colon in patients with UC with Bone morphogenetic protein/Retinoic acid Inducible Neural-specific 3 (BRINP3) being the most significantly underexpressed. Attenuated expression of BRINP3 in UC was independent of current inflammation, unrelated to phenotype or treatment, and remained low at rebiopsy an average of 22 months later. BRINP3 is localized to the brush border of the colonic epithelium and expression is influenced by DNA methylation within its promoter. Conclusions: Genome-wide expression analysis of noninflamed mucosal biopsies from patients with UC identified BRINP3 as significantly underexpressed throughout the colon in a large subset of patients with UC. Low levels of this gene could predispose or contribute to the maintenance of the characteristic mucosal inflammation seen in this condition. PMID:25171508

Mucin gene expression in the intestine of ulcerative colitis patients: a systematic review and meta-analysis.

PubMed

Niv, Yaron

2016-11-01

The mucus layer of the colon is the main barrier between luminal microbes and the mucosa, and plays a significant role in the body defense mechanisms. Several studies have examined mucin gene (MUC) expression in ulcerative colitis (UC) without conclusive results. The aim of the study was to establish the knowledge of mucin expression in UC as a basis for further investigation. English medical literature searches were performed for mucin expression in the colonic mucosa of UC patients in comparison with controls. Case-control studies were included. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios (ORs) and 95% confidence intervals were calculated. Altogether, we found 311 eligible studies. Only 10 case-control studies from five countries fulfilled the inclusion criteria. A moderate heterogeneity was found in the studies included: Q=52.703, d.f. (Q)=15.000, I=71.539%. OR for mucin expression in UC patients versus healthy controls was 1.868 with a 95% confidence interval (CI) 1.263-2.764, P=0.002. Thus, we could find a significant increase of 87% of mucin expression in UC patients. OR for MUC2 was 2.520, 95% CI 1.320-4.809, P<0.001. MUC3 was also increased with OR 2.599, 95% CI 1.389-4.861, P=0.003. Funnel plot did not indicate a significant publication bias. We found a global increase in mucin expression in UC patients, specifically in MUC2 and MUC3. Further studies are needed, especially in patients treated with biologics for mucosal healing, to understand the role of mucin expression in the natural history of UC.

A Novel Model for Predicting Incident Moderate to Severe Anemia and Iron Deficiency in Patients with Newly Diagnosed Ulcerative Colitis.

PubMed

Khan, Nabeel; Patel, Dhruvan; Shah, Yash; Yang, Yu-Xiao

2017-05-01

Anemia and iron deficiency are common complications of ulcerative colitis (UC). We aimed to develop and internally validate a prediction model for the incidence of moderate to severe anemia and iron deficiency anemia (IDA) in newly diagnosed patients with UC. Multivariable logistic regression was performed among a nationwide cohort of patients who were newly diagnosed with UC in the VA health-care system. Model development was performed in a random two-third of the total cohort and then validated in the remaining one-third of the cohort. As candidate predictors, we examined routinely available data at the time of UC diagnosis including demographics, medications, laboratory results, and endoscopy findings. A total of 789 patients met the inclusion criteria. For the outcome of moderate to severe anemia, age, albumin level and mild anemia at UC diagnosis were predictors selected for the model. The AUC for this model was 0.69 (95% CI 0.64-0.74). For the outcome of moderate to severe anemia with evidence of iron deficiency, the predictors included African-American ethnicity, mild anemia, age, and albumin level at UC diagnosis. The AUC was 0.76, (95% CI 0.69-0.82). Calibration was consistently good in all models (Hosmer-Lemeshow goodness of fit p > 0.05). The models performed similarly in the internal validation cohort. We developed and internally validated a prognostic model for predicting the risk of moderate to severe anemia and IDA among newly diagnosed patients with UC. This will help identify patients at high risk of these complications, who could benefit from surveillance and preventive measures.

Prognostic value of the urea:creatinine ratio in decompensated heart failure and its relationship with acute kidney damage.

PubMed

Josa-Laorden, C; Sola, A; Giménez-López, I; Rubio-Gracia, J; Garcés-Horna, V; Pérez-Calvo, J I

Worsening renal function is associated with an adverse prognosis for patients with acute heart failure (AHF). Urea-creatinine ratio (U:C ratio) might be useful for measuring renal function and could help stratify patients with AHF. An observational and prospective study was conducted to analyse the prognostic value of the U:C ratio, measured during the first 24-28 hours of admission, for patients hospitalised for decompensated Heart failure, and its relationship with estimated glomerular filtration rate (eGFR) and acute kidney injury (AKI). The study included 204 patients, with a mean age of 79.3 years, and a median eGFR of 55 mL/min/1.73m 2 . In the multivariate analysis, an U:C ratio above the median (50) was related to the development of AKI (36.5% vs. 21.9%) and to increased mortality, both overall (OR 2.75) and by HF (OR 3.50) in long term. In combination with eGFR, the U:C ratio showed prognostic value in patients with normal eGFR (mortality of 4.4% for an U:C ratio ≤ 50 vs. 22% for U:C ratio > 50; p=0.01), as well as a better predictive capacity for AKI than each of them separately (AUC, 0.718; 95% CI 0.643-0.793; p>.000). An U:C ratio > 50 is a predictor of increased long-term mortality for patients hospitalised for decompensated HF and with normal eGFR. Given the simplicity of this biomarker, its use in clinical practice should be more systematic. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Using Optical Markers of Non-dysplastic Rectal Epithelial Cells to Identify Patients With Ulcerative Colitis (UC) - Associated Neoplasia

PubMed Central

Bista, Rajan K.; Brentnall, Teresa A.; Bronner, Mary P.; Langmead, Christopher J.; Brand, Randall E.; Liu, Yang

2011-01-01

BACKGROUND Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study is to evaluate whether optical markers of rectal mucosa derived from a novel optical technique – partial-wave spectroscopic microscopy (PWS) could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. METHODS Banked frozen non-dysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. RESULTS We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. CONCLUSIONS Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for a high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. PMID:21351200

Ulcerative colitis in northern Portugal and Galicia in Spain.

PubMed

Barreiro-de Acosta, Manuel; Magro, Fernando; Carpio, Daniel; Lago, Paula; Echarri, Ana; Cotter, José; Pereira, Santos; Gonçalves, Raquel; Lorenzo, Aurelio; Carvalho, Laura; Castro, Javier; Barros, Luisa; Dias, Jorge Amil; Rodrigues, Susana; Portela, Francisco; Dias, Camila; da Costa-Pereira, Altamiro

2010-07-01

Clinical and therapeutic patterns of ulcerative colitis (UC) are variable in different world regions. The purpose of this study was to examine two close independent southern European UC populations from 2 bordering countries and observe how demographic and clinical characteristics of patients can influence the severity of UC. A cross-sectional study was conducted during a 15-month period (September 2005 to December 2006) based on data of 2 Web registries of UC patients. Patients were stratified according to the Montreal Classification and disease severity was defined by the type of treatment taken. A total of 1549 UC patients were included, 1008 (65%) from northern Portugal and 541 (35%) from Galicia (northwest Spain). A female predominance (57%) was observed in Portuguese patients (P < 0.001). The median age at diagnosis was 35 years and median years of disease was 7. The majority of patients (53%) were treated only with mesalamine, while 15% had taken immunosuppressant drugs, and 3% biologic treatment. Most patients in both groups were not at risk for aggressive therapy. Extensive colitis was a predictive risk factor for immunosuppression in northern Portugal and Galicia (odds ratio [OR] 2.737, 95% confidence interval [CI]: 1.846-4.058; OR 5.799, 95% CI: 3.433-9.795, respectively) and biologic treatment in Galicia (OR 6.329, 95% CI: 2.641-15.166). Younger patients presented a severe course at onset with more frequent use of immunosuppressors in both countries. In a large population of UC patients from two independent southern European countries, most patients did not require aggressive therapy, but extensive colitis was a clear risk factor for more severe disease.

Multi-Center Experience of Vedolizumab Effectiveness in Pediatric Inflammatory Bowel Disease.

PubMed

Singh, Namita; Rabizadeh, Shervin; Jossen, Jacqueline; Pittman, Nanci; Check, Morgan; Hashemi, Ghonche; Phan, Becky L; Hyams, Jeffrey S; Dubinsky, Marla C

2016-09-01

Though vedolizumab has received regulatory approval for the treatment of Crohn's disease (CD) and ulcerative colitis (UC) in adults, there is increasing off-label use in children. To describe the experience with vedolizumab in pediatric inflammatory bowel disease (IBD) patients at 3 tertiary IBD centers and examine predictors of remission. A retrospective review identified pediatric IBD patients (age < 18 yrs) receiving vedolizumab. Data on demographics, disease behavior, location, activity, and previous treatments/surgeries were collected. Disease activity was assessed using the weighted pediatric CD activity index or pediatric UC activity index. Primary outcome was week 14 remission, defined as pediatric UC activity index <10 or weighted pediatric CD activity index <12.5. Descriptive statistics and univariate analyses were performed to examine associations of clinical characteristics with efficacy. Fifty-two patients, 58% CD and 42% UC, initiated vedolizumab between June 2014 and August 2015. Median age at vedolizumab initiation was 14.9 (range 7-17) years. Ninety percent had failed ≥1 anti-tumor necrosis factor (TNF) agent. Week 14 remission rates for UC and CD were 76% and 42%, respectively (P < 0.05). Eighty percent of anti-TNF-naive patients experienced week 14 remission. At week 22, anti-TNF-naive patients had higher remission rates than TNF-exposed patients (100% versus 45%, P = 0.04). There were no infusion reactions or serious adverse events/infections. Our results suggest that vedolizumab is efficacious and safe in pediatric IBD patients, with UC patients experiencing earlier and higher rates of remission than CD patients. Anti-TNF-naive patients experienced higher remission rates than those with anti-TNF exposure. Controlled clinical trial data are needed to confirm these observations.

Covered Metallic Stents With an Anti-Migration Design vs. Uncovered Stents for the Palliation of Malignant Gastric Outlet Obstruction: A Multicenter, Randomized Trial

PubMed Central

Lee, Hyuk; Min, Byung-Hoon; Lee, Jeong Hoon; Shin, Cheol Min; Kim, Younjoo; Chung, Hyunsoo; Lee, Sang Hyub

2015-01-01

OBJECTIVES: Previous studies reported comparable stent patency between covered self-expandable metallic stents (SEMS) and uncovered SEMS (UCS) for palliation of malignant gastric outlet obstruction (GOO). The aim of this study was to evaluate the efficacy and safety of the newly developed WAVE-covered SEMS (WCS), which has an anti-migration design, compared with UCS in gastric cancer patients with symptomatic GOO. METHODS: A total of 102 inoperable gastric cancer patients with symptomatic GOO were prospectively enrolled from five referral centers and randomized to undergo UCS or WCS placement. Stent patency and recurrence of obstructive symptoms were assessed at 8 weeks and 16 weeks after stent placement. RESULTS: At the 8-week follow-up, both stent patency rates (72.5% vs. 62.7%) and re-intervention rates (19.6% vs. 19.6%) were comparable between the WCS and the UCS groups. Both stent stenosis (2.4% vs. 8.1%) and migration rates (9.5% vs. 5.4%) were comparable between WCS and UCS groups. At the 16-week follow-up, however, the WCS group had a significantly higher stent patency rate than the UCS group (68.6% vs. 41.2%). Re-intervention rates in the WCS and UCS groups were 23.5% and 39.2%, respectively. Compared with the UCS group, the WCS group had a significantly lower stent restenosis rate (7.1% vs. 37.8%) and a comparable migration rate (9.5% vs. 5.4%). Overall stent patency was significantly longer in the WCS group than in the UCS group. No stent-associated significant adverse events occurred in either the WCS or UCS groups. In the multivariate analysis, WCS placement and chemotherapy were identified as independent predictors of 16-week stent patency. CONCLUSIONS: WCS group showed comparable migration rate and significantly more durable long-term stent patency compared with UCS group for the palliation of GOO in patients with inoperable gastric cancer. PMID:26372507

Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia.

PubMed

Lazarevic, Vladimir; Hörstedt, Ann-Sofi; Johansson, Bertil; Antunovic, Petar; Billström, Rolf; Derolf, Åsa; Lehmann, Sören; Möllgård, Lars; Peterson, Stefan; Stockelberg, Dick; Uggla, Bertil; Vennström, Lovisa; Wahlin, Anders; Höglund, Martin; Juliusson, Gunnar

2015-05-01

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases

PubMed Central

Jakubowska, Katarzyna; Pryczynicz, Anna; Iwanowicz, Piotr; Niewiński, Andrzej; Maciorkowska, Elżbieta; Hapanowicz, Jerzy; Jagodzińska, Dorota; Kemona, Andrzej; Guzińska-Ustymowicz, Katarzyna

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression. PMID:27034654

Expressions of Matrix Metalloproteinases (MMP-2, MMP-7, and MMP-9) and Their Inhibitors (TIMP-1, TIMP-2) in Inflammatory Bowel Diseases.

PubMed

Jakubowska, Katarzyna; Pryczynicz, Anna; Iwanowicz, Piotr; Niewiński, Andrzej; Maciorkowska, Elżbieta; Hapanowicz, Jerzy; Jagodzińska, Dorota; Kemona, Andrzej; Guzińska-Ustymowicz, Katarzyna

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) belong to a group of inflammatory bowel diseases (IBD). The aim of our study was to evaluate the expression of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 in ulcerative colitis and Crohn's disease. The study group comprised 34 patients with UC and 10 patients with CD. Evaluation of MMP-2, MMP-7, MMP-9, TIMP-1, and TIMP-2 expression in tissue samples was performed using immunohistochemistry. The overexpression of MMP-9 and TIMP-1 was dominant in both the glandular epithelium and inflammatory infiltration in UC patients. In contrast, in CD subjects the positive expression of MMP-2 and TIMP-1 was in glandular tubes while mainly MMP-7 and TIMP-2 expression was in inflammatory infiltration. Metalloproteinases' expression was associated with the presence of erosions, architectural tissue changes, and inflammatory infiltration in the lamina propria of UC patients. The expression of metalloproteinase inhibitors correlated with the presence of eosinophils and neutrophils in UC and granulomas in CD patients. Our studies indicate that the overexpression of metalloproteinases and weaker expression of their inhibitors may determine the development of IBD. It appears that MMP-2, MMP-7, and MMP-9 may be a potential therapeutic target and the use of their inhibitors may significantly reduce UC progression.

[Infection frequency in patients with chronic idiopathic ulcerative colitis].

PubMed

Yamamoto-Furusho, J K; de León-Rendón, J L; Rodas, L

2012-01-01

Ulcerative Colitis (UC) is a chronic inflammatory bowel disease characterized by diffuse inflammation of the mucosa of the colon. Up to now, diverse observational studies have implicated a wide variety of pathogenic microorganisms as causal and exacerbating factors in UC. Clostridium difficile (C. difficile) infection has been associated with recurrence and treatment failure and its incidence in patients with UC has been on the rise in the last few years. To determine the frequency of infection by different microorganisms in Mexican UC patients. A total of 150 patients with definitive UC diagnosis were studied. All the stool tests for parasites and ova, stool cultures, tests for the C. difficile toxins A and B, and immunohistochemistry for Cytomegalovirus in colon segment biopsies were analyzed. Other demographic and clinical variables of the disease were recorded for their correlation with infection frequency. Infection frequency in UC patients was 28.00%. C. difficile infection was present in 0.013%. Other pathogens were found, such as Endolimax nana (9.00%), Entamoeba histolytica (3.00%), Cytomegalovirus (2.00%), Salmonella (2.00%), Shigella (0.70%), Toxoplasma gondii (0.70%) and Iodamoeba bütschlii (0.70%). Infection frequency was 28.00% in our study and C. difficile infection represented only 0.013%. Copyright © 2012 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Achievement of sustained deep remission with adalimumab in a patient with both refractory ulcerative colitis and seronegative erosive rheumatoid arthritis.

PubMed

Andrisani, G; Gremese, E; Guidi, L; Papa, A; Marzo, M; Felice, C; Pugliese, D; Armuzzi, A

2013-05-27

Inflammatory bowel disease (IBD) is commonly associated with peripheral inflammatory arthritis, and it has been estimated that as many as 12% of IBD patients report these manifestations. However, rheumatoid arthritis (RA) is rarely associated with ulcerative colitis (UC). Among all the biological agents available, nine have been currently approved for the treatment of RA. Conversely, only Infliximab and recently Adalimumab have been approved for UC. In particular, the efficacy of Adalimumab in UC has been demonstrated by both recent randomized controlled trials and real-life studies. Moreover, Adalimumab is a well-established treatment for RA. Herein, we describe a patient with RA and UC treated successfully with ADA.

Reduced total serum bilirubin levels are associated with ulcerative colitis.

PubMed

Schieffer, Kathleen M; Bruffy, Shannon M; Rauscher, Richard; Koltun, Walter A; Yochum, Gregory S; Gallagher, Carla J

2017-01-01

Chronic inflammation associated with inflammatory bowel disease (IBD) results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn's disease (CD). Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC). We identified a retrospective case-control population (n = 6,649) from a single tertiary care center, Penn State Hershey Medical Center (PSU) and a validation cohort (n = 1,996) from Virginia Commonwealth University Medical Center (VCU). Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124). Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels) to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09-3.63]) and VCU cohorts (OR: 6.07 [95% CI: 3.01-12.75]). Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients.

Partners of patients with ulcerative colitis exhibit a biologically relevant dysbiosis in fecal microbial metacommunities.

PubMed

Chen, Guang-Lan; Zhang, Ye; Wang, Wang-Yue; Ji, Xue-Liang; Meng, Fei; Xu, Pei-Song; Yang, Ning-Min; Ye, Fu-Qiang; Bo, Xiao-Chen

2017-07-07

To investigate alterations in the fecal microbiome using 16S rRNA amplicon sequencing in couples in the same cohabitation environment. Fecal samples were collected from eight ulcerative colitis (UC) patients and their healthy partners at Lishui People's Hospital, Zhejiang Province, China. DNA was extracted and the variable regions V3 and V4 of the 16S rRNA genes were PCR amplified using a two-step protocol. Clear reads were clustered into operational taxonomic units (OTUs) at the 97% sequence similarity level using UCLUST v1.2.22. The Wilcoxon rank-sum test (R v3.1.2) was used to compare inter-individual differences. Differences with a P value < 0.05 were considered statistically significant. Fecal microbial communities were more similar among UC patients than their healthy partners ( P = 0.024). UC individuals had a lower relative abundance of bacteria belonging to the Firmicutes , especially Blautia , Clostridium , Coprococcus and Roseburia ( P < 0.05). Microbiota dysbiosis was detected in UC patients and their healthy partners. Relevant genera included Akkermansiam , Bacteroides , Escherichia , Lactobacillales , Klebsiella and Parabacteroides . The enriched pathways in fecal samples of UC patients were related to lipid and nucleotide metabolism. Additionally, the pathways involved in membrane transport and metabolism of cofactors and vitamins were more abundant in the healthy partners. Our results suggested that the microbial composition might be affected in healthy partners cohabiting with UC patients, especially in terms of microbiota dysbiosis.

Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn's disease, and pouchitis: meta-analysis of randomized controlled trials.

PubMed

Shen, Jun; Zuo, Zhi-Xiang; Mao, Ai-Ping

2014-01-01

Whether probiotics are beneficial at all stages of treatment in inflammatory bowel disease or superior to placebo remains controversial. Two reviewers independently selected randomized controlled trials comparing probiotics with controls in inflammatory bowel disease and extracted data related to remission/response rates, relapse rates, and adverse events. Subanalyses were also performed. Twenty-three randomized controlled trials with a total of 1763 participants met the inclusion criteria. From the meta-analysis, probiotics significantly increase the remission rates in patients with active ulcerative colitis (UC) (P = 0.01, risk ratio [RR] = 1.51). The remission rates were significantly higher in patients with active UC treated with probiotics than placebo (P < 0.0001, RR = 1.80). Unfortunately, subgroup analysis found that only VSL#3 significantly increased the remission rates compared with controls in patients with active UC (P = 0.004, RR = 1.74). Interestingly, VSL#3 (P < 0.00001, RR = 0.18) also significantly reduced the clinical relapse rates for maintaining remission in patients with pouchitis. No significantly different adverse events were detected between probiotics and controls in the treatment of UC (P = 0.94, RR = 0.99) or CD (P = 0.33, RR = 0.87). Administration of probiotics results in additional benefit in inducing remission of patients with UC. VSL#3 are beneficial for maintaining remission in patients with pouchitis. And, probiotics can provide the similar effect as 5-aminosalicylic acid on maintaining remission of UC, although no additional adverse events presented.

Presence of intestinal Mycobacterium avium subspecies paratuberculosis (MAP) DNA is not associated with altered MMP expression in ulcerative colitis

PubMed Central

2011-01-01

Background Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in human Crohn's disease (CD). Recent evidence suggests that pathogenic mycobacteria and MAP can induce the expression of Matrix Metalloproteinases (MMP), which are the main proteases in the pathogenesis of mucosal ulcerations in inflammatory bowel disease (IBD). Within this study we assessed the prevalence of intestinal MAP specific DNA in patients with Crohn's disease, ulcerative colitis (UC), and healthy controls. We further analysed regulation patterns of MMPs in mucosal tissues of UC patients with and without intestinal MAP DNA detection. Methods Colonic biopsy samples were obtained from 63 Norwegian and German IBD patients and 21 healthy controls. RNA was quantified by quantitative real-time polymerase chain reaction (PCR) to study MMP gene expression in both pathological and healthy mucosal specimens. The presence of MAP DNA in colonic mucosa was examined using MAP specific PCR. Results MAP DNA was detected in 20% of UC patients and 33% of healthy controls but only in 7% of patients with CD. UC patients treated with corticosteroids exhibited a significantly increased frequency of intestinal MAP DNA compared to those not receiving corticosteroids. Expression of MMP-1, -2, -7, -9, -13, -19, -28 and TNF-α did not differ between UC patients with presence of intestinal MAP DNA compared to those without. MMP-2, MMP-9 and MMP-13 were significantly decreased in UC patients receiving corticosteroids. Conclusions The presence of intestinal MAP specific DNA is not associated with altered MMP expression in UC in vivo. Corticosteroids are associated with increased detection of intestinal MAP DNA and decreased expression of certain MMPs. Frequent detection of MAP DNA in healthy controls might be attributable to the wide environmental distribution of MAP and its presence in the food-chain. PMID:21477272

Patient considerations in the management of ulcerative colitis – role of vedolizumab

PubMed Central

Kothari, Megha; Mudireddy, Prashant; Swaminath, Arun

2015-01-01

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease which causes inflammation of the large intestine and affects approximately 7.6–24.6 per 100,000 persons. The therapeutic goal for UC patients is inducing remission, maintaining remission, and ideally, obtaining mucosal healing. Vedolizumab, approved by the US Food and Drug Administration in May 2014 for the treatment of moderate-to-severe UC and Crohn’s disease, is a newly developed anti-integrin therapy. This review focuses on the preclinical development of vedolizumab and data from early trials, and details the results of the landmark trails that led to its approval in the USA with a specific focus on the management of UC. Additionally, data on safety and the current UC management protocols are also discussed. PMID:26316768

Clinical Efficacy and Safety of Oral Qing-Dai in Patients with Ulcerative Colitis: A Single-Center Open-Label Prospective Study.

PubMed

Sugimoto, Shinya; Naganuma, Makoto; Kiyohara, Hiroki; Arai, Mari; Ono, Keiko; Mori, Kiyoto; Saigusa, Keiichiro; Nanki, Kosaku; Takeshita, Kozue; Takeshita, Tatsuya; Mutaguchi, Makoto; Mizuno, Shinta; Bessho, Rieko; Nakazato, Yoshihiro; Hisamatsu, Tadakazu; Inoue, Nagamu; Ogata, Haruhiko; Iwao, Yasushi; Kanai, Takanori

2016-01-01

Chinese herbal medicine Qing-Dai (also known as indigo naturalis) has been used to treat various inflammatory conditions. However, not much has been studied about the use of oral Qing-Dai in the treatment for ulcerative colitis (UC) patients. Studies exploring alternative treatments for UC are of considerable interest. In this study, we aimed at prospectively evaluating the safety and efficacy of Qing-Dai for UC patients. The open-label, prospective pilot study was conducted at Keio University Hospital. A total of 20 patients with moderate UC activity were enrolled. Oral Qing-Dai in capsule form was taken twice a day (daily dose, 2 g) for 8 weeks. At week 8, the rates of clinical response, clinical remission, and mucosal healing were 72, 33, and 61%, respectively. The clinical and endoscopic scores, CRP levels, and fecal occult blood results were also significantly improved. We observed 2 patients with mild liver dysfunction; 1 patient discontinued due to infectious colitis and 1 patient discontinued due to mild nausea. This is the first prospective study indicating that oral Qing-Dai is effective for inducing remission in patients with moderate UC activity and can be tolerated. Thus, Qing-Dai may be considered an alternative treatment for patients, although further investigation is warranted. © 2016 S. Karger AG, Basel.

Altered STAT4 Isoform Expression in Patients with Inflammatory Bowel Disease.

PubMed

Jabeen, Rukhsana; Miller, Lucy; Yao, Weiguo; Gupta, Sandeep; Steiner, Steven; Kaplan, Mark H

2015-10-01

Crohn's disease (CD) and ulcerative colitis (UC) are the major forms of inflammatory bowel disease, and pathogenesis involves a complex interplay among genetic, environmental, and immunological factors. We evaluated isoform expression of the IL-12-activated transcription factor STAT4 in children with CD and UC. We collected biopsy samples from both patients newly diagnosed with CD and with UC. We further collected blood samples from patients newly diagnosed with CD and with UC as well as from patients who had a flare-up after being in clinical remission, and we examined the ratios of STAT4β/STAT4α mRNA. In addition to STAT4 isoforms, we measured the expression of the cytokines TNFα, IFNγ, granulocyte macrophage-colony stimulating factor, and IL-17 using polymerase chain reaction of biopsy samples and multiplex analysis of patient serum samples. Ratios of STAT4β/STAT4α were increased in specific gastrointestinal tract segments in both patients with CD and those with UC that correlate with the location and severity of inflammation. In contrast, we did not observe changes in STAT4β/STAT4α ratios in biopsy specimens from patients with eosinophilic esophagitis. We also observed increased STAT4β/STAT4α ratios in the peripheral blood mononuclear cells of patients with UC and those with CD, compared with healthy controls. Ratios were normalized after patients were treated with steroids. Collectively, these data indicate that STAT4 isoforms could be an important noninvasive biomarker in the diagnosis and treatment of inflammatory bowel disease and that expression of these isoforms might provide further insight into the pathogenesis of IBD.

Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort.

PubMed

Romberg-Camps, Mariëlle; Kuiper, Edith; Schouten, Leo; Kester, Arnold; Hesselink-van de Kruijs, Martine; Limonard, Charles; Bos, Rens; Goedhard, Jelle; Hameeteman, Wim; Wolters, Frank; Russel, Maurice; Stockbrügger, Reinhold; Dagnelie, Pieter

2010-08-01

The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.

Maintenance therapy options for ulcerative colitis.

PubMed

Chaparro, María; Gisbert, Javier P

2016-07-01

Medical therapy is the cornerstone of the management of ulcerative colitis (UC) and the goal of the treatment is the induction and maintenance of remission. Mesalamine is the first line treatment in patients with mild to moderate UC. Despite having different formulations available, clinically significant differences in pharmacokinetics and exposure to these drugs have not been observed. Evidence supporting the efficacy of azathioprine and mercaptopurine for maintaining remission is UC patients come from both observational cohorts and clinical trials. The main limitation of the treatment with thiopurines is the onset of adverse events that occur in over one-third of patients. Infliximab, adalimumab and golimumab are anti-TNF drugs, which are generally used for more severe or refractory cases. Finally, vedolizumab, a drug directed against the integrins α4β7 has been shown to be effective for the induction and maintenance of remission in moderate-to-severe UC patients. Several new drugs have enriched the therapeutic armamentarium of UC. Whether the administration of biologics earlier on in the course of the disease would have an impact on the natural history of the disease, avoiding the need for colectomy, remains unknown.

Analysis of cytotoxic T lymphocyte associated antigen 4 gene polymorphisms in patients with ulcerative colitis.

PubMed

Lankarani, Kamran B; Karbasi, Ashraf; Kalantari, Tahereh; Yarmohammadi, Hooman; Saberi-Firoozi, Mehdi; Alizadeh-Naeeni, Mahvash; Taghavi, Ali R; Fattahi, Mahammad R; Ghaderi, Abbas

2006-02-01

Ulcerative colitis (UC) is a multifactorial disease associated with dysregulated immunity. Recently, cytotoxic T lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms have been reported in association with several autoimmune diseases in several populations. In the present study, the possible implication of the CTLA-4 gene as a risk factor for UC in the Iranian population was investigated. One hundred UC patients and 100 healthy subjects were studied. CTLA-4 exon 1 position 49 (A/G: codon 17: Thr/Ala) polymorphisms were investigated by polymerase chain reaction single strand confirmation polymorphism method. Four of the patients and one of the healthy controls were excluded from the study because of incomplete DNA extraction. The allele frequencies of A and G in 96 patients (A: 66.1%; G: 33.9%) were not significantly different from the 99 control subjects (A: 63.1%; G: 36.9%, P > 0.05). No significant differences in the distribution of genotype frequencies were observed between A + 49G gene polymorphisms and UC in the Iranian population (P > 0.05). CTLA-4 polymorphism is not associated with UC in the Iranian population.

Successful Use of Tocilizumab in a Patient with Coexisting Rheumatoid Arthritis and Ulcerative Colitis

PubMed Central

Yalçın, Metin Devrim; Khan, Abdul; Piotrowicz, Andrzej

2016-01-01

Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation. However, alternative treatments such as glucocorticoid and nonsteroidal anti-inflammatory drugs may carry a higher bowel perforation risk. The presence of gastrointestinal ulceration therefore should not constitute an absolute contraindication for Tocilizumab therapy. Future studies of registry data will inform clinician of the Tocilizumab-related risk of gastrointestinal toxicity in “real-life” settings. Contrary to previous case report, we found Tocilizumab therapy to have a positive effect on UC. Laboratory studies supported a role for interleukin-6 in the pathophysiology of UC. Further clinical trial to evaluate the therapeutic role of Tocilizumab in UC would be warranted. PMID:27818807

Successful Use of Tocilizumab in a Patient with Coexisting Rheumatoid Arthritis and Ulcerative Colitis.

PubMed

Szeto, Matthew Chak Hin; Yalçın, Metin Devrim; Khan, Abdul; Piotrowicz, Andrzej

2016-01-01

Tocilizumab is an interleukin-6 receptor inhibitor licensed for moderate to severe rheumatoid arthritis (RA). We report a case of Tocilizumab monotherapy for severe active RA in a patient with coexisting ulcerative colitis (UC). The patient was intolerant to multiple disease-modifying drugs, so Tocilizumab monotherapy was commenced. We found clinical improvement in both RA and UC. There was no major adverse event after 2 years. Manufacturer advised caution in using Tocilizumab in patient with gastrointestinal ulceration due to an increased risk of bowel perforation. However, alternative treatments such as glucocorticoid and nonsteroidal anti-inflammatory drugs may carry a higher bowel perforation risk. The presence of gastrointestinal ulceration therefore should not constitute an absolute contraindication for Tocilizumab therapy. Future studies of registry data will inform clinician of the Tocilizumab-related risk of gastrointestinal toxicity in "real-life" settings. Contrary to previous case report, we found Tocilizumab therapy to have a positive effect on UC. Laboratory studies supported a role for interleukin-6 in the pathophysiology of UC. Further clinical trial to evaluate the therapeutic role of Tocilizumab in UC would be warranted.

Mild-to-moderate ulcerative colitis: your role in patient compliance and health care costs.

PubMed

Tindall, William N; Boltri, John M; Wilhelm, Sheila M

2007-09-01

Ulcerative colitis (UC) is a chronic relapsing disease necessitating lifelong treatment. Most patients present with mild-to-moderate disease characterized by alternating periods of remission and clinical relapse. Continued disease progression and relapse of UC over time are associated with an increased risk of colorectal cancer (CRC). To discuss the latest treatment options for mild-to-moderate UC, to review the current data involving the economics of UC, and to demonstrate the relationship between treatment adherence, clinical relapse, inflammation severity, CRC risk, and treatment outcomes. One of the main goals of therapy in UC is to induce and maintain a long-lasting remission of disease to reduce or avoid the high personal and financial costs of relapse. In recent studies, researchers have demonstrated a link between increased colonic inflammation and CRC risk, highlighting the importance of preventing relapse, which can lead to costly surgical procedures and hospital stays and thus increase the cost of treatment 2- to 20-fold. The risk of disease relapse is affected by several factors, of which the most prominent is nonadherence to maintenance therapy. Nonadherence to therapy can be associated with several other factors, including forgetfulness, male sex, complicated dosing regimens, treatment delivery methods (oral vs. rectal), and pill burden. In the treatment of mild-to-moderate UC, 5-aminosalicyclic acid (5-ASA) is the standard first-line therapy and the treatment of choice for maintaining remission of disease. Novel formulations of 5-ASA and newly devised high-dose 5-ASA regimens offer more options for the treatment of UC and thus may lead to improved treatment adherence, longer remission, and improved patient well-being. Periods of remission during UC treatment must be aggressively maintained to prevent relapse and decrease the risk of an unfavorable outcome. By controlling the risks and conditions that lead to therapeutic nonadherence and relapse among patients with UC, clinicians can increase the likelihood of long-term remission and ensure favorable long-term outcomes.

PD-1 and PD-L1 inhibitors after platinum-based chemotherapy or in first-line therapy in cisplatin-ineligible patients: Dramatic improvement of prognosis and overall survival after decades of hopelessness in patients with metastatic urothelial cancer.

PubMed

Resch, Irene; Shariat, Shahrokh F; Gust, Kilian M

2018-01-01

Until recently, there were no true innovations in the management of locally advanced (aUC) and metastatic urothelial cancer (mUC) in the last three decades. Vinflunine has been approved by the EMA (European Medicines Agency) with only limited improvement compared to best supportive care in second line treatment. In addition, gemcitabine/cisplatin has been established as an alternative to methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). The advent of checkpoint inhibitors (CPI) revolutionized the care of these patients, transforming a unanimously deadly disease into one with hope through sustained disease control. Five immune CPI have recently been approved for aUC/mUC by the US Food and Drug Administration (FDA) including atezolizumab, nivolumab, pembrolizumab, durvalumab and avelumab. All five CPI are FDA-approved as second-line therapy with atezolizumab and pembrolizumab also being approved for first-line therapy in cisplatin-ineligible patients. The rapid acceptance in the treatment algorithm of UC is based on the impressive clinical efficacy of these agents in some patients, combined with their excellent safety profile. These new agents are indeed the most important advancement in UC care. However, the challenge in the age of precision medicine is to identify the patients who are most likely to benefit from CPIs, as the majority of patients do not respond to CPI. Toward this goal, validation of clinical, molecular and imaging biomarkers that serve for prediction and monitoring of treatment response are of central necessity.

Safety and Efficacy of Combination Treatment With Calcineurin Inhibitors and Vedolizumab in Patients With Refractory Inflammatory Bowel Disease.

PubMed

Christensen, Britt; Gibson, Peter; Micic, Dejan; Colman, Ruben J; Goeppinger, Sarah R; Kassim, Olufemmi; Yarur, Andres; Weber, Christopher R; Cohen, Russell D; Rubin, David T

2018-05-08

Little is known about the efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab for patients with Crohn's disease (CD) or ulcerative colitis (UC). We analyzed the outcomes of patients receiving vedolizumab along with calcineurin inhibitors METHODS: We collected data on patients with CD (n=9) or UC (n=11) who began treatment with vedolizumab from May 20, 2014 through March 30, 2015 and received calcineurin inhibitors (tacrolimus or cyclosporin) during the first 12 months of vedolizumab therapy. Clinical activity scores and inflammatory markers were measured at baseline and at weeks 14, 30, and 52 of vedolizumab treatment. Clinical remission was defined as a Harvey Bradshaw index score ≤4 or short clinical colitis activity index score ≤2; steroid-free clinical remission was defined as clinical remission without corticosteroids. By week 14 of treatment, 44% of the patients with CD and 55% of the patients with UC achieved steroid-free clinical remission; after 52 weeks of treatment, 33% of the patients with CD and 45% of the patients with UC were in steroid-free clinical remission. Seven patients received salvage therapy with a calcineurin inhibitor after primary non-response to vedolizumab-1 of the 2 patients with UC and 2 of 5 patients with CD stopped taking the calcineurin inhibitors and achieved steroid-free remission at week 52. In total, 16 patients (59%) received 52 weeks of treatment with vedolizumab. Three serious adverse events were associated with calcineurin inhibitors. Combination therapy of vedolizumab with either cyclosporin or tacrolimus is effective and safe at inducing and maintaining clinical remission in patients with CD and UC with up to 52 weeks of follow-up. Larger studies of the ability of calcineurin inhibitors to induce remission in patients on vedolizumab are warranted. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Patient satisfaction with different interpreting methods: a randomized controlled trial.

PubMed

Gany, Francesca; Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C; Changrani, Jyotsna

2007-11-01

Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (beta 0.10, 95% CI 0.02-0.18, scale 0-1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care.

Patient Satisfaction with Different Interpreting Methods: A Randomized Controlled Trial

PubMed Central

Leng, Jennifer; Shapiro, Ephraim; Abramson, David; Motola, Ivette; Shield, David C.; Changrani, Jyotsna

2007-01-01

Background Growth of the foreign-born population in the U.S. has led to increasing numbers of limited-English-proficient (LEP) patients. Innovative medical interpreting strategies, including remote simultaneous medical interpreting (RSMI), have arisen to address the language barrier. This study evaluates the impact of interpreting method on patient satisfaction. Methods 1,276 English-, Spanish-, Mandarin-, and Cantonese-speaking patients attending the primary care clinic and emergency department of a large New York City municipal hospital were screened for enrollment in a randomized controlled trial. Language-discordant patients were randomized to RSMI or usual and customary (U&C) interpreting. Patients with language-concordant providers received usual care. Demographic and patient satisfaction questionnaires were administered to all participants. Results 541 patients were language-concordant with their providers and not randomized; 371 were randomized to RSMI, 167 of whom were exposed to RSMI; and 364 were randomized to U&C, 198 of whom were exposed to U&C. Patients randomized to RSMI were more likely than those with U&C to think doctors treated them with respect (RSMI 71%, U&C 64%, p < 0.05), but they did not differ in other measures of physician communication/care. In a linear regression analysis, exposure to RSMI was significantly associated with an increase in overall satisfaction with physician communication/care (β 0.10, 95% CI 0.02–0.18, scale 0–1.0). Patients randomized to RSMI were more likely to think the interpreting method protected their privacy (RSMI 51%, U&C 38%, p < 0.05). Patients randomized to either arm of interpretation reported less comprehension and satisfaction than patients in language-concordant encounters. Conclusions While not a substitute for language-concordant providers, RSMI can improve patient satisfaction and privacy among LEP patients. Implementing RSMI should be considered an important component of a multipronged approach to addressing language barriers in health care. PMID:17957417

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis.

PubMed

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P

2013-11-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66b(high)) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14(+)CD33(+) cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14(+)CCL11(+) mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14(+)CD33(+) myeloid cells, CCL11, and eosinophils in adult UC.

CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis

PubMed Central

Lampinen, Maria; Waddell, Amanda; Ahrens, Richard; Carlson, Marie; Hogan, Simon P.

2013-01-01

This study tested the hypothesis that eotaxins (CCL11, CCL24, and CCL26) and IL-5 contribute to eosinophil recruitment to the intestine in UC and that intestinal macrophages are important producers of CCL11 in this disease. Peripheral blood and rectal biopsy samples were obtained from patients with active (n=18) and quiescent UC (n=9), and control patients (n=7). Eosinophil and macrophage levels and activation were analyzed by flow cytometry. Rectal mRNA levels of CCL11, CCL24, CCL26, and IL-5 were determined by qRT-PCR. The cellular source of CCL11 was visualized by immunofluorescence analyses. Eosinophil numbers were elevated in the blood and rectum of active and quiescent UC patients compared with controls. Levels of activated eosinophils (CD66bhigh) correlated with disease severity. Rectal CCL11, CCL24, and CCL26 mRNA levels were increased in active UC, whereas only CCL11 was elevated in quiescent UC. Levels of CCL11, but not CCL24 and CCL26, positively correlated with eosinophil numbers. Numbers of CD14+CD33+ cells correlated with CCL11 and eosinophil levels. Immunofluorescence analyses revealed the presence of CD14+CCL11+ mononuclear cells in colonic biopsies in UC. These results support the hypothesis that CCL11 contributes to eosinophil recruitment in UC and that intestinal myeloid cells are a source of CCL11. Interestingly, rectal levels of CCL24, CCL26, and IL-5 only increase during active UC, coinciding with further elevation of eosinophil numbers and with the activation of rectal eosinophils. In conclusion, there is a link among CD14+CD33+ myeloid cells, CCL11, and eosinophils in adult UC. PMID:23904440

Ulcerative colitis in a multiracial Asian country: racial differences and clinical presentation among Malaysian patients.

PubMed

Tan, Yan-Mei; Goh, Khean-Lee

2005-10-07

Inflammatory bowel disease appears to be uncommon among Asians. This study was conducted to determine the prevalence of ulcerative colitis (UC) in Malaysian patients and to establish the spectrum of the disease seen in Malaysian patients. Three major Asian races: Malay, Chinese, and Indian co-exist in Malaysia and we sought to determine if there were any racial differences in the prevalence and presentation of disease. Racial differences for several other gastrointestinal diseases have previously been observed and found to be extremely interesting. Data were obtained retrospectively from a review of the medical records of in- and out-patients with a diagnosis of UC at the University Hospital, Kuala Lumpur between 1985 and 1998. There were 45 confirmed cases of UC of which 3 were foreigners, who were excluded from analysis. Thirty new cases of UC were diagnosed during the study period. Their mean age at presentation was 33.0+/-10.0 years. The highest prevalence of UC was 17.9/100 000 hospital admissions in the Indians, followed by 11.2/100 000 hospital admissions in the Chinese. The lowest prevalence was 3.7/100 000 hospital admissions in the Malays. The prevalence of UC was significantly higher in the Indians and the Chinese when compared with the Malays with an OR of 4.89 (CI = 2.02-12.24; chi2 = 15.45, P<0.001) and 3.06 (CI = 1.24-7.78; chi2 = 6.30; P = 0.012) respectively. The extent of colonic disease was similar in the Malay and Indian patients. In contrast, distal or left-sided colitis predominated in the Chinese with an OR of 8.17 (95%CI = 1.31-64.87; chi2 = 5.53, P = 0.02). Extraintestinal manifestations were uncommon (11.9%). UC is an uncommon disease in Malaysia, but racial differences exist. The Indians had the highest prevalence of UC with the Chinese demonstrating the least extensive disease.

Fecal immunochemical test for predicting mucosal healing in ulcerative colitis patients: A systematic review and meta-analysis.

PubMed

Dai, Cong; Jiang, Min; Sun, Ming-Jun; Cao, Qin

2018-05-01

Fecal immunochemical test (FIT) is a promising marker for assessment of inflammatory bowel disease activity. However, the utility of FIT for predicting mucosal healing (MH) of ulcerative colitis (UC) patients has yet to be clearly demonstrated. The objective of our study was to perform a diagnostic test accuracy test meta-analysis evaluating the diagnostic accuracy of FIT in predicting MH of UC patients. We systematically searched the databases from inception to November 2017 that evaluated MH in UC. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Six studies comprising 625 UC patients were included in the meta-analysis. The pooled sensitivity and specificity values for predicting MH in UC were 0.77 (95% confidence interval [CI], 0.72-0.81) and 0.81 (95% CI, 0.76-0.85), respectively. The FIT level had a high rule-in value (positive likelihood ratio, 3.79; 95% CI, 2.85-5.03) and a moderate rule-out value (negative likelihood ratio, 0.26; 95% CI, 0.16-0.43) for predicting MH in UC. The results of the receiver operating characteristic curve analysis (area under the curve, 0.88; standard error of the mean, 0.02) and diagnostic odds ratio (18.08; 95% CI, 9.57-34.13) also revealed improved discrimination for identifying MH in UC with FIT concentration. Our meta-analysis has found that FIT is a simple, reliable non-invasive marker for predicting MH in UC patients. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Epidemiology, demographic characteristics and prognostic predictors of ulcerative colitis

PubMed Central

da Silva, Bruno César; Lyra, Andre Castro; Rocha, Raquel; Santana, Genoile Oliveira

2014-01-01

Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the mucosa of the colon and rectum. The hallmark clinical symptom of UC is bloody diarrhea. The clinical course is marked by exacerbations and remissions, which may occur spontaneously or in response to treatment changes or intercurrent illnesses. UC is most commonly diagnosed in late adolescence or early adulthood, but it can occur at any age. The incidence of UC has increased worldwide over recent decades, especially in developing nations. In contrast, during this period, therapeutic advances have improved the life expectancy of patients, and there has been a decrease in the mortality rate over time. It is important to emphasize that there is considerable variability in the phenotypic presentation of UC. Within this context, certain clinical and demographic characteristics are useful in identifying patients who tend to have more severe evolution of the disease and a poor prognosis. In this group of patients, better clinical surveillance and more intensive therapy may change the natural course of the disease. The aim of this article was to review the epidemiology and demographic characteristics of UC and the factors that may be associated with its clinical prognosis. PMID:25071340

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis

PubMed Central

Grewal, Suman; LaComb, Joseph F.; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M.; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E.; Frank, Daniel N.; Li, Ellen

2018-01-01

Background Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). Method V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Results Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. Conclusion The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients. PMID:29385143

Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.

PubMed

Mintz, Michael; Khair, Shanawaj; Grewal, Suman; LaComb, Joseph F; Park, Jiyhe; Channer, Breana; Rajapakse, Ramona; Bucobo, Juan Carlos; Buscaglia, Jonathan M; Monzur, Farah; Chawla, Anupama; Yang, Jie; Robertson, Charlie E; Frank, Daniel N; Li, Ellen

2018-01-01

Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only). V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group. Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT. The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.

Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies.

PubMed

Jess, Tine; Rungoe, Christine; Peyrin-Biroulet, Laurent

2012-06-01

Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Studies examining the magnitude of this association have yielded conflicting results. We performed a meta-analysis of population-based cohort studies to determine the risk of CRC in patients with UC. We used MEDLINE, EMBASE, Cochrane, and CINAHL to perform a systematic literature search. We included 8 studies in the meta-analysis on the basis of strict inclusion and exclusion criteria. We calculated pooled standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for risk of CRC in patients with UC and performed meta-regression analyses of the effect of cohort size, calendar period, observation time, percentage with proctitis, and rates of colectomy on the risk of CRC. An average of 1.6% of patients with UC was diagnosed with CRC during 14 years of follow-up. SIRs ranged from 1.05 to 3.1, with a pooled SIR of 2.4 (95% CI, 2.1-2.7). Men with UC had a greater risk of CRC (SIR, 2.6; 95% CI, 2.2-3.0) than women (SIR, 1.9; 95% CI, 1.5-2.3). Young age was a risk factor for CRC (SIR, 8.6; 95% CI, 3.8-19.5; although this might have resulted from small numbers), as was extensive colitis (SIR, 4.8; 95% CI, 3.9-5.9). In meta-regression analyses, only cohort size was associated with risk of CRC. In population-based cohorts, UC increases the risk of CRC 2.4-fold. Male sex, young age at diagnosis with UC, and extensive colitis increase the risk. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Online disease management of diabetes: engaging and motivating patients online with enhanced resources-diabetes (EMPOWER-D), a randomized controlled trial.

PubMed

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-05-01

To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational 'nuggets' dispensed electronically by the care team. A1C was the primary outcome variable. Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (-1.32% INT vs -0.66% UC; p<0.001). At 12 months, the differences were not significant (-1.14% INT vs -0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204.

Online disease management of diabetes: Engaging and Motivating Patients Online With Enhanced Resources-Diabetes (EMPOWER-D), a randomized controlled trial

PubMed Central

Tang, Paul C; Overhage, J Marc; Chan, Albert Solomon; Brown, Nancy L; Aghighi, Bahar; Entwistle, Martin P; Hui, Siu Lui; Hyde, Shauna M; Klieman, Linda H; Mitchell, Charlotte J; Perkins, Anthony J; Qureshi, Lubna S; Waltimyer, Tanya A; Winters, Leigha J; Young, Charles Y

2013-01-01

Objective To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes. Materials and methods Engaging and Motivating Patients Online With Enhanced Resources for Diabetes was a 12-month parallel randomized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin (A1C) values ≥7.5% from primary care sites sharing an electronic health record. The intervention included: (1) wirelessly uploaded home glucometer readings with graphical feedback; (2) comprehensive patient-specific diabetes summary status report; (3) nutrition and exercise logs; (4) insulin record; (5) online messaging with the patient's health team; (6) nurse care manager and dietitian providing advice and medication management; and (7) personalized text and video educational ‘nuggets’ dispensed electronically by the care team. A1C was the primary outcome variable. Results Compared with usual care (UC, n=189), patients in the intervention (INT, n=193) group had significantly reduced A1C at 6 months (−1.32% INT vs −0.66% UC; p<0.001). At 12 months, the differences were not significant (−1.14% INT vs −0.95% UC; p=0.133). In post hoc analysis, significantly more INT patients had improved diabetes control (>0.5% reduction in A1C) than UC patients at 12 months (69.9 (95% CI 63.2 to 76.5) vs 55.4 (95% CI 48.4 to 62.5); p=0.006). Conclusions A nurse-led, multidisciplinary health team can manage a population of diabetic patients in an online disease management program. INT patients achieved greater decreases in A1C at 6 months than UC patients, but the differences were not sustained at 12 months. More INT than UC patients achieved improvement in A1C (>0.5% decrease). Trial registered in clinical trials.gov: #NCT00542204 PMID:23171659

Inflammatory bowel disease associations with HLA Class II genes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Castro, R.; Yang, H.; Targan, S.

1994-09-01

A PCR-SSOP assay has been used to analyze HLA-Class II DRB1 and DQB1 alleles in 378 Caucasians from a population in Southern California. The data has been analyzed separately for the Ashkenasi Jews and non-Jewish patients (n=286) and controls (n=92). Two common clinical forms of inflammatory bowel disease (IBD) have been studied: ulcerative colitis (UC) and Crohn`s disease (CD). In CD, we observed a susceptible effect with the rare DR1 allele - DRB*0103 [O.R.=4.56; 95% CI (0.96, 42.97); p=0.03]; a trend for an increase in DRB1*0103 was also observed in UC patients. A susceptible effect with DRB1*1502 [O.R.=5.20; 95% CImore » (1.10, 48.99); p=0.02] was observed in non-Jewish UC patients. This susceptible effect was restricted to UC ANCA-positive (antineutrophil cytoplasmic antibodies) patients. In addition, a significant association with DRB1*1101-DQB1*0301 [O.R.=9.46; 95% CI (1.30, 413.87); p=0.01] was seen with UC among non-Jewish patients: this haplotype was increased with CD among non-Jewish patients. Two protective haplotypes were detected among CD non-Jewish patients: DRB1*1301-DQB1*0603 [O.R.=0.34; 95% CI (0.09, 1.09); p=0.04], and DRB*0404-DQB1*0302 [O.R.=<0.08; 95% CI (0.0, 0.84); p=0.01]. When the same data were analyzed at the serology level, we observed a positive association in UC with DR2 [O.R.6.77; 95% CI (2.47, 22.95); p=2 x 10{sup -4}], and a positive association in CD with DR1 [O.R.=2.63; 95% CI (1.14, 6.62); p=0.01] consistent with previous reports. Thus, some IBD disease associations appear to be common to both UC and CD, while some are unique to one disease.« less

High within-day variability of fecal calprotectin levels in patients with active ulcerative colitis: what is the best timing for stool sampling?

PubMed

Calafat, Margalida; Cabré, Eduard; Mañosa, Míriam; Lobatón, Triana; Marín, Laura; Domènech, Eugeni

2015-05-01

Fecal calprotectin (FC) is considered the best noninvasive way to assess disease activity in ulcerative colitis (UC). However, it is not known which is the more suitable moment for stool sampling in patients with increased stool frequency. The aims of this study were to assess the intraindividual variation of FC within day and to evaluate if the first bowel movement in the morning is the more suitable sample for FC measurement in patients with acute flares of UC. Patients admitted because of active UC were invited to collect samples from several bowel movements (including the first in the morning) during the same day providing their ordinal chronology. FC was measured by means of a quantitative rapid point-of-care test based on lateral flow assay immunochromatography. Eighteen patients were included for a total of 56 stool samples. Most patients had extensive UC and severe disease activity. Within-day FC values varied widely, and the median coefficient of variation was 40% (5%-114%) with a median range of variation of FC values of 3887 mg/kg (69-9946). The sample from the first stool in the morning obtained the highest individual FC within-day value in 33.3% of cases and the lowest in 38.9%. FC values widely vary between motions in patients with active UC. Stool sample collection from the first bowel movement in the morning does not ensure the highest or lowest within-day FC value. In patients with overt active UC, a single FC determination should not be used as the basis for therapeutic strategies.

Compassionate access anti-tumour necrosis factor-α therapy for ulcerative colitis in Australia: the benefits to patients.

PubMed

Costello, S P; Ghaly, S; Beswick, L; Pudipeddi, A; Agarwal, A; Sechi, A; O'Connor, S; Connor, S J; Sparrow, M P; Bampton, P; Walsh, A J; Andrews, J M

2015-06-01

The efficacy of infliximab has been demonstrated in patients with both acute severe and moderate-severe ulcerative colitis (UC). However, there is a need for 'real-life data' to ensure that conclusions from trial settings are applicable in usual care. We therefore examined the national experience of anti-tumour necrosis factor-α (TNF-α) therapy in UC. Case notes review of patients with UC who had received compassionate access (CA) anti-TNF-α therapy from prospectively maintained inflammatory bowel disease databases of six Australian adult teaching hospitals. Patients either received drug for acute severe UC (ASUC) failing steroids (n = 29) or for medically refractory UC (MRUC) (n = 35). In ASUC, the treating physicians judged that anti-TNF-α therapy was successful in 20/29 patients (69%); in these cases, anti-TNF-α was able to be discontinued (after 1-3 infusions in 19/20 responders) as clinical remission was achieved. Consistent with this perceived benefit, only 7/29 (24%) subsequently underwent colectomy during a median follow up of 12 months (interquartile range (IQR) 5-16). Eight of the 35 patients with MRUC (23%) required colectomy during a median follow up of 28 months (IQR 11-43). The majority of these patients (20/35 or 57%) had anti-TNF-α therapy for ≥4 months, whereas, 27/29 (93%) of ASUC patients had CA for ≤3 months. These data show an excellent overall benefit for anti-TNF-α therapy in both ASUC and MRUC. In particular, only short-duration anti-TNF-α was required in ASUC. These real-life data thus support the clinical trial data and should lead to broader use of this therapy in UC. © 2015 Royal Australasian College of Physicians.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice.

PubMed

Vivio, Emily E; Kanuri, Navya; Gilbertsen, Joanna J; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M; Ciorba, Matthew A

2016-04-01

Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn's disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn's Disease Activity Index (p = 0.04) and Harvey-Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Vedolizumab Effectiveness and Safety Over the First Year of Use in an IBD Clinical Practice

PubMed Central

Vivio, Emily E.; Kanuri, Navya; Gilbertsen, Joanna J.; Monroe, Kelly; Dey, Neelendu; Chen, Chien-Huan; Gutierrez, Alexandra M.

2016-01-01

Background and aims: Vedolizumab inhibits leucocyte vascular adhesion and migration into the gastrointestinal tract through α4β7 integrin blockade. This agent became available in mid-2014 for the treatment of moderate to severe Crohn’s disease (CD) and UC (UC). The aim of this study was to assess the patterns of use, effectiveness and safety of vedolizumab in an inflammatory bowel disease (IBD) clinical practice. Methods: Patients beginning vedolizumab were enrolled with informed consent. A prospective cohort was followed with laboratory, disease activity and quality-of-life assessments made during infusion visits up to week 14. Duration of vedolizumab use, mucosal healing and safety were analysed retrospectively for all patients not captured in the prospective component of this study. Results: One hundred and two patients started vedolizumab, with 51 patients (30 CD, 21 UC) followed prospectively. The CD patients exhibited a significant decrease in Crohn’s Disease Activity Index (p = 0.04) and Harvey–Bradshaw index (p < 0.01) by week 14. The UC patients demonstrated improved partial Mayo scores at weeks 6 (p < 0.01) and 14 (p < 0.001). Ninety percent of all CD and UC patients remained on vedolizumab up to week 14. IBD-related quality of life was improved by week 6 in CD and UC cohorts (p = 0.02 and p < 0.01 respectively). Colectomy for lack of response and systemic histoplamosis were notable reasons for early discontinuation of vedolizumab, which was otherwise well tolerated. Conclusions: Vedolizumab was efficacious and a high percentage of patients continued this therapy beyond induction dosing. Observed safety signals may be attributed to the refractory IBD disease state of this early-adopting clinical cohort. PMID:26681763

Histological and immunological features of appendix in patients with ulcerative colitis.

PubMed

Jo, Yukihiko; Matsumoto, Takayuki; Yada, Shinichiro; Nakamura, Shotaro; Yao, Takashi; Hotokezaka, Masayuki; Mibu, Ryuichi; Iida, Mitsuo

2003-01-01

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Characterization of IBS-like symptoms in patients with ulcerative colitis in clinical remission.

PubMed

Jonefjäll, B; Strid, H; Ohman, L; Svedlund, J; Bergstedt, A; Simren, M

2013-09-01

Gastrointestinal symptoms compatible with Irritable Bowel Syndrome (IBS) are common in patients with inflammatory bowel disease. It has been suggested that these symptoms are a reflection of occult inflammation rather than coexisting IBS. The aim of this study was to characterize IBS-like symptoms in patients with Ulcerative Colitis (UC) in clinical remission by assessing inflammatory markers, psychological symptoms, and quality of life. Ninety-four patients with new onset of UC were followed prospectively during 3 years with yearly follow-up visits. The patients completed self-administrated questionnaires. Fecal calprotectin was used as an inflammatory biomarker. Remission was defined as a total Mayo-score ≤2 and an endoscopic subscore ≤1, with no relapse during the 3-month period prior to visit. The prevalence of patients that fulfilled Rome II criteria for IBS among UC patients in remission was 11% at visit 1, 23% at visit 2, and 17% at visit 3. When comparing UC patients in remission with and without IBS-like symptom, patients with IBS-like symptoms had more severe gastrointestinal symptoms, tendencies toward more severe psychological symptoms and reduced levels of quality of life, but the calprotectin levels did not differ between the two groups. IBS-like symptoms are common in patients with UC in clinical remission and these fluctuate over time. The symptoms are associated with poor psychological well-being and reduced quality of life, and do not seem to be a reflection of low-grade inflammatory activity. © 2013 John Wiley & Sons Ltd.

Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

PubMed

Kirchgesner, J; Lemaitre, M; Rudnichi, A; Racine, A; Zureik, M; Carbonnel, F; Dray-Spira, R

2017-01-01

Management of inflammatory bowel disease (IBD) has evolved in the last decade. To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected. © 2016 John Wiley & Sons Ltd.

Prevalence and clinical importance of mesenteric venous thrombosis in the Swiss Inflammatory Bowel Disease Cohort.

PubMed

Violi, N Vietti; Vietti Violi, Naïk; Schoepfer, Alain M; Fournier, Nicolas; Guiu, Boris; Bize, Pierre; Denys, Alban

2014-07-01

The purpose of this study was to evaluate the prevalence of mesenteric venous thrombosis (MVT) in the Swiss Inflammatory Bowel Disease Cohort Study and to correlate MVT with clinical outcome. Abdominal portal phase CT was used to examine patients with inflammatory bowel disease (IBD). Two experienced abdominal radiologists retrospectively analyzed the images, focusing on the superior and inferior mesenteric vein branches and looking for signs of acute or chronic thrombosis. The location of abnormalities was registered. The presence of MVT was correlated with IBD-related radiologic signs and complications. The cases of 160 patients with IBD (89 women, 71 men; Crohn disease [CD], 121 patients; ulcerative colitis [UC], 39 patients; median age at diagnosis, 27 years for patients with CD, 32 years for patients with UC) were analyzed. MVT was detected in 43 patients with IBD (26.8%). One of these patients had acute MVT; 38, chronic MVT; and four, both. The prevalence of MVT did not differ between CD (35/121 [28.9%]) and UC (8/39 [20.5%]) (p = 0.303). The location of thrombosis was different between CD and UC (CD, jejunal or ileal veins only [p = 0.005]; UC, rectocolic veins only [p = 0.001]). Almost all (41/43) cases of thrombosis were peripheral. MVT in CD patients was more frequently associated with bowel wall thickening (p = 0.013), mesenteric fat hypertrophy (p = 0.005), ascites (p = 0.002), and mesenteric lymph node enlargement (p = 0.036) and was associated with higher rate of bowel stenosis (p < 0.001) and more intestinal IBD-related surgery (p = 0.016) in the outcome. Statistical analyses for patients with UC were not relevant because of the limited population (n = 8). MVT is frequently found in patients with IBD. Among patients with CD, MVT is associated with bowel stenosis and CD-related intestinal surgery.

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

PubMed

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

Reduced total serum bilirubin levels are associated with ulcerative colitis

PubMed Central

Schieffer, Kathleen M.; Bruffy, Shannon M.; Rauscher, Richard; Koltun, Walter A.; Gallagher, Carla J.

2017-01-01

Chronic inflammation associated with inflammatory bowel disease (IBD) results in increased oxidative stress that damages the colonic microenvironment. Low levels of serum bilirubin, an endogenous antioxidant, have been associated with increased risk for Crohn’s disease (CD). Therefore, the aim of this study was to examine whether total serum bilirubin levels are associated with ulcerative colitis (UC). We identified a retrospective case-control population (n = 6,649) from a single tertiary care center, Penn State Hershey Medical Center (PSU) and a validation cohort (n = 1,996) from Virginia Commonwealth University Medical Center (VCU). Cases were age- and sex-matched to controls (PSU: CD n = 254, UC n = 187; VCU: CD n = 233, UC n = 124). Total serum bilirubin levels were obtained from de-identified medical records and segregated into quartiles. Logistic regression analysis was performed on each quartile of total serum bilirubin compared to the last quartile (highest bilirubin levels) to determine the association of total serum bilirubin with UC. Similar to CD patients, UC patients demonstrated reduced levels of total serum bilirubin compared to controls at PSU and VCU. The lowest quartile of total serum bilirubin was independently associated with UC for the PSU (OR: 1.98 [95% CI: 1.09–3.63]) and VCU cohorts (OR: 6.07 [95% CI: 3.01–12.75]). Lower levels of the antioxidant bilirubin may reduce the capability of UC patients to remove reactive oxygen species leading to an increase in intestinal injury. Therapeutics that reduce oxidative stress may be beneficial for these patients. PMID:28594959

Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.

PubMed

Tsai, Hsin-Lin; Chang, Jei-Wen; Wu, Tsai-Hun; King, Kuang-Liang; Yang, Ling-Yu; Chan, Yu-Jiun; Yang, An-Hang; Chang, Fu-Pang; Pan, Chin-Chen; Yang, Wu-Chang; Loong, Che-Chuan

2014-07-15

To date, the outcomes of transplant tourism have not been reported extensively. In addition, data about the accuracy of urine cytology for the detection and the role of the BK virus (BKV) in the carcinogenesis of urothelial carcinoma (UC) after renal transplantation are lacking. Three hundred seven patients who received deceased donor kidney transplants between January 2003 and December 2009 were retrospectively studied. The clinical parameters and outcomes between the domestic and tourist groups were compared. We also investigated the risk factors and role of BKV in the carcinogenesis of de novo UC by quantitative real-time polymerase chain reaction. The subjects in the tourist group were older at transplantation and had a shorter dialysis time before transplantation. There were significantly higher incidence rates of BKV viruria, Pneumocystis jiroveci pneumonia, and malignancy in the tourist group. Graft and patient survival were superior in the domestic group. A total of 43 cancers were identified, and the most common type of malignancy was UC (23 patients, 53.5%). The tourist group had a significantly higher incidence of tumors. The sensitivity and specificity of urine cytology for detecting UC were 73.9% and 94.7%, respectively. Independent predictors of UC included female sex, use of Chinese herbal medicine, and transplant tourism. Only two patients (8.7%) with UC had detectable BKV. Transplant tourism was a risk factor for infection and de novo malignancy. Urothelial carcinoma was the most common malignancy after kidney transplantation. Regular screening for the early detection of UC by urine cytology or periodic sonographic surveys is mandatory, especially for those at high risk.

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients.

PubMed

Lucendo, Alfredo J; Arias, Ángel; Roncero, Óscar; Hervías, Daniel; Verdejo, Cristina; Naveas-Polo, Carmen; Bouhmidi, Abdelmouneim; Lorente, Rufo; Alcázar, Luis Miguel; Salueña, Irina; García-Quiñones, Julio A; Carrillo-Ramos, María Jesús

2017-04-01

The prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated. Retrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn's disease/ulcerative colitis (CD/UC): 718/560] were collected. Anemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p<0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18-12.10 and 6.55; 95%CI 3.39-12.63, respectively), followed by elevated (≥2mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39-6.97 and 4.58; 95%CI 2.26-9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24-4.02), but a protective one in UC (OR 0.36; 95%CI 0.14-0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36-8.21); in UC, anemia increased with disease extension (E2+E3) (OR 1.80; 95%CI 1.13-2.86). Female sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC. Copyright © 2016. Published by Elsevier Ltd.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort.

PubMed

Hiroz, Philippe; Vavricka, Stephan R; Fournier, Nicolas; Safroneeva, Ekaterina; Pittet, Valérie; Rogler, Gerhard; Schoepfer, Alain M

2014-10-01

Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Understanding performance and behavior of tightly coupled outpatient systems using RFID: initial experience.

PubMed

Stahl, James E; Holt, Julie K; Gagliano, Nancy J

2011-06-01

Understanding how clinical systems actually behave in an era of limited medical resources is critical. The purpose of this study was to determine if a radiofrequency-identification-based indoor positioning system (IPS) could objectively and unobtrusively capture outpatient clinic behavior. Primary outcomes were flowtime, wait time and patient/clinician face time. Two contrasting clinics were evaluated: a primary care clinic (PC) with templated scheduling and an urgent care clinic (UC) with unconstrained visit time and first-in, first-out scheduling. All staff wore transponders throughout the study period. Patients carried transponders from check in to check out. All patients and staff were allowed to opt out. The study was approved by hospital IRB. Standard descriptive and analytic statistical methods were used. Five hundred twenty-six patients (309 patients (PC), 217 patients (UC)) and 38 clinicians (eight (PC) and 30 (UC)) volunteered between April 30 and July 1, 2008. Total FT was not significantly different across clinics. PC wait time was significantly shorter (7.6 min [SD 15.8]) vs. UC (19.7 min [SD 25.3], p < 0.0001), and PC Face time was significantly longer (29.9 min, [SD 19.1] vs. UC (9.8 min [SD 8.5], p < 0.0001). PC Face time distributions reflected template scheduling structure. In contrast, face time distributions in UC had a smooth log normal distribution with a lower mean value. Our study seems to indicate that an IPS can successfully measure important clinic process measures in live clinical outpatient settings and capture behavioral differences across different outpatient organizational structures.

Forensic ancestry analysis in two Chinese minority populations using massively parallel sequencing of 165 ancestry-informative SNPs.

PubMed

He, Guanglin; Wang, Zheng; Wang, Mengge; Luo, Tao; Liu, Jing; Zhou, You; Gao, Bo; Hou, Yiping

2018-06-04

Ancestry inference based on single nucleotide polymorphism (SNP) with marked allele frequency differences in diverse populations (called ancestry-informative SNP, AISNP) is rapidly developed with the technology advancements of massively parallel sequencing (MPS). Despite the decade of exploration and broad public interest in the peopling of East-Asians, the genetic landscape of Chinese Silk Road populations based on the AISNPs is still little known. In this work, 206 unrelated individuals from Chinese Uyghur and Hui populations were firstly genotyped by 165 AISNPs (The Precision ID Ancestry Panel) using the Ion Torrent PGM system. The ethnic origin of two investigated populations and population structures and genetic relationships were subsequently investigated. The 165 AISNPs panel not only can differentiate Uyghur and Hui populations but also has potential applications in individual identification. Comprehensive population comparisons and admixture estimates demonstrated a predominantly higher European-related ancestry (36.30%) in Uyghurs than Huis (3.66%). Overall, the Precision ID Ancestry Panel can provide good resolution at the intercontinental level, but has limitations on the genetic homogeneous populations, such as the Hui and Han. Additional population-specific AISNPs remain necessary to get better-scale resolution within geographically proximate populations in East Asia. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Prognostic Value of Pre-operative Renal Insufficiency in Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

PubMed

Cao, Jian; Zhao, Xiaokun; Zhong, Zhaohui; Zhang, Lei; Zhu, Xuan; Xu, Ran

2016-10-11

The effect of pre-operative renal insufficiency on urothelial carcinoma (UC) prognosis has been investigated by numerous studies. While the majority report worse UC outcomes in patients with renal insufficiency, the results between the studies differed wildly. To enable us to better estimate the prognostic value of renal insufficiency on UC, we performed a systematic review and meta-analysis based on the published literature. A total of 16 studies which involved 5,232 patients with UC, investigated the relationship between pre-operative renal insufficiency and disease prognosis. Estimates of combined hazard ratio (HR) for bladder urothelial carcinoma recurrence, cancer-specific survival (CSS) and overall survival (OS) were 1.65 (95% CI, 1.11-2.19), 1.59 (95% CI, 1.14-2.05) and 1.45 (95% CI, 1.19-1.71), respectively; and for upper urinary tract urothelial carcinoma recurrence, CSS and OS were 2.27 (95% CI, 1.42-3.12), 1.02 (95% CI, 0.47-1.57) and 1.52 (95% CI, 1.05-1.99), respectively. Our results indicate that UC patients with pre-operative renal insufficiency tend to have higher recurrence rates and poorer survival compared to those with clinically normal renal function, thus renal function should be closely monitored in these patients. The impact of intervention for renal insufficiency on the prognosis of UC needs to be further studied.

Paediatric Inflammatory Bowel Disease: Clinical Presentation and Disease Location.

PubMed

Aziz, Danish Abdul; Moin, Maryum; Majeed, Atif; Sadiq, Kamran; Biloo, Abdul Gaffar

2017-01-01

To determine different clinical presentationsand disease location demarcatedby upper and lower gastrointestinal endoscopyand relevant histopathologyin children diagnosed with inflammatory bowel disease (IBD). This is 5 years (2010 to 2015) retrospective studyconducted at the Aga Khan University Hospitalenrolling65admitted children between 6 months to 15years from either gender, diagnosed with IBD on clinical presentation, endoscopy and biopsy. Different clinical presentations at the time of diagnosis were noted in different categories of the disease. All patients underwent upper and lower (up to the terminal ileum) endoscopy with multiple punch biopsies and histologic assessment of mucosal specimens. All endoscopies were done by paediatric gastroenterologists at endoscopy suite of the hospital and all specimens were reported by the pathology department. ESPGHAN revised criteria for the diagnosis of inflammatory bowel disease in children and an adolescent was used to standardize our diagnosis. Extent of disease on endoscopy and relevant histopathology of the biopsy samples were noted at the time of diagnosis. Data was summarized using mean, standard deviation, numbers and percentages for different variables. Total 56 children were enrolled according to inclusion criteria. There were 34children (61.53%) diagnosed with ulcerative colitis (UC), 10 patients (16.92%) had Crohn'sDisease (CD) and 11 (21.53%) patients were labeled as Indeterminate colitis (IC). Mean age at onset of symptoms was10.03±2.44 and mean age at diagnosis was11.10±2.36. Abdominal pain (80%) and chronic diarrhea (70%) were common symptoms in CD whereas bloody diarrhea (79.41%) and rectal bleeding(64.70%)were common presentation in UC. Patients diagnosed with indeterminate colitis(IC) had similar clinical features as in UC patients. Only 7% patients had some extra-intestinal features in the form of joint pain and/or uveitis. Aspartate aminotransferase level (95.18 ±12.89) was relatively high in patients withCD in comparison with other categories of IBD. Endoscopic findings and relevant histopathology of biopsy samples in UC showed 65% patient had pan-colitis and 13 % with disease restricted to rectum only whereas in CD 70% patient had disease in ileo-colon and only 10 % had involvement of ileum at the time diagnosis. Patients with UC dominated in our cohort. The most common clinical presentation in UC was bloody diarrhea and rectal bleeding and patients with CDhad abdominal pain and chronic diarrhea as predominant clinical features. Extraintestinal features were uncommon in our cohort. In endoscopic findings, pan-colitis was the mostfrequentfinding in UC and ileo-colonwas common location in CD. IC and UC shared common clinical features and disease location on endoscopy.

MiR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1.

PubMed

Lv, Bo; Liu, Zhihui; Wang, Shuping; Liu, Fengbin; Yang, Xiaojun; Hou, Jiangtao; Hou, Zhengkun; Chen, Bin

2014-01-01

While it's widely accepted that the etiology of ulcerative colitis (UC) involves both genetic and environmental factors, the pathogenesis of ulcerative colitis is still poorly understood. Intestinal epithelial apoptosis is one of the most common histopathological changes of UC and the expression of a number of apoptosis genes may contribute to the progression of UC. MicroRNAs have recently emerged as powerful regulators of diverse cellular processes and have been shown to be involved in many immune-mediated disorders such as psoriasis, rheumatoid arthritis, lupus, and asthma. A unique microRNA expression profile has been identified in UC, suggesting that, microRNAs play an important role in the pathogenesis of UC. We investigated the role of miR-29a in intestinal epithelial apoptosis in UC. The expression of miR-29a and Mcl-1, an anti-apoptotic BCL-2 family member, was evaluated in both UC patients and UC mice model induced by dextran sodium sulfate (DSS). The apoptosis rate of intestinal epithelial cells was also evaluated. In UC patients and DSS-induced UC in mice, the expression of miR-29a and Mcl-1, were up-regulated and down-regulated, respectively. We identified a miR-29a binding site (7 nucleotides) on the 3'UTR of mcl-1 and mutation in this binding site on the 3'UTR of mcl-1 led to mis-match between miR-29a and mcl-1. Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1. miR-29a is involved in the pathogenesis of UC by regulating intestinal epithelial apoptosis via Mcl-1.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Huang, Chao-Yuan

Inter-individual variation in the metabolism of xenobiotics, caused by factors such as cigarette smoking or inorganic arsenic exposure, is hypothesized to be a susceptibility factor for urothelial carcinoma (UC). Therefore, our study aimed to evaluate the role of gene–environment interaction in the carcinogenesis of UC. A hospital-based case–control study was conducted. Urinary arsenic profiles were measured using high-performance liquid chromatography–hydride generator-atomic absorption spectrometry. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism technique. Information about cigarette smoking exposure was acquired from a lifestyle questionnaire. Multivariate logistic regression was applied to estimate the UC risk associated with certain riskmore » factors. We found that UC patients had higher urinary levels of total arsenic, higher percentages of inorganic arsenic (InAs%) and monomethylarsonic acid (MMA%) and lower percentages of dimethylarsinic acid (DMA%) compared to controls. Subjects carrying the GSTM1 null genotype had significantly increased UC risk. However, no association was observed between gene polymorphisms of CYP1A1, EPHX1, SULT1A1 and GSTT1 and UC risk after adjustment for age and sex. Significant gene–environment interactions among urinary arsenic profile, cigarette smoking, and GSTM1 wild/null polymorphism and UC risk were observed after adjustment for potential risk factors. Overall, gene–environment interactions simultaneously played an important role in UC carcinogenesis. In the future, large-scale studies should be conducted using tag-SNPs of xenobiotic-metabolism-related enzymes for gene determination. -- Highlights: ► Subjects with GSTM1 null genotype had significantly increased UC risk. ► UC patients had poor arsenic metabolic ability compared to controls. ► GSTM1 null genotype may modify arsenic related UC risk.« less

Comparison of Costs and Quality of Life in Ulcerative Colitis Patients with an Ileal Pouch-Anal Anastomosis, Ileostomy and Anti-TNFα Therapy.

PubMed

van der Valk, Mirthe E; Mangen, Marie-Josée J; Severs, Mirjam; van der Have, Mike; Dijkstra, Gerard; van Bodegraven, Ad A; Fidder, Herma H; de Jong, Dirk J; Pierik, Marieke; van der Woude, C Janneke; Romberg-Camps, Mariëlle J L; Clemens, Cees H M; Jansen, Jeroen M; van de Meeberg, Paul C; Mahmmod, Nofel; van der Meulen-de Jong, Andrea E; Ponsioen, Cyriel Y; Bolwerk, Clemens; Vermeijden, J Reinoud; Siersema, Peter D; Leenders, Max; Oldenburg, Bas

2015-11-01

More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (€5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (€1581 versus €407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (€483 versus €377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (€1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

One-Year Effectiveness of a 3-Week Balneotherapy Program for the Treatment of Overweight or Obesity

PubMed Central

Hanh, Thierry; Serog, Patrick; Fauconnier, Jérôme; Batailler, Pierre; Mercier, Florence; Roques, Christian F.; Blin, Patrick

2012-01-01

Objective. To assess the one-year effectiveness on weight loss of a 3-week balneotherapy program (BT). Method. A Zelen double consent randomised controlled trial to compare one-year BMI loss between a 3-week BT program versus usual care (UC) for overweight or obese patients (BMI: 27–35 kg/m2), associated or not with a dietary motivational interview (DMI) during the follow-up, using a 2 × 2 factorial design. Main analysis was a per protocol analysis comparing patients attending BT to patients managed by UC, matched on sex, overweight or obese status, DMI randomisation and a propensity score to attend BT or to be managed by UC. Results. From the 257 patients who completed the follow-up, 70 patients of each group could be matched. Mean BMI loss was 1.91 kg/m2 [95%CI: 1.46; 2.35] for the BT patients and 0.20 kg/m2 [−0.24; 0.64] for the UC patients (P < 0.001), corresponding to a significant BT benefit of 1.71 kg/m2 [1.08; 2.33]. There was no significant effect of DMI and no interaction with BT or UC. No adverse reaction was observed for patients attending BT. Conclusion. A 3-week BT program provided a significant one-year benefit over the usual GP dietary advice for overweight and obese patients. PMID:23346190

[The risk factor for low bone mineral density in patients with inflammatory bowel disease].

PubMed

Liu, Jian-bin; Gao, Xiang; Zhang, Fang-bin; Yang, Li; Xiao, Ying-lian; Zhang, Rui-dong; Li, Zi-ping; Hu, Pin-jin; Chen, Min-hu

2009-10-01

To evaluate the prevalence of low bone mineral density in patients with inflammatory bowel disease (IBD)and to identify its risk factors. A cross-sectional survey was carried out in IBD patients. Anthropometric measures, biochemical markers of nutrition and bone mineral density measurement were completed for these patients as well as healthy control subjects. Seventy-seven Crohn's disease (CD) and 43 ulcerative colitis (UC) patients were enrolled, and 37 healthy volunteers were recruited as healthy controls (HC). The T value of CD patients, UC patients and HC was -1.72 +/- 1.20, -1.26 +/- 1.12 and -0.62 +/- 0.87 respectively and the T value of CD patients was significantly lower than that of HC (P = 0.000). The prevalence of osteoporosis in CD, UC and HC was 23.3%, 14.0% and 0 respectively. The prevalence of osteoporosis in CD was higher than that in HC (P = 0.003). Logistic regression analysis indicated that low BMI (BMI < or = 18.4 kg/m(2)) was an independent risk factor for osteoporosis both in CD (OR = 11.25, 95%CI 3.198 - 39.580, P = 0.000) and in UC (OR = 14.50, 95%CI 1.058 - 88.200, P = 0.045) patients. Age, disease duration, clinical activity active index (CDAI), oral steroid therapy, immunosuppressant treatment and serum vitamin D concentration were not found to be correlated with osteoporosis in IBD patients. Low bone mineral density is common in both CD and UC patients and low BMI is an independent risk factor for osteoporosis in IBD patients.

Incidence and Clinical Outcomes of Inflammatory Bowel Disease in South Korea, 2011-2014: A Nationwide Population-Based Study.

PubMed

Jung, Yoon Suk; Han, Minkyung; Kim, Won Ho; Park, Sohee; Cheon, Jae Hee

2017-08-01

The incidence of inflammatory bowel disease (IBD) is increasing in East Asia; however, population-based data from this region are lacking. We conducted a nationwide, population-based study to examine the incidence and disease course of IBD in South Korea. Using the National Health Insurance claims data, we collected data on patients diagnosed with IBD [10,049 with ulcerative colitis (UC) and 5595 with Crohn's disease (CD)] from 2011 to 2014. During the study period, the average annual incidence of UC was 5.0 per 10 5 , while that of CD was 2.8 per 10 5 . Among patients with UC, the cumulative rates of surgery 1 and 4 years after diagnosis were 1.0 and 2.0%; those among patients with CD were 9.0 and 13.9%, respectively. The 1- and 4-year cumulative rates of moderate- to high-dose corticosteroid use were, respectively, 26.6 and 45.2% among patients with UC, and 29.9 and 50.8% among those with CD. Similarly, the 1- and 4-year cumulative rates of immunomodulator use were 14.1 and 26.4% among patients with UC, and 58.3 and 76.1% among those with CD, respectively. With regard to biologic use, the 1- and 4-year cumulative rates were 3.0 and 9.0% among patients with UC, and 11.1 and 31.7% among those with CD, respectively. The recent incidence of IBD in South Korea has been the highest in East Asia. Patients who had been diagnosed recently with IBD showed lower rates of surgery and higher rates of immunomodulator and biologic use compared to those reported ever in South Korea.

Time to Remission for Depression with Collaborative Care Management (CCM) in Primary Care.

PubMed

Garrison, Gregory M; Angstman, Kurt B; O'Connor, Stephen S; Williams, Mark D; Lineberry, Timothy W

2016-01-01

Collaborative care management (CCM) has been shown to have superior outcomes to usual care (UC) for depressed patients with a fixed end point. This study was a survival analysis over time comparing CCM with UC using remission (9-item Patient Health Questionnaire [PHQ-9] score <5) and persistent depressive symptoms (PDSs; PHQ-9 score ≥10) as end points. A retrospective cohort study of 7340 patients with depression cared for at 4 outpatient primary care clinics was conducted from March 2008 through June 2013. All adult patients diagnosed with depression (International Classification of Diseases, 9th Revision [ICD-9], codes 296.2-3) or dysthymia (ICD-9 code 300.4) with an initial PHQ-9 score ≥10 were included. CCM was implemented at all clinics between 2008 and 2010. Kaplan-Meyer survival curves for time to remission and PDSs were plotted. A Cox proportional hazards model was used to adjust for expected differences between patients choosing CCM versus UC. Median time to remission was 86 days (95% confidence interval [CI], 81-91 days) for the CCM group versus 614 days (95% CI, 565-692 days) for the UC group. Likewise, median duration of PDSs was 31 days (95% CI, 30-33 days) for the CCM group versus 154 days (95% CI, 138-182 days) for the UC group. In the Cox proportional hazards model, which controlled for covariates such as age, sex, race, diagnosis, and initial PHQ-9 score, CCM was associated with faster remission (hazard ratio of the CCM group [HRCCM], 2.48; 95% CI, 2.31-2.65). This study demonstrated that patients enrolled in CCM have a faster rate of remission and a shorter duration of PDSs than patients choosing UC. © Copyright 2016 by the American Board of Family Medicine.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

PubMed

Gecse, Krisztina B; Lovász, Barbara D; Farkas, Klaudia; Banai, János; Bene, László; Gasztonyi, Beáta; Golovics, Petra Anna; Kristóf, Tünde; Lakatos, László; Csontos, Ágnes Anna; Juhász, Márk; Nagy, Ferenc; Palatka, Károly; Papp, Mária; Patai, Árpád; Lakner, Lilla; Salamon, Ágnes; Szamosi, Tamás; Szepes, Zoltán; Tóth, Gábor T; Vincze, Áron; Szalay, Balázs; Molnár, Tamás; Lakatos, Péter L

2016-02-01

Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Depression among Low-Income Female Muslim Uyghur and Kazakh Informal Caregivers of Disabled Elders in Far Western China: Influence on the Caregivers’ Burden and the Disabled Elders’ Quality of Life

PubMed Central

Wu, Fuchen; Chen, Xuefeng; Wang, Wenting; Yang, Xue

2016-01-01

Background Paying attention to and improving the mental health of the informal caregivers of disabled elders has become a global public health priority. This study focused on low-income female Uyghur and Kazakh informal caregivers of disabled elders residing in China’s far west. It investigated the prevalence of and the major related factors of depressive emotion. Methods A cross-sectional study was performed from September 2013 to January 2014 in Shawan Prefectures, Tuokexun Prefectures, Bole Prefecture and Urumchi city. Shawan Prefecture has the highest proportion of Kazakhs, whereas Tuokexun Prefectures, Bole Prefecture and Urumchi city have the highest proportion of Uyghurs in Muslim ethnic Uygur and Kazakh communities. Xinjiang Uyghur Autonomous Region is located in remote western China; this area is approximately 3,105 km (1,929 miles) away from Beijing. A total of 444 female Uyghur and Kazakh informal caregivers of disabled elders participated in this study. The self-rating depression scale, the Zarit burden interview, and the SF-36 questionnaire were used to evaluate the state of caregiver depression, caregiver burden, and quality of life (QOL), respectively. Statistical analyses were performed using multivariate logistic regression analyses, correlation with Spearman’s rho and independent-sample t-tests; a P-value of <0.05 was considered statistically significant. Results Up to 38.5% (n = 217) of informal caregivers reported having depression, whereas 61.5% (n = 273) of them reported a lack of depression. Age of disabled elders more than 60 years old, total hours spent on caring daily≥8h, duration of caring≥5 years, negative self-evaluation of health condition, having caregiver burden, elders’ medium degree of disability and elders’ heavy degree of disability had a higher risk of caregiver depression. By contrast, daughter/daughter-in-law of disabled elders; unemployed carers, family’s per capita income >US$235.48(1500 yuan), high social support, and high QOL of disabled elders were each associated with a lower risk of depressive emotion. Moreover, informal caregivers with depression obtained high care burden scores; at the same time, disabled elders who were looked after by caregivers with depression obtained low QOL scores. Conclusions Our findings suggest that the demographics characteristics of informal caregivers, and caregiver burden, and the disabled elders’ degree of disability and QOL had the most significant correlation with depressive emotion among women informal caregivers. The results had a enlighten that these variables should be considered while planning interventions to improve depression of informal caregivers. PMID:27244459

Depression among Low-Income Female Muslim Uyghur and Kazakh Informal Caregivers of Disabled Elders in Far Western China: Influence on the Caregivers' Burden and the Disabled Elders' Quality of Life.

PubMed

Wang, Meiyan; He, Bin; Wang, Yuhuan; Wu, Fuchen; Chen, Xuefeng; Wang, Wenting; Yang, Xue

2016-01-01

Paying attention to and improving the mental health of the informal caregivers of disabled elders has become a global public health priority. This study focused on low-income female Uyghur and Kazakh informal caregivers of disabled elders residing in China's far west. It investigated the prevalence of and the major related factors of depressive emotion. A cross-sectional study was performed from September 2013 to January 2014 in Shawan Prefectures, Tuokexun Prefectures, Bole Prefecture and Urumchi city. Shawan Prefecture has the highest proportion of Kazakhs, whereas Tuokexun Prefectures, Bole Prefecture and Urumchi city have the highest proportion of Uyghurs in Muslim ethnic Uygur and Kazakh communities. Xinjiang Uyghur Autonomous Region is located in remote western China; this area is approximately 3,105 km (1,929 miles) away from Beijing. A total of 444 female Uyghur and Kazakh informal caregivers of disabled elders participated in this study. The self-rating depression scale, the Zarit burden interview, and the SF-36 questionnaire were used to evaluate the state of caregiver depression, caregiver burden, and quality of life (QOL), respectively. Statistical analyses were performed using multivariate logistic regression analyses, correlation with Spearman's rho and independent-sample t-tests; a P-value of <0.05 was considered statistically significant. Up to 38.5% (n = 217) of informal caregivers reported having depression, whereas 61.5% (n = 273) of them reported a lack of depression. Age of disabled elders more than 60 years old, total hours spent on caring daily≥8h, duration of caring≥5 years, negative self-evaluation of health condition, having caregiver burden, elders' medium degree of disability and elders' heavy degree of disability had a higher risk of caregiver depression. By contrast, daughter/daughter-in-law of disabled elders; unemployed carers, family's per capita income >US$235.48(1500 yuan), high social support, and high QOL of disabled elders were each associated with a lower risk of depressive emotion. Moreover, informal caregivers with depression obtained high care burden scores; at the same time, disabled elders who were looked after by caregivers with depression obtained low QOL scores. Our findings suggest that the demographics characteristics of informal caregivers, and caregiver burden, and the disabled elders' degree of disability and QOL had the most significant correlation with depressive emotion among women informal caregivers. The results had a enlighten that these variables should be considered while planning interventions to improve depression of informal caregivers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Colburn, W.A.; Vane, F.M.; Bugge, C.J.

The pharmacokinetics of isotretinoin and 4-oxoisotretinoin in blood, as well as the blood concentrations and urinary, biliary, and fecal excretion of carbon-14 were studied using liquid scintillation counting techniques and reverse phase HPLC methods following a single 80-mg oral suspension dose of UC-isotretinoin to four healthy male subjects and two patients with biliary T-tube drainage. Approximately 80% of the dose was recovered as UC in excreta during the course of the study of which about equal fractions were in the urine and feces. Secondary peaks in blood concentrations of UC were observed in the healthy subjects whereas they were notmore » seen in the patients with T-tubes. The harmonic mean apparent half-life for isotretinoin in the blood of the healthy subjects was 13.6 hr, whereas the corresponding value for the UC was 90 hr. The data for isotretinoin and 4-oxoisotretinoin coupled with the total carbon-14 data suggest that the oral dose of UC-isotretinoin is absorbed to a similar extent by the healthy subjects and T-tube patients, whereas T-tube patients clear the drug more rapidly. The biliary excretion and possible enterohepatic circulation of isotretinoin and its metabolites may have significant impact on the pharmacokinetic profile of isotretinoin in man.« less

Mucosal Expression of Type 2 and Type 17 Immune Response Genes Distinguishes Ulcerative Colitis From Colon-Only Crohn's Disease in Treatment-Naive Pediatric Patients.

PubMed

Rosen, Michael J; Karns, Rebekah; Vallance, Jefferson E; Bezold, Ramona; Waddell, Amanda; Collins, Margaret H; Haberman, Yael; Minar, Phillip; Baldassano, Robert N; Hyams, Jeffrey S; Baker, Susan S; Kellermayer, Richard; Noe, Joshua D; Griffiths, Anne M; Rosh, Joel R; Crandall, Wallace V; Heyman, Melvin B; Mack, David R; Kappelman, Michael D; Markowitz, James; Moulton, Dedrick E; Leleiko, Neal S; Walters, Thomas D; Kugathasan, Subra; Wilson, Keith T; Hogan, Simon P; Denson, Lee A

2017-05-01

There is controversy regarding the role of the type 2 immune response in the pathogenesis of ulcerative colitis (UC)-few data are available from treatment-naive patients. We investigated whether genes associated with a type 2 immune response in the intestinal mucosa are up-regulated in treatment-naive pediatric patients with UC compared with patients with Crohn's disease (CD)-associated colitis or without inflammatory bowel disease (IBD), and whether expression levels are associated with clinical outcomes. We used a real-time reverse-transcription quantitative polymerase chain reaction array to analyze messenger RNA (mRNA) expression patterns in rectal mucosal samples from 138 treatment-naive pediatric patients with IBD and macroscopic rectal disease, as well as those from 49 children without IBD (controls), enrolled in a multicenter prospective observational study from 2008 to 2012. Results were validated in real-time reverse-transcription quantitative polymerase chain reaction analyses of rectal RNA from an independent cohort of 34 pediatric patients with IBD and macroscopic rectal disease and 17 controls from Cincinnati Children's Hospital Medical Center. We measured significant increases in mRNAs associated with a type 2 immune response (interleukin [IL]5 gene, IL13, and IL13RA2) and a type 17 immune response (IL17A and IL23) in mucosal samples from patients with UC compared with patients with colon-only CD. In a regression model, increased expression of IL5 and IL17A mRNAs distinguished patients with UC from patients with colon-only CD (P = .001; area under the receiver operating characteristic curve, 0.72). We identified a gene expression pattern in rectal tissues of patients with UC, characterized by detection of IL13 mRNA, that predicted clinical response to therapy after 6 months (odds ratio [OR], 6.469; 95% confidence interval [CI], 1.553-26.94), clinical response after 12 months (OR, 6.125; 95% CI, 1.330-28.22), and remission after 12 months (OR, 5.333; 95% CI, 1.132-25.12). In an analysis of rectal tissues from treatment-naive pediatric patients with IBD, we observed activation of a type 2 immune response during the early course of UC. We were able to distinguish patients with UC from those with colon-only CD based on increased mucosal expression of genes that mediate type 2 and type 17 immune responses. Increased expression at diagnosis of genes that mediate a type 2 immune response is associated with response to therapy and remission in pediatric patients with UC. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Unfavorable outcome of antiviral therapy in cytomegalovirus-positive ulcerative colitis may be due to inappropriate study inclusion in meta-analysis.

PubMed

Wu, Xiao-Wei; Yang, Miao-Fang; Li, Nan; Wang, Fang-Yu

2015-02-07

Some previous articles reported that antiviral treatment was effective to reduce the colectomy rate in ulcerative colitis (UC) patients with cytomegalovirus (CMV) infection. Kopylov et al recently carried out a systematic review and meta-analysis to evaluate the impact of antiviral therapy on CMV-positive UC. The results showed that patients who received antiviral treatment had a higher risk of 30-d colectomy. We found that in this meta-analysis, some studies were inappropriately included, leading to an unfavorable outcome of anti-CMV therapy in UC patients.

Thrombin generation in mesalazine refractory ulcerative colitis and the influence of low molecular weight heparin.

PubMed

Vrij, Anton A; Oberndorff-Klein-Woolthuis, Ardi; Dijkstra, Gerard; de Jong, Andrea E; Wagenvoord, Rob; Hemker, Hendrik C; Stockbrügger, Reinhold W

2007-10-01

In ulcerative colitis (UC), a state of hypercoagulation has frequently been observed. Low molecular weight heparin (LMWH) has shown beneficial effects as an adjuvant treatment of steroid refractory UC in open trials. We assessed potential therapeutic effects of the LMWH reviparin in hospitalised patients with mesalazine refractory UC, as well as its influence on haemostasis factors. Twenty-nine patients with mild-to-moderately active UC were included in a double-blind placebo controlled trial. All patients had a flare-up of disease under mesalazine treatment. Reviparin (Clivarin) 3,436 IU anti-Xa/0.6 ml or placebo s.c. was added, and self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events and changes in clinical symptoms. Endoscopical, histological, biochemical and haemostasis parameters were analysed. Tolerability and compliance were excellent and no serious adverse events occurred. No significant differences were observed on the clinical, endoscopical and histological outcome, as compared to placebo. A high intrinsic and extrinsic thrombin potential was found before LMWH therapy. However, the significant reduction in the thrombin generation by LMWH was not related to the reduction in disease activity. The LMWH reviparine reduces thrombin generation in patients with mild-to-moderately active, mesalazine refractory UC, but is not associated with a reduction in disease activity.

The safety of vedolizumab for the treatment of ulcerative colitis.

PubMed

Novak, Gregor; Hindryckx, Pieter; Khanna, Reena; Jairath, Vipul; Feagan, Brian G

2017-04-01

Vedolizumab is a humanized monoclonal antibody to the α4β7-integrin that blocks lymphocyte trafficking to the gut and is approved for treatment of patients with moderate-to-severe ulcerative colitis (UC). The gut-selective mechanism of action has the potential to improve vedolizumab's safety profile compared to other approved biologic drugs. Areas covered: We review the mechanism of action, efficacy and safety of vedolizumab treatment for UC. The positioning of vedolizumab in management algorithms is also discussed. Expert opinion: The highly selective mechanism of action of vedolizumab restricts immunosuppressive effects to the gut. Vedolizumab is efficacious as induction and maintenance therapy in UC patients who are naïve or refractory to tumor necrosis factor antagonists. No clinically important safety signals have been identified. Infusion reactions are reported in <5% of cases. The rates of adverse events (AE), serious AEs, and serious infections were not different between patients treated with placebo and those who received vedolizumab in a pooled analysis of six randomized controlled trials. Rates of malignancy and mortality in vedolizumab-exposed patients are similar to those of the general UC patient population. Progressive multifocal leukoencephalopathy has not been observed. Vedolizumab is a safe and effective therapy for UC with a unique mechanism of action.

Immunohistochemical study of intestinal eosinophils in inflammatory bowel disease.

PubMed

Carvalho, Ana Teresa Pugas; Elia, Celeste Carvalho Siqueira; de Souza, Heitor Siffert Pereira; Elias, Paulo Roberto Pinheiro; Pontes, Eduardo Lopes; Lukashok, Hannah Pitanga; de Freitas, Fernanda Cristina Dias; Lapa e Silva, José Roberto

2003-02-01

Eosinophil accumulation and activation are characteristic features of inflammation in allergic diseases and in host defense against parasites. To investigate the involvement of eosinophils in inflamed and noninflamed mucosa of patients with inflammatory bowel disease (IBD). Specimens of inflamed colonic mucosa from 15 patients with ulcerative colitis (UC) and inflamed and noninflamed colonic mucosa from 15 patients with Crohn's disease (CD) were submitted to histologic and immunohistochemical studies. Twelve patients with irritable bowel syndrome were studied as controls. Sirius red was used to label eosinophils in tissue. EG1, EG2, and anti-hIL-5 were used as primary antibodies in an indirect alkaline phosphatase-labeled immunostaining protocol. Both positive and negative lamina propria cells were assessed by a quantitative grading system and the results expressed as cell numbers per mm. Increased proportions of eosinophils stained with Sirius red, EG1, EG2, and anti-hIL-5+ cells were found in the colon of patients with UC and in inflamed and noninflamed colon of CD patients as compared with controls. Crohn's disease patients showed increased proportions of EG1+ and EG2+ cells as compared with those with UC. Increased proportions of IL-5+ cells were detected in UC patients as compared with those with CD. Quantitative eosinophil alterations and IL-5+ cells may indicate enhanced cellular activation with degranulation, which is implicated in the pathogenesis of IBD. Increase in IL-5+ cells may reflect a predominant local Th2 response in UC as compared with CD.

Incidence, Risk Factors, and Outcomes of Colorectal Cancer in Patients With Ulcerative Colitis With Low-Grade Dysplasia: A Systematic Review and Meta-analysis.

PubMed

Fumery, Mathurin; Dulai, Parambir S; Gupta, Samir; Prokop, Larry J; Ramamoorthy, Sonia; Sandborn, William J; Singh, Siddharth

2017-05-01

Little is known about outcomes of patients with ulcerative colitis with low-grade dysplasia (UC-LGD). We estimated the incidence of and risk factors for progression to colorectal cancer (CRC) in cohorts of patients with UC-LGD who underwent surveillance (surveillance cohort), and the prevalence of dysplasia-related findings among patients who underwent colectomy for UC-LGD (surgical cohort). We performed a systematic literature review through June 1, 2016, to identify cohort studies of adults with UC-LGD. We estimated pooled incidence rates of CRC and risk factors associated with dysplasia progression in surveillance cohorts, and prevalence of synchronous advanced neoplasia (CRC and/or high-grade dysplasia) in surgical cohorts. In 14 surveillance cohort studies of 671 patients with UC-LGD (52 developed CRC), the pooled annual incidence of CRC was 0.8% (95% confidence interval [CI], 0.4-1.3); the pooled annual incidence of advanced neoplasia was 1.8% (95% CI, 0.9-2.7). Risk of CRC was higher when LGD was diagnosed by expert gastrointestinal pathologist (1.5%) than by community pathologists (0.2%). Factors significantly associated with dysplasia progression were concomitant primary sclerosing cholangitis (odds ratio [OR], 3.4; 95% CI, 1.5-7.8), invisible dysplasia (vs visible dysplasia; OR, 1.9; 95% CI, 1.0-3.4), distal location (vs proximal location; OR, 2.0; 95% CI, 1.1-3.7), and multifocal dysplasia (vs unifocal dysplasia; OR, 3.5; 95% CI, 1.5-8.5). In 12 surgical cohort studies of 450 patients who underwent colectomy for UC-LGD, 34 patients had synchronous CRC (pooled prevalence, 17%; 95% CI, 8-33). In a systematic review of the literature, we found that among patients with UC-LGD under surveillance, the annual incidence of progression to CRC was 0.8%; differences in rates of LGD diagnosis varied with pathologists' level of expertise. Concomitant primary sclerosing cholangitis, invisible dysplasia, distal location, and multifocal LGD are high-risk features associated with dysplasia progression. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Circulating cathelicidin levels correlate with mucosal disease activity in ulcerative colitis, risk of intestinal stricture in Crohn's disease, and clinical prognosis in inflammatory bowel disease.

PubMed

Tran, Diana Hoang-Ngoc; Wang, Jiani; Ha, Christina; Ho, Wendy; Mattai, S Anjani; Oikonomopoulos, Angelos; Weiss, Guy; Lacey, Precious; Cheng, Michelle; Shieh, Christine; Mussatto, Caroline C; Ho, Samantha; Hommes, Daniel; Koon, Hon Wai

2017-05-12

Cathelicidin (LL-37) is an antimicrobial peptide known to be associated with various autoimmune diseases. We attempt to determine if cathelicidin can accurately reflect IBD disease activity. We hypothesize that serum cathelicidin correlates with mucosal disease activity, stricture, and clinical prognosis of IBD patients. Serum samples were collected from two separate cohorts of patients at the University of California, Los Angeles. Cohort 1 consisted of 50 control, 23 UC, and 28 CD patients. Cohort 2 consisted of 20 control, 57 UC, and 67 CD patients. LL-37 levels were determined by ELISA. Data from both cohorts were combined for calculation of accuracies in indicating mucosal disease activity, relative risks of stricture, and odds ratios of predicting disease development. Serum cathelicidin levels were inversely correlated with Partial Mayo Scores of UC patients and Harvey-Bradshaw Indices of CD patients. Among IBD patients with moderate or severe initial disease activity, the patients with high initial LL-37 levels had significantly better recovery than the patients with low initial LL-37 levels after 6-18 months, suggesting that high LL-37 levels correlate with good prognosis. Co-evaluation of LL-37 and CRP levels was more accurate than CRP alone or LL-37 alone in the correlation with Mayo Endoscopic Score of UC patients. Low LL-37 levels indicated a significantly elevated risk of intestinal stricture in CD patients. Co-evaluation of LL-37 and CRP can indicate mucosal disease activity in UC patients. LL-37 can predict future clinical activity in IBD patients and indicate risk of intestinal stricture in CD patients.

Ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis for prevention of colon cancer: a meta-analysis.

PubMed

Ashraf, Imran; Choudhary, Abhishek; Arif, Murtaza; Matteson, Michelle L; Hammad, Hazem T; Puli, Srinivas R; Bechtold, Matthew L

2012-04-01

Colon cancer risk is high in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). Ursodeoxycholic acid has been shown to have some promise as a chemopreventive agent. A meta-analysis was performed to compare the efficacy of ursodeoxycholic acid in the prevention of colonic neoplasia in patients with UC and PSC. Multiple databases were searched (January 2011). Studies examining the use of ursodeoxycholic acid vs. no ursodeoxycholic acid or placebo in adult patients with UC and PSC were included. Data were extracted in standard forms by two independent reviewers. Meta-analysis for the effect of ursodeoxycholic acid was performed by calculating pooled estimates of adenoma or colon cancer formation by odds ratio (OR) with random effects model. Heterogeneity was assessed by calculating the I (2) measure of inconsistency. RevMan 5 was utilized for statistical analysis. Four studies (n = 281) met the inclusion criteria. The studies were of adequate quality. Ursodeoxycholic acid demonstrated no overall improvement in adenoma (OR 0.53; 95 % CI: 0.19-1.48, p = 0.23) or colon cancer occurrence (OR 0.50; 95 % CI: 0.18-1.43, p = 0.20) as compared to no ursodeoxycholic acid or placebo in patients with UC and PSC. Ursodeoxycholic acid use in patients with UC and PSC does not appear to decrease the risk of adenomas or colon cancer.

The course of newly presented unexplained complaints in general practice patients: a prospective cohort study.

PubMed

Koch, H; van Bokhoven, M A; Bindels, P J E; van der Weijden, T; Dinant, G J; ter Riet, G

2009-12-01

Newly presented unexplained complaints (UCs) are common in general practice. Factors influencing the transition of newly presented into persistent UCs have been scarcely investigated. We studied the number and the nature of diagnoses made over time, as well as factors associated with UCs becoming persistent. Finally, we longitudinally studied factors associated with quality of life (QoL). Prospective cohort study in general practice of patients presenting with a new UC. Data sources were case record forms, patient questionnaires and electronic medical registries at inclusion, 1, 6 and 12 months. Presence of complaints and diagnoses made over time were documented. Potential risk factors were assessed in mixed-effect logistic and linear regression models. Sixty-three GPs included 444 patients (73% women; median age 42) with unexplained fatigue (70%), abdominal complaints (14%) and musculoskeletal complaints (16%). At 12 months, 43% of the patients suffered from their initial complaints. Fifty-seven percent of the UCs remained unexplained. UCs had (non-life-threatening) somatic origins in 18% of the patients. QoL was often poor at presentation and tended to remain poor. Being a male [odds ratio (OR) 0.6; 95% confidence interval (CI) 0.4-0.8] and GPs' being more certain about the absence of serious disease (OR 0.9; 95% CI 0.8-0.9) were the strongest predictors of a diminished probability that the complaints would still be present and unexplained after 12 months. The strongest determinants of complaint persistence [regardless of (un)explicability] were duration of complaints >4 weeks before presentation (OR 2.6; 95% CI 1.6-4.3), musculoskeletal complaint at baseline (OR 2.3; 1.2-4.5), while the passage of time acted positively (OR 0.8 per month; 95% CI 0.78-0.84). Musculoskeletal complaints, compared to fatigue, decreased QoL on the physical domain (4.6 points; 2.6-6.7), while presence of psychosocial factors decreased mental QoL (5.0; 3.1-6.9). One year after initial presentation, a large proportion of newly presented UCs remained unexplained and unresolved. We identified determinants that GPs might want to consider in the early detection of patients at risk of UC persistence and/or low QoL.

[Medical therapy of inflammatory bowel diseases: ulcerative colitis].

PubMed

Lakatos, László; Lakatos, Péter László

2007-06-24

There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to better organize the patient-doctor relationship and for greater adherence to medical therapy.

Extension and flexion in the upper cervical spine in neck pain patients.

PubMed

Ernst, Markus J; Crawford, Rebecca J; Schelldorfer, Sarah; Rausch-Osthoff, Anne-Kathrin; Barbero, Marco; Kool, Jan; Bauer, Christoph M

2015-08-01

Neck pain is a common problem in the general population with high risk of ongoing complaints or relapses. Range of motion (ROM) assessment is scientifically established in the clinical process of diagnosis, prognosis and outcome evaluation in neck pain. Anatomically, the cervical spine (CS) has been considered in two regions, the upper and lower CS. Disorders like cervicogenic headache have been clinically associated with dysfunctions of the upper CS (UCS), yet ROM tests and measurements are typically conducted on the whole CS. A cross-sectional study assessing 19 subjects with non-specific neck pain was undertaken to examine UCS extension-flexion ROM in relation to self-reported disability and pain (via the Neck Disability Index (NDI)). Two measurement devices (goniometer and electromagnetic tracking) were employed and compared. Correlations between ROM and the NDI were stronger for the UCS compared to the CS, with the strongest correlation between UCS flexion and the NDI-headache (r = -0.62). Correlations between UCS and CS ROM were fair to moderate, with the strongest correlation between UCS flexion and CS extension ROM (r = -0.49). UCS flexion restriction is related to headache frequency and intensity. Consistency and agreement between both measurement systems and for all tests was high. The results demonstrate that separate UCS ROM assessments for extension and flexion are useful in patients with neck pain. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hybrid constructs for tridimensional correction of the thoracic spine in adolescent idiopathic scoliosis: a comparative analysis of universal clamps versus hooks.

PubMed

Ilharreborde, Brice; Even, Julien; Lefevre, Yan; Fitoussi, Franck; Presedo, Ana; Penneçot, Georges-François; Mazda, Keyvan

2010-02-01

Retrospective study of prospectively collected data. Compare Universal Clamps (UCs) and hooks for the thoracic correction of adolescent idiopathic scoliosis (AIS). In scoliosis surgery, sagittal correction is as important as frontal correction due to the risk of junctional kyphosis. Compared to all-screw constructs, hybrid constructs with lumbar pedicle screws and thoracic hooks or sublaminar wires have been shown to achieve similar coronal correction while providing superior postoperative thoracic kyphosis. The authors used a novel sublaminar thoracic implant, the UC with improvements over sublaminar wires. Hybrid constructs using thoracic UCs were compared to those with thoracic hooks. This series involved 150 patients treated for AIS with hybrid constructs. A total of 75 consecutive patients operated from 2001 to 2003, who had thoracic hooks with in situ contouring, distraction, and compression (Group 1), were compared to 75 consecutive patients operated from 2004 to 2006, who had thoracic UCs with posteromedial translation (Group 2). All had intraoperative somatosensory/motor-evoked potential monitoring and at least 2-years follow-up. Except for follow-up (longer in Group 1), the 2 groups were similar before surgery. The UCs achieved better thoracic coronal correction (P < 0.001), Cincinnati index (P < 0.001), kyphosis (P = 0.02), and apical rotation (P < 0.001). In normokyphotic or hypokyphotic patients, the UC corrected thoracic kyphosis by 11.2 degrees (55%) versus 0.4 degrees (2%) achieved by hooks (P < 0.0001). These differences were stable at last follow-up. There were no intraoperative complications or changes in somatosensory/motor-evoked potentials. UC reduced operative time by 20% (60 minutes; P < 0.001) and blood loss by 23% (250 mL; P < 0.001). Although both of these hybrid constructs efficaciously corrected the coronal and axial deformities in AIS, the results of the UC technique were superior to those achieved with hooks in all 3 planes, especially the sagittal plane. Moreover, the UC technique is straightforward and safe, reducing both operative duration and blood loss.

Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

PubMed

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Gonczi, Lorant; Golovics, Petra Anna; Lovasz, Barbara Dorottya; Szita, Istvan; Balogh, Mihaly; Pandur, Tunde; Vavricka, Stephan R; Rogler, Gerhard; Lakatos, Laszlo; Lakatos, Peter Laszlo

2016-07-01

The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

Genetic characteristics of inflammatory bowel disease in a Japanese population.

PubMed

Fuyuno, Yuta; Yamazaki, Keiko; Takahashi, Atsushi; Esaki, Motohiro; Kawaguchi, Takaaki; Takazoe, Masakazu; Matsumoto, Takayuki; Matsui, Toshiyuki; Tanaka, Hiroki; Motoya, Satoshi; Suzuki, Yasuo; Kiyohara, Yutaka; Kitazono, Takanari; Kubo, Michiaki

2016-07-01

Crohn's disease (CD) and ulcerative colitis (UC) are two major forms of inflammatory bowel disease (IBD). Meta-analyses of genome-wide association studies (GWAS) have identified 163 susceptibility loci for IBD among European populations; however, there is limited information for IBD susceptibility in a Japanese population. We performed a GWAS using imputed genotypes of 743 IBD patients (372 with CD and 371 with UC) and 3321 controls. Using 100 tag single-nucleotide polymorphisms (SNPs) (P < 5 × 10(-5)), a replication study was conducted with an independent set of 1310 IBD patients (949 with CD and 361 with UC) and 4163 controls. In addition, 163 SNPs identified by a European IBD GWAS were genotyped, and genetic backgrounds were compared between the Japanese and European populations. In the IBD GWAS, two East Asia-specific IBD susceptibility loci were identified in the Japanese population: ATG16L2-FCHSD2 and SLC25A15-ELF1-WBP4. Among 163 reported SNPs in European IBD patients, significant associations were confirmed in 18 (8 CD-specific, 4 UC-specific, and 6 IBD-shared). In Japanese CD patients, genes in the Th17-IL23 pathway showed stronger genetic effects, whereas the association of genes in the autophagy pathway was limited. The association of genes in the epithelial barrier and the Th17-IL23R pathways were similar in the Japanese and European UC populations. We confirmed two IBD susceptibility loci as common for CD and UC, and East Asian-specific. The genetic architecture in UC appeared to be similar between Europeans and East Asians, but may have some differences in CD.

Patient and Genetic Counselor Perceptions of In-person versus Telephone Genetic Counseling for Hereditary Breast/Ovarian Cancer

PubMed Central

Jacobs, Aryana S.; Schwartz, Marc D.; Valdimarsdottir, Heiddis; Nusbaum, Rachel H.; Hooker, Gillian W.; DeMarco, Tiffani A.; Heinzmann, Jessica E.; McKinnon, Wendy; McCormick, Shelley R.; Davis, Claire; Forman, Andrea D.; Lebensohn, Alexandra Perez; Dalton, Emily; Tully, Diana Moglia; Graves, Kristi D.; Similuk, Morgan; Kelly, Scott; Peshkin, Beth N.

2016-01-01

Telephone genetic counseling (TC) for high-risk women interested in BRCA1/2 testing has been shown to yield positive outcomes comparable to usual care (UC; in-person) genetic counseling. However, little is known about how genetic counselors perceive the delivery of these alternate forms of genetic counseling. As part of a randomized trial of TC versus UC, genetic counselors completed a 5-item genetic counselor process questionnaire (GCQ) assessing key elements of pre-test sessions (information delivery, emotional support, addressing questions and concerns, tailoring of session, and facilitation of decision- making) with the 479 female participants (TC, N=236; UC, N=243). The GCQ scores did not differ for TC vs. UC sessions (t (477) = 0.11, p = 0.910). However, multivariate analysis showed that participant race/ethnicity significantly predicted genetic counselor perceptions (β = 0.172, p<0.001) in that the GCQ scores were lower for minorities in TC and UC. Exploratory analyses suggested that GCQ scores may be associated with patient preference for UC versus TC (t (79) = 2.21, p=0.030). Additionally, we found that genetic counselor ratings of session effectiveness were generally concordant with patient perceptions of the session. These data indicate that genetic counselors perceive that key components of TC can be delivered as effectively as UC, and that these elements may contribute to specific aspects of patient satisfaction. However, undefined process differences may be present which account for lower counselor perceptions about the effectiveness of their sessions with minority women (i.e., those other than non-Hispanic Whites). We discuss other potential clinical and research implications of our findings. PMID:26969308

A case-control study of the association between ulcerative colitis and hyperthyroidism in an Asian population.

PubMed

Tsai, Ming-Chieh; Lin, Herng-Ching; Lee, Cha-Ze

2017-06-01

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease with significant clinical diversity. However, the aetiology, pathogenesis and optimal treatment of UC remain unclear. The purpose of this case-control study was to investigate the association between previously diagnosed hyperthyroidism and UC using a large population-based data set in Taiwan. The data for this population-based case-control study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. We included 2709 patients with UC as cases and 8127 sex- and age-matched patients without UC as controls. A conditional logistic regression analysis was conducted to compute the odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between UC and prior hyperthyroidism. We found that, in total, 327 of the 10 836 sampled patients (3.02%) had previously been diagnosed with hyperthyroidism. There was a higher proportion of prior hyperthyroidism among cases than controls (4.10% vs 2.66%, P<.001). A conditional logistic regression showed that the OR of prior hyperthyroidism was 1.57 (95% CI=1.24-1.98) compared to controls. Similarly, after adjusting for monthly income, geographic location and urbanization level, cases were still more likely to have previously been diagnosed with hyperthyroidism than controls (OR=1.61, 95% CI=1.27-2.05). Furthermore, we analysed the ORs of prior hyperthyroidism between cases and controls according to age group. We found that of the youngest group of sampled patients (18-39 years), cases had the greatest adjusted OR for having previously been diagnosed with hyperthyroidism than controls (OR=1.98, 95% CI=1.04-3.79). This study demonstrated an association between UC and hyperthyroidism. © 2017 John Wiley & Sons Ltd.

Pseudoprogression and hyperprogression during immune checkpoint inhibitor therapy for urothelial and kidney cancer.

PubMed

Soria, Francesco; Beleni, Andrea I; D'Andrea, David; Resch, Irene; Gust, Kilian M; Gontero, Paolo; Shariat, Shahrokh F

2018-03-16

A small subset of patients treated with immune checkpoint inhibitors manifest atypical patterns of response, the so-called pseudoprogression (PP) and hyperprogression (HP). Their prevalence in urothelial (UC) and renal cancer (RCC) remains, to date, mostly uninvestigated. Therefore, we aimed to provide a summary of the current knowledge about PP and HP during immune checkpoint inhibitor therapy in UC and RCC patients. A systematic medline/pubmed © literature search was performed. The atypical patterns of response to systemic immunotherapy were reviewed. Endpoints were PP and HP in UC and RCC. Tumors respond differently to immunotherapy compared to systemic chemotherapy. To evaluate response to immunotherapy, new guidelines (iRECIST) have been developed. To date, no studies focused on PP in UC and RCC, and the only way to evaluate its role is to take patients who respond to treatment beyond progression as surrogate for pseudoprogressors. PP seems to occur in a non-negligible rate of UC and RCC (from 1.5 to 17% and from 5 to 15%, respectively). The concept of HP, defined as a rapid progression after treatment, just took the first steps, and therefore, data from ongoing trials are awaited to elucidate its impact in genitourinary cancers. PP and HP are not uncommon entities in UC and RCC patients, treated with PD-1/PD-L1 inhibitors. Further investigation is warranted to define which patients are likely to experience PP and could benefit from treatment beyond progression and which ones will instead rapidly experience progression despite treatment and should, therefore, avoid systemic immunotherapy.

Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis

PubMed Central

2012-01-01

Background Accurate diagnostic and monitoring tools for ulcerative colitis (UC) are missing. Our aim was to describe the proteomic profile of UC and search for markers associated with disease exacerbation. Therefore, we aimed to characterize specific proteins associated with inflamed colon mucosa from patients with acute UC using mass spectrometry-based proteomic analysis. Methods Biopsies were sampled from rectum, sigmoid colon and left colonic flexure from twenty patients with active proctosigmoiditis and from four healthy controls for proteomics and histology. Proteomic profiles of whole colonic biopsies were characterized using 2D-gel electrophoresis, and peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for identification of differently expressed protein spots. Results A total of 597 spots were annotated by image analysis and 222 of these had a statistically different protein level between inflamed and non-inflamed tissue in the patient group. Principal component analysis clearly grouped non-inflamed samples separately from the inflamed samples indicating that the proteomic signature of colon mucosa with acute UC is strong. Totally, 43 individual protein spots were identified, including proteins involved in energy metabolism (triosephosphate isomerase, glycerol-3-phosphate-dehydrogenase, alpha enolase and L-lactate dehydrogenase B-chain) and in oxidative stress (superoxide dismutase, thioredoxins and selenium binding protein). Conclusions A distinct proteomic profile of inflamed tissue in UC patients was found. Specific proteins involved in energy metabolism and oxidative stress were identified as potential candidate markers for UC. PMID:22726388

Clinical Outcomes of Golimumab as First, Second or Third Anti-TNF Agent in Patients with Moderate-to-Severe Ulcerative Colitis.

PubMed

Taxonera, Carlos; Rodríguez, Cristina; Bertoletti, Federico; Menchén, Luís; Arribas, Julia; Sierra, Mónica; Arias, Lara; Martínez-Montiel, Pilar; Juan, Alba; Iglesias, Eva; Algaba, Alicia; Manceñido, Noemí; Rivero, Montserrat; Barreiro-de Acosta, Manuel; López-Serrano, Pilar; Argüelles-Arias, Federico; Gutierrez, Ana; Busquets, David; Gisbert, Javier P; Olivares, David; Calvo, Marta; Alba, Cristina

2017-08-01

Golimumab efficacy data in ulcerative colitis (UC) are limited to anti-tumor necrosis factor α (TNF)-naive patients. The aim of this study was to assess the short-term and long-term efficacy of golimumab used as first, second, or third anti-TNF in UC in a real-life clinical setting. This retrospective multicenter cohort study included patients with moderate-to-severe UC treated with golimumab. The primary efficacy endpoints were short-term partial Mayo score response, long-term golimumab failure-free survival, and colectomy-free survival. In 142 patients with UC, golimumab was administered as first (40%), second (23%), or third anti-TNF (37%). Ninety-two patients (65%, 95% confidence interval 56.6-73) achieved short-term clinical response. Forty-five patients (32%, 95% confidence interval 23.7-39.7) achieved clinical remission. Response rates for golimumab were 75% as first anti-TNF, 70% as second anti-TNF (ns versus first anti-TNF), and 50% as third anti-TNF (P = 0.007 versus first anti-TNF). After 12 months median follow-up (interquartile range 6-18), 60 patients (42%, 95% confidence interval 34-51) had golimumab failure, and 15 patients (11%) needed colectomy. Thirty-one patients (22%) needed golimumab dose escalation, and 71% of these regained response after escalation. Starting maintenance with 100 mg golimumab doses and short-term nonresponse were independent predictors of golimumab failure. In this real-life cohort of patients with UC, golimumab therapy was effective for inducing and maintaining clinical response. Although anti-TNF-naive patients had better outcomes, golimumab was also effective in anti-TNF-experienced patients. Only the patients given golimumab after previous failure of 2 anti-TNF agents had significantly worse outcomes. Golimumab dose escalation was beneficial and safe.

Current approaches to the management of new-onset ulcerative colitis

PubMed Central

Marchioni Beery, Renée; Kane, Sunanda

2014-01-01

Ulcerative colitis (UC) is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity) but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to- moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids) or thiopurines (as bridging therapy). Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide a comprehensive evidence-based approach to current treatment options for new-onset UC with discussion of long-term therapeutic efficacy and safety, patient-centered perspectives including quality of life and medication compliance, and future directions in related inflammatory bowel disease care. PMID:24872716

The diagnostic value of a new fecal marker, matrix metalloprotease-9, in different types of inflammatory bowel diseases.

PubMed

Farkas, Klaudia; Saródi, Zoltán; Bálint, Anita; Földesi, Imre; Tiszlavicz, László; Szűcs, Mónika; Nyári, Tibor; Tajti, János; Nagy, Ferenc; Szepes, Zoltán; Bor, Renáta; Annaházi, Anita; Róka, Richárd; Molnár, Tamás

2015-03-01

Only limited data are available regarding the diagnostic accuracy of fecal matrix metalloprotease-9 [MMP-9] for inflammatory bowel disease [IBD]. The aims of our study were to assess the diagnostic accuracy of fecal MMP-9 in patients with active Crohn's disease [CD], ulcerative colitis [UC], and pouchitis, and to compare the diagnostic accuracy of fecal MMP-9 and fecal calprotectin [CP] in IBD. Stool and blood samples were collected in 50 CD, 54 UC, and 34 ileal pouch-anal anastomosis patients before control endoscopies were performed. Biopsies were taken for histologic purposes. The activities of CD, UC, and pouchitis were defined with the use of clinical, endoscopic, and histologic activity scores. Fecal CP and MMP-9 levels were quantified by enzyme-linked immunosorbent assay. Active CD, UC, and pouchitis were detected in 38%, 54%, and 29% of the patients, respectively. A significant correlation was revealed between fecal CP and the clinical activities of CD and UC, and between fecal CP and the endoscopic activity of UC and pouchitis. Fecal MMP-9 did not correlate with any of the activity indices of CD; however, strong associations were shown between fecal MMP-9 and clinical, endoscopic, and histologic activities of both UC and pouchitis. This is the first study assessing the diagnostic accuracy of MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has high sensitivity in the detection of endoscopically active UC and pouchitis. These non-invasive methods help assess intestinal inflammation. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Impact of MMX® mesalamine on improvement and maintenance of health-related quality of life in patients with ulcerative colitis.

PubMed

Hodgkins, Paul; Yen, Linnette; Yarlas, Aaron; Karlstadt, Robyn; Solomon, Dory; Kane, Sunanda

2013-02-01

Ulcerative colitis (UC) substantially reduces patients' health-related quality of life (HRQoL). The current study examined the burden of disease and the impact of daily multimatrix (MMX®) mesalamine treatment on HRQoL for patients with active or quiescent mild-to-moderate UC. Data were from a two-phase, multicenter, open-label study with mild-to-moderate UC patients. In the acute phase, 132 patients with active disease received MMX mesalamine 2.4-4.8 g/day QD for 8 weeks. In the maintenance phase, 207 patients with quiescent disease received MMX mesalamine 2.4 g/day QD for 12 months. The Short Form-12 (version 2) (SF-12v2) measured HRQoL during each phase. Disease burden was examined by comparing acute-phase baseline scores with a U.S. general population sample. Repeated-measures analyses assessed change in SF-12v2 scores for each phase. Correspondence between HRQoL and disease activity was examined through correlations between SF-12v2 scores with patient-reported symptom measures. Baseline SF-12v2 scores for patients with UC were generally much lower than for the general population sample, indicating a broad disease burden. In the acute phase, significant improvement was observed for most SF-12v2 scores at week 8; a comparison with the matched norms showed a complete elimination of burden. No changes in SF-12v2 scores were observed during the maintenance phase. Changes in symptom measures and SF-12v2 scores were moderately correlated. The sizeable burden of active mild-to-moderate UC on HRQoL was eliminated following 8 weeks' treatment with MMX mesalamine 2.4-4.8 g/day. HRQoL remained stable over 12 months of maintenance treatment in patients with quiescent UC.

Pretreatment Neutrophil-Lymphocyte Ratio as a Predictor in Bladder Cancer and Metastatic or Unresectable Urothelial Carcinoma Patients: a Pooled Analysis of Comparative Studies.

PubMed

Wu, Shuiqing; Zhao, Xiaokun; Wang, Yinhuai; Zhong, Zhaohui; Zhang, Lei; Cao, Jian; Ai, Kai; Xu, Ran

2018-01-01

Emerging studies have shown that the neutrophil-lymphocyte ratio (NLR) is a potential predictor in various tumors. Our study was conducted to assess the prognostic value of the pretreatment NLR in bladder cancer and metastatic or unresectable urothelial carcinoma (mUC or uUC) patients up to July 2017. The correlation between the pretreatment NLR and pathological characteristics was also evaluated in bladder cancer patients. The hazard ratio (HR) and odds ratio (OR) with the 95% confidence interval (CI) were extracted or calculated from the included studies for further pooled analysis. A total of 21 studies were included in a pooled analysis. The pooled results indicated that a high pretreatment NLR was associated with reduced overall survival (OS) (HR=1.27, 95% CI=1.12-1.43), relapse-free survival (RFS) (HR=1.41, 95% CI=1.23-1.60), progression-free survival (PFS) (HR=1.75, 95% CI=1.36-2.15), disease-specific survival (DSS) and cancer-specific survival (CSS) (HR=1.27, 95% CI=1.19-1.35) in the bladder cancer patients. Additionally, an elevated pretreatment NLR suggested a worse OS rate in the mUC or uUC patients (HR=1.63, 95% CI=1.34-1.91). The pooled ORs and 95% CIs showed that a high pretreatment NLR could be a risk indicator for certain pathological features, such as lymphovascular invasion, a positive margin status and advanced tumor stage. our results showed that a high pretreatment NLR predicted poor prognosis in bladder cancer, mUC and uUC patients. © 2018 The Author(s). Published by S. Karger AG, Basel.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

PubMed

Bopanna, Sawan; Kedia, Saurabh; Das, Prasenjit; Dattagupta, S; Sreenivas, V; Mouli, V Pratap; Dhingra, Rajan; Pradhan, Rajesh; Kumar, N Suraj; Yadav, Dawesh P; Makharia, Govind; Ahuja, Vineet

2017-08-01

As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Expression Levels of DNA Damage Repair Proteins Are Associated With Overall Survival in Platinum-Treated Advanced Urothelial Carcinoma.

PubMed

Mullane, Stephanie A; Werner, Lillian; Guancial, Elizabeth A; Lis, Rosina T; Stack, Edward C; Loda, Massimo; Kantoff, Philip W; Choueiri, Toni K; Rosenberg, Jonathan; Bellmunt, Joaquim

2016-08-01

Combination platinum chemotherapy is standard first-line therapy for metastatic urothelial carcinoma (mUC). Defining the platinum response biomarkers for patients with mUC could establish personalize medicine and provide insights into mUC biology. Although DNA repair mechanisms have been hypothesized to mediate the platinum response, we sought to analyze whether increased expression of DNA damage genes would correlate with worse overall survival (OS) in patients with mUC. We retrospectively identified a clinically annotated cohort of patients with mUC, who had been treated with first-line platinum combination chemotherapy. A tissue microarray was constructed from formalin-fixed paraffin-embedded tissue from the primary tumor before treatment. Immunohistochemical analysis of the following DNA repair proteins was performed: ERCC1, RAD51, BRCA1/2, PAR, and PARP-1. Nuclear and cytoplasmic expression was analyzed using multispectral imaging. Nuclear staining was used for the survival analysis. Cox regression analysis was used to evaluate the associations between the percentage of positive nuclear staining and OS in multivariable analysis, controlling for known prognostic variables. In a cohort of 104 patients with mUC, a greater percentage of nuclear staining of ERCC1 (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.5-4.9; P = .0007), RAD51 (HR, 5.6; 95% CI, 1.7-18.3; P = .005), and PAR (HR, 2.2; 95% CI, 1.1-4.4; P = .026) was associated with worse OS. BRCA1, BRCA2, and PARP-1 expression was not associated with OS (P = .76, P = .38, and P = .09, respectively). A greater percentage of combined ERCC1 and RAD51 nuclear staining was strongly associated with worse OS (P = .005). A high percentage of nuclear staining of ERCC1, RAD51, and PAR, assessed by immunohistochemistry, correlated with worse OS for patients with mUC treated with first-line platinum combination chemotherapy, supporting the evidence of the DNA repair pathways' role in the prognosis of mUC. We also report new evidence that RAD51 and PAR might play a role in the platinum response. Additional prospective studies are required to determine the prognostic or predictive nature of these biomarkers in mUC. Copyright © 2015 Elsevier Inc. All rights reserved.

Glans size is an independent risk factor for urethroplasty complications after hypospadias repair.

PubMed

Bush, Nicol C; Villanueva, Carlos; Snodgrass, Warren

2015-12-01

We hypothesized small glans size could increase urethroplasty complications (UC) following hypospadias repair. To test this, we measured glans width at its widest point in consecutive patients with hypospadias, and following a protocol for surgical decision-making, we then assessed post-operative UC using pre-determined definitions. We now report analysis of glans size as a potential additional independent risk factor for UC after hypospadias repair. Consecutive prepubertal patients undergoing hypospadias repair (2009-2013) had maximum glans width measured using calipers (Fig. 1). There were no differences in surgical technique for urethroplasty or glansplasty in this series based on the measured size of the glans. Multivariate logistic regression analyzed UC (fistula, glans dehiscence, diverticulum, stricture and/or meatal stenosis) based on glans size while adjusting for patient age, meatus (distal or midshaft/proximal), type of repair (TIP, inlay, 2-stage), surgeon, and primary or reoperative repair. Glans size was analyzed as both a continuous and dichotomous variable, with small glans defined as <14 mm. Mean glans size was 15 mm (10-27 mm) in 490 boys (mean 1.5 years) undergoing 432 primary repairs (380d/19mid/33prox), and 58 reoperations (28d/7mid/23prox). Increasing age between 3 months and 10 years did not correlate with increasing glans size (R = 0.01, p = 0.18). 17% had small glans <14 mm. UC occurred in 61 (13%) primary TIP, 2-stage, and reoperative repairs, including 20/81 (25%) patients with small glans <14 mm, versus 41/409 (10%) in patients with glans width ≥14 mm (p = 0.0003). On multivariate analysis, small glans size (OR 3.5, 95% CI 1.8-6.8), reoperations (OR 3.0, 95% CI 1.4-6.5) and mid/proximal meatus (OR 3.1, 95% CI 1.6-6.2) were independent risk factors for UC. Surgeon, repair type, and patient age did not impact risk for UC. Analysis with glans size as a continuous variable demonstrated each 1 mm increase in size decreased odds of UC (OR 0.8, 95% CI 0.7-0.9). Our analysis of prospectively-collected data from a standardized management protocol in 490 consecutive boys undergoing hypospadias repair adds small glans size, defined as width <14 mm, to proximal meatal location and reoperation as an independent risk factor for UC. Best means to modify this factor remain to be determined. Our data suggest that others analyzing potential risks for hypospadias UC should similarly measure and report glans width. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Umbilical Cord Mesenchymal Stem Cell Treatment for Crohn’s Disease: A Randomized Controlled Clinical Trial

PubMed Central

Zhang, Jian; Lv, Samei; Liu, Xiaojing; Song, Bin; Shi, Liping

2018-01-01

Background/Aims Stem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn’s disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD. Methods Eighty-two patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months were included in this study. Forty-one patients were randomly selected to receive a total of four peripheral intravenous infusions of 1×106 UC-MSCs/kg, with one infusion per week. Patients were followed up for 12 months. The Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), and corticosteroid dosage were assessed. Results Twelve months after treatment, the CDAI, HBI, and corticosteroid dosage had decreased by 62.5±23.2, 3.4±1.2, and 4.2±0.84 mg/day, respectively, in the UC-MSC group and by 23.6±12.4, 1.2±0.58, and 1.2±0.35 mg/day, respectively, in the control group (p<0.01, p<0.05, and p<0.05 for UC-MSC vs control, respectively). Four patients developed a fever after cell infusion. No serious adverse events were observed. Conclusions UC-MSCs were effective in the treatment of CD and produced mild side effects. PMID:28873511

Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners.

PubMed

Bennett, A L; Buckton, S; Lawrance, I; Leong, R W; Moore, G; Andrews, J M

2015-12-01

Current models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non-specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed. © 2015 Royal Australasian College of Physicians.

Primary Care Provider Perceptions of the Effectiveness of Two Self-Management Support Programs for Vulnerable Patients with Diabetes

PubMed Central

Ratanawongsa, Neda; Bhandari, Vijay K; Handley, Margaret; Rundall, Thomas; Hammer, Hali; Schillinger, Dean

2012-01-01

Background Primary care providers (PCPs) in safety net settings face barriers to optimizing care for patients with diabetes. We conducted this study to assess PCPs' perspectives on the effectiveness of two language-concordant diabetes self-management support programs. Methods One year postintervention, we surveyed PCPs whose patients with diabetes participated in a three-arm multiclinic randomized controlled trial comparing usual care (UC), weekly automated telephone self-management (ATSM) support with nurse care management, and monthly group medical visits (GMVs). We compared PCP perspectives on patient activation to create and achieve goals, quality of care, and barriers to care using regression models accounting for within-PCP clustering. Results Of 113 eligible PCPs caring for 330 enrolled patients, 87 PCPs (77%) responded to surveys about 245 (74%) enrolled patients. Intervention patients were more likely to be perceived by PCPs as activated to create and achieve goals for chronic care when compared with UC patients (standardized effect size, ATSM vs UC, +0.41, p = 0.01; GMV vs UC, +0.31, p = 0.05). Primary care providers rated quality of care as higher for patients exposed to ATSM compared to UC (odds ratio 3.6, p < 0.01). Compared with GMV patients, ATSM patients were more likely to be perceived by PCPs as overcoming barriers related to limited English proficiency (82% ATSM vs 44% GMV, p = 0.01) and managing medications (80% ATSM vs 53% GMV, p = 0.01). Conclusions Primary care providers perceived that patients receiving ATSM support had overcome barriers, participated more actively, and received higher quality diabetes care. These views of clinician stakeholders lend additional evidence for the potential to upscale ATSM more broadly to support PCPs in their care of diverse, multilinguistic populations. PMID:22401329

Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study.

PubMed

Kopylov, Uri; Papamichael, Konstantinos; Katsanos, Konstantinos; Waterman, Matti; Bar-Gil Shitrit, Ariella; Boysen, Trine; Portela, Francisco; Peixoto, Armando; Szilagyi, Andrew; Silva, Marco; Maconi, Giovanni; Har-Noy, Ofir; Bossuyt, Peter; Mantzaris, Gerassimos; Barreiro de Acosta, Manuel; Chaparro, Maria; Christodoulou, Dimitrios K; Eliakim, Rami; Rahier, Jean-Francois; Magro, Fernando; Drobne, David; Ferrante, Marc; Sonnenberg, Elena; Siegmund, Britte; Muls, Vinciane; Thurm, Tamara; Yanai, Henit; Dotan, Iris; Raine, Tim; Levin, Avi; Israeli, Eran; Ghalim, Fahd; Carbonnel, Franck; Vermeire, Severine; Ben-Horin, Shomron; Roblin, Xavier

2017-09-01

Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Family partnership and education interventions to reduce dietary sodium by patients with heart failure differ by family functioning.

PubMed

Dunbar, Sandra B; Clark, Patricia C; Stamp, Kelly D; Reilly, Carolyn M; Gary, Rebecca A; Higgins, Melinda; Kaslow, Nadine

2016-01-01

Determine if family functioning influences response to family-focused interventions aimed at reducing dietary sodium by heart failure (HF) patients. Lowering dietary sodium by HF patients often occurs within the home and family context. Secondary analysis of 117 dyads randomized to patient and family education (PFE), family partnership intervention (FPI) or usual care (UC). Dietary sodium measures were obtained from 3-day food record and 24-h urine samples. In the poor family functioning groups, FPI and PFE had lower mean urine sodium than UC (p < .05) at 4 months, and FPI remained lower than UC at 8 months (p < .05). For good family functioning groups, FPI and PFE had lower mean sodium levels by 3-day food record at 4 and 8 months compared to the UC group. Optimizing family-focused interventions into HF clinical care maybe indicated. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of noninvasive evaluations in monitoring inflammatory bowel disease activity: A prospective study in China

PubMed Central

Chen, Jin-Min; Liu, Tao; Gao, Shan; Tong, Xu-Dong; Deng, Fei-Hong; Nie, Biao

2017-01-01

AIM To optimize the efficacy of noninvasive evaluations in monitoring the endoscopic activity of inflammatory bowel disease (IBD). METHODS Fecal calprotectin (FC), clinical activity index (CDAI or CAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) were measured for 136 IBD patients. Also, FC was measured in 25 irritable bowel syndrome (IBS) patients that served as controls. Then, endoscopic activity was determined by other two endoscopists for colonic or ileo-colonic Crohn’s disease (CICD) with the “simple endoscopic score for Crohn’s disease” (SES-CD), CD-related surgery patients with the Rutgeerts score, and ulcerative colitis (UC) with the Mayo score. The efficacies of these evaluations to predict the endoscopic disease activity were assessed by Mann-Whitney test, χ2 test, Spearman’s correlation, and multiple linear regression analysis. RESULTS The median FC levels in CD, UC, and IBS patients were 449.6 (IQR, 137.9-1344.8), 497.9 (IQR, 131.7-118.0), and 9.9 (IQR, 049.7) μg/g, respectively (P < 0.001). For FC, CDAI or CAI, CRP, and ESR differed significantly between endoscopic active and remission in CICD and UC patients, but not in CD-related surgery patients. The SES-CD correlated closely with levels of FC (r = 0.802), followed by CDAI (r = 0.734), CRP (r = 0.658), and ESR (r = 0.557). The Mayo score also correlated significantly with FC (r = 0.837), CAI (r = 0.776), ESR (r = 0.644), and CRP (r = 0.634). For FC, a cut-off value of 250 μg/g indicated endoscopic active inflammation with accuracies of 87.5%, 60%, and 91.1%, respectively, for CICD, CD-related surgery, and UC patients. Moreover, clinical FC activity (CFA) calculated as 0.8 × FC + 4.6 × CDAI showed higher area under the curve (AUC) of 0.962 for CICD and CFA calculated as 0.2 × FC + 50 × CAI showed higher AUC (0.980) for UC patients than the FC. Also, the diagnostic accuracy of FC in identifying patients with mucosal inflammation in clinical remission was reflected by an AUC of 0.91 for CICD and 0.96 for UC patients. CONCLUSION FC is the most promising noninvasive evaluation for monitoring the endoscopic activity of CICD and UC. CFA might be more accurate for IBD activity evaluation. PMID:29290660

Disease-specific Alterations in the Enteric Virome in Inflammatory Bowel Disease

PubMed Central

Norman, Jason M.; Handley, Scott A.; Baldridge, Megan T.; Droit, Lindsay; Liu, Catherine Y.; Keller, Brian C.; Kambal, Amal; Monaco, Cynthia L.; Zhao, Guoyan; Fleshner, Phillip; Stappenbeck, Thaddeus S.; McGovern, Dermot P.B.; Keshavarzian, Ali; Mutlu, Ece A.; Sauk, Jenny; Gevers, Dirk; Xavier, Ramnik J.; Wang, David; Parkes, Miles; Virgin, Herbert W.

2015-01-01

SUMMARY Decreases in the diversity of enteric bacterial populations are observed in patients with Crohn’s disease (CD) and ulcerative colitis (UC). Less is known about the virome in these diseases. We show that the enteric virome is abnormal in CD and UC patients. In-depth analysis of preparations enriched for free virions in the intestine revealed that CD and UC were associated with a significant expansion of Caudovirales bacteriophages. The viromes of CD and UC patients were disease- and cohort-specific. Importantly, it did not appear that expansion and diversification of the enteric virome was secondary to changes in bacterial populations. These data support a model in which changes in the virome may contribute to intestinal inflammation and bacterial dysbiosis. We conclude that the virome is a candidate for contributing to, or being a biomarker for, human inflammatory bowel disease and speculate that the enteric virome may play a role in other diseases. PMID:25619688

Specific immunotherapy ameliorates ulcerative colitis.

PubMed

Cai, Min; Zeng, Lu; Li, Lin-Jing; Mo, Li-Hua; Xie, Rui-Di; Feng, Bai-Sui; Zheng, Peng-Yuan; Liu, Zhi-Gang; Liu, Zhan-Ju; Yang, Ping-Chang

2016-01-01

Hypersensitivity reaction to certain allergens plays a role in the pathogenesis of inflammatory bowel disease (IBD). This study aims to observe the effect of specific immunotherapy in a group of IBD patients. Patients with both ulcerative colitis (UC) and food allergy were recruited into this study. Food allergy was diagnosed by skin prick test and serum specific IgE. The patients were treated with specific immunotherapy (SIT) and Clostridium butyricum (CB) capsules. After treating with SIT and CB, the clinical symptoms of UC were markedly suppressed as shown by reduced truncated Mayo scores and medication scores. The serum levels of specific IgE, interleukin (IL)-4 and tumor necrosis factor (TNF)-α were also suppressed. Treating with SIT alone or CB alone did not show appreciable improvement of the clinical symptoms of UC. UC with food allergy can be ameliorated by administration with SIT and butyrate-production probiotics.

Emerging role of immunotherapy in urothelial carcinoma-Future directions and novel therapies.

PubMed

Park, Jong Chul; Hahn, Noah M

2016-12-01

Tremendous advances in our understanding of the tumor immunology and molecular biology of urothelial carcinoma (UC) have led to the recent approval of immunotherapy as a novel option for patients with UC with advanced disease. Despite the promising data of novel immune checkpoint inhibitors, only a small subset of patients with UC achieves durable remissions. Because an optimal antitumor response requires coordination of multiple immune, tumor, and microenvironment effector cells, novel approaches targeting distinct mechanisms of action likely in combination are needed. In addition, discovery of reliable immune biomarkers, understanding of mechanisms of resistance, and novel clinical trial designs are warranted for maximum benefit of UC immunotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Gut microbiota differs between children with Inflammatory Bowel Disease and healthy siblings in taxonomic and functional composition: a metagenomic analysis.

PubMed

Knoll, Rebecca L; Forslund, Kristoffer; Kultima, Jens Roat; Meyer, Claudius U; Kullmer, Ulrike; Sunagawa, Shinichi; Bork, Peer; Gehring, Stephan

2017-04-01

Current treatment for pediatric inflammatory bowel disease (IBD) patients is often ineffective, with serious side effects. Manipulating the gut microbiota via fecal microbiota transplantation (FMT) is an emerging treatment approach but remains controversial. We aimed to assess the composition of the fecal microbiome through a comparison of pediatric IBD patients to their healthy siblings, evaluating risks and prospects for FMT in this setting. A case-control (sibling) study was conducted analyzing fecal samples of six children with Crohn's disease (CD), six children with ulcerative colitis (UC) and 12 healthy siblings by metagenomic sequencing. In addition, lifetime antibiotic intake was retrospectively determined. Species richness and diversity were significantly reduced in UC patients compared with control [Mann-Whitney U -test false discovery rate (MWU FDR) = 0.011]. In UC, bacteria positively influencing gut homeostasis, e.g., Eubacterium rectale and Faecalibacterium prausnitzii , were significantly reduced in abundance (MWU FDR = 0.05). Known pathobionts like Escherichia coli were enriched in UC patients (MWU FDR = 0.084). Moreover, E. coli abundance correlated positively with that of several virulence genes (SCC > 0.65, FDR < 0.1). A shift toward antibiotic-resistant taxa in both IBD groups distinguished them from controls [MWU Benjamini-Hochberg-Yekutieli procedure (BY) FDR = 0.062 in UC, MWU BY FDR = 0.019 in CD). The collected results confirm a microbial dysbiosis in pediatric UC, and to a lesser extent in CD patients, replicating associations found previously using different methods. Taken together, these observations suggest microbiotal remodeling therapy from family donors, at least for children with UC, as a viable option. NEW & NOTEWORTHY In this sibling study, prior reports of microbial dysbiosis in IBD patients from 16S rRNA sequencing was verified using deep shotgun sequencing and augmented with insights into the abundance of bacterial virulence genes and bacterial antibiotic resistance determinants, seen against the background of data on the specific antibiotic intake of each of the study participants. The observed dysbiosis, which distinguishes patients from siblings, highlights such siblings as potential donors for microbiotal remodeling therapy in IBD. Copyright © 2017 the American Physiological Society.

Intermittent granulocyte and monocyte apheresis versus mercaptopurine for maintaining remission of ulcerative colitis: a pilot study.

PubMed

Sakuraba, Atsushi; Sato, Toshiro; Morohoshi, Yuichi; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Takaishi, Hiromasa; Ogata, Haruhiko; Iwao, Yasushi; Hibi, Toshifumi

2012-06-01

The effect of granulocyte and monocyte adsorption apheresis (GMA) on prevention of relapse of ulcerative colitis (UC) is not clear. This was a pilot open-labeled, prospective, randomized, unblinded study to compare the tolerability and efficacy of intermittent GMA (once every 2 weeks) with mercaptopurine to maintain remission of UC. Twenty-one patients with UC, who had achieved remission by induction therapies were randomly assigned to receive either intermittent GMA (N = 10) or oral mercaptopurine (0.5 mg/kg per day; N = 11). The study period was 24 months. The rate of the patients maintaining remission and the incidences of adverse effects were compared between the two groups. At 24 months, seven of 10 patients (70.0%) on intermittent GMA and seven of 11 patients (63.6%, P = 1.00) on oral mercaptopurine were still in remission. Three patients relapsed in each group. One patient taking mercaptopurine, but none receiving intermittent GMA, dropped out because of adverse effects. Intermittent therapy with GMA was well tolerated and a substantial proportion of patients maintained remission. Intermittent GMA therapy in maintaining remission of UC merits further investigation. © 2012 The Authors. Therapeutic Apheresis and Dialysis © 2012 International Society for Apheresis.

Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis

PubMed Central

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Ibba-Manneschi, Lidia

2015-01-01

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin-embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility. PMID:25283476

Assessing health status in inflammatory bowel disease using a novel single-item numeric rating scale.

PubMed

Surti, Bijal; Spiegel, Brennan; Ippoliti, Andrew; Vasiliauskas, Eric A; Simpson, Peter; Shih, David Q; Targan, Stephan R; McGovern, Dermot P B; Melmed, Gil Y

2013-05-01

Current instruments used to measure disease activity and health-related quality of life in patients with Crohn's disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome that can capture the patient's overall perception of health. The aim of this study was to assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn's disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. The patient-reported NRS showed excellent correlation with CDAI (R (2) = 0.59, p < 0.0001), IBDQ (R (2) = 0.66, p < 0.0001), and HBI (R (2) = 0.32, p < 0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R (2) = 0.25, p < 0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

PubMed

Bank, S; Andersen, P S; Burisch, J; Pedersen, N; Roug, S; Galsgaard, J; Turino, S Y; Brodersen, J B; Rashid, S; Rasmussen, B K; Avlund, S; Olesen, T B; Hoffmann, H J; Nexø, B A; Sode, J; Vogel, U; Andersen, V

2018-01-01

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.

Overweight and obesity in children with newly diagnosed inflammatory bowel disease.

PubMed

Pituch-Zdanowska, Aleksandra; Banaszkiewicz, Aleksandra; Dziekiewicz, Marcin; Łazowska-Przeorek, Izabella; Gawrońska, Agnieszka; Kowalska-Duplaga, Kinga; Iwańczak, Barbara; Klincewicz, Beata; Grzybowska-Chlebowczyk, Urszula; Walkowiak, Jarosław; Albrecht, Piotr

2016-03-01

Determination of overweight and obesity prevalence in children with inflammatory bowel disease (IBD) at the time of diagnosis. This was a multicenter retrospective study. The study group consisted of children with new cases of IBD diagnosed in 2005-2013 according to the Porto criteria. Hospital admission records were reviewed for demographic and clinical characteristics. BMI-for-age and gender percentile charts were used to define overweight as ≥85th BMI percentile and obesity as ≥95th BMI percentile. 675 patients were evaluated: 368 with Crohn's disease (CD) and 307 with ulcerative colitis (UC). Of these, 54.8% were boys and 45.2% were girls. There were no statistically significant differences in age, weight, height and disease activity between the CD and UC patients. The UC patients had higher BMI values than the CD patients. The prevalence of overweight and obesity was higher in the UC than the CD patients (4.89% CI95 2.76-7.93 vs. 2.45% CI95 1.12-4.59 and 8.47% CI95 5.61-12.16 vs. 1.9% CI95 0.77-3.88, respectively); the differences were statistically significant (-2.44% CI95 -5.45 to 0.49 and -6.57% CI95 -10 to -3.1, respectively). The risk of overweight/obesity was 3.5 times higher for patients with UC (OR=0.272, CI95 0.14-0.49, p=0.0004). The prevalence of overweight and obesity in newly diagnosed children with IBD was 8.4% and was higher in patients with UC than in patients with CD. The results of this study have shown that not only malnourished children may suffer from IBD but also children who are overweight or obese at the time of diagnosis. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[Multicentric prospective randomized and controlled study assessing effectiveness of intravaginal electrostimulation at home compared to usual care in female patients with urinary incontinence and prior perineal reeducation].

PubMed

Lopès, P; Rimbault, F; Scheffler, M; André, C; Cappelletti, M-C; Marès, P

2014-11-01

In order to maintain the benefits of perineal reeducation, patients with stress urinary incontinence need to perform self-retraining exercises of the perineal muscles at home. The aim of this randomized prospective multicentric study is to assess the effectiveness of GYNEFFIK(®), a perineal electrostimulator, during this home-care phase. Two parallel groups of women with stress urinary incontinence (UI) or with mixed UI (composed predominantly of stress UI), improved by physiotherapy, have followed a self-reeducation program, either with electrostimulation sessions (GYNEFFIK(®) or home perineal electrostimulation [HPES] arm) or with usual care (UC) only, without electrostimulation. The comparison of the two groups was based on the rate of women in which the benefit of the initial perineal reeducation was maintained (defined as the ICIQ and Ditrovie scales' score not worsening) at 2, 4 and 6 months. A total of 161 patients were analyzed (76 in the HPES arm and 85 in the UC arm). The therapeutic benefit of the initial perineal reeducation at the last available measure (6 months for a wide majority of patients) was maintained in 81.6% in the HPES arm versus 62.4% in the UC arm (P=0.007). This significant difference reflects a significant improvement both in clinical symptomatology and in quality of life. ICIQ score was improved in 44% of patients of HPES arm while it was improved in 14% of patients of UC arm (P<0.001) and daily number of urine leakage decreased of 1.2 leakage in the HPES arm versus 0.1 leakage in UC arm (P<0.05). Likewise, improvement of quality of life was superior in the HPES arm (48% improvement of Ditrovie score versus 19% in the UC group ; P<0.05). Investigator global impression was more favorable in the HPES arm (clinical improvement in 83% of patients versus 68% in the UC arm). At the last measure (i.e. endpoint), the benefit of initial physiotherapy was considered maintained or improved in all patients of the HPES arm while it was reported as worsened in 16.5% of the UC group. Using GYNEFFIK(®) favorably impacts quality of life, particularly physical activity and vitality and decreases emotional consequences of UI (i.e. anxiety and depression score as assessed by HAD scale). Copyright © 2014 Elsevier Masson SAS. All rights reserved.

When should ulcerative colitis patients undergo colectomy for dysplasia? Mismatch between patient preferences and physician recommendations.

PubMed

Siegel, Corey A; Schwartz, Lisa M; Woloshin, Steven; Cole, Elisabeth B; Rubin, David T; Vay, Tegan; Baars, Judith; Sands, Bruce E

2010-10-01

If dysplasia is found on biopsies during surveillance colonoscopy for ulcerative colitis (UC), many experts recommend colectomy given the substantial risk of synchronous colon cancer. The objective was to learn if UC patients' perceptions of their colon cancer risk and if their preferences for elective colectomy match with physicians' recommendations if dysplasia was found. A self-administered written survey included 199 patients with UC for at least 8 years (mean age 49 years, 52% female) who were recruited from Dartmouth-Hitchcock (n = 104) and the University of Chicago (n = 95). The main outcome was the proportion of patients who disagree with physicians' recommendations for colectomy because of dysplasia. Almost all respondents recognized that UC raised their chance of getting colon cancer. In all, 74% thought it was "unlikely" or "very unlikely" to get colon cancer within the next 10 years and they quantified this risk to be 23%; 60% of patients would refuse a physician's recommendation for elective colectomy if dysplasia was detected, despite being told that they had a 20% risk of having cancer now. On average, these patients would only agree to colectomy if their risk of colon cancer "right now" were at least 73%. UC patients recognize their increased risk of colon cancer and undergo frequent surveillance to reduce their risk. Nonetheless, few seem prepared to follow standard recommendations for elective colectomy if dysplasia is found. This may reflect the belief that surveillance alone is sufficient to reduce their colon cancer risk or genuine disagreement about when it is worth undergoing colectomy.

Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus: Systematic Review and Meta-analysis.

PubMed

Shukla, Tushar; Singh, Siddharth; Loftus, Edward V; Bruining, David H; McCurdy, Jeffrey D

2015-11-01

The role of antiviral therapy in patients with ulcerative colitis (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a systematic review and meta-analysis to assess the association between antiviral therapy and the risk of colectomy. Multiple electronic databases were searched systematically through July 2014 for studies reporting the risk of colectomy in patients with UC with CMV stratified by treatment with antiviral agents. Colectomy rates were assessed for the overall cohort and stratified by corticosteroid (CS) refractoriness. We estimated summary odds ratios and 95% confidence intervals, using random-effects model, and used Grading of Recommendations Assessment, Development, and Evaluation criteria to appraise the quality of evidence. Fifteen observational studies (333 patients with UC with CMV, 43.2% treated with antiviral agents) were identified, of which 8 stratified patients according to CS-refractory disease (55.4% treated with antiviral agents). Antiviral therapy resulted in a significantly lower risk of colectomy in patients with CS-refractory disease (odds ratio, 0.20; 95% confidence interval, 0.08-0.49; I = 0%) but not in the overall population of patients with UC (odds ratio, 0.92; 95% confidence interval, 0.31-2.76; I = 65). The quality evidence was low. The results were stable when restricting the analysis to patients with a tissue diagnosis of CMV and studies that defined CS-refractory disease as a failure to respond to intravenous CS. Antiviral therapy may benefit a subgroup of patients with UC who are refractory to CS. Further prospective trials are required to confirm these findings.

Using optical markers of nondysplastic rectal epithelial cells to identify patients with ulcerative colitis-associated neoplasia.

PubMed

Bista, Rajan K; Brentnall, Teresa A; Bronner, Mary P; Langmead, Christopher J; Brand, Randall E; Liu, Yang

2011-12-01

Current surveillance guidelines for patients with long-standing ulcerative colitis (UC) recommend repeated colonoscopy with random biopsies, which is time-consuming, discomforting, and expensive. A less invasive strategy is to identify neoplasia by analyzing biomarkers from the more accessible rectum to predict the need for a full colonoscopy. The goal of this pilot study was to evaluate whether optical markers of rectal mucosa derived from a novel optical technique, partial-wave spectroscopic microscopy (PWS), could identify UC patients with high-grade dysplasia (HGD) or cancer (CA) present anywhere in their colon. Banked frozen nondysplastic mucosal rectal biopsies were used from 28 UC patients (15 without dysplasia and 13 with concurrent HGD or CA). The specimen slides were made using a touch prep method and underwent PWS analysis. We divided the patients into two groups: 13 as a training set and an independent 15 as a validation set. We identified six optical markers, ranked by measuring the information gain with respect to the outcome of cancer. The most effective markers were selected by maximizing the cross-validated training accuracy of a Naive Bayes classifier. The optimal classifier was applied to the validation data yielding 100% sensitivity and 75% specificity. Our results indicate that the PWS-derived optical markers can accurately predict UC patients with HGD/CA through assessment of rectal epithelial cells. By aiming for high sensitivity, our approach could potentially simplify the surveillance of UC patients and improve overall resource utilization by identifying patients with HGD/CA who should proceed with colonoscopy. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Health literacy in the urgent care setting: What factors impact consumer comprehension of health information?

PubMed

Alberti, Traci L; Morris, Nancy J

2017-05-01

An increasing number of Americans are using urgent care (UC) clinics due to: improved health insurance coverage, the need to decrease cost, primary care offices with limited appointment availability, and a desire for convenient care. Patients are treated by providers they may not know for episodic illness or injuries while in pain or not feeling well. Treatment instructions and follow-up directions are provided quickly. To examine health literacy in the adult UC population and identify patient characteristics associated with health literacy risk. As part of a larger cross-sectional study, UC patients seen between October 2013 and January 2014 completed a demographic questionnaire and the Newest Vital Sign. Descriptive, nonparametric analyses, and a multinomial logistic regression were done to assess health literacy, associated and predictive factors. A total of 57.5% of 285 participants had adequate health literacy. The likelihood of limited health literacy was associated with increased age (p < .001), less education (p < .001), and lower income (p = .006). Limited health literacy is common in a suburban UC setting, increasing the risk that consumers may not understand vital health information. Clear provider communication and confirmation of comprehension of discharge instructions for self-management is essential to optimize outcomes for UC patients. ©2017 American Association of Nurse Practitioners.

Differential expression of GPR15 on T cells during ulcerative colitis

PubMed Central

Adamczyk, Alexandra; Gageik, Daniel; Frede, Annika; Pastille, Eva; Hansen, Wiebke; Rueffer, Andreas; Buer, Jan; Büning, Jürgen; Langhorst, Jost

2017-01-01

G protein–coupled receptor 15 (GPR15) was recently highlighted as a colon-homing receptor for murine and human CD4+ T cells. The aim of this study was to explore the functional phenotype of human GPR15+CD4+ T cells, focusing on Tregs and effector T cells (Teffs), and to determine whether GPR15 is the driver for the migration of T cells to the colon during ulcerative colitis (UC). In the peripheral blood, GPR15 was expressed on Tregs and Teffs; both GPR15+ T cell subsets produced less IFN-γ and IL-4 but more IL-17 after stimulation and showed a higher migration activity compared with GPR15–CD4+ T cells. In UC patients, GPR15 expression was increased on Tregs in the peripheral blood but not on Teffs. Interestingly, the expression of GPR15 was significantly enhanced on colonic T cells of UC patients in noninflamed biopsies but not in inflamed biopsies. The differential expression of GPR15 in UC patients was accompanied by a significant reduction of bacterial immunoregulatory metabolites in the feces. In conclusion, GPR15 expression on CD4+ T cells is altered in UC patients, which may have implications for the development of therapeutic approaches to target T cell trafficking to the colon. PMID:28422750

Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

PubMed Central

Tanida, Satoshi; Mizoshita, Tsutomu; Ozeki, Keiji; Katano, Takahito; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

2015-01-01

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis (UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-2, and the cell-surface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues (azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody (vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin (ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease (IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment. PMID:26269667

Fecal level of calprotectin identifies histologic inflammation in patients with ulcerative colitis in clinical and endoscopic remission.

PubMed

Guardiola, Jordi; Lobatón, Triana; Rodríguez-Alonso, Lorena; Ruiz-Cerulla, Alexandra; Arajol, Claudia; Loayza, Carolina; Sanjuan, Xavier; Sánchez, Elena; Rodríguez-Moranta, Francisco

2014-11-01

Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136-696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30-172 μg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Assessing Health Status in Inflammatory Bowel Disease using a Novel Single-Item Numeric Rating Scale

PubMed Central

Surti, Bijal; Spiegel, Brennan; Ippoliti, Andrew; Vasiliauskas, Eric; Simpson, Peter; Shih, David; Targan, Stephan; McGovern, Dermot; Melmed, Gil Y.

2014-01-01

Background Current instruments used to measure disease activity and health-related quality of life (HRQOL) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome (PRO) that can capture the patient’s overall perception of health. Aims To assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC. Methods We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC. Results The patient-reported NRS showed excellent correlation with CDAI (R2=0.59, p<0.0001), IBDQ (R2=0.66, p<0.0001), and HBI (R2=0.32, p<0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R2=0.25, p<0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change. Conclusions The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC. PMID:23250673

Effects of behavioral therapy on weight loss in overweight and obese patients with schizophrenia or schizoaffective disorder.

PubMed

Brar, Jaspreet S; Ganguli, Rohan; Pandina, Gahan; Turkoz, Ibrahim; Berry, Sally; Mahmoud, Ramy

2005-02-01

Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). BT may be an effective method for weight reduction in patients with chronic psychotic illness.

Occurrence of Anaemia in the First Year of Inflammatory Bowel Disease in a European Population-based Inception Cohort-An ECCO-EpiCom Study.

PubMed

Burisch, Johan; Vegh, Zsuzsanna; Katsanos, Konstantinnos H; Christodoulou, Dimitrios K; Lazar, Daniela; Goldis, Adrian; O'Morain, Colm; Fernandez, Alberto; Pereira, Santos; Myers, Sally; Sebastian, Shaji; Pedersen, Natalia; Olse, Jóngerð; Rubek Nielsen, Kári; Schwartz, Doron; Odes, Selwyn; Almer, Sven; Halfvarson, Jonas; Turk, Niksa; Cukovic-Cavka, Silvja; Nikulina, Inna; Belousova, Elena; Duricova, Dana; Bortlik, Martin; Shonová, Olga; Salupere, Riina; Barros, Louisa; Magro, Fernando; Jonaitis, Laimas; Kupcinskas, Limas; Turcan, Svetlana; Kaimakliotis, Ioannis; Ladefoged, Karin; Kudsk, Karen; Andersen, Vibeke; Vind, Ida; Thorsgaard, Niels; Oksanen, Pia; Collin, Pekka; Dal Piaz, Giulia; Santini, Alessia; Niewiadomski, Ola; Bell, Sally; Moum, Bjørn; Arebi, Naila; Kjeldsen, Jens; Carlsen, Katrine; Langholz, Ebbe; Lakatos, Peter Laszlo; Munkholm, Pia; Gerdes, Lars Ulrik; Dahlerup, Jens Frederik

2017-10-01

Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort. Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria. A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed. Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study.

PubMed

Wada, Yasuyo; Hisamatsu, Tadakazu; Naganuma, Makoto; Matsuoka, Katsuyoshi; Okamoto, Susumu; Inoue, Nagamu; Yajima, Tomoharu; Kouyama, Keisuke; Iwao, Yasushi; Ogata, Haruhiko; Hibi, Toshifumi; Abe, Takayuki; Kanai, Takanori

2015-12-01

Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers.

PubMed

Noguchi, Masanori; Koga, Noriko; Moriya, Fukuko; Suekane, Shigetaka; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Kakuma, Tatuyuki; Itoh, Kyogo

2018-06-25

Peptide-based cancer vaccines are able to induce strong immune responses, but their clinical results are unsatisfactory. To determine clinically correlated peptides, we analyzed survival data from urological cancer patients treated by personalized peptide vaccination (PPV), in which different multiple peptides were used for individual patients based on human leukocyte antigen (HLA) type and pre-existing immunity. Survival data were obtained from a database of 265 urological cancer patients treated in 5 clinical PPV trials comprising 154 patients with castration-resistant prostate cancer (CRPC) and 111 patients with advanced urothelial cancer (UC). The expression of tumor-associated antigens (TAAs) was evaluated in 10 prostate cancer tissues, 4 metastatic lymph nodes from prostate cancer and 10 UC tissues using immunohistochemical staining. The clinical efficacy of individual peptides for overall survival was evaluated by the Cox proportional hazards regression model. All TAAs coding candidate peptides used in PPV treatment were expressed in tumor cells from prostate cancer and UC samples except for p56Lck in both, and PSA, PAP and PSMA in the UC samples. Patients with the following peptides had a significantly longer survival than patients without the peptides (Hazard ratio < 1.0, 95% confidence intervals < 1.0 and P < 0.05): SART3-109, PTHrP-102, HNPRL-140, SART3-302 and Lck-90 in CRPC patients, and EGF-R-800, Lck-486, PSMA-624, CypB-129 and SART3-734 in advanced UC patients, respectively. Correlated peptides selected using both survival data and pre-existing immunity for PPV treatment may enhance the clinical benefits for urological cancer patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessment of Histological Remission in Ulcerative Colitis: Discrepancies Between Daily Practice and Expert Opinion.

PubMed

Römkens, Tessa E H; Kranenburg, Pim; Tilburg, Arjan van; Bronkhorst, Carolien; Nagtegaal, Iris D; Drenth, Joost P H; Hoentjen, Frank

2018-03-28

Histological remission [HR] is a potential treatment target in ulcerative colitis [UC]. Limited 'real world' data are available on the reliability of histological scoring when assessing minimal histological inflammation. The aim of this study was to investigate the reliability of UC histological scores in colonic biopsies showing mucosal healing [MH] and limited histological inflammation, and to compare the 'daily practice' histological assessment with expert reviews by gastrointestinal [GI] pathologists. We performed a retrospective single-centre study. Colonic biopsies from UC patients with MH [Mayo score ≤ 1] were included. All biopsies assessed in daily practice were reassessed by three blinded GI pathologists using three histological scores (Geboes score [GS], Riley score [RS], Harpaz [Gupta] Index [HGI]) and a global visual scale [GVS]. We evaluated inter- and intra-observer variation between GI pathologists and correlations between scores including the initial histological assessment using Cronbach's alpha and Spearman rho analysis. In total, 270 biopsies from 39 UC patients were included. The inter-observer concordance for all histological indexes was substantial to almost perfect [GS 0.84; HGI 0.61; GVS 0.74, RS 0.91]. Correlation between the RS and GS was almost perfect [R = 0.86], but we found no correlation between the primary histological assessment and reassessment by GI pathologists. Current UC histological scores reliably assess limited histological inflammation in UC patients. The discrepancy between the initial histological assessment and the reassessment by dedicated GI pathologists suggests a gap between daily practice and academic expertise. This issue may limit the implementation of HR as a treatment target for UC in daily practice.

Clinical epidemiology of ulcerative colitis in Mexico: a single hospital-based study in a 20-year period (1987-2006).

PubMed

Yamamoto-Furusho, Jesús K

2009-03-01

Ulcerative colitis (UC) is a chronic disease with a heterogeneous clinical evolution. The prevalence and incidence of UC vary widely and depend on multiple factors including ethnicity and geographic location. To determine the frequency of new cases of UC and their clinical characteristics in a large cohort from a referral hospital in Mexico City. Patients with confirmed diagnosis of UC were included during a period between January 1987 and December 2006. Demographic and clinical data were collected from medical records. A total of 848 new cases of UC were diagnosed during a 20-year period. All the patients had endoscopic and histologic confirmation. The mean of annual new UC cases increased from 28.8 in the first period (1987 to 1996) to 76.1 in the second period (1997 to 2006) (P<0.00008). The incidence of new cases increased 2.6-fold comparing both periods of time. This study consisted of 467 females and 382 males, with a mean age at diagnosis of 31.3+/-12.3 years. The clinical manifestations were pancolitis (59.1%), and extraintestinal manifestations (41.5%). Most of the patients, 762 (89.8%) were taking sulfasalazine or 5-aminosalicylic acid, 282 (33.3%) used oral or systemic steroids, 237 (28%) were taking azathioprine. The frequency of new UC cases has increased significantly in the last 10 years in Mexico, largely due to the unique genetic make-up and the environmental factors (infectious diseases including parasites) not found in other countries.

Endoscopy-coupled Raman spectroscopy for in vivo discrimination of inflammatory bowel disease

NASA Astrophysics Data System (ADS)

Pence, I. J.; Nguyen, Q. T.; Bi, X.; Herline, A. J.; Beaulieu, D. M.; Horst, S. N.; Schwartz, D. A.; Mahadevan-Jansen, A.

2014-03-01

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's colitis (CC), affects nearly 2 million Americans, and the incidence is increasing worldwide. It has been established that UC and CC are distinct forms of IBD and require different medical care, however the distinction made between UC and CC is based upon inexact clinical, radiological, endoscopic, and pathologic features. A diagnosis of indeterminate colitis occurs in up to 15% of patients when UC and CC features overlap and cannot be differentiated; in these patients, diagnosis relies on long term followup, success or failure of existing treatment, and recurrence of the disease. Thus, there is need for a tool that can improve the sensitivity and specificity for fast, accurate and automated diagnosis of IBD. Here we present colonoscopy-coupled fiber probe-based Raman spectroscopy as a novel in vivo diagnostic tool for IBD. This in vivo study of both healthy control (NC, N=10) and diagnosed IBD patients with UC (N=15) and CC (N=26) aims to characterize spectral signatures of NC, UC, and CC. Samples are correlated with tissue pathology markers and endoscopic evaluation. Optimal collection parameters for detection have been identified based upon the new, application specific instrument design. The collected spectra are processed and analyzed using multivariate statistical techniques to identify spectral markers and discriminate NC, UC, and CC. Development of spectral markers to discriminate disease type is a necessary first step in the development of real-time, accurate and automated in vivo detection of IBD during colonoscopy procedures.

Colectomy is a risk factor for venous thromboembolism in ulcerative colitis.

PubMed

Kaplan, Gilaad G; Lim, Allen; Seow, Cynthia H; Moran, Gordon W; Ghosh, Subrata; Leung, Yvette; Debruyn, Jennifer; Nguyen, Geoffrey C; Hubbard, James; Panaccione, Remo

2015-01-28

To compare venous thromboembolism (VTE) in hospitalized ulcerative colitis (UC) patients who respond to medical management to patients requiring colectomy. Population-based surveillance from 1997 to 2009 was used to identify all adults admitted to hospital for a flare of UC and those patients who underwent colectomy. All medical charts were reviewed to confirm the diagnosis and extract clinically relevant information. UC patients were stratified by: (1) responsive to inpatient medical therapy (n=382); (2) medically refractory requiring emergent colectomy (n=309); and (3) elective colectomy (n=329). The primary outcome was the development of VTE during hospitalization or within 6 mo of discharge. Heparin prophylaxis to prevent VTE was assessed. Logistic regression analysis determined the effect of disease course (i.e., responsive to medical therapy, medically refractory, and elective colectomy) on VTE after adjusting for confounders including age, sex, smoking, disease activity, comorbidities, extent of disease, and IBD medications (i.e., corticosteroids, mesalamine, azathioprine, and infliximab). Point estimates were presented as odds ratios (OR) with 95%CI. The prevalence of VTE among patients with UC who responded to medical therapy was 1.3% and only 16% of these patients received heparin prophylaxis. In contrast, VTE was higher among patients who underwent an emergent (8.7%) and elective (4.9%) colectomy, despite greater than 90% of patients receiving postoperative heparin prophylaxis. The most common site of VTE was intra-abdominal (45.8%) followed by lower extremity (19.6%). VTE was diagnosed after discharge from hospital in 16.7% of cases. Elective (adjusted OR=3.69; 95%CI: 1.30-10.44) and emergent colectomy (adjusted OR=5.28; 95%CI: 1.93-14.45) were significant risk factors for VTE as compared to medically responsive UC patients. Furthermore, the odds of a VTE significantly increased across time (adjusted OR=1.10; 95%CI: 1.01-1.20). Age, sex, comorbidities, disease extent, disease activity, smoking, corticosteroids, mesalamine, azathioprine, and infliximab were not independently associated with the development of VTE. VTE was associated with colectomy, particularly, among UC patients who failed medical management. VTE prophylaxis may not be sufficient to prevent VTE in patients undergoing colectomy.

Abdominal pain and the neurotrophic system in ulcerative colitis.

PubMed

Deberry, Jennifer J; Bielefeldt, Klaus; Davis, Brian M; Szigethy, Eva M; Hartman, Douglas J; Coates, Matthew D

2014-12-01

We undertook a study to test the hypothesis that inflammation alters peripheral sensory mechanisms, thereby contributing to chronic abdominal pain in ulcerative colitis (UC). Patients with UC and healthy individuals rated abdominal pain using a visual analog scale and completed surveys describing anxiety or depression (Hospital Anxiety and Depression Score) and gastrointestinal symptoms (Rome III questionnaire). Patient age, sex, and severity of inflammation were determined. Rectal biopsies were processed using immunohistochemical techniques to assess nerve fiber density and real-time PCR to determine transcript expression of neurotrophins (nerve growth factor, glial cell-derived neurotrophic factor, artemin, neurturin), ion channels (transient receptor potential vanilloid type 1, transient receptor potential ankyrin 1) and inflammatory mediators (tumor necrosis factor-α, interleukin [IL]-1β, IL-6, IL-10, IL-17). A total of 77 patients with UC (27 female, 50 male) and 21 controls (10 female, 11 male) were enrolled. Patients with UC with pain had significantly higher depression scores than controls and patients with UC without pain (P < 0.05). There was no correlation between any of the inflammatory markers and pain scores. Visual analog scale pain scores significantly correlated with younger age, higher depression scores, increased expression of neurturin and decreased expression of transient receptor potential ankyrin 1 in the mucosa. Mucosal nerve fiber density did not correlate with any measures of inflammation or pain. Only higher depression scores independently predicted pain in UC (r > 0.5). We did not observe changes in mucosal innervation and did not see a significant relationship between nerve fiber density, inflammatory mediators, neurotrophic factors, or mucosal ion channel expression and pain. In contrast, the importance of depression as the only independent predictor of pain ratings mirrors functional disorders, where central processes significantly contribute to symptom development and/or perpetuation.

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis.

PubMed

Zhu, Mingming; Xu, Xitao; Nie, Fang; Tong, Jinlu; Xiao, Shudong; Ran, Zhihua

2011-08-01

The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC. All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials. Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60-5.18) and remission rate (OR, 2.04; 95% CI, 1.36-3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44-31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22-29.90). The incidence of mild-moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04-0.60). Few severe adverse events were observed. Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.

Brief strategic therapy in first myocardial infarction patients with increased levels of stress: a randomized clinical trial.

PubMed

Rakowska, Jadwiga Małgorzata

2015-01-01

Little is known about the impact of interventions targeting chronic stress levels on clinical outcomes among myocardial infarction (MI) patients with increased levels of stress. To examine the impact of the addition of brief strategic therapy (BST) to usual care (UC) on clinical outcomes in first MI patients with increased levels of stress. Eighty-one patients were randomly assigned to BST in conjunction with UC (medical treatment, risk factor information, and guidance on unhealthy behavior change) or to UC. The outcome measures were scores on the Perceived Stress Scale, reinfarction and cardiac mortality rates, and scores on the Health Survey. Measures were taken before, post-treatment, and at two follow-ups. Patients subjected to BST showed reduced perceived stress at post-treatment and maintained decreased levels at follow-ups. At 1-year follow-up, they had a lower rate of non-fatal reinfarction, and at 2.5-year follow-up, they had a lower rate of fatal reinfarction. Their mental and physical health was improved at post-treatment and this was sustained at follow-ups. The addition of BST to UC favorably influences the disease course after MI in patients with increased levels of stress.

Coexistence of ulcerative colitis and Sjögren's syndrome in a patient with Takayasu's arteritis and Hashimoto's thyroiditis.

PubMed

Park, Hyun Woo; Lee, Hyun Seok; Hwang, Sejin; Lee, Han Sol; Bae, Han-Ik; Yoon, Ghilsuk

2017-04-01

A 31-year-old woman with a 15-year history of Takayasu's arteritis (TA) and a 13-year history of Hashimoto's thyroiditis presented with hematochezia. She received a diagnosis of Sjögren's syndrome at 1 month before her visit to Kyungpook National University Medical Center. Her colonoscopic findings were compatible with a diagnosis of ulcerative colitis (UC). She was treated with oral mesalazine, and her hematochezia symptoms subsequently disappeared. The coexistence of UC and TA has been reported; however, reports on the coexistence of UC and Sjögren's syndrome, or of UC and Hashimoto's thyroiditis are rare. Although the precise etiologies of these diseases are unknown, their presence together suggests that they may have a common pathophysiologic background. Furthermore, in patients with autoimmune or vascular diseases, including TA, systemic manifestations should be assessed with consideration of inflammatory bowel diseases including UC in the presence of gastrointestinal symptoms such as diarrhea and hematochezia.

Counseling African Americans to Control Hypertension: cluster-randomized clinical trial main effects.

PubMed

Ogedegbe, Gbenga; Tobin, Jonathan N; Fernandez, Senaida; Cassells, Andrea; Diaz-Gloster, Marleny; Khalida, Chamanara; Pickering, Thomas; Schwartz, Joseph E

2014-05-20

Data are limited on the implementation of evidence-based multilevel interventions targeted at blood pressure (BP) control in hypertensive blacks who receive care in low-resource primary care practices. Counseling African Americans to Control Hypertension is a cluster-randomized clinical trial in which 30 community health centers were randomly assigned to the intervention condition (IC) or usual care (UC). Patients at the IC sites received patient education, home BP monitoring, and monthly lifestyle counseling, whereas physicians attended monthly hypertension case rounds and received feedback on their patients' home BP readings and chart audits. Patients and physicians at the UC sites received printed patient education material and hypertension treatment guidelines, respectively. The primary outcome was BP control, and secondary outcomes were mean changes in systolic and diastolic BPs at 12 months, assessed with an automated BP device. A total of 1059 patients (mean age, 56 years; 28% men, 59% obese, and 36% with diabetes mellitus) were enrolled. The BP control rate was similar in both groups (IC=49.3% versus UC=44.5%; odds ratio, 1.21 [95% confidence interval, 0.90-1.63]; P=0.21). In prespecified subgroup analyses, the intervention was associated with greater BP control in patients without diabetes mellitus (IC=54.0% versus UC=44.7%; odds ratio, 1.45 [confidence interval, 1.02-2.06]); and small-sized community health centers (IC=51.1% versus UC=39.6%; odds ratio, 1.45 [confidence interval, 1.04-2.45]). A practice-based, multicomponent intervention was no better than UC in improving BP control among hypertensive blacks. Future research on the implementation of behavioral modification strategies for hypertension control in low-resource settings should focus on the development of more efficient and tailored interventions in this high-risk population. http://www.clinicaltrials.gov. Unique identifier: NCT00233220. © 2014 American Heart Association, Inc.

Mucosal barrier in ulcerative colitis and Crohn's disease.

PubMed

Dorofeyev, A E; Vasilenko, I V; Rassokhina, O A; Kondratiuk, R B

2013-01-01

Background. The mucus layer in the gastrointestinal tract plays important role in host innate defense, regulation of secretion, and absorption processes, maintaining colonization resistance, which composes the integrity of protective mucus barrier in the large intestine. Investigations of mucin expression in the colon mucosa can improve the understanding of protective function of mucosal barrier in ulcerative colitis (UC) and Crohn's disease (CD). Materials and Methods. 77 patients with UC and CD were examined. Histological analysis of colon mucosa was done by standard method (haematoxylin-eosin, alcian blue at pH 1.0 and 2.5 to determine sulfated and nonsulfated glycosaminoglycans and glycoproteins, and goblet cells). To characterize the mucus production the PAS-reaction was performed. Immunohistochemistry was performed using monoclonal mouse antibodies raised against MUC2, MUC3, MUC4, and TFF3 (USBiological, USA). Results. The moderate expression of MUC2 and MUC3 (50.0% and 32.1%, P = 0.03) and high expression of MUC4 and TFF3 in the colon mucosa were observed in all patients with CD. The intensive labeling of MUC4 and TFF3 occurred more often (42.9% and 57.1%, P = 0.03) in patients with CD. The level of expression of secretory MUC2 and transmembrane MUC3 and MUC4 in all patients with UC was low, up to its complete absence (59.2% and 53.1% cases, P = 0.05). TFF3 expression had high and medium staining intensity in patients with UC. Conclusions. Different types of mucins synthesis, secretion, and expression were found in patients with UC and CD. The expression of mucin MUC2, MUC3, MUC4, and TFF3 correlated with the activity of disease and the extent of the inflammatory process in the large intestine. The most pronounced alteration of mucins expression was observed in patients with severe UC and CD.

[Catalase gene rs1001179 polymorphism and oxidative stress in patients with chronic hepatitis C and ulcerative colitis].

PubMed

Bulatova, I A; Tretyakova, Yu I; Shchekotov, V V; Shchekotova, A P; Ulitina, P V; Krivtsov, A V; Nenasheva, O Yu

2015-01-01

To study the rs1001179 polymorphism of the catalase (CAT) gene and to estimate the serum levels of the enzymes catalase and glutathione peroxidase (GP) in patients with chronic hepatitis C (CHC) and in those with ulcerative colitis (UC) in the Perm Territory. Ninety patients with reactivation-phase CHC and 50 patients with exacerbation-phase UC were examined. The serum levels of catalase and GP were determined and the polymorphic variants of the marker of CAT gene rs1001179 in the DNA isolated from whole blood were found in all the patients. In the CHC and UC groups, the levels of catalase and GP were found to be lower than that in apparently healthy individuals. Furthermore, both groups showed a direct correlation between the activities of the enzymes. In the patients with CHC and in those with UC, the spread of genotypes and alleles generally failed to virtually differ from that in the control group. The G/G genotype was prevalent in all the groups. In the patients with CHC, the minor A allele demonstrated a significant inverse correlation with the enzyme catalase (r = -0.16; p = 0.02) and GP (r = -0.13; p = 0.047). The lower serum levels of catalase and GP are indicative of oxidative stress in the patients with CHC or UC. In the patients with CHC, the significant correlation of the pathological rs1701179 A allele marker with the processes of synthesis of antioxidant enzymes may suggest that CAT gene polymorphism in the A/A homozygotes might affect the regulation mechanism involved in the antioxidant system in the liver.

Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

PubMed

Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

2010-08-01

The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Urethral versus suprapubic catheter: choosing the best bladder management for male spinal cord injury patients with indwelling catheters.

PubMed

Katsumi, H K; Kalisvaart, J F; Ronningen, L D; Hovey, R M

2010-04-01

Bladder management for male patients with spinal cord injury (SCI) challenges the urologist to work around physical and social restrictions set forth by each patient. The objective of this study was to compare the complications associated with urethral catheter (UC) versus suprapubic tube (SPT) in patients with SCI. A retrospective review of records at Long Beach Veterans Hospital was carried out to identify SCI patients managed with SPT or UC. Chart review identified morbidities including urinary tract infection (UTI), bladder stones, renal calculi, urethral complications, scrotal abscesses, epididymitis, gross hematuria and cancer. Serum creatinine measurements were evaluated to determine whether renal function was maintained. In all, 179 patients were identified. There was no significant difference between the two catheter groups in any areas in which they could be compared. There were catheter-specific complications specific to each group that could not be compared. These included erosion in the UC group and urethral leak, leakage from the SPT and SPT revision in the SPT group. Average serum creatinine for the UC and SPT groups was 0.74 and 0.67 mg per 100 ml, respectively. SCI patients with a chronic catheter have similar complication rates of UTIs, recurrent bladder/renal calculi and cancer. Urethral and scrotal complications may be higher with UC; however, morbidity from SPT-specific procedures may offset benefits from SPT. Serum creatinine was maintained in both groups. Overall, bladder management for patients with chronic indwelling catheters should be selected on the basis of long-term comfort for the patient and a physician mind-set that allows flexibility in managing these challenges.

Mucosal Healing Is Associated With Improved Long-term Outcomes of Patients With Ulcerative Colitis: A Systematic Review and Meta-analysis.

PubMed

Shah, Shailja C; Colombel, Jean-Frederic; Sands, Bruce E; Narula, Neeraj

2016-09-01

The paradigm for treatment for ulcerative colitis (UC) is shifting from resolving symptoms toward objective measures such as mucosal healing (MH). However, it is unclear whether MH is associated with improved long-term outcomes. We performed a systematic review and meta-analysis to identify and analyze studies comparing long-term outcomes of patients with MH with those without MH. We performed a systematic search of 3 large databases to identify prospective studies of patients with active UC that included outcomes of patients found to have MH at the first endoscopic evaluation after initiation of UC therapy (MH1) compared with those without MH1. The primary outcome was clinical remission after at least 52 weeks. Secondary outcomes included proportions of patients who were free of colectomy or corticosteroids and rate of MH after at least 52 weeks. We analyzed 13 studies comprising 2073 patients with active UC. Patients with MH1 had pooled odds ratio of 4.50 for achieving long-term (after at least 52 weeks) clinical remission (95% confidence interval [CI], 2.12-9.52), 4.15 for remaining free of colectomy (95% CI, 2.53-6.81), 8.40 for achieving long-term MH (95% CI, 3.13-22.53), and 9.70 for achieving long-term corticosteroid-free clinical remission (95% CI, 0.94-99.67), compared with patients without MH1. We found no difference in outcomes if patients achieved MH1 while receiving biologic versus non-biologic therapy. In a meta-analysis, we associated MH with long-term clinical remission, avoidance of colectomy, and corticosteroid-free clinical remission. MH is therefore appropriate goal of UC therapy. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ulcerative colitis associated with Takayasu's disease in two patients who received proctocolectomy.

PubMed

Masuda, Hideki; Ishii, Ukimoto; Aoki, Nobuhiko; Nakayama, Hisashi; Sato, Fumii; Karube, Hideaki; Suzuki, Shigeru; Kondo, Toshihiko

2002-01-01

Ulcerative colitis (UC) associated with Takayasu's disease (TD) is not common in Japan. Here, we report two patients with both diseases who received a total proctocolectomy. Patient 1, a 41-year-old woman with chronic continuous type UC, was first diagnosed with TD at the age of 10 years. Subsequently, she was diagnosed with UC and rectal cancer. HLA typing showed A2, A31(19), B52(5), and DR2(DRB1*1502). Coronary angiography showed 90% narrowing of the right coronary artery (RCA). After alleviating the RCA narrowing by percutaneous transluminal coronary angioplasty (PTCA), we performed a total proctocolectomy and ileostomy. Patient 2, a 20-year-old woman, was first diagnosed with TD at the age of 13 years. Severe symptoms, indicating fulminant UC, started 1 month prior to hospitalization. She was judged as needing surgery because the symptoms were not alleviated even with high doses of prednisolone. HLA typing showed A2, A31(19), B52, B61(40), DR2(DRB1*1502), and DR4 (DRB1*0405). Aortography showed a narrowing of the right renal artery; however, her renal function was normal. Based on these findings, we performed a three-stage operation for total proctocolectomy. Previously, we have reported that the DRB1*1502 and DRw11 genes were closely related to the intractability of UC. To date, we have not determined whether or how the DRB1*1502 gene might be related to TD. As the number of cases of UC associated with TD increases, it will be necessary to examine their DR2 subtypes.

Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease.

PubMed

Romberg-Camps, M J L; Dagnelie, P C; Kester, A D M; Hesselink-van de Kruijs, M A M; Cilissen, M; Engels, L G J B; Van Deursen, C; Hameeteman, W H A; Wolters, F L; Russel, M G V M; Stockbrügger, R W

2009-02-01

Disease course in inflammatory bowel disease (IBD) is variable and difficult to predict. To optimize prognosis, it is of interest to identify phenotypic characteristics at disease onset and other prognostic factors that predict disease course. The aim of this study was to evaluate such factors in a population-based IBD group. IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. A follow-up questionnaire was developed and medical records were reviewed. Patients were classified according to phenotype at diagnosis and risk factors were registered. Disease severity, cumulative medication use, and "surgical" and "nonsurgical" recurrence rates were calculated as outcome parameters. In total, 476 Crohn's disease (CD), 630 ulcerative colitis (UC), and 81 indeterminate colitis (IC) patients were diagnosed. In CD (mean follow-up 7.6 years), 50% had undergone resective surgery. In UC (mean follow-up 7 years), colectomy rate was 8.3%. First year cumulative recurrence rates per 100 patient-years for CD, UC, and IC were 53, 44, and 42%, respectively. In CD, small bowel localization and stricturing disease were negative prognostic factors for surgery, as was young age. Overall recurrence rate was increased by young age and current smoking. In UC, extensive colitis increased surgical risk. In UC, older age at diagnosis initially increased recurrence risk but was subsequently protective. This population-based IBD study showed high recurrence rates in the first year. In CD, small bowel localization, stricturing disease, and young age were predictive for disease recurrence. In UC, extensive colitis and older age at diagnosis were negative prognostic predictors.

Nationwide prevalence and drug treatment practices of inflammatory bowel diseases in Hungary: A population-based study based on the National Health Insurance Fund database.

PubMed

Kurti, Zsuzsanna; Vegh, Zsuzsanna; Golovics, Petra A; Fadgyas-Freyler, Petra; Gecse, Krisztina B; Gonczi, Lorant; Gimesi-Orszagh, Judit; Lovasz, Barbara D; Lakatos, Peter L

2016-11-01

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases associated with a substantial healthcare utilization. Our aim was to estimate the national prevalence of inflammatory bowel disease (IBD), CD and UC and to describe current drug treatment practices in CD and UC. Patients and drug dispensing events were identified according to international classification codes for UC and CD in in-patient care, non-primary out-patient care and drug prescription databases (2011-2013) of the National Health Insurance Fund. A total of 55,039 individuals (men: 44.6%) with physician-diagnosed IBD were alive in Hungary in 2013, corresponding to a prevalence of 0.55% (95% CI, 0.55-0.56). The prevalence of CD 0.20% (95% CI, 0.19-0.20), and UC was 0.34% (95% CI, 0.33-0.34). The prevalence both in men and women was the highest in the 20-39 year-olds in CD. Current use of immunosuppressives and biological therapy was highest in the pediatric CD population (44% and 15%) followed by adult CD (33% and 9%), while their use was lowest in elderly patients. Interestingly, current use of 5-ASA (5-aminosalicylates) was high in both UC and CD irrespective of the age group. The Hungarian IBD prevalence based on nationwide database of the National Health Insurance Fund was high. We identified significant differences in the drug prescription practices according to age-groups. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Clostridium difficile infection worsens the prognosis of ulcerative colitis

PubMed Central

Negrón, María E; Barkema, Herman W; Rioux, Kevin; De Buck, Jeroen; Checkley, Sylvia; Proulx, Marie-Claude; Frolkis, Alexandra; Beck, Paul L; Dieleman, Levinus A; Panaccione, Remo; Ghosh, Subrata; Kaplan, Gilaad G

2014-01-01

BACKGROUND: The impact of Clostridium difficile infections among ulcerative colitis (UC) patients is well characterized. However, there is little knowledge regarding the association between C difficile infections and postoperative complications among UC patients. OBJECTIVE: To determine whether C difficile infection is associated with undergoing an emergent colectomy and experiencing postoperative complications. METHODS: The present population-based case-control study identified UC patients admitted to Calgary Health Zone hospitals for a flare between 2000 and 2009. C difficile toxin tests ordered in hospital or 90 days before hospital admission were provided by Calgary Laboratory Services (Calgary, Alberta). Hospital records were reviewed to confirm diagnoses and to extract clinical data. Multivariate logistic regression analyses were performed among individuals tested for C difficile to examine the association between C difficile infection and emergent colectomy and diagnosis of any postoperative complications and, secondarily, an infectious postoperative complication. Estimates were presented as adjusted ORs with 95% CIs. RESULTS: C difficile was tested in 278 (58%) UC patients and 6.1% were positive. C difficile infection was associated with an increased risk for emergent colectomy (adjusted OR 3.39 [95% CI 1.02 to 11.23]). Additionally, a preoperative diagnosis of C difficile was significantly associated with the development of postoperative infectious complications (OR 4.76 [95% CI 1.10 to 20.63]). CONCLUSION: C difficile diagnosis worsened the prognosis of UC by increasing the risk of colectomy and postoperative infectious complications following colectomy. Future studies are needed to explore whether early detection and aggressive management of C difficile infection will improve UC outcomes. PMID:25157528

Medical Therapy of Active Ulcerative Colitis

PubMed Central

Bürger, Martin; Schmidt, Carsten; Teich, Niels; Stallmach, Andreas

2015-01-01

Summary Background Medical therapy of mild and moderate ulcerative colitis (UC) of any extent is evidence-based and standardized by national and international guidelines. However, patients with steroid-refractory UC still represent a challenge. Methods A literature search using PubMed (search terms: ulcerative colitis, therapy, new, 1-2008-2015) resulted in 821 publications. For the current article, 88 citations were extracted including 36 randomized controlled studies, 18 reviews, and 8 meta-analyses. Results In steroid-refractory UC, early intensive therapy using anti-tumor necrosis factor (TNF) antibodies or the calcineurin inhibitors cyclosporine and tacrolimus is indicated in any case to prevent progression to a toxic megacolon and/or to avoid proctocolectomy. In patients with chronic disease activity, treatment with anti-TNF antibodies has a higher level of evidence than azathioprine therapy and should therefore be preferred. However, there is a subgroup of UC patients who may achieve prolonged steroid-free remission on azathioprine monotherapy. The importance of vedolizumab, a newly registered inhibiting antibody against integrin, has not yet been fully clarified since direct comparison studies are lacking, in particular in relation to anti-TNF antibodies. Conclusion There is a great need for additional innovative therapies, especially in cases of primary non-response or secondary loss of response to anti-TNF antibodies. New small molecules (Janus kinase inhibitors) are promising with an acceptable safety profile and efficacy in UC. Further, strategies that target the intestinal microbiome are currently considered for patients with active or relapsing UC, and may in the future open up new therapeutic options. PMID:26557831

Second-generation corticosteroids for the treatment of Crohn's disease and ulcerative colitis: more effective and less side effects?

PubMed

De Cassan, Chiara; Fiorino, Gionata; Danese, Silvio

2012-01-01

Systemic corticosteroids are highly effective at inducing clinical remission in cases of acute exacerbation of Crohn's disease (CD) and ulcerative colitis (UC); however, their use is limited by their frequent and sometimes severe side effects. Thus, a second generation of corticosteroids with less systemic effects has been developed. This review analyzed all of the studies on the new formulations of steroids with limited absorption (budesonide, budesonide MMX®, beclomethasone dipropionate and erythrocyte-mediated delivery of dexamethasone) in patients with CD and UC. All relevant articles published in English between September 1960 and April 2011 were reviewed. Budesonide is superior to placebo, and as effective as systemic corticosteroids in inducing clinical remission in patients with ileo-colonic CD, but evidence of mucosal healing is limited. When administered as an MMX formula, budesonide can also effectively induce clinical remission in patients with UC, but budesonide alone is not effective in maintaining clinical remission in CD or UC. Beclomethasone dipropionate seems to be effective in patients with mild-to-moderate left-sided and extensive UC, while data on erythrocyte-mediated delivery of dexamethasone are encouraging but still limited. The safety profile for all these products is good but more studies are needed. Steroids remain the mainstay for the induction of clinical remission in cases of acute relapse of both CD and UC. Second-generation corticosteroids are an interesting alternative, with the advantage of high topical activity, less systemic toxicity and limited side effects. Copyright © 2012 S. Karger AG, Basel.

Gene expression profile of endoscopically active and inactive ulcerative colitis: preliminary data.

PubMed

Ţieranu, Cristian George; Dobre, Maria; Mănuc, Teodora Ecaterina; Milanesi, Elena; Pleşea, Iancu Emil; Popa, Caterina; Mănuc, Mircea; Ţieranu, Ioana; Preda, Carmen Monica; Diculescu, Mihai Mircea; Ionescu, Elena Mirela; Becheanu, Gabriel

2017-01-01

Multiple cytokines and chemokines related to immune response, apoptosis and inflammation have been identified as molecules implicated in ulcerative colitis (UC) pathogenesis. The aim of this study was to identify the differences at gene expression level of a panel of candidate genes in mucosa from patients with active UC (UCA), patients in remission (UCR), and normal controls. Eleven individuals were enrolled in the study: eight UC patients (four with active lesions, four with mucosal healing) and three controls without inflammatory bowel disease (IBD) seen on endoscopy. All the individuals underwent mucosal biopsy during colonoscopy. Gene expression profile was evaluated by polymerase chain reaction (PCR) array, investigating 84 genes implicated in apoptosis, inflammation, immune response, cellular adhesion, tissue remodeling and mucous secretion. Seventeen and three genes out of 84 were found significantly differentially expressed in UCA and UCR compared to controls, respectively. In particular, REG1A and CHI3L1 genes reported an up-regulation in UCA with a fold difference above 200. In UCR patients, the levels of CASP1, LYZ and ISG15 were different compared to controls. However, since a significant up-regulation of both CASP1 and LYZ was observed also in the UCA group, only ISG15 levels remained associated to the remission state. ISG15, that plays a key role in the innate immune response, seemed to be specifically associated to the UC remission state. These preliminary data represent a starting point for defining the gene profile of UC in different stages in Romanian population. Identification of genes implicated in UC pathogenesis could be useful to select new therapeutic targets.

Effect of Yoga-Based Intervention in Patients with Inflammatory Bowel Disease.

PubMed

Sharma, Purnima; Poojary, Gopal; Dwivedi, Sada Nand; Deepak, Kishore Kumar

2015-01-01

Inflammatory bowel disease (IBD) is a chronic illness characterized by gross inflammation in the gastrointestinal tract that can result in symptoms such as abdominal pain, cramping, diarrhea, and bloody stools. IBD is believed to be influenced by psychological factors such as stress and anxiety. Therefore, a yoga intervention that reduces stress and anxiety may be an effective complementary treatment for these disorders. A total of 100 IBD patients [ulcerative colitis (UC) n = 60 and Crohn's disease (CD) n = 40] during the clinical remission phase of disease were included in the study. These patients were allocated randomly to either the yoga group that underwent an 8-week yoga intervention (physical postures, pranayama, and meditation) 1- hour/day in addition to standard medical therapy (UC, n = 30; CD, n = 20) or the control group (UC, n = 30; CD n = 20), which continued with standard medical therapy alone. The main outcome measures were cardiovascular autonomic functions, serum eosinophilic cationic protein, interleukin- 2 soluble receptors, Speilberger's State Trait Anxiety Inventory (STAI) scores, and clinical symptoms. Before the intervention, all the outcome measures were comparable in the two groups. After the 8-week yoga intervention, fewer UC patients reported arthralgia. The number of patients reporting intestinal colic pain in the control group was higher. State and trait anxiety levels were significantly reduced in patients with UC. However, no significant changes were observed in cardiovascular autonomic functions, eosinophilic cationic proteins, or interleukin-2 soluble receptors. A simplified yoga-based regimen is a safe and effective complementary clinical treatment modality for patients with inflammatory bowel disease during the clinical remission phase.

Nurse management for hypertension. A systems approach.

PubMed

Rudd, Peter; Miller, Nancy Houston; Kaufman, Judy; Kraemer, Helena C; Bandura, Albert; Greenwald, George; Debusk, Robert F

2004-10-01

Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP. We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period. Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group. Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.

Economic evaluation of a disease management program for chronic obstructive pulmonary disease.

PubMed

Dewan, Naresh A; Rice, Kathryn L; Caldwell, Michael; Hilleman, Daniel E

2011-06-01

The data on cost savings with disease management (DM) in chronic obstructive pulmonary disease (COPD) is limited. A multicomponent DM program in COPD has recently shown in a large randomized controlled trial to reduce hospitalizations and emergency department visits compared to usual care (UC). The objectives of this study were to determine the cost of implementing the DM program and its impact on healthcare resource utilization costs compared to UC in high-risk COPD patients. This study was a post-hoc economic analysis of a multicenter randomized, adjudicator-blinded, controlled, 1-year trial comparing DM and UC at 5 Midwest region Department of Veterans Affairs (VA) medical centers. Health-care costs (hospitalizations, ED visits, respiratory medications, and the cost of the DM intervention) were compared in the COPD DM intervention and UC groups. The composite outcome for all hospitalizations or ED visits were 27% lower in the DM group (123.8 mean events per 100 patient-years) compared to the UC group (170.5 mean events per 100 patient-years) (rate ratio 0.73; 0.56-0.90; p < 0.003). The cost of the DM intervention was $241,620 or $650 per patient. The total mean ± SD per patient cost that included the cost of DM in the DM group was 4491 ± 4678 compared to $5084 ± 5060 representing a $593 per patient cost savings for the DM program. The DM intervention program in this study was unique for producing an average cost savings of $593 per patient after paying for the cost of DM intervention.

Demography and clinical course of ulcerative colitis in Arabs - a study based on the Montreal classification.

PubMed

Siddique, Iqbal; Alazmi, Waleed; Al-Ali, Jaber; Longenecker, Joseph C; Al-Fadli, Ahmad; Hasan, Fuad; Memon, Anjum

2014-12-01

Ulcerative colitis (UC) is generally considered a disease of the Caucasian populations in developed countries, but its incidence is increasing rapidly in many developing countries, including the Middle East. The objective of this study was to determine the clinical epidemiology of UC in Arabs. This cross-sectional medical record-based descriptive study collected sociodemographic and clinical information on 182 Arab patients with UC in Kuwait. Age at diagnosis, extent and severity of disease were determined according to the Montreal classification. results: Among the 182 patients, 91 (50.0%) were males. The median age at diagnosis was 28.5 years. Family history of UC was reported by 26 (14.3%) patients. The extent of the disease was limited to the rectum in 34 (18.7%) patients, left sided in 67 (36.8%) and pan colitis in 81 (44.5%). At the time of inclusion in the study, 127 (69.8%) patients were in clinical remission, 53 (29.1%) had mild-to-moderate disease and 2 (1.1%) had severe colitis. Younger age at diagnosis and non-smoking were associated with more extensive colitis. The majority of patients were treated with mesalamine, steroids and immunomodulators, while biologic therapy and surgery were needed in 5% and 4% of the patients, respectively. UC presents more commonly at younger age among Arabs in Kuwait. Extensive disease at presentation is associated with younger age at diagnosis and absence of tobacco smoking. There also appears to be less need for surgery and biologic therapy for the disease in this population.

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases.

PubMed

Merra, Giuseppe; Gasbarrini, Giovanni; Laterza, Lucrezia; Pizzoferrato, Marco; Poscia, Andrea; Scaldaferri, Franco; Arena, Vincenzo; Fiore, Francesca; Cittadini, Achille; Sgambato, Alessandro; Franceschi, Francesco; Gasbarrini, Antonio

2012-09-28

To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn's disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P < 0.01) after treatment. Only patients with UC showed a significant reduction of DAI, from a median 6.5 (IQR: 4-9) before treatment to 2 (IQR: 1-3) after treatment (P < 0.01). Conversely, in CD patients, although displaying a clear reduction of DAI from 7 (IQR: 5.5-7.5) before therapy to 1.5 (IQR: 0.5-2.5) after therapy, differences observed were not significant (P = 0.06). Seventy-nine percent (SE 11%) of patients showed improvement of HI of at least 1 point, while only one CD and two UC patients showed HI stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant). The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients. No side effects were reported during treatment or at 4 wk follow-up visit. PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD patients.

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

PubMed Central

Merra, Giuseppe; Gasbarrini, Giovanni; Laterza, Lucrezia; Pizzoferrato, Marco; Poscia, Andrea; Scaldaferri, Franco; Arena, Vincenzo; Fiore, Francesca; Cittadini, Achille; Sgambato, Alessandro; Franceschi, Francesco; Gasbarrini, Antonio

2012-01-01

AIM: To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride (PLC) in colonic inflammatory bowel disease. METHODS: Patients suffering from mild to moderate ulcerative colitis (UC) or Crohn’s disease (CD) colitis, with disease activity index (DAI) between 3 and 10 and under stable therapy with oral aminosalicylates, mercaptopurine or azathioprine, for at least 8 wk prior to baseline assessments, were considered suitable for enrollment. Fourteen patients were enrolled to assume PLC 2 g/d (two active tablets twice daily) orally. Clinical-endoscopic and histological activity were assessed by DAI and histological index (HI), respectively, following a colonoscopy performed immediately before and after 4 wk treatment. Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2. Histological response was defined as an improvement of HI of at least 1 point. We used median values for the analysis. Differences pre- and post-treatment were analyzed by Wilcoxon signed rank test. RESULTS: All patients enrolled completed the study. One patient, despite medical advice, took deflazacort 5 d before follow-up colonoscopy examination. No side effects were reported by patients during the trial. After treatment, 71% (SE 12%) of patients achieved clinical response, while 64% (SE 13%) obtained remission. Separating UC from CD patients, we observed a clinical response in 60% (SE 16%) and 100%, respectively. Furthermore 60% (SE 16%) of UC patients and 75% (SE 25%) of CD patients were in clinical remission after therapy. The median DAI was 7 [interquartile range (IQR): 4-8] before treatment and decreased to 2 (IQR: 1-3) (P < 0.01) after treatment. Only patients with UC showed a significant reduction of DAI, from a median 6.5 (IQR: 4-9) before treatment to 2 (IQR: 1-3) after treatment (P < 0.01). Conversely, in CD patients, although displaying a clear reduction of DAI from 7 (IQR: 5.5-7.5) before therapy to 1.5 (IQR: 0.5-2.5) after therapy, differences observed were not significant (P = 0.06). Seventy-nine percent (SE 11%) of patients showed improvement of HI of at least 1 point, while only one CD and two UC patients showed HI stability; none showed HI worsening. Median HI decreased from 1 (IQR: 1-2), to 0.5 (IQR: 0-1) at the endoscopic control in the whole population (P < 0.01), while it changed from 1 (IQR: 1-2) to 0.5 (IQR: 0-1) in UC patients (P < 0.01) and from 1.5 (IQR: 1-2) to 0.5 (IQR: 0-1) in CD patients (P = not significant). The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients. No side effects were reported during treatment or at 4 wk follow-up visit. CONCLUSION: PLC improves endoscopic and histological activity of mild to moderate UC. Further studies are required to evaluate PLC efficacy in colonic CD patients. PMID:23049215

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds.

PubMed

Baumgart, Daniel C; le Claire, Marie

2016-01-01

Crohn's disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. DRGs challenge sophisticated IBD care.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo

PubMed Central

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-01-01

Objective Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. Design We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Results Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn’s disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. Conclusions α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. PMID:26209553

Telocytes are reduced during fibrotic remodelling of the colonic wall in ulcerative colitis.

PubMed

Manetti, Mirko; Rosa, Irene; Messerini, Luca; Ibba-Manneschi, Lidia

2015-01-01

Ulcerative colitis (UC) is characterized by chronic relapsing intestinal inflammation finally leading to extensive tissue fibrosis and resulting in a stiff colon unable to carry out peristalsis or to resorb fluids. Telocytes, a peculiar type of stromal cells, have been recently identified in the human gastrointestinal tract. Several roles have been proposed for telocytes, including mechanical support, intercellular signalling and modulation of intestinal motility. The aim of the present work was to investigate the presence and distribution of telocytes in colonic specimens from UC patients compared with controls. Archival paraffin-embedded samples of the left colon from UC patients who underwent elective bowel resection and controls were collected. Tissue sections were stained with Masson's trichrome to detect fibrosis. Telocytes were identified by CD34 immunohistochemistry. In early fibrotic UC cases, fibrosis affected the muscularis mucosae and submucosa, while the muscularis propria was spared. In advanced fibrotic UC cases, fibrosis extended to affect the muscle layers and the myenteric plexus. Few telocytes were found in the muscularis mucosae and submucosa of both early and advanced fibrotic UC colonic wall. In the muscle layers and myenteric plexus of early fibrotic UC, telocytes were preserved in their distribution. In the muscularis propria of advanced fibrotic UC, the network of telocytes was reduced or even completely absent around smooth muscle bundles and myenteric plexus ganglia, paralleling the loss of the network of interstitial cells of Cajal. In UC, a loss of telocytes accompanies the fibrotic remodelling of the colonic wall and might contribute to colonic dysmotility. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Identifying continence options after stroke (ICONS): a cluster randomised controlled feasibility trial.

PubMed

Thomas, Lois H; Watkins, Caroline L; Sutton, Christopher J; Forshaw, Denise; Leathley, Michael J; French, Beverley; Burton, Christopher R; Cheater, Francine; Roe, Brenda; Britt, David; Booth, Joanne; McColl, Elaine

2014-12-23

Urinary incontinence (UI) affects half of patients hospitalised after stroke and is often poorly managed. Cochrane systematic reviews have shown some positive impact of conservative interventions (such as bladder training) in reducing UI, but their effectiveness has not been demonstrated with stroke patients. We conducted a cluster randomised controlled feasibility trial of a systematic voiding programme (SVP) for the management of UI after stroke. Stroke services were randomised to receive SVP (n = 4), SVP plus supported implementation (SVP+, n = 4), or usual care (UC, n = 4).Feasibility outcomes were participant recruitment and retention. The main effectiveness outcome was presence or absence of UI at six and 12 weeks post-stroke. Additional effectiveness outcomes included were the effect of the intervention on different types of UI, continence status at discharge, UI severity, functional ability, quality of life, and death. It was possible to recruit patients (413; 164 SVP, 125 SVP+, and 124 UC) and participant retention was acceptable (85% and 88% at six and 12 weeks, respectively). There was no suggestion of a beneficial effect on the main outcome at six (SVP versus UC: odds ratio (OR) 0.94, 95% CI: 0.46 to 1.94; SVP+ versus UC: OR: 0.62, 95% CI: 0.28 to 1.37) or 12 weeks (SVP versus UC: OR: 1.02, 95% CI: 0.54 to 1.93; SVP+ versus UC: OR: 1.06, 95% CI: 0.54 to 2.09).No secondary outcomes showed a strong suggestion of clinically meaningful improvement in SVP and/or SVP+ arms relative to UC at six or 12 weeks. However, at 12 weeks both intervention arms had higher estimated odds of continence than UC for patients with urge incontinence. The trial has met feasibility outcomes of participant recruitment and retention. It was not powered to demonstrate effectiveness, but there is some evidence of a potential reduction in the odds of specific types of incontinence. A full trial should now be considered. ISRCTN Registry, ISRCTN08609907, date of registration: 7 July 2010.

Systematic analysis of factors associated with progression and regression of ulcerative colitis in 918 patients.

PubMed

Safroneeva, E; Vavricka, S; Fournier, N; Seibold, F; Mottet, C; Nydegger, A; Ezri, J; Straumann, A; Rogler, G; Schoepfer, A M

2015-09-01

Studies that systematically assess change in ulcerative colitis (UC) extent over time in adult patients are scarce. To assess changes in disease extent over time and to evaluate clinical parameters associated with this change. Data from the Swiss IBD cohort study were analysed. We used logistic regression modelling to identify factors associated with a change in disease extent. A total of 918 UC patients (45.3% females) were included. At diagnosis, UC patients presented with the following disease extent: proctitis [199 patients (21.7%)], left-sided colitis [338 patients (36.8%)] and extensive colitis/pancolitis [381 (41.5%)]. During a median disease duration of 9 [4-16] years, progression and regression was documented in 145 patients (15.8%) and 149 patients (16.2%) respectively. In addition, 624 patients (68.0%) had a stable disease extent. The following factors were identified to be associated with disease progression: treatment with systemic glucocorticoids [odds ratio (OR) 1.704, P = 0.025] and calcineurin inhibitors (OR: 2.716, P = 0.005). No specific factors were found to be associated with disease regression. Over a median disease duration of 9 [4-16] years, about two-thirds of UC patients maintained the initial disease extent; the remaining one-third had experienced either progression or regression of the disease extent. © 2015 John Wiley & Sons Ltd.

Rapid response to vedolizumab therapy in biologic-naïve patients with inflammatory bowel diseases.

PubMed

Feagan, Brian G; Lasch, Karen; Lissoos, Trevor; Cao, Charlie; Wojtowicz, Abigail M; Khalid, Javaria Mona; Colombel, Jean-Frédéric

2018-05-29

Vedolizumab, a humanized monoclonal antibody against α4β7 integrin, is used to treat adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). We investigated the time course of clinical response to vedolizumab in patients who were and were not previously treated with tumor necrosis factor (TNF) antagonists. We performed a post-hoc analysis of data from phase 3, randomized, controlled trials of vedolizumab vs placebo in adult patients with UC (n=374) or CD (n=784). We collected data on patient-reported symptoms (rectal bleeding and stool frequency for patients with UC, abdominal pain and loose stool frequency for patients with CD) reported at weeks 2, 4, and 6 of treatment. We reported mean percentage score changes from baseline and proportions of patients who achieved predefined scores. We performed multivariate logistic regression analysis to identify factors associated with an early response (at week 2). In patients with UC (overall or naïve to TNF antagonist therapy), a significantly greater percentage of patients given vedolizumab achieved the predefined composite symptom score at weeks 2, 4, and 6 compared to those given placebo. In patients with CD who were naïve to TNF antagonists, a significantly greater percentage of patients given vedolizumab achieved the predefined score at weeks 2 and 4 compared to those given placebo. Among patients with UC given vedolizumab, 19.1% (overall) and 22.3% (TNF antagonist naïve) achieved a composite score of rectal bleeding of 0 and stool frequency ≤1 at week 2 compared to 10% (overall) and 6.6% (TNF antagonist naïve) of those receiving placebo. Among TNF antagonist-naïve patients with CD, 15.0% of those given vedolizumab achieved an average daily composite score of abdominal pain ≤1 and loose stool frequency ≤3 at week 2 (compared to 7.9% given placebo), and 23.8% of those given vedolizumab achieved these by week 4 (compared to 10.3% given placebo). In a post-hoc analysis of data from phase 3 clinical trials, vedolizumab significantly improved patient-reported symptoms of UC and CD as early as week 2 of treatment, continuing through the first 6 weeks-especially when given as first-line biologic therapy. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ulcerative colitis followed by the development of typical intestinal Behçet disease: A case report.

PubMed

Zhu, Zhenhua; Shu, Xu; Long, Shunhua; Jiang, Xiaozhen; Lu, Nonghua; Zhu, Xuan; Liao, Wangdi

2018-02-01

Intestinal Behçet disease (intestinal BD) and inflammatory bowel disease (IBD) share a lot of characteristics, including genetic background, clinical manifestations, and therapeutic strategies, especially the extraintestinal manifestations, such as oral ulcers, arthralgia, eye lesions, skin lesions, etc, but the coexistence of these 2 diseases are uncommon. Behçet disease with gastrointestinal involvement in ulcerative colitis (UC) patient has been reported in just 1 previous case report, but, which can not be diagnosed as definite intestinal BD based on Korean novel diagnositic criteria due to lacking the typical ileocecal ulcer. We present a 23-year-old woman with ulcerative disease who developed typical intestinal BD, which is the first case report of patient with coexisting UC and typical intestinal BD. This patient was diagnosed as coexistence of intestinal BD and UC base on the clinical manifestations, extra intestinal manifestations and typical colonoscopic findings. Steroid and methotrexate were administered. This patient achieved clinical remission and mucosal healing. Coexistence of intestinal BD and UC is uncommon, and the combination with steroid, methotrexate, and 5-aminosalicylic acids is an effective therapy.

Efficacy of Bifidobacterium breve Fermented Milk in Maintaining Remission of Ulcerative Colitis.

PubMed

Matsuoka, Katsuyoshi; Uemura, Yukari; Kanai, Takanori; Kunisaki, Reiko; Suzuki, Yasuo; Yokoyama, Kaoru; Yoshimura, Naoki; Hibi, Toshifumi

2018-02-15

Fermented milk products containing Bifidobacterium breve strain Yakult (BFM) may improve clinical status in ulcerative colitis (UC) patients. To assess efficacy of BFM in maintaining remission in Japanese patients with quiescent UC. This double-blind study (B-FLORA) enrolled 195 patients with quiescent UC, randomized to receive one pack of BFM fermented milk per day [Bifidobacterium breve strain Yakult (10 billion bacteria) and Lactobacillus acidophilus (1 billion bacteria)] (n = 98) or matching placebo (n = 97) for 48 weeks. The primary efficacy endpoint was relapse-free survival (relapse: rectal bleeding score ≥ 2 on Sutherland disease activity index scale for 3 consecutive days and/or initiation of remission induction therapy for worsening of UC). An interim analysis was conducted after inclusion and follow-up of one-third of patients for the first phase of the study (n = 195). Relapse-free survival was not significantly different between the BFM and placebo groups (P = 0.643; hazard ratio 1.16; 95% CI 0.63-2.14, log-rank test), nor was the incidence of relapse. Therefore, the study was discontinued for lack of efficacy. An exploratory analysis of fecal samples from a subgroup of patients revealed no effects of either study beverage on intestinal microbiota, but there was a significant decrease in Bifidobacterium species before relapse, regardless of treatment group. Three mild adverse events occurred for which a causal relationship with the study beverage could not be ruled out (placebo: abdominal bloating and stress in one patient; BFM: body odor in one patient). BFM had no effect on time to relapse in UC patients compared with placebo. UMIN000007593.

Intestinal protozoa infections among patients with ulcerative colitis: prevalence and impact on clinical disease course.

PubMed

Yamamoto-Furusho, Jesús K; Torijano-Carrera, Emma

2010-01-01

Epidemiological and microbiologic studies suggest that enteropathogenic microorganisms play a substantial role in the clinical initiation and relapses of inflammatory bowel disease. To explore the prevalence of intestinal protozoa in patients with ulcerative colitis (UC) and its impact on clinical disease course. A total of 215 patients with definitive diagnosis of UC were studied. Fresh feces samples taken from all UC patients were examined immediately using trichrome-staining methods. A total of 103 female and 112 male UC patients were analyzed. The mean age at diagnosis was 30.5 +/- 10.8 years. The prevalence of overall parasitic infections was 24% and distributed as follows: Blastocystis hominis in 22 patients (10%), Endolimax nana in 19 cases (9%), and Entamoebahistolytica in 11 cases (5%). A significantly increased frequency of protozoa infection was found in those patients with persistent activity and intermittent activity as compared to active than inactive group (p = 1 x 10(-7), OR 13.05, 95% CI 4.28-42.56, and p = 0.003, OR 1.42-14.47, respectively). Interestingly, this association remained significant when we compared the persistent activity group versus intermittent activity group (p = 0.003, OR 2.97, 95% CI 1.35-6.59). Subgroup analysis showed no association between protozoa infection (E. histolytica, B. hominis, and E. nana) and other clinical variables such as gender, extent of disease, extraintestinal complications, medical treatment and grade of disease activity. The prevalence of intestinal protozoa infections in Mexican UC patients was 24% and these microorganisms could be a contributing cause of persistent activity despite medical treatment in our population. 2010 S. Karger AG, Basel.

Increased Epithelial Gap Density in the Noninflamed Duodenum of Children With Inflammatory Bowel Diseases.

PubMed

Zaidi, Deenaz; Bording-Jorgensen, Michael; Huynh, Hien Q; Carroll, Matthew W; Turcotte, Jean-Francois; Sergi, Consolato; Liu, Julia; Wine, Eytan

2016-12-01

Inflammatory bowel diseases (IBD) present commonly in childhood, with unknown etiology, but an important role for the epithelial lining is suggested. Epithelial cell extrusion, measured by counting gaps between epithelial cells, is higher in adult patients with Crohn disease (CD) than in controls. Our objectives were to compare epithelial gaps in the duodenum of IBD and non-IBD pediatric patients, to study the correlation between epithelial gaps, inflammation, and disease activity, and identify potential mechanisms. Epithelial gap density of the duodenum was evaluated using probe-based confocal laser endomicroscopy in 26 pediatric patients with IBD (16 CD, 10 ulcerative colitis [UC]) and 17 non-IBD controls during endoscopy. Epithelial gaps were correlated with serum inflammatory markers, disease activity indices, and intraepithelial lymphocytes. A panel of 10 inflammatory cytokines and expression of TNFAIP3 (A20; inhibits NF-κβ-induced inflammation) were analyzed in duodenal and ileal biopsies. Confocal imaging showed significantly higher epithelial gap density in patients with IBD, including UC. Interleukin (IL)-2 and IL-8 were higher in duodenal but not ileal biopsies of patients with UC. No significant correlation was present between C-reactive protein, erythrocyte sedimentation rate, disease activity indices, and epithelial gaps in patients with UC. In patients with CD, C-reactive protein positively correlated with epithelial gaps. A20 expression in the duodenum was unchanged among non-IBD and IBD cases. Duodenal epithelial gaps are increased in pediatric patients with IBD (including UC) but are unrelated to inflammation. This suggests that altered epithelial barrier is an important systemic feature of pediatric IBD and is not only secondary to inflammation.

Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens.

PubMed

Perez-Gracia, Jose Luis; Loriot, Yohann; Rosenberg, Jonathan E; Powles, Thomas; Necchi, Andrea; Hussain, Syed A; Morales-Barrera, Rafael; Retz, Margitta M; Niegisch, Günter; Durán, Ignacio; Théodore, Christine; Grande, Enrique; Shen, Xiaodong; Wang, Jingjing; Nelson, Betty; Derleth, Christina L; van der Heijden, Michiel S

2017-12-19

Patients with metastatic urothelial carcinoma (mUC) who progress after platinum-based chemotherapy have had few treatment options and uniformly poor outcomes. Atezolizumab (anti-programmed death-ligand 1) was approved in the USA for cisplatin-ineligible and platinum-treated mUC based on IMvigor210, a phase 2, single-arm, two-cohort study. To evaluate the efficacy and safety of atezolizumab by the number of prior lines of systemic therapy in patients with pretreated mUC. IMvigor210 enrolled 315 patients with mUC with progression during or following platinum-based therapy at 70 international sites between May 2014 and November 2014. Key inclusion criteria included age ≥18 yr, creatinine clearance ≥30ml/min, and Eastern Cooperative Oncology Group performance status 0-1, with no limit on prior lines of treatment. Patients in this cohort received atezolizumab 1200mg intravenously every 3 wk until loss of clinical benefit. Centrally assessed Response Evaluation Criteria In Solid Tumors v1.1 objective response rate (ORR), median duration of response, overall survival (OS), and adverse events were evaluated by prior treatment. Potential differences between subgroups were evaluated using log-rank (for OS) and chi-square (for ORR and adverse events frequencies) testing. Three hundred and ten patients were efficacy and safety evaluable (median follow-up, 21 mo). Objective responses and prolonged OS occurred across all prespecified subgroups; median duration of response was not reached in most subgroups. In patients without prior systemic mUC therapy (first-line subgroup), ORR was 25% (95% confidence interval: 14-38), and median OS was 9.6 mo (95% confidence interval: 5.9-15.8). No significant differences in efficacy or toxicity by therapy line were observed. Atezolizumab demonstrated comparable efficacy and safety in previously treated patients with mUC across all lines of therapy evaluated. We investigated effects of previous treatment in patients with metastatic urothelial carcinoma that progressed after platinum-based therapy. Atezolizumab was active and tolerable no matter how many treatment regimens patients had received. ClinicalTrials.gov, NCT02108652. Copyright © 2017. Published by Elsevier B.V.

Outcomes after coronary computed tomography angiography in the emergency department: a systematic review and meta-analysis of randomized, controlled trials.

PubMed

Hulten, Edward; Pickett, Christopher; Bittencourt, Marcio Sommer; Villines, Todd C; Petrillo, Sara; Di Carli, Marcelo F; Blankstein, Ron

2013-02-26

The aim of the study was to systematically review and perform a meta-analysis of randomized, controlled trials of coronary computed tomography angiography (CCTA) versus usual care (UC) triage of acute chest pain in the emergency department (ED). CCTA allows rapid evaluation of patients presenting to the ED with acute chest pain syndromes; however, the impact of such testing on patient management and downstream testing has emerged as a concern. We systematically searched for randomized, controlled trials of CCTA in the ED and performed a meta-analysis of clinical outcomes. Four randomized, controlled trials were included, with 1,869 patients undergoing CCTA and 1,397 undergoing UC. There were no deaths and no difference in the incidence of myocardial infarction, post-discharge ED visits, or rehospitalizations. Four studies reported decreased length of stay with CCTA and 3 reported cost savings; 8.4% of patients undergoing CCTA versus 6.3% of those receiving UC underwent invasive coronary angiography (ICA), whereas 4.6% of patients undergoing CCTA versus 2.6% of those receiving UC underwent coronary revascularization. The odds ratio of ICA for CCTA patients versus UC patients was 1.36 (95% confidence interval [CI]: 1.03 to 1.80, p = 0.030), and for revascularization, it was 1.81 (95% CI: 1.20 to 2.72, p = 0.004). The absolute increase in ICA after CCTA was 21 per 1,000 CCTA patients (95% CI: 1.8 to 44.9), and the number needed to scan was 48. The absolute increase in revascularization after CCTA was 20 per 1,000 patients (95% CI: 5.0 to 41.4); the number needed to scan was 50. Both percutaneous coronary intervention and coronary artery bypass graft surgery independently contributed to the significant increase in revascularization. Compared with UC, the use of CCTA in the ED is associated with decreased ED cost and length of stay but increased ICA and revascularization. Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Overweight and obesity among low-income Muslim Uyghur women in far western China: correlations of body mass index with blood lipids and implications in preventive public health.

PubMed

Cong, Li; Zhan, Jin Qiong; Yang, Lan; Zhang, Wei; Li, Shu Gang; Chen, Cheng; Zhang, Hong Yan; Ma, Zhi Ping; Hao, Xiao Ling; Simayi, Dilixia; Tao, Lin; Zhao, Jin; Amanguli, A; Mohemaiti, Meiliguli; Jing, Ming Xia; Wang, Wei; Saimaiti, Abudukeyoumu; Zou, Xiao Guang; Gu, Yan; Li, Li; Wang, Ying Hong; Li, Feng; Zhang, Wen Jie

2014-01-01

The pandemic of obesity is a global public health concern. Most studies on obesity are skewed toward high-income and urban settings and few covers low-income populations. This study focused on the prevalence of overweight and obesity and their correlations with blood lipids/metabolites/enzymes (bio-indicators) in a rural community typical of low-income in remote western China. This study was performed in a Muslim ethnic Uyghur rural community in Kashi Prefecture of Xinjiang, about 4,407 km (2,739 miles) away from Beijing. Body mass index (BMI) and major blood bio-indicators (25 total items) were measured and demographic information was collected from 1,733 eligible healthy women aged 21 to 71 yrs, of whom 1,452 had complete data for analysis. More than 92% of the women lived on US$1.00/day or less. According to the Chinese criteria, overweight and obesity were defined as BMI at 24 to <28 kg/m(2) and at ≥ 28 kg/m(2), respectively. The average BMI among these low-income women was 24.0 ± 4.0 (95% CI, 17.5-33.7) kg/m(2). The prevalence of obesity and overweight was high at 15.1% and 28.9%, respectively. Among 25 bio-indicators, BMI correlated positively with the levels of 11 bio-indicators including triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TCHOL), glucose (GLU), and uric acid (UA); but negatively with the levels of 5 bio-indicators including high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A/B (APO A/B). This is the first investigation reporting overweight and obesity being common in low-income Muslim Uyghur women, whose BMI correlates with several important blood bio-indicators which are risk factors for diabetes and cardiovascular diseases. These findings may help make preventive public health policies in Uyghur communities. To prevent diabetes and cardiovascular diseases in low-income settings, we therefore propose a cost-effective, two-step strategy first to screen for obesity and then to screen persons with obesity for diabetes and cardiovascular diseases.

Burden and Correlates of Geriatric Depression in the Uyghur Elderly Population, Observation from Xinjiang, China

PubMed Central

Lu, Chen; Tang, Weiming; Mahapatra, Tanmay; Wang, Yu; Wang, Xihua; Ma, Ying; Ben, Yanli; Cao, Xiaolin; Mahapatra, Sanchita; Ling, Min; Gou, Anshuan; Wang, Yanmei; Xiao, Jiangqin; Hou, Ming; Wang, Xiuli; Lin, Bo; Chen, Ruoling; Wang, Faxing; Hu, Zhi

2014-01-01

Background With the gradual aging of the population, geriatric depression has become a major public health issue in China owing to its overall upward trend and associated negative socio-economic impact. Dearth of information regarding the burden and correlates of geriatric depression among Uyghur minority population in Xinjiang Autonomous Region, called for a comprehensive survey involving representative sample for designing efficient targeted intervention to control this disabling disease. Methods A cross-sectional study was conducted among 1329 consenting Uyghur elderly in 2011 in six randomly selected communities/villages in Xinjiang. Information about socio-demographics, behavior, negative life-events, satisfaction regarding income/quality of life and other chronic diseases were collected while assessment of geriatric depression was done using Geriatric Mental State Schedule (GMS). Results Among these participants, majority were currently married, had attended elementary school or less, had an average annual family income of less than 3000 Yuan/person, had strong religious beliefs while 10.61% (2.77% in urban and 23.60% in rural area) had geriatric depression (5.91% among male and 14.58% among females). 61.83% were suffering from other chronic diseases, 96.16% could take care of themselves and 39.28% had experienced negative events during last two years. Religious belief (AOR = 3.92, 95% CI 1.18–13.03), satisfaction regarding quality of life (AOR = 0.53, 95% CI 0.37–0.84) and income (AOR = 0.75, 95% CI 0.35–1.60), suffering from more chronic diseases (AOR = 1.70, 95% CI 1.42–2.04), experiencing three or more negative events (AOR = 1.72, 95% CI 0.92–3.22) and lack of ability to take self-care (AOR = 2.20, 95% CI 1.09–4.48) were all associated with having geriatric depression with or without adjustment for gender, education and occupation. Conclusion High prevalence of geriatric depression among Uyghur elderly in Xinjiang seemed to call for urgent interventions, specifically targeting rural residents, who experienced more negative life-events, were suffering from chronic diseases and were dissatisfied with their income and quality of life. PMID:25437860

Review article: non-malignant oral manifestations in inflammatory bowel diseases.

PubMed

Katsanos, K H; Torres, J; Roda, G; Brygo, A; Delaporte, E; Colombel, J-F

2015-07-01

Patients with inflammatory bowel diseases (IBD) may present with lesions in their oral cavity. Lesions may be associated with the disease itself representing an extraintestinal manifestation, with nutritional deficiencies or with complications from therapy. To review and describe the spectrum of oral nonmalignant manifestations in patients with inflammatory bowel diseases [ulcerative colitis (UC), Crohn's disease (CD)] and to critically review all relevant data. A literature search using the terms and variants of all nonmalignant oral manifestations of inflammatory bowel diseases (UC, CD) was performed in November 2014 within Pubmed, Embase and Scopus and restricted to human studies. Oral lesions in IBD can be divided into three categories: (i) lesions highly specific for IBD, (ii) lesions highly suspicious of IBD and (iii) nonspecific lesions. Oral lesions are more common in CD compared to UC, and more prevalent in children. In adult CD patients, the prevalence rate of oral lesions is higher in CD patients with proximal gastrointestinal tract and/or perianal involvement, and estimated to range between 20% and 50%. Oral lesions can also occur in UC, with aphthous ulcers being the most frequent type. Oral manifestations in paediatric UC may be present in up to one-third of patients and are usually nonspecific. Oral manifestations in IBD can be a diagnostic challenge. Treatment generally involves managing the underlying intestinal disease. In cases presenting with local disabling symptoms and impaired quality of life, local and systemic medical therapy must be considered and/or oral surgery may be required. © 2015 John Wiley & Sons Ltd.

Mutational Hotspots in the Mitochondrial D-Loop Region of Cancerous and Precancerous Colorectal Lesions in Egyptian Patients

PubMed Central

El-Guendy, Nadia; Tantawy, Marwa; Abdelhady, Hala; El-Ghor, Akmal; Abdel Wahab, Abdel Hady

2011-01-01

Mutations in the mitochondrial genome (mtDNA) are associated with different types of cancer, specifically colorectal cancer (CRC). However, few studies have been performed on precancerous lesions, such as ulcerative colitis (UC) lesions and adenomatous polyps (AP). The aim of this study was to identify mtDNA mutations in the cancerous and precancerous lesions of Egyptian patients. An analysis of the mutations found in six regions of the mtDNA genome (ND1, ND5, COI, tRNAser, D-loop 1, and 2) in 80 Egyptian patients (40 CRC, 20 UC, and 20 AP) was performed using polymerase chain reaction–single-strand conformational polymorphism techniques and followed up by direct sequencing. The overall incidence of mutations was 25%, 25%, and 35% in CRC, UC, and AP cases, respectively. Although there was no common mutation pattern within each group, a large number of mutations were detected in the D-loop region in all of the groups. Some mutations (e.g., T414G) were detected repeatedly in precancerous (UC and AP) and cancerous lesions. Mutations detected in patients with CRC were predominantly found in the ND1 gene (40%). Our preliminary study suggests that Egyptian patients with CRC have a large number of mtDNA mutations, especially in the D-loop region, which have not been previously reported. Mutations in the mtDNA of precancerous lesions (i.e., AP and UC) may contribute to transformation events that lead to CRC. PMID:21612400

Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort

PubMed Central

Bank, Steffen; Andersen, Paal Skytt; Burisch, Johan; Pedersen, Natalia; Roug, Stine; Galsgaard, Julied; Ydegaard Turino, Stine; Broder Brodersen, Jacob; Rashid, Shaista; Kaiser Rasmussen, Britt; Avlund, Sara; Bastholm Olesen, Thomas; Hoffmann, Hans Jürgen; Andersen Nexø, Bjørn; Sode, Jacob; Vogel, Ulla; Andersen, Vibeke

2015-01-01

Background The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), result from the combined effects of susceptibility genes and environmental factors. Previous studies have shown that polymorphisms in the Toll-like receptor (TLR), the apoptosis, the IL-23/IL-17 and the interferon gamma (IFNG) pathways are associated with risk of both CD and UC. Methods Using a candidate gene approach, 21 functional single nucleotide polymorphisms (SNPs) in 15 genes were assessed in a clinical homogeneous group of severely diseased ethnic Danish patients consisting of 624 patients with CD, 411 patients with UC and 795 controls. The results were analysed using logistic regression. Results The polymorphisms TLR5 (rs5744174) and IL12B (rs6887695) were associated with risk of CD, and TLR1 (rs4833095) and IL18 (rs187238) were associated with risk of both CD and UC (p<0.05). After Bonferroni correction for multiple testing, the homozygous variant genotype of TLR1 743 T>C (rs4833095) was associated with increased risk CD (OR: 3.15, 95% CI: 1.59–6.26, p = 0.02) and CD and UC combined (OR: 2.96, 95% CI: 1.64–5.32, p = 0.005). Conclusion Our results suggest that genetically determined high activity of TLR1 and TLR5 was associated with increased risk of both CD and UC and CD, respectively. This supports that the host microbial composition or environmental factors in the gut are involved in risk of IBD. Furthermore, genetically determined high activity of the IL-23/IL-17 pathway was associated with increased risk of CD and UC. Overall, our results support that genetically determined high inflammatory response was associated with increased risk of both CD and UC. PMID:26698117

Fistulizing pattern in Crohn's disease and pancolitis in ulcerative colitis are independent risk factors for cancer: a single-center cohort study.

PubMed

Biancone, Livia; Zuzzi, Sara; Ranieri, Micaela; Petruzziello, Carmelina; Calabrese, Emma; Onali, Sara; Ascolani, Marta; Zorzi, Francesca; Condino, Giovanna; Iacobelli, Simona; Pallone, Francesco

2012-06-01

The combined role of immunomodulators (IMM) and clinical characteristics of Inflammatory Bowel Disease (IBD) in determining the cancer risk is undefined. The aim was to assess whether clinical characteristics of IBD are independent risk factors for cancer, when considering thiopurines and anti-TNFs use. In a single-center cohort study, clinical characteristics of IBD patients with IBD duration ≥1 year and ≥2 visits from 2000 to 2009 were considered. Tests for crude rates and survival analysis methods were used to assess differences of incidence of cancer between groups. The methods were adjusted for the time interval between diagnosis and immunomodulatory treatments. IBD population included 1222 patients :615 Crohn's disease (CD), 607 ulcerative colitis (UC). Cancer was diagnosed in 51 patients (34 CD,17 UC), with an incidence rate of 4.3/1000 pt/year. The incidence rate of cancer was comparable between CD and UC (4.6/1000 pt/year vs 2.9/1000 pt/year ;p=n.s.). Cancer most frequently involved the breast, the GI tract, the skin. Lymphoma was diagnosed in CD (1HL, 1NHL,0 HSTCL). Risk factors for cancer included older age at diagnosis of IBD (CD: HR 1.25;95%CI 1.08-1.45; UC:HR 1.33;95%CI 1.15-1.55 for an increase by 5 years; p=0.0023; p=0.0002), fistulizing pattern in CD (HR 2.55; 95%CI 1.11-5.86,p=0.0275), pancolitis in UC (HR 2.79;95%CI 1.05-7.40 p=0.0396 vs distal). IMM and anti-TNFs did not increase the cancer risk in CD, neither IMM in UC (anti-TNFs risk in UC not feasible as no cases observed). Fistulizing pattern in CD, pancolitis in UC and older age at diagnosis of IBD are independent risk factors for cancer. Copyright © 2011 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Nutritional status of children with inflammatory bowel disease in Saudi Arabia.

PubMed

El Mouzan, Mohammad Issa; Al Edreesi, Mohammed Hadi; Al-Hussaini, Abdulrahman Abdullah; Saadah, Omar Ibrahim; Al Qourain, Abdulaziz Abdullatif; Al Mofarreh, Mohammad Abdullah; Al Saleem, Khalid Abdulrahman

2016-02-07

To assess the prevalence of nutritional disorders in children with inflammatory bowel disease (IBD) in Saudi Arabia. The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn's disease (CD) and ulcerative colitis (UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index (BMI) of each child [weight (kg)/height(2) (m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and < -2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older. There were 374 children from 0.33 to 17 years of age, including 119 (32%) children with UC and 255 (68%) with CD. All of the children were Saudi nationals, and 68 (57%) of the UC and 150 (59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30 (25%) patients with UC and 99 (39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC (P = 0.037) only in the age group of 10-17 years (P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years (P = 0.020). A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care.

Nutritional status of children with inflammatory bowel disease in Saudi Arabia

PubMed Central

El Mouzan, Mohammad Issa; Al Edreesi, Mohammed Hadi; Al-Hussaini, Abdulrahman Abdullah; Saadah, Omar Ibrahim; Al Qourain, Abdulaziz Abdullatif; Al Mofarreh, Mohammad Abdullah; Al Saleem, Khalid Abdulrahman

2016-01-01

AIM: To assess the prevalence of nutritional disorders in children with inflammatory bowel disease (IBD) in Saudi Arabia. METHODS: The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn’s disease (CD) and ulcerative colitis (UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index (BMI) of each child [weight (kg)/height2 (m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and < -2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age-related variation in the prevalence of nutritional status between children < 10 years of age and older. RESULTS: There were 374 children from 0.33 to 17 years of age, including 119 (32%) children with UC and 255 (68%) with CD. All of the children were Saudi nationals, and 68 (57%) of the UC and 150 (59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30 (25%) patients with UC and 99 (39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC (P = 0.037) only in the age group of 10-17 years (P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years (P = 0.020). CONCLUSION: A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care. PMID:26855544

Effectiveness and Safety of Vedolizumab Induction Therapy for Patients With Inflammatory Bowel Disease.

PubMed

Amiot, Aurelien; Grimaud, Jean-Charles; Peyrin-Biroulet, Laurent; Filippi, Jerome; Pariente, Benjamin; Roblin, Xavier; Buisson, Anthony; Stefanescu, Carmen; Trang-Poisson, Caroline; Altwegg, Romain; Marteau, Philippe; Vaysse, Thibaud; Bourrier, Anne; Nancey, Stephane; Laharie, David; Allez, Matthieu; Savoye, Guillaume; Moreau, Jacques; Gagniere, Charlotte; Vuitton, Lucine; Viennot, Stephanie; Aubourg, Alexandre; Pelletier, Anne-Laure; Bouguen, Guillaume; Abitbol, Vered; Bouhnik, Yoram

2016-11-01

Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Aberrant methylation of PSD disturbs Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis in ulcerative colitis-associated carcinogenesis.

PubMed

Kato, Takaharu; Suzuki, Koichi; Okada, Shinichiro; Kamiyama, Hidenori; Maeda, Takafumi; Saito, Masaaki; Koizumi, Kei; Miyaki, Yuichiro; Konishi, Fumio

2012-04-01

We previously reported that the Pleckstrin and Sec7 domain-containing (PSD) gene is preferentially methylated in patients with ulcerative colitis (UC) who developed colorectal cancer (CRC), and is implicated in UC-associated carcinogenesis through its inhibition of apoptosis. This study aimed to determine the potential effect of PSD methylation on its downstream molecule, Ras-related C3 botulinum toxin substrate 1 (Rac1), which governs neutrophil chemotaxis and apoptosis signaling. PSD was knocked down in a normal human fibroblast cell line (HNDF) and a neutrophil-like cell line (HL-60). Both NHDF and HL-60 cells exhibited numerous filamentous-actin (F-actin) rich membrane extensions, resulting in the activation of Rac1; this activation was hampered by PSD silencing. Lipopolysaccharide, a reactive oxygen species (ROS) inducer, stimulated NHDF cells to release ROS and activated caspase‑3/7 in the presence of neutrophils, which was inhibited by PSD knockdown. Migration assays demonstrated that chemotaxis of HL-60 cells was affected by PSD silencing in NHDF cells. Tissue sections from 6 UC patients with CRC and 15 UC patients without CRC were examined. To verify Rac1-mediated chemotaxis in tissue sections, we evaluated the grade of neutrophil infiltration by histological assessment and assessed F-actin and PSD expression by immunohistochemistry. Neutrophil infiltration, F-actin and PSD expression were significantly decreased in specimens from UC patients with PSD methylation compared with those without. Decreased levels of F-actin expression were observed in colorectal mucosa, as well as in infiltrating cells with PSD methylation. PSD expression was preferentially inhibited in colorectal mucosa by PSD methylation, whereas PSD expression was rarely observed in infiltrating cells, regardless of PSD methylation status. These data indicate that aberrant methylation of PSD occurs in UC-associated colorectal mucosa, enabling circumvention of Rac1-mediated immune responses governing neutrophil chemotaxis and apoptosis, and thus plays a pivotal role in the mechanisms underlying UC-associated carcinogenesis.

miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis.

PubMed

Benderska, Natalya; Dittrich, Anna-Lena; Knaup, Sabine; Rau, Tilman T; Neufert, Clemens; Wach, Sven; Fahlbusch, Fabian B; Rauh, Manfred; Wirtz, Ralph M; Agaimy, Abbas; Srinivasan, Swetha; Mahadevan, Vijayalakshmi; Rümmele, Petra; Rapti, Emmanouela; Gazouli, Maria; Hartmann, Arndt; Schneider-Stock, Regine

2015-09-01

Longstanding ulcerative colitis (UC) bears a high risk for development of UC-associated colorectal carcinoma (UCC). The inflammatory microenvironment influences microRNA expression, which in turn deregulates target gene expression. microRNA-26b (miR-26b) was shown to be instrumental in normal tissue growth and differentiation. Thus, we aimed to investigate the impact of miR-26b in inflammation-associated colorectal carcinogenesis. Two different cohorts of patients were investigated. In the retrospective group, a tissue microarray with 38 samples from 17 UC/UCC patients was used for miR-26b in situ hybridization and quantitative reverse transcription polymerase chain reaction analyses. In the prospective group, we investigated miR-26b expression in 25 fresh-frozen colon biopsies and corresponding serum samples of 6 UC and 15 non-UC patients, respectively. In silico analysis, Ago2-RNA immunoprecipitation, luciferase reporter assay, quantitative reverse transcription polymerase chain reaction examination, and miR-26b mimic overexpression were employed for target validation. miR-26b expression was shown to be upregulated with disease progression in tissues and serum of UC and UCC patients. Using miR-26b and Ki-67 expression levels, an UCC was predicted with high accuracy. We identified 4 novel miR-26b targets (DIP1, MDM2, CREBBP, BRCA1). Among them, the downregulation of the E3 ubiquitin ligase DIP1 was closely related to death-associated protein kinase stabilization along the normal mucosa-UC-UCC sequence. In silico functional pathway analysis revealed that the common cellular pathways affected by miR-26b are highly related to cancerogenesis and the development of gastrointestinal diseases. We suggest that miR-26b could serve as a biomarker for inflammation-associated processes in the gastrointestinal system. Because miR-26b expression is downregulated in sporadic colon cancer, it could discriminate between UCC and the sporadic cancer type.

Prevalence of Inflammatory Bowel Disease in the Canton of Vaud (Switzerland): A population-based cohort study.

PubMed

Juillerat, Pascal; Pittet, Valérie; Bulliard, Jean-Luc; Guessous, Idris; Antonino, Anca Teodora; Mottet, Christian; Felley, Christian; Vader, John-Paul; Michetti, Pierre

2008-06-01

Because of the changing epidemiology of Inflammatory Bowel Diseases (IBD), we set out to characterize the population-based prevalence of Crohn's Disease (CD) and Ulcerative Colitis (UC) in a defined population of Switzerland. Adult IBD patients were identified by a cross-matched review of histological, hospital and gastroenterologist files throughout a geographical defined population (Canton of Vaud). Demographic factors statistically significantly associated with prevalence were evaluated using a stepwise Poisson regression analysis. Results were compared to IBD prevalence rates in other population-based studies and time trends were performed, based on a systematic literature review. Age and sex-adjusted prevalence rates were 205.7 IBD (100.7 CD and 105.0 UC) cases per 10(5) inhabitants. Among 1016 IBD patients (519 CD and 497 UC), females outnumbered males in CD (p<0.001), but males were more represented in elderly UC patients (p=0.008). Thus, being a male was statistically associated with UC (Relative Risk (RR) 1.25; p=0.013), whereas being a female was associated with CD (RR 1.27; p=0.007). Living in an urban zone was associated with both CD and UC (RR 1.49; p<0.001, 1.63; p<0.001, respectively). From 1960 to 2005, increases in UC and CD prevalences of 2.4% (95%CI, 2.1%-2.8%; p<0.001) and 3.6% (95%CI, 3.1%-4.1%; p<0.001) per annum were found in industrialised countries. Extrapolating our data to all of Switzerland yields an estimate of 12,000 IBD cases for the country, or 1 in 500 inhabitants. Our study gives support to an increase in IBD prevalence in Europe.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up

PubMed Central

van der Valk, Mirthe E.; Mangen, Marie-Josée J.; Severs, Mirjam; van der Have, Mike; Dijkstra, Gerard; van Bodegraven, Ad A.; Fidder, Herma H.; de Jong, Dirk J.; van der Woude, C. Janneke; Romberg-Camps, Mariëlle J. L.; Clemens, Cees H. M.; Jansen, Jeroen M.; van de Meeberg, Paul C.; Mahmmod, Nofel; van der Meulen-de Jong, Andrea E.; Ponsioen, Cyriel Y.; Bolwerk, Clemens; Vermeijden, J. Reinoud; Siersema, Peter D.; Leenders, Max; Oldenburg, Bas

2016-01-01

Background With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02–3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61–13.86)). Conclusions BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC. PMID:27099937

High-Throughput Multi-Analyte Luminex Profiling Implicates Eotaxin-1 in Ulcerative Colitis

PubMed Central

Coburn, Lori A.; Horst, Sara N.; Chaturvedi, Rupesh; Brown, Caroline T.; Allaman, Margaret M.; Scull, Brooks P.; Singh, Kshipra; Piazuelo, M. Blanca; Chitnavis, Maithili V.; Hodges, Mallary E.; Rosen, Michael J.; Williams, Christopher S.; Slaughter, James C.; Beaulieu, Dawn B.; Schwartz, David A.; Wilson, Keith T.

2013-01-01

Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies. PMID:24367513

Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001

PubMed Central

Lakatos, Laszlo; Mester, Gabor; Erdelyi, Zsuzsanna; Balogh, Mihaly; Szipocs, Istvan; Kamaras, Gyorgy; Lakatos, Peter Laszlo

2004-01-01

AIM: An investigation into inflammatory bowel disease and colorectal cancer in Veszprem Province was conducted from 1977 to 2001. METHODS: Both hospital and outpatient records were collected and reviewed comprehensively. The majority of patients were followed up regularly. RESULTS: The population of the province was decreased from 386000 to 376000 during the period. Five hundred sixty new cases of ulcerative colitis (UC), 212 of Crohn’s disease (CD), and 40 of indeterminate colitis (IC) were diagnosed. The incidence rates increased from 1.66 to 11.01 cases per 100000 persons for UC, from 0.41 to 4.68 for CD and from 0.26 to 0.74 for IC. The prevalence rate at the end of 2001 was 142.6 for UC and 52.9 cases per 100000 persons for CD. The peak onset age in UC patients was between 30 and 40 years, in CD between 20 and 30 years. A family history of IBD was present in 3.4 % in UC and 9.9 % in CD patients. Smoking increased the risk for CD (OR = 1.94) while it decreased the risk for UC (OR = 0.25). Twelve colorectal carcinomas were observed in this cohort, the cumulative colorectal cancer risk after 10 years in UC was 2%, after 20 years 8.8%, after 30 years 13.3%. CONCLUSION: The incidence and prevalence rates of IBD have increased steadily in Veszprem Province, now equivalent to that in Western European countries. Rapid increase in incidence rates supports a probable role for environmental factors. The rate of colorectal cancers in IBD is similar to that observed in Western countries. PMID:14760767

Relationships among DNA hypomethylation, Cd, and Pb exposure and risk of cigarette smoking-related urothelial carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chung, Chi-Jung

Cigarette smoking and environmental exposure to heavy metals are important global health issues, especially for urothelial carcinoma (UC). However, the effects of cadmium and lead exposure, as well as the levels of DNA hypomethylation, on UC risk are limited. We evaluated the possible exposure sources of Cd and Pb and the relationship among DNA hypomethylation, urinary Cd and Pb levels, and UC risk. We recruited 209 patients with UC and 417 control patients for a hospital-based case–control study between June 2011 and August 2014. We collected environmental exposure-related information with questionnaires. Blood and urine samples were analyzed to measure themore » Cd and Pb exposure and 5-methyl-2′-deoxycytidine levels as a proxy for DNA methylation. Multivariate logistic regression and 95% confidence intervals were applied to estimate the risk for UC. Study participants with high Cd and Pb exposure in blood or urine had significantly increased risk of UC, especially among the smokers. After adjusting for age and gender, the possible connections of individual cumulative cigarette smoking or herb medicine exposure with the increased levels of Cd and Pb were observed in the controls. Participants with 8.66%–12.39% of DNA hypomethylation had significantly increased risk of UC compared with those with ≥ 12.39% of DNA hypomethylation. Environmental factors including cigarette smoking and herb medicine may contribute to the internal dose of heavy metals levels. Repeat measurements of heavy metals with different study design, detailed dietary information, and types of herb medicine should be recommended for exploring UC carcinogenesis in future studies. - Highlights: • Smoking and herb medicine ingestion is associated with increased urinary Cd and Pb levels. • Urinary levels of Cd and Pb are associated with increased risk of UC. • UC carcinogenesis might have partially resulted from DNA hypomethylation.« less

Longitudinal Analyses of Gut Mucosal Microbiotas in Ulcerative Colitis in Relation to Patient Age and Disease Severity and Duration

PubMed Central

Fite, Alemu; Furrie, Elizabeth; Bahrami, Bahram; Cummings, John H.; Steinke, Douglas T.; Macfarlane, George T.

2013-01-01

Bacteria belonging to the normal colonic microbiota are associated with the etiology of ulcerative colitis (UC). Although several mucosal species have been implicated in the disease process, the organisms and mechanisms involved are unknown. The aim of this investigation was to characterize mucosal biofilm communities over time and to determine the relationship of these bacteria to patient age and disease severity and duration. Multiple rectal biopsy specimens were taken from 33 patients with active UC over a period of 1 year. Real-time PCR was used to quantify mucosal bacteria in UC patients compared to 18 noninflammatory bowel disease controls, and the relationship between indicators of disease severity and bacterial colonization was evaluated by linear regression analysis. Significant differences were detected in bacterial populations on the UC mucosa and in the control group, which varied over the study period. High clinical activity indices (CAI) and sigmoidoscopy scores (SS) were associated with enterobacteria, desulfovibrios, type E Clostridium perfringens, and Enterococcus faecalis, whereas the reverse was true for Clostridium butyricum, Ruminococcus albus, and Eubacterium rectale. Lactobacillus and bifidobacterium numbers were linked with low CAI. Only E. rectale and Clostridium clostridioforme had a high age dependence. These findings demonstrated that longitudinal variations in mucosal bacterial populations occur in UC and that bacterial community structure is related to disease severity. PMID:23269735

5-ASA in ulcerative colitis: improving treatment compliance.

PubMed

Prantera, Cosimo; Rizzi, Marina

2009-09-21

5-Aminosalicylic acid (5-ASA) compounds are a highly effective treatment for ulcerative colitis (UC). While UC patient compliance in clinical studies is over 90%, only 40% of patients in every day life take their prescribed therapy. Adherence to medication has been emphasized recently by a Cochrane meta-analysis that has suggested that future trials of 5-ASA in UC should look at patient compliance rather than drug efficacy. Better compliance can be obtained by reducing the number of tablets and times of administration. Given that the 5-ASA formulations have different delivery systems that split the active moiety in various regions of the intestine, it is particularly important that an adequate dose of the drug arrives at the inflamed part of the colon. 5-ASA Multi matrix (MMx) is a novel, high strength (1.2 g), oral formulation designed for once-daily dosing. It releases the active moiety throughout the colon. Different studies with this compound have shown that it is as effective as 5-ASA enema in the treatment of mild-to-moderate, left-sided UC, and is comparable to a pH-dependent, delayed release 5-ASA (Asacol), even if given once daily. Recently, the effectiveness in the acute phase of UC has been confirmed also in maintenance. In conclusion, at present, 5-ASA MMx seems theoretically the best agent for maintaining patient compliance, and consequently, treatment effectiveness.

Patient Perspectives on the Experience of Being Newly Diagnosed with HIV in the Emergency Department/Urgent Care Clinic of a Public Hospital

PubMed Central

Christopoulos, Katerina A.; Massey, Amina D.; Lopez, Andrea M.; Hare, C. Bradley; Johnson, Mallory O.; Pilcher, Christopher D.; Fielding, Hegla; Dawson-Rose, Carol

2013-01-01

We sought to understand patient perceptions of the emergency department/urgent care (ED/UC) HIV diagnosis experience as well as factors that may promote or discourage linkage to HIV care. We conducted in-depth interviews with patients (n=24) whose HIV infection was diagnosed in the ED/UC of a public hospital in San Francisco at least six months prior and who linked to HIV care at the hospital HIV clinic. Key diagnosis experience themes included physical discomfort and limited functionality, presence of comorbid diagnoses, a wide spectrum of HIV risk perception, and feelings of isolation and anxiety. Patients diagnosed with HIV in the ED/UC may not have their desired emotional supports with them, either because they are alone or they are with family members or friends to whom they do not want to immediately disclose. Other patients may have no one they can rely on for immediate support. Nearly all participants described compassionate disclosure of test results by ED/UC providers, although several noted logistical issues that complicated the disclosure experience. Key linkage to care themes included the importance of continuity between the testing site and HIV care, hospital admission as an opportunity for support and HIV education, and thoughtful matching by linkage staff to a primary care provider. ED/UC clinicians and testing programs should be sensitive to the unique roles of sickness, risk perception, and isolation in the ED/UC diagnosis experience, as these things may delay acceptance of HIV diagnosis. The disclosure and linkage to care experience is crucial in forming patient attitudes towards HIV and HIV care, thus staff involved in disclosure and linkage activities should be trained to deliver compassionate, informed, and thoughtful care that bridges HIV testing and treatment sites. PMID:23991214

Yokukansan in the Treatment of Behavioral and Psychological Symptoms of Dementia: An Updated Meta-Analysis of Randomized Controlled Trials.

PubMed

Matsunaga, Shinji; Kishi, Taro; Iwata, Nakao

2016-09-06

Previous clinical studies found that yokukansan has a therapeutic effect on behavioral and psychological symptoms of dementia (BPSD) in dementia patients. To perform an updated meta-analysis of randomized controlled trials (RCTs) testing yokukansan for patients with BPSD. Primary efficacy and safety endpoints were BPSD total scores and all-cause discontinuation, respectively. Secondary outcomes were BPSD subscales, cognitive function scores [Mini-mental state examination (MMSE)], activities of daily living (ADL) scores, discontinuation due to adverse events (AEs), and incidences of AEs. Five RCTs with 381 patients with BPSD were included. Compared with controls [placebo+usual care (UC)], yokukansan significantly decreased BPSD total scores [standardized mean difference (SMD) = -0.32, 95% confidence interval (CI) = -0.53 to -0.11, p = 0.003, I2 = 0%, N = 5 studies, n = 361]. Yokukansan was more efficacious in reducing BPSD subscale scores (delusions: SMD = -0.51, 95% CI = -0.98 to -0.04, hallucinations: SMD = -0.54, 95% CI = -0.96 to -0.12, agitation/aggression: SMD = -0.37, 95% CI = -0.60 to -0.15) than placebo+UC. However, yokukansan was not superior to placebo+UC for BPSD total as well as any subscales scores only in Alzheimer's disease patients. Compared with UC, yokukansan treatment improved ADL scores (SMD = -0.32, 95% CI = -0.62 to -0.01). MMSE scores did not differ between the yokukansan and placebo+UC treatment groups. No significant differences were found in all-cause discontinuation, discontinuation due to AEs, and incidences of AEs between yokukansan and placebo+UC treatments. Our results suggest that yokukansan is beneficial for the treatment of patients with BPSD and is well-tolerated; it was not beneficial for BPSD total and any subscale scores only in Alzheimer's disease patients.

Efficacy of vedolizumab as induction therapy in refractory IBD patients: Amulticenter cohort

PubMed Central

Shelton, Edward; Allegretti, Jessica R.; Stevens, Betsy; Lucci, Matthew; Khalili, Hamed; Nguyen, Deanna D.; Sauk, Jenny; Giallourakis, Cosmas; Garber, John; Hamilton, Matthew J; Tomczak, Michal; Makrauer, Fredrick; Burakoff, Robert B; Levine, Jonathan; de Silva, Punyaganie; Friedman, Sonia; Ananthakrishnan, Ashwin; Korzenik, Joshua R.; Yajnik, Vijay

2015-01-01

Background Vedolizumab (VDZ) demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC) in the GEMINI trials. Our aim was to evaluate the efficacy of VDZ at week 14 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Methods Patients at Massachusetts General Hospital and Brigham and Women's Hospital were considered for inclusion. VDZ (300mg) was administered at weeks 0, 2, 6 and 14. Efficacy was assessed using the Harvey Bradshaw index (HBI) for CD, the simple clinical colitis activity index (SCCAI) for UC and physician assessment, along with C-reactive protein (CRP) and decrease of corticosteroid therapy. Clinical response was defined as decrease in HBI ≥ 3 and SCCAI ≥ 3 and remission as HBI ≤ 4, SCCAI ≤ 2 and physician assessment of response and remission. Results Our study included 172 patients (107 CD, 59 UC, 6 IBD-U, male 48.3%, mean age 40 years and disease duration 14 years). Fourteen patients had an ostomy and 9 an ileoanal pouch and only 35.5% fulfilled eligibility for the GEMINI trials. Previous treatment failures with ≥ 2 anti-TNFs occurred in 70.9%, one-third were on an immunomodulator and 46% systemic steroids at baseline. In CD, 48.9% and 23.9% and in UC, 53.9% and 29.3% had clinical response and clinical remission at week 14. Adverse events occurred in 10.5%. Conclusions VDZ is safe and well tolerated in refractory IBD patients in a clinical practice with efficacy in UC and CD with responses similar to what was seen in clinical trials. PMID:26288002

Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

2016-06-01

Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC.A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome.Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6-39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events.FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT.

Fecal Microbiota Transplantation as a Novel Therapy for Ulcerative Colitis

PubMed Central

Sun, Dali; Li, Weiming; Li, Shumin; Cen, Yunyun; Xu, Qingwen; Li, Yijun; Sun, Yanbo; Qi, Yuxing; Lin, Yueying; Yang, Ting; Xu, Pengyuan; Lu, Qiping

2016-01-01

Abstract Variation in clinical evidence has prevented the adoption of fecal microbiota transplantation (FMT) in patients with ulcerative colitis (UC). We aimed to conduct a systematic review and meta-analysis to determine the efficacy and safety of FMT in UC. A systematic literature search was performed in 5 electronic databases from inception through September 2015. Inclusion criteria were reports of FMT in patients with UC. Studies were excluded if they did not report clinical outcomes or included patients with infections. Clinical remission (CR) was defined as the primary outcome. Eleven studies (2 randomized controlled trials (RCTs), 1 open-label case-control study, and 8 cohort studies) with a total of 133 UC patients were included in the analysis. In 11 studies (including 8 noncontrol cohort studies and the treatment arms of 3 clinical control trials), the pooled proportion of patients who achieved CR was 30.4% (95% CI 22.6–39.4%), with a low risk of heterogeneity (Cochran Q test, P = 0.139; I2 = 33%). A subgroup analysis suggested that no difference in CR was detected between upper gastrointestinal delivery versus lower gastrointestinal delivery. Furthermore, subgroup analysis revealed that there was no difference in CR between single infusion versus multiple infusions (>1) of FMT. All studies reported mild adverse events. FMT is potentially useful in UC disease management but better-designed RCTs are still required to confirm our findings before wide adoption of FMT is suggested. Additionally, basic guidelines are needed imminently to identify the right patient population and to standardize the process of FMT. PMID:27281075

Mode of action and effects of standardized collaborative disease management on mortality and morbidity in patients with systolic heart failure: the Interdisciplinary Network for Heart Failure (INH) study.

PubMed

Angermann, Christiane E; Störk, Stefan; Gelbrich, Götz; Faller, Hermann; Jahns, Roland; Frantz, Stefan; Loeffler, Markus; Ertl, Georg

2012-01-01

Trials investigating efficacy of disease management programs (DMP) in heart failure reported contradictory results. Features rendering specific interventions successful are often ill defined. We evaluated the mode of action and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). Patients hospitalized for systolic heart failure were randomly assigned to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC addressed individual problems raised by patients, pursued networking of health care providers and provided training for caregivers. End points were time to death or rehospitalization (combined primary), heart failure symptoms, and quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned (HNC: n=352; UC: n=363; age, 69±12 years; 29% female; 40% New York Heart Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81-1.30; P=0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored hazard ratio was 0.62 (0.40-0.96; P=0.03). HNC patients improved more regarding New York Heart Association class (P=0.05), physical functioning (P=0.03), and physical health component (P=0.03). Except for HNC, health care utilization was comparable between groups. However, HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure-related issues. The primary end point of this study was neutral. However, mortality risk and surrogates of well-being improved significantly. Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes. URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.

Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

PubMed

Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

2016-03-01

In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001). Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American Cancer Society. © 2015 American Cancer Society.

Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

PubMed

Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

2016-01-01

Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective trials due to its potential survival benefit in advanced UC patients.

Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

PubMed

Mijwel, Sara; Cardinale, Daniele A; Norrbom, Jessica; Chapman, Mark; Ivarsson, Niklas; Wengström, Yvonne; Sundberg, Carl Johan; Rundqvist, Helene

2018-05-11

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

Gastric myoelectrical activity in patients with inflammatory bowel disease

PubMed Central

Sharma, Purnima; Makharia, Govind; Yadav, Rajeev; Dwivedi, Sada Nand; Deepak, Kishore Kumar

2015-01-01

Aim: Inflammatory bowel disease is characterized by the presence of gastrointestinal motility disturbances; however alterations in the gastric myoelectrical activity have not been characterized. In this study we have recorded the gastric myoelectrical activity in patients with ulcerative colitis (UC) and Crohn's disease (CD) during their clinical remission. Materials and Methods: Gastric activity was assessed using electrogastrography (EGG) in patients with UC (n = 60), CD (n = 40) and healthy controls (n = 40). In each case, their response to water load test, as well as the dominant frequency (DF), dominant power (DP) and the power ratio (PR) of the electrical activity were recorded. Results: In healthy controls, the resting DF was 2.57 ± 1.05 cycles per minute (cpm), which decreased after water ingestion (2.34 ± 0.99 cpm; P = 0.001). Compared to healthy controls, patients with UC had low resting DF (bradygastria) (2.57 ± 1.05 vs. 1.86 ± 1.28 cpm; P = 0.01). The change in DF after water ingestion was insignificant in patients with UC and CD. Post-water ingestion, healthy controls exhibited an increase in the DP as compared to the resting state, (7.1 [2.93, 102.56] vs. 15.94 [3.92, 133.41] µV2; P = 0.02). Patients with UC (1.26 [0.14, 9.83] vs. 3.27 [0.61, 42.12] µV2) and CD (2.54 [0.44, 47.06] vs. 15.8 [0.1, 126.68] µV2) also showed a significant increase in the DP post-water ingestion. Conclusions: Patients with ulcerative colitis have altered resting gastric myoelectrical activity during the remission phase of the disease. PMID:26447103

Vedolizumab Induces Long-term Mucosal Healing in Patients With Crohn's Disease and Ulcerative Colitis.

PubMed

Noman, Maja; Ferrante, Marc; Bisschops, Raf; De Hertogh, Gert; Van den Broeck, Karolien; Rans, Karen; Rutgeerts, Paul; Vermeire, Séverine; Van Assche, Gert

2017-09-01

Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia. Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia. Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

When Should Ulcerative Colitis Patients Undergo Colectomy for Dysplasia? Mismatch Between Patient Preferences and Physician Recommendations

PubMed Central

Siegel, Corey A.; Schwartz, Lisa M.; Woloshin, Steven; Cole, Elisabeth B.; Rubin, David T.; Vay, Tegan; Baars, Judith; Sands, Bruce E.

2010-01-01

Background If dysplasia is found on biopsies during surveillance colonoscopy for ulcerative colitis (UC), many experts recommend colectomy given the substantial risk of synchronous colon cancer. The objective was to learn if UC patients’ perceptions of their colon cancer risk and if their preferences for elective colectomy match with physicians’ recommendations if dysplasia was found. Methods A self-administered written survey included 199 patients with UC for at least 8 years (mean age 49 years, 52% female) who were recruited from Dartmouth-Hitchcock (n = 104) and the University of Chicago (n = 95). The main outcome was the proportion of patients who disagree with physicians’ recommendations for colectomy because of dysplasia. Results Almost all respondents recognized that UC raised their chance of getting colon cancer. In all, 74% thought it was “unlikely” or “very unlikely” to get colon cancer within the next 10 years and they quantified this risk to be 23%; 60% of patients would refuse a physician’s recommendation for elective colectomy if dysplasia was detected, despite being told that they had a 20% risk of having cancer now. On average, these patients would only agree to colectomy if their risk of colon cancer “right now” were at least 73%. Conclusions UC patients recognize their increased risk of colon cancer and undergo frequent surveillance to reduce their risk. Nonetheless, few seem prepared to follow standard recommendations for elective colectomy if dysplasia is found. This may reflect the belief that surveillance alone is sufficient to reduce their colon cancer risk or genuine disagreement about when it is worth undergoing colectomy. PMID:20186940

Squamous cell dysplasia in the proximal rectum of three patients treated for ulcerative colitis on immunomodulators.

PubMed

Connolly, James G; Goldstone, Stephen E

2017-05-01

Anal canal high-grade squamous intraepithelial lesion (HSIL) is the precursor to anal cancer. Immunocompromised patients are at increased risk and disease is usually within 3 cm from the anal verge. High-resolution anoscopy (HRA) with an 8-cm anoscope is used to identify and guide cautery treatment of HSIL. We report three patients with a long-term history of ulcerative colitis (UC) treated with systemic immunomodulators who developed proximally located rectal HSIL. Two patients were HIV-negative women, 63 and 48 years old, and the third was a 51-year-old HIV-positive man with underlying UC for 10, 16, and 3 years, respectively. They each presented with a HPV-positive HSIL visibly extending above the limits of the anoscope used for HRA. None developed cancer. All had episodes of active UC. It is unclear what causative role systemic immunomodulators play in predisposing UC patients to proximal HSIL. HSIL probably developed on a tongue of HPV-infected squamous epithelium growing proximally over the inflamed rectum. Islands developed when areas of squamous epithelium degenerated, creating skip areas. This study highlights the potential for HSIL to extend into the rectum either as a contiguous patch or isolated islands and the need for heightened surveillance in patients with extensive anal canal HSIL treated with immunodulator therapy. HSIL identified at the limit of the anoscope should be investigated further with colonoscopy, and argon plasma coagulation (APC) ablation can serve as an effective treatment option. Patients are at risk for stricture, but it is unclear what role the UC or the ablation played in stricture formation.

Diagnostic Yield of Routine Enteropathogenic Stool Tests in Pediatric Ulcerative Colitis.

PubMed

Ihekweazu, Faith D; Ajjarapu, Avanthi; Kellermayer, Richard

2015-01-01

It can be important to exclude infectious etiologies prior to adjusting immunosuppressive therapy in patients with ulcerative colitis (UC) exacerbation. We sought to determine the diagnostic yield of routine infectious stool studies in pediatric UC patients. We conducted a retrospective review of 152 pediatric UC patients at Texas Children's Hospital between January 2003 and December 2009. The patient records were followed through July 2014. The number and type of infectious stool studies performed and the results of those were collected. Three hundred fifty-four diagnostic stool tests were conducted for Clostridium difficile; 13.6% were positive. Two hundred twenty stool bacterial cultures were performed, and 1.8% were positive, all growing non-typhoid Salmonella. One of 13 (7.7%) Adenovirus PCR tests was positive. Two of 152 examinations (1.3%) for Ova and Parasites were positive. No stool tests for viral culture, viral particles, Yersinia or Rotavirus were positive. Clostridium difficile infection is common in pediatric UC, and routine screening during flares is strongly recommended. Other bacterial and parasitic infections routinely tested for are uncommon, but Salmonella may be a potentially important attribute to disease exacerbations in select patients. In patients without co-morbid conditions, the utility of performing non-specific fecal viral tests is questionable. © 2015 by the Association of Clinical Scientists, Inc.

Natural history and outcome of inflammatory bowel diseases in children in Saudi Arabia: A single-center experience.

PubMed

Alreheili, Khalid M; Alsaleem, Khalid A; Almehaidib, Ali I

2018-01-01

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder which includes ulcerative colitis (UC), Crohn's disease (CD), and indeterminate colitis (IC). The natural history of pediatric IBDs is poorly understood and generally unpredictable. We aim to study the natural history of IBD in Saudi children including the extraintestinal manifestations, changes in diagnosis, disease behavior, medical management, and surgical outcome. A retrospective review of all the charts of children less than 14 years of age who were diagnosed as IBD and followed up in King Faisal Specialist Hospital and Research Center (KFSH and RC) from January 2001 to December 2011 was performed. Sixty-six children were diagnosed with IBD, 36 patients (54.5%) had CD, 27 patients (41%) had UC, and 3 patients (4.5%) had IC. Change in the diagnosis from UC to CD was made in 5 patients (7.6%). Extraintestinal manifestations were documented in 32% of all patients, and the most common was bone involvement (osteopenia/osteoporosis) in 16.7% of the patients. Arthritis (13.6%) was the second most common manifestation. Sclerosing cholangitis was reported in 2.8% in CD compared to 14.8% in UC. At the time of data collection, 8 patients (12%) were off therapy, 38 patients (57.6) were on 5-ASA, 31 patients (47%) were on azathioprine, and 12 patients (18.2%) were receiving anti-TNF. Of the children with CD, 10 patients (27.8%) underwent 1 or more major operations. Of the children with UC, 18.5% underwent 1 or more major intraabdominal procedures. Many issues in pediatric IBD can predict the natural history of the disease including growth failure, complications, need for more aggressive medical treatment, and/or surgery. More studies are needed from the region focusing on factors that may affect the natural history and disease progression.

Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn's disease: a retrospective cohort study

PubMed Central

Shiga, Hisashi; Miyazawa, Teruko; Kinouchi, Yoshitaka; Takahashi, Seiichi; Tominaga, Gen; Takahashi, Hiroki; Takagi, Sho; Obana, Nobuya; Kikuchi, Tatsuya; Oomori, Shinya; Nomura, Eiki; Shiraki, Manabu; Sato, Yuichirou; Takahashi, Shuichiro; Umemura, Ken; Yokoyama, Hiroshi; Endo, Katsuya; Kakuta, Yoichi; Aizawa, Hiroki; Matsuura, Masaki; Kimura, Tomoya; Kuroha, Masatake; Shimosegawa, Tooru

2013-01-01

Objective Stress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake. Design A retrospective cohort study. Settings 13 hospitals in Japan. Participants 546 ulcerative colitis (UC) and 357 Crohn's disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patient's clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records. Primary outcome We evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined ‘active’ as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD). Results Among the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p<0.0001). A total of 86 patients relapsed (relapse rate=15.8%). The relapse rate was about twice that of the corresponding period in the previous year. Among the CD patients, 86 patients had active disease and 271 had inactive disease before the earthquake. After the earthquake, the activity indices changed little. A total of 25 patients experienced a relapse (relapse rate=7%). The relapse rate did not differ from that of the corresponding period in the previous year. Multivariate analyses revealed that UC, changes in dietary oral intake and anxiety about family finances were associated with the relapse. Conclusions Life-event stress induced by the Great East Japan Earthquake was associated with relapse in UC but not CD. PMID:23396562

Clonal Evolution of Chemotherapy-resistant Urothelial Carcinoma

PubMed Central

Faltas, Bishoy M.; Prandi, Davide; Tagawa, Scott T.; Molina, Ana M.; Nanus, David M.; Sternberg, Cora; Rosenberg, Jonathan; Mosquera, Juan Miguel; Robinson, Brian; Elemento, Olivier; Sboner, Andrea; Beltran, Himisha; Demichelis, Francesca; Rubin, Mark A.

2017-01-01

Chemotherapy-resistant urothelial carcinoma (UC) has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs UC’s evolution and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 UCs including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated UC is characterized by intra-patient mutational heterogeneity and the majority of mutations are not shared, (ii) both branching evolution and metastatic spread are very early events in the natural history of UC; (iii) chemotherapy-treated UC is enriched with clonal mutations involving L1-cell adhesion molecule (L1CAM) and integrin signaling pathways; (iv) APOBEC induced-mutagenesis is clonally-enriched in chemotherapy-treated UC and continues to shape UC’s evolution throughout its lifetime. PMID:27749842

[Clinical extraintestinal manifestations in patients with ulcerative colitis].

PubMed

Toader, Elena

2007-01-01

Ulcerative colitis (UC) is a chronic disease clinically manifest either by bowel symptoms alone or extraintestinal symptoms. Our prospective study included 635 patients with ulcerative colitis (334 males and 301 females, mean age 37.54 +/- 13.84, range 20-70 years). The presence of the common extraintestinal symptoms (ES) was analyzed. Of the 635 investigated patients, these symptoms were found in 83 (13%, 49 males and 34 females, mean age 41.6 +/- 13.95 range 21-70). Patients with ES suffered longer from UC on the average, that is 60.6 years. Most commonly ES involved the joints, 38 (45.8%) patients, hepatobiliary, 28 patients (33.7%), skin, 10 patients (12%) and eyes, 7 patients (8.4%). In 18% of the patients two or more ES were present. ES were clinically detectable after the intestinal symptoms in 81% patients. An increased tendency of ES to occur in patients with a more extensive disease was noticed. The prevalence of ES in the UC patients from NE Romania is in agreement with data from other countries. The number of ES supports the need for complex follow-up in these patients.

Emerging Treatment Options in Mild to Moderate Ulcerative Colitis

PubMed Central

Lichtenstein, Gary R.; Hanauer, Stephen B.; Sandborn, William J.

2015-01-01

Ulcerative colitis (UC) is a chronic inflammatory condition associated with rectal bleeding and urgency, tenesmus, and diarrhea. Several medical therapies can be used in the treatment of UC. Aminosalicylates are widely used based on their efficacy in the induction and maintenance of remission. Although corticosteroids are effective in patients with more severe disease, systemic use is associated with significant safety concerns. The newer corticosteroid budesonide has lower systemic bioavailability and, consequently, a more favorable safety profile. A budesonide extended-release formulation allows once-daily dosing and delivers the agent locally throughout the colon. Biologic agents used for the treatment of moderate to severe UC include the tumor necrosis factor inhibitors infliximab, adalimumab, and golimumab, and the integrin inhibitor vedolizumab. Rectally administered therapy can also be useful in the treatment of UC. In October 2014, the US Food and Drug Administration approved a budesonide foam formulation for inducing remission in patients with active mild to moderate distal UC extending up to 40 cm from the anal verge. Budesonide foam rapidly distributes to the sigmoid colon and the rectum and avoids some of the drawbacks of suppositories and enemas. PMID:26491415

Mesalamine in the treatment and maintenance of remission of ulcerative colitis

PubMed Central

Ham, Maggie; Moss, Alan C

2012-01-01

Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA. PMID:22390554

Mesalamine in the treatment and maintenance of remission of ulcerative colitis.

PubMed

Ham, Maggie; Moss, Alan C

2012-03-01

Ulcerative colitis (UC) is a chronic disease of the GI tract that is characterized by mucosal inflammation in the colon. Mesalamine (mesalazine) is a 5-aminosalicylic acid compound that is the first-line treatment for patients with mild-to-moderate UC. There are multiple formulations of mesalamine available, primarily differentiated by their means of delivering active mesalamine to the colon. Mesalamine has been demonstrated in randomized controlled trials to induce both clinical response and remission, and maintain clinical remission, in these patients. It has few serious adverse effects and is generally well tolerated by patients. The main areas of uncertainty with use of mesalamine in patients with UC center on the optimal dose for induction of response, how to maintain patient adherence and the role of mesalamine in cancer chemoprophylaxis. Generic forms of mesalamine have yet to be approved by regulatory bodies in the USA.

Pooled Resequencing of 122 Ulcerative Colitis Genes in a Large Dutch Cohort Suggests Population-Specific Associations of Rare Variants in MUC2.

PubMed

Visschedijk, Marijn C; Alberts, Rudi; Mucha, Soren; Deelen, Patrick; de Jong, Dirk J; Pierik, Marieke; Spekhorst, Lieke M; Imhann, Floris; van der Meulen-de Jong, Andrea E; van der Woude, C Janneke; van Bodegraven, Adriaan A; Oldenburg, Bas; Löwenberg, Mark; Dijkstra, Gerard; Ellinghaus, David; Schreiber, Stefan; Wijmenga, Cisca; Rivas, Manuel A; Franke, Andre; van Diemen, Cleo C; Weersma, Rinse K

2016-01-01

Genome-wide association studies have revealed several common genetic risk variants for ulcerative colitis (UC). However, little is known about the contribution of rare, large effect genetic variants to UC susceptibility. In this study, we performed a deep targeted re-sequencing of 122 genes in Dutch UC patients in order to investigate the contribution of rare variants to the genetic susceptibility to UC. The selection of genes consists of 111 established human UC susceptibility genes and 11 genes that lead to spontaneous colitis when knocked-out in mice. In addition, we sequenced the promoter regions of 45 genes where known variants exert cis-eQTL-effects. Targeted pooled re-sequencing was performed on DNA of 790 Dutch UC cases. The Genome of the Netherlands project provided sequence data of 500 healthy controls. After quality control and prioritization based on allele frequency and pathogenicity probability, follow-up genotyping of 171 rare variants was performed on 1021 Dutch UC cases and 1166 Dutch controls. Single-variant association and gene-based analyses identified an association of rare variants in the MUC2 gene with UC. The associated variants in the Dutch population could not be replicated in a German replication cohort (1026 UC cases, 3532 controls). In conclusion, this study has identified a putative role for MUC2 on UC susceptibility in the Dutch population and suggests a population-specific contribution of rare variants to UC.

Association Study of Klotho Gene Polymorphism With Calcium Oxalate Stones in The Uyghur Population of Xinjiang, China.

PubMed

Ali, Abdusamat; Tursun, Halmurat; Talat, Alim; Abla, Akpar; Muhtar, Erpan; Zhang, Tao; Mahmut, Murat

2017-01-18

The aim of the present study was to investigate the correlation between Klotho gene polymorphisms andcalcium oxalate stones in Xinjiang Uyghur people. We compared 128 patients with calcium oxalate stones (case group) and 94 healthypeople (control group), detected the genotype and allele distributions of single-nucleotide polymorphisms (SNPs)of the Klotho gene (rs3752472, rs650439, and rs1207568) by reverse transcription polymerase chain reaction. The distributions of the genotype and allele frequencies of the SNPs were consistent with the Hardy-Weinberg equilibrium in the two groups. There were statistically significant differences between the genotype andallele distributions of rs3752472 between the case and control groups; the allele frequencies in the case/controlgroups were C = 240 (93.7%)/151 (80.3%) and T = 16 (6.3%)/37 (19.7%). There was no statistically significantdifference in the genotype distribution of rs650439 between the case and control groups, but there was a differencein the allele distribution; the allele frequencies in the case/control groups were A = 202 (78.9%)/143 (57.2%) andT = 54 (21.1%)/107 (42.8%). There were no statistically significant differences in genotype and allele distributionsbetween the case and control groups of rs1207568; the allele frequencies in the case/control groups were C = 194(71.3%)/145 (77.1%) and T = 78 (28.7%)/43 (22.9%). In rs3752472, the risk for patients with the C and A allelesincreased by 3.675 and 2.799 times, respectively. The rs3752472 and rs650439 SNPs are related to the risk of calcium oxalate stones in Xinjiang Uyghurpeople, and might be one of the risk factors.

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

PubMed

Gurudu, S R; Griffel, L H; Gialanella, R J; Das, K M

1999-09-01

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

Systematic analysis of annual health resource utilization and costs in hospitalized patients with inflammatory bowel disease in Switzerland.

PubMed

Schoepfer, Alain; Vavricka, Stephan R; Brüngger, Beat; Reich, Oliver; Blozik, Eva; Bähler, Caroline

2018-05-11

Real-life data on health resource utilization and costs of hospitalized patients with inflammatory bowel disease are lacking in Switzerland. We aimed to assess health resource utilization and costs during a 1-year follow-up period starting with an index hospitalization. On the basis of claims data of the Helsana health insurance group, health resource utilization was assessed and costs reimbursed by mandatory basic health insurance [in Swiss Francs (CHF); 1 CHF=0.991 US$] were calculated during a 1-year follow-up period starting with an index hospitalization in the time period between 1 January 2013 and 31 December 2014. Of 202 002 patients with at least one hospitalization in 2013-2014, a total of 270 (0.13%) patients had inflammatory bowel disease as main diagnosis [112 (41.5%) ulcerative colitis (UC), 158 (58.5%) Crohn's disease (CD), 154/270 (57.0%) females]. In comparison with patients with UC, patients with CD were significantly more frequently treated with biologics (45.6 vs. 20.5%, P<0.001) and more frequently underwent surgery during index hospitalization (27.8 vs. 9.8%, P=0.002). Compared with patients with UC, those with CD had significantly more consultations [odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01-1.12, P=0.016], higher median annual total costs (OR: 1.25, 95% CI: 1.05-1.48, P=0.012), and higher outpatient costs (OR: 1.33, 95% CI: 1.07-1.66, P=0.011). In the bivariate model, median total costs for patients with CD and those with UC were 24 270 and 17 270 CHF, respectively (P=0.032). When compared with patients with UC, hospitalized patients with CD have during a 1-year follow-up a higher rate of outpatient consultations and generate higher costs.

Serum levels of soluble CD30 are increased in ulcerative colitis (UC) but not in Crohn's disease (CD)

PubMed Central

Giacomelli, R; Passacantando, A; Parzanese, I; Vernia, P; Klidara, N; Cucinelli, F; Lattanzio, R; Santori, E; Cipriani, P; Caprilli, R; Tonietti, G

1998-01-01

Imbalance in Th1 and Th2 subsets and their derived cytokines seems to be involved in the immune abnormalities underlying UC and CD. CD30 is a member of the tumour necrosis factor/nerve growth receptor superfamily expressed on T cells producing Th2 cytokines and released as a soluble form. In this study high levels of soluble CD30 were found in sera of UC patients independently of disease activity. Furthermore, increased titres of soluble CD30 molecule were shown, in the same patients, by mitogen-stimulated cultures of peripheral blood mononuclear cells. Our data seem to indicate that an activation of Th2 immune response is involved in the pathogenesis of UC, but not of CD. Furthermore, this finding indicates that serum soluble CD30 measurement may be helpful for differentiating these two forms of inflammatory bowel disease. PMID:9528894

A case of pyoderma gangrenosum with ulcerative colitis treated with mesalazine.

PubMed

Lee, Jae In; Park, Hyun Jeong; Lee, Jun Young; Cho, Baik Kee

2010-11-01

Pyoderma gangrenosum (PG) manifests as recurrent deep ulceration of the skin and PG is associated with a variety of disorders. Approximately 30% of the cases of PG develop in patients with inflammatory bowel disease. A 34-year-old woman presented with a one-week history of recurrent ulcers on the right cheek and back. She was diagnosed with ulcerative colitis (UC) 4 years previously and with PG 1 year previously. The clinical course of the skin lesions followed the status of her UC. The patient's skin lesions and bowel symptoms were not improved with prednisolone. After she was started on mesalazine, we observed rapid resolution of skin lesions and bowel symptoms. Herein, we report a case of recurrent PG with UC, and we discuss the possible association between these two conditions, and the efficacy of mesalazine therapy for the treatment of PG combined with UC.

Plant-based ointments versus usual care in the management of chronic skin diseases: a comparative analysis on outcome and safety.

PubMed

Jong, Miek C; Ermuth, Ulrike; Augustin, Matthias

2013-10-01

To assess the outcome and safety of plant-based ointments versus usual care in the management of chronic skin diseases. Prospective mono-centric comparative analysis. Patients were recruited at an outpatient dermatology clinic and treated with plant-based ointments or care as usual. Main outcome criterion was the response rate, defined as the proportion of patients experiencing 'complete recovery' or 'major improvement' at 6, 12 and 24 months. Secondary outcome criteria were quality of life (SF-12 and EQ-5D), patient satisfaction and safety of treatment. A total of 112 patients with chronic skin diseases were evaluated of which 44 were treated with plant-based ointments (PO) and 68 received usual care (UC). The majority of patients suffered from psoriasis (PO: 50%; UC: 56%) or eczema (PO: 41%; UC: 32%) and were treated with homoeopathic topical ointments containing mahonia or cardiospermum or usual care creams containing calcipotriene and corticosteroids. The only significant difference in baseline status between the two groups was in disease severity score (PO: 1.8±0.7 versus UC: 2.4±0.8, p=0.0004). After two years, the main outcome of responders to treatment was 52.3% (95%-CI: 36.1-64.9) in the ointment and 41.2% (95%-CI: 20.4-42.2) in the UC group. Change in SF-12 (2 years compared to baseline), adjusted for baseline disease severity, was not significantly different between both groups; PO: 5.4 (95%-CI: 3.4-7.3) versus UC: 3.2 (95%-CI: 1.5-4.9). The adjusted EQ-5D was found to be significantly different between the two groups after two years, in favour of the ointment group; PO: 0.113 (95%-CI: 0.052-0.174) and UC: -0.008 (95%-CI: -0.055-0.038). Other secondary outcome parameters such as patient satisfaction and number of adverse drug reactions were comparable. The outcome of this study suggests at least therapeutic equivalence between plant-based ointments and usual care management of chronic skin diseases. As this non-randomised study was open to selection and other bias, further rigorous studies are needed to demonstrate the effectiveness of these topical products. Copyright © 2013 Elsevier Ltd. All rights reserved.

Telemonitoring of CPAP therapy may save nursing time.

PubMed

Anttalainen, Ulla; Melkko, Sari; Hakko, Sirkka; Laitinen, Tarja; Saaresranta, Tarja

2016-12-01

Telemonitoring might enhance continuous positive airway pressure (CPAP) adherence and save nursing time at the commencement of CPAP therapy. We tested wireless telemonitoring (ResTraxx Online System®, ResMed) during the habituation phase of the CPAP therapy in obstructive sleep apnea syndrome (OSAS). In total, 111 consecutive OSAS patients were enrolled. After CPAP titration, patients were followed with the telemonitoring (TM, N = 50) or the usual care (UC, N = 61). The TM group used fixed pressure CPAP device with and the UC group similar device without wireless telemonitoring. Patients and study nurses were unblinded. The evaluated end-points were hours of CPAP use >4 h/day, mask leak <0.4 L/s, and AHI <5/h. Nursing time including extra phone calls, visits, and telemonitoring time was recorded during the habituation phase. CPAP adherence was controlled in the beginning and at the end of the habituation phase and after 1-year of use. TM and UC groups did not differ in terms of patient characteristics. The average length of the habituation phase was 4 weeks in the TM group and fixed 3 months in the UC group. Median nursing time was 39 min (range 12-132 min) in the TM group and shorter compared to that of 58 min (range 40-180 min) (p < 0.001) per patient in the UC group. Both treatment groups had high CPAP usage hours (>4 h/day) and the change in usage at the end of the habituation phase did not differ between the groups (p = 0.39). Patients in both groups were equally satisfied with the treatment protocol. CPAP adherence (6.4 h in TM vs. 6.1 h in UC group, p = 0.63) and residual AHI (1.3 in TM vs. 3.2 in UC group, p = 0.04) were good in both groups at 1-year follow-up. Wireless telemonitoring of CPAP treatment could be relevant in closing the gap between the increasing demand and available health-care resources. It may save nursing time without compromising short- or long-term effectiveness of CPAP treatment in OSAS.

Novel, Objective, Multivariate Biomarkers Composed of Plasma Amino Acid Profiles for the Diagnosis and Assessment of Inflammatory Bowel Disease

PubMed Central

Hisamatsu, Tadakazu; Okamoto, Susumu; Hashimoto, Masaki; Muramatsu, Takahiko; Andou, Ayatoshi; Uo, Michihide; Kitazume, Mina T.; Matsuoka, Katsuyoshi; Yajima, Tomoharu; Inoue, Nagamu; Kanai, Takanori; Ogata, Haruhiko; Iwao, Yasushi; Yamakado, Minoru; Sakai, Ryosei; Ono, Nobukazu; Ando, Toshihiko; Suzuki, Manabu; Hibi, Toshifumi

2012-01-01

Background Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). Methodology and Principal Findings We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898–0.983) and 0.894 (95%CI: 0.853–0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853–0.935) and 0.849 (95%CI: 0.770–0.928), and correlated with clinical disease activity indexes for CD (rs = 0.592, 95%CI: 0.385–0.742, p<0.001) or UC (rs = 0.598, 95%CI: 0.452–0.713, p<0.001), respectively. Conclusions and Significance In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease. PMID:22303484

A multicenter, randomized trial of a nurse-led, home-based intervention for optimal secondary cardiac prevention suggests some benefits for men but not for women: the Young at Heart study.

PubMed

Carrington, Melinda J; Chan, Yih-Kai; Calderone, Alicia; Scuffham, Paul A; Esterman, Adrian; Goldstein, Stan; Stewart, Simon

2013-07-01

We examined the impact of a prolonged secondary prevention program on recurrent hospitalization in cardiac patients with private health insurance. The Young at Heart multicenter, randomized, controlled trial compared usual postdischarge care (UC) with nurse-led, home-based intervention (HBI). The primary end point was rate of all-cause hospital stay (31.5±7.5 months follow-up). In total, 602 patients (aged 70±10 years, 72% men) were randomized to UC (n=296) or HBI (n=306, 96% received ≥1 home visit). Overall, 42 patients (7.0%) died, and 492 patients (82%) accumulated 2397 all-cause hospitalizations associated with 10,258 hospital days costing >$17 million. There were minimal group differences (HBI versus UC) in the primary end point of all-cause hospital stay (5405 versus 4853 days; median [interquartile range], 0.08 [0.03-0.17] versus 0.07 [0.03-0.13]/patient per month). There were similar trends with respect to all hospitalizations (1197 versus 1200; P=0.802) and associated costs ($8.66 versus $8.58 million; P=0.375). At 2 years, however, more HBI versus UC (39% versus 27%; odds ratio, 1.67; 95% confidence interval, 1.15-2.41; P=0.007) patients were assessed as stable and optimally managed. For women, HBI outcomes were predominantly worse than UC outcomes. In men, HBI was associated with reduced risk of cardiovascular hospitalization (adjusted hazard ratio, 0.68; 95% confidence interval, 0.46-0.99; P=0.044) with less cardiovascular hospitalizations (192 versus 269; P=0.054) and costs ($2.49 versus $3.53 million; P=0.046). HBI did not reduce recurrent all-cause hospitalization compared with UC in privately insured cardiac patients overall. However, it did convey some benefits in cardiac outcomes for men. Australian New Zealand Clinical Trials Registry Unique Identifier: 12608000014358. URL: http://www.anzctr.org.au/trial_view.aspx?id=82509.

Palliative Care in Heart Failure: The PAL-HF Randomized, Controlled Clinical Trial.

PubMed

Rogers, Joseph G; Patel, Chetan B; Mentz, Robert J; Granger, Bradi B; Steinhauser, Karen E; Fiuzat, Mona; Adams, Patricia A; Speck, Adam; Johnson, Kimberly S; Krishnamoorthy, Arun; Yang, Hongqiu; Anstrom, Kevin J; Dodson, Gwen C; Taylor, Donald H; Kirchner, Jerry L; Mark, Daniel B; O'Connor, Christopher M; Tulsky, James A

2017-07-18

Advanced heart failure (HF) is characterized by high morbidity and mortality. Conventional therapy may not sufficiently reduce patient suffering and maximize quality of life. The authors investigated whether an interdisciplinary palliative care intervention in addition to evidence-based HF care improves certain outcomes. The authors randomized 150 patients with advanced HF between August 15, 2012, and June 25, 2015, to usual care (UC) (n = 75) or UC plus a palliative care intervention (UC + PAL) (n = 75) at a single center. Primary endpoints were 2 quality-of-life measurements, the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary and the Functional Assessment of Chronic Illness Therapy-Palliative Care scale (FACIT-Pal), assessed at 6 months. Secondary endpoints included assessments of depression and anxiety (measured via the Hospital Anxiety and Depression Scale [HADS]), spiritual well-being (measured via the FACIT-Spiritual Well-Being scale [FACIT-Sp]), hospitalizations, and mortality. Patients randomized to UC + PAL versus UC alone had clinically significant incremental improvement in KCCQ and FACIT-Pal scores from randomization to 6 months (KCCQ difference = 9.49 points, 95% confidence interval [CI]: 0.94 to 18.05, p = 0.030; FACIT-Pal difference = 11.77 points, 95% CI: 0.84 to 22.71, p = 0.035). Depression improved in UC + PAL patients (HADS-depression difference = -1.94 points; p = 0.020) versus UC-alone patients, with similar findings for anxiety (HADS-anxiety difference = -1.83 points; p = 0.048). Spiritual well-being was improved in UC + PAL versus UC-alone patients (FACIT-Sp difference = 3.98 points; p = 0.027). Randomization to UC + PAL did not affect rehospitalization or mortality. An interdisciplinary palliative care intervention in advanced HF patients showed consistently greater benefits in quality of life, anxiety, depression, and spiritual well-being compared with UC alone. (Palliative Care in Heart Failure [PAL-HF]; NCT01589601). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Once-daily Mesalamine Formulation for Maintenance of Remission in Ulcerative Colitis: A Randomized, Placebo-controlled Clinical Trial.

PubMed

Gordon, Glenn L; Zakko, Salam; Murthy, Uma; Sedghi, Shahriar; Pruitt, Ronald; Barrett, Andrew C; Bortey, Enoch; Paterson, Craig; Forbes, William P; Lichtenstein, Gary R

2016-04-01

To evaluate the efficacy and safety of mesalamine granules 1.5 g once daily for maintenance of ulcerative colitis (UC) remission. Mesalamine is a first-line treatment for induction and maintenance of UC remission. A phase 3, randomized, double-blind, placebo-controlled trial of patients with a history of mild to moderate UC, currently in remission, who received mesalamine granules once daily for 6 months. The primary efficacy endpoint was percentage of patients maintaining UC remission at 6 months. A significantly greater percentage of patients receiving mesalamine granules versus placebo were in remission at 6 months (79.9% vs. 66.7%; P=0.03). A greater percentage of patients receiving mesalamine granules maintained a revised Sutherland Disease Activity Index (SDAI)≤2 with no individual component of revised SDAI>1 and rectal bleeding=0 at 6 months (72.0% vs. 58.1%; P=0.04). No significant differences between groups were observed for change from baseline to 6 months for total SDAI score or its components (ie, stool frequency, rectal bleeding, mucosal appearance, physician's rating of disease). Mesalamine granules treatment resulted in a significantly longer remission duration versus placebo (P=0.02) and decreased patients' risk of relapse by 43% (hazard ratio=0.57; 95% confidence interval, 0.35-0.93; P=0.02). Mesalamine granules were well tolerated, and adverse events related to hepatic, renal, and pancreatic function-potential concerns with long-term treatment-occurred at a rate similar to placebo. Once-daily mesalamine granules are efficacious and safe for the maintenance of UC remission.

Population pharmacokinetics-pharmacodynamics of vedolizumab in patients with ulcerative colitis and Crohn's disease.

PubMed

Rosario, M; Dirks, N L; Gastonguay, M R; Fasanmade, A A; Wyant, T; Parikh, A; Sandborn, W J; Feagan, B G; Reinisch, W; Fox, I

2015-07-01

Vedolizumab, an anti-α(4)β(7) integrin monoclonal antibody (mAb), is indicated for treating patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). As higher therapeutic mAb concentrations have been associated with greater efficacy in inflammatory bowel disease, understanding determinants of vedolizumab clearance may help to optimise dosing. To characterise vedolizumab pharmacokinetics in patients with UC and CD, to identify clinically relevant determinants of vedolizumab clearance, and to describe the pharmacokinetic-pharmacodynamic relationship using population modelling. Data from a phase 1 healthy volunteer study, a phase 2 UC study, and 3 phase 3 UC/CD studies were included. Population pharmacokinetic analysis for repeated measures was conducted using nonlinear mixed effects modelling. Results from the base model, developed using extensive phase 1 and 2 data, were used to develop the full covariate model, which was fit to sparse phase 3 data. Vedolizumab pharmacokinetics was described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half-life of vedolizumab was 25.5 days; linear clearance (CL(L)) was 0.159 L/day for UC and 0.155 L/day for CD; central compartment volume of distribution (V(c)) was 3.19 L; and peripheral compartment volume of distribution was 1.66 L. Interindividual variabilities (%CV) were 35% for CLL and 19% for V(c); residual variance was 24%. Only extreme albumin and body weight values were identified as potential clinically important predictors of CL(L). Population pharmacokinetic parameters were similar in patients with moderately to severely active UC and CD. This analysis supports use of vedolizumab fixed dosing in these patients. Clinicaltrials.gov Identifiers: NCT01177228; NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2); NCT01224171 (GEMINI 3). © 2015 Takeda Pharmaceuticals International Co published by John Wiley & Sons Ltd.

Cost and resource utilization associated with use of computed tomography to evaluate chest pain in the emergency department: the Rule Out Myocardial Infarction using Computer Assisted Tomography (ROMICAT) study.

PubMed

Hulten, Edward; Goehler, Alexander; Bittencourt, Marcio Sommer; Bamberg, Fabian; Schlett, Christopher L; Truong, Quynh A; Nichols, John; Nasir, Khurram; Rogers, Ian S; Gazelle, Scott G; Nagurney, John T; Hoffmann, Udo; Blankstein, Ron

2013-09-01

Coronary computed tomographic angiography (cCTA) allows rapid, noninvasive exclusion of obstructive coronary artery disease (CAD). However, concern exists whether implementation of cCTA in the assessment of patients presenting to the emergency department with acute chest pain will lead to increased downstream testing and costs compared with alternative strategies. Our aim was to compare observed actual costs of usual care (UC) with projected costs of a strategy including early cCTA in the evaluation of patients with acute chest pain in the Rule Out Myocardial Infarction Using Computer Assisted Tomography I (ROMICAT I) study. We compared cost and hospital length of stay of UC observed among 368 patients enrolled in the ROMICAT I study with projected costs of management based on cCTA. Costs of UC were determined by an electronic cost accounting system. Notably, UC was not influenced by cCTA results because patients and caregivers were blinded to the cCTA results. Costs after early implementation of cCTA were estimated assuming changes in management based on cCTA findings of the presence and severity of CAD. Sensitivity analysis was used to test the influence of key variables on both outcomes and costs. We determined that in comparison with UC, cCTA-guided triage, whereby patients with no CAD are discharged, could reduce total hospital costs by 23% (P<0.001). However, when the prevalence of obstructive CAD increases, index hospitalization cost increases such that when the prevalence of ≥ 50% stenosis is >28% to 33%, the use of cCTA becomes more costly than UC. cCTA may be a cost-saving tool in acute chest pain populations that have a prevalence of potentially obstructive CAD <30%. However, increased cost would be anticipated in populations with higher prevalence of disease.

[Integrated management of patients with chronic inflammatory bowel disease in the Rhine-Main Region: results of the first integrated health-care project IBD in Germany].

PubMed

Blumenstein, I; Tacke, W; Filmann, N; Zosel, C; Bock, H; Heuzeroth, V; Zeuzem, S; Schröder, O

2013-07-01

In our previous studies investigating the drug therapy in patients suffering from inflammatory bowel disease (IBD) in the Rhein-Main region, Germany, we detected serious discrepancies between treatment reality and treatment guidelines. Consecutively, patient outcome in this cohort was compromised. Following this pilot project a network between primary deliverers of care for IBD patients and one large health-care insurance company [BKK Taunus (Gesundheit), the second largest insurance company in Hessen, Germany] was established. An analysis of treatment and socioeconomic data from 220 IBD patients (Crohn's disease - CD = 96, ulcerative colitis - UC = 124) entering the integrative health-care programme between 1.1.-30.9.2009 was performed. Remission rates for CD and UC in the integrated health-care programme could be improved from 60 - 73 % (CD) and from 61 - 79 % (UC). Guideline-conform treatment was observed in 81 % of patients with CD and 85 % with UC, respectively. Although medication costs increased, total costs could be cut by 162 304.- €, as secondary costs for hospitalisation and days off work could be reduced. The study shows that networking of deliverers of care for IBD patients with health insurances provides an excellent possibility to optimise medical treatment and can cut down costs significantly. © Georg Thieme Verlag KG Stuttgart · New York.

Prospective randomized controlled trial comparing the outcomes and costs of two eyecare adherence interventions in diabetes patients.

PubMed

Pizzi, Laura T; Zangalli, Camila S; Murchison, Ann P; Hale, Nicole; Hark, Lisa; Dai, Yang; Leiby, Benjamin E; Haller, Julia A

2015-04-01

Diabetic retinopathy is one of the leading causes of vision impairment among adults in the USA. While it is suggested that diabetics receive annual dilated fundus examinations (DFE), many patients do not adhere to these recommendations. This paper investigates the outcomes and costs of an educational and telephone intervention on DFE follow-up adherence in patients with diabetes. In a prospective trial, 356 diabetic patients due for a DFE at an urban eye clinic were randomly assigned to usual care (UC; reference case), mailed intervention (MI), or telephone intervention (TI). UC patients (n = 119) received a standard form letter. MI patients (n = 117) received a personalized letter encouraging scheduling of an eye examination with an educational brochure about diabetic eye disease. TI patients (n = 120) received personal calls (up to three attempts) to schedule a follow-up with standard form letter. The primary outcome was obtaining a DFE within 90 days of suggested return. Costs (US$ 2013) included time costs for staff, phone charges, supplies, and postage. Since TI involved greater cost components compared to MI, univariate sensitivity analysis examined the impact of reducing phone costs. Patients were mostly female (66 %) and African American (70 %) with a mean age of 61 years. TI patients were more likely to schedule DFE [65 vs. 42 %; relative risk (RR) 1.54; CI 1.20-1.96; P < 0.001] versus UC patients. Obtaining a DFE within 90 days of suggested return was also significantly higher among TI patients compared to UC patients (51 vs. 36 %, RR 1.41; CI 1.05-1.89; P = 0.024). MI patients were slightly less likely to schedule DFE versus UC patients (38 vs. 42 %, RR 0.90; CI 0.66-1.22; P = NSS) and obtain a DFE (32 vs. 36 %; RR 0.90; CI 0.63-1.28; P = NSS). The total cost of TI was US$798.28 or US$6.65/patient and the cost/follow-up DFE was US$26.05. Sensitivity analyses revealed that the cost/follow-up can be greatly reduced but remains greater compared to UC (US$2.76 if US$0.25/call, US$11.13 if $1/call; US$22.29 if US$2/call). Personal phone assistance in scheduling DFE follow-up is more effective but also more costly. Follow-up research has been initiated to determine whether automated phone reminders can achieve similar effectiveness at a lower cost.

The Relevance of Vitamin and Iron Deficiency in Patients with Inflammatory Bowel Diseases in Patients of the Swiss IBD Cohort.

PubMed

Madanchi, Matiar; Fagagnini, Stefania; Fournier, Nicolas; Biedermann, Luc; Zeitz, Jonas; Battegay, Edouard; Zimmerli, Lukas; Vavricka, Stephan R; Rogler, Gerhard; Scharl, Michael

2018-04-13

Vitamin and iron deficiencies are common in patients with inflammatory bowel disease (IBD) as a result of chronic intestinal inflammation, increase in demand, or dietary restrictions. Here, we assessed the frequency of complications in relation to deficiency of iron, folate acid, and vitamin B12 in patients enrolled in the nationwide Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). A total of 2666 patients were included in the study, 1558 with Crohn's disease (CD) and 1108 with ulcerative colitis (UC). Iron deficiency anemia was detected in 19.6% of CD patients and 21.6% of UC patients. In CD patients low BMI and nonsmoker status were positively associated with anemia. In both CD and UC, malabsorption syndrome, defined as failure of the GI tract to absorb 1 or more substances from the diet, was found to be significantly associated with anemia (6.2% and 3.8%, respectively) and current steroid use (40% CD, 52.7% UC). In CD patients with ileal (31.7% vs 20%) and colonic (29.9% vs 25%) disease location folate deficiency was significantly higher than in patients with ileocolonic CD or upper GI involvement. In CD patients, vitamin B12 deficiency was associated with the onset of stenosis and intestinal surgery (42.9% vs 32.8% and 46% vs 33% for patients with versus without B12 deficiency). Our data indicate that due to frequent occurrence of deficiency states, regular monitoring and substitution of vitamins and iron are mandatory and may prevent long-term intestinal and extraintestinal complications in IBD patients.

Systematic review with meta-analysis: the effect of tobacco smoking on the natural history of ulcerative colitis.

PubMed

To, N; Ford, A C; Gracie, D J

2016-07-01

Tobacco smoking is associated with a reduced risk of developing ulcerative colitis (UC). A high proportion of UC patients perceive a benefit in disease outcomes secondary to smoking. However, the effects of smoking on the natural history of UC are uncertain. To conduct a systematic review and meta-analysis of the effects of tobacco smoking on the natural history of UC. A search of MEDLINE, EMBASE and EMBASE classic was carried out (up to December 2015) to identify observational studies reporting data on smoking and rates of colectomy, flare of disease activity, proximal disease extension, and development of pouchitis following panproctocolectomy and ileal pouch-anal anastomosis in patients with UC. Dichotomous data were pooled to obtain odds ratios (ORs), with 95% confidence intervals (CIs). The search identified 16 eligible studies: five (2615 patients) studying colectomy; four (620 patients) reporting on flare of disease activity; four (687 patients) examining proximal disease extension and three (355 patients) assessing development of pouchitis. Compared with nonsmokers, the odds of colectomy (OR = 0.89; 95% CI 0.62-1.26), flare of disease activity (OR = 1.26; 95% CI 0.65-2.44), proximal extension of disease (OR = 0.57; 95% CI 0.20-1.66) or the development of pouchitis (OR = 0.57; 95% CI 0.21-1.53) were not significantly lower in smokers. Smoking may not improve the natural history of ulcerative colitis. Given the health benefits of smoking cessation and the lack of clear benefit in ulcerative colitis, smoking cessation advice should be incorporated into guidance on the management of ulcerative colitis. © 2016 John Wiley & Sons Ltd.

Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease.

PubMed

Israeli, E; Grotto, I; Gilburd, B; Balicer, R D; Goldin, E; Wiik, A; Shoenfeld, Y

2005-09-01

Several antibodies have been reported in the sera of patients with Crohn's disease (CD) and ulcerative colitis (UC). The most commonly described are anti-Saccharomyces cerevisiae mannan antibodies (ASCA) in CD and perinuclear antineutrophil cytoplasm antibodies (pANCA) in UC. Familial clustering of these antibodies has been described, suggesting they might be genetic markers. Our aim was to investigate the presence of these antibodies before the emergence of overt clinical manifestations. Since 1980, the Israeli Defense Force (IDF) Medical Corps Serum Repository has stored serum samples obtained systematically from 5% of all recruits on enlistment, and from the same population on discharge from compulsory military service. We evaluated serum samples obtained from 32 subjects with CD and eight with UC before they were clinically diagnosed, along with samples from matched controls. ASCA were present in 10/32 (31.3%) CD patients before clinical diagnosis compared with 0/95 (0%) controls (p<0.001). None of the eight patients with serum samples available before diagnosis of UC were ASCA positive. ASCA was positive in 54.5% of patients after diagnosis of CD. The mean interval between ASCA detection and diagnosis was 38 months. In 90% of patients, antibodies were detected in the first available serum sample; therefore, measurements of the average time from the presence of ASCA to diagnosis may be even longer. pANCA were present in 2/8 (25%) patients with available sera before the diagnosis of UC. None of their 24 matched controls were positive (p = 0.014). ASCA and pANCA may predict development of inflammatory bowel disease years before the disease is clinically diagnosed.

ATM/RB1 mutations predict shorter overall survival in urothelial cancer.

PubMed

Yin, Ming; Grivas, Petros; Emamekhoo, Hamid; Mendiratta, Prateek; Ali, Siraj; Hsu, JoAnn; Vasekar, Monali; Drabick, Joseph J; Pal, Sumanta; Joshi, Monika

2018-03-30

Mutations of DNA repair genes, e.g. ATM/RB1 , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of ATM/RB1 mutations in UC can inform clinical decision making and trial designs. In the discovery dataset, ATM/RB1 mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, p = 0.002). There was a higher mutation load in patients carrying ATM/RB1 mutations (median mutation load: 6.7 versus 5.5 per Mb, p = 0.072). In the validation dataset, ATM/RB1 mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, p = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, p = 0.126). Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of ATM/RB1 mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS). ATM/RB1 mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of ATM/RB1 mutation status to immunotherapy and platinum-based chemotherapy.

Cost-Effectiveness of a Technology-Facilitated Depression Care Management Adoption Model in Safety-Net Primary Care Patients with Type 2 Diabetes.

PubMed

Hay, Joel W; Lee, Pey-Jiuan; Jin, Haomiao; Guterman, Jeffrey J; Gross-Schulman, Sandra; Ell, Kathleen; Wu, Shinyi

2018-05-01

The Diabetes-Depression Care-Management Adoption Trial is a translational study of safety-net primary care predominantly Hispanic/Latino patients with type 2 diabetes in collaboration with the Los Angeles County Department of Health Services. To evaluate the cost-effectiveness of an information and communication technology (ICT)-facilitated depression care management program. Cost-effectiveness of the ICT-facilitated care (TC) delivery model was evaluated relative to a usual care (UC) and a supported care (SC) model. TC added automated low-intensity periodic depression assessment calls to patients. Patient-reported outcomes included the 12-Item Short Form Health Survey converted into quality-adjusted life-years (QALYs) and the 9-Item Patient Health Questionnaire-calculated depression-free days (DFDs). Costs and outcomes data were collected over a 24-month period (-6 to 0 months baseline, 0 to 18 months study intervention). A sample of 1406 patients (484 in UC, 480 in SC, and 442 in TC) was enrolled in the nonrandomized trial. TC had a significant improvement in DFDs (17.3; P = 0.011) and significantly greater 12-Item Short Form Health Survey utility improvement (2.1%; P = 0.031) compared with UC. Medical costs were statistically significantly lower for TC (-$2328; P = 0.001) relative to UC but not significantly lower than for SC. TC had more than a 50% probability of being cost-effective relative to SC at willingness-to-pay thresholds of more than $50,000/QALY. An ICT-facilitated depression care (TC) delivery model improved QALYs, DFDs, and medical costs. It was cost-effective compared with SC and dominant compared with UC. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

[Ulcerative colitis in remission with cerebral abscess and septic pulmonary emboli: a case report].

PubMed

Yamauchi, Takahiro; Katsumura, Hirotoshi; Noguchi, Yoshiyuki; Kikuta, Ken-ichiro

2013-12-01

A 69-year-old man with a 4-year history of ulcerative colitis (UC) presented at our hospital with high fever, dysarthria, and right hemiparesis. Computed tomography (CT) of the head revealed a low-density area in the left temporal lobe. Chest CT exposed multiple pulmonary nodules in his right lung. Gadolinium-enhanced magnetic resonance imaging (MRI) indicated a 3-cm tumor with ring enhancement located in the left temporal lobe. The patient was diagnosed with a brain abscess and septic pulmonary emboli (SPE); antibiotic therapy was initiated. Shrinkage of the brain abscess was not observed in a follow-up MRI;thus, he underwent aspiration and drainage of the abscess 11 days after his hospitalization. Intravenous antibiotic therapy was continued for 6 weeks after the operation. Follow-up chest CT performed 48 days after his hospitalization revealed disappearance of the SPE. Follow-up head MRI conducted 63 days after his hospitalization indicated that the cyst had almost disappeared. Occurrence of a brain abscess in patients with UC has been very rarely reported in Japan. To the best of our knowledge, this is the first report of a case of a brain abscess in conjunction with UC and SPE. It is believed that patients with UC have compromised immunity and exhibit activation of the blood coagulation system. Our report suggests that medical practitioners should consider the possibility of a brain abscess and SPE for patients with UC.

Similar risk of Depression and Anxiety following surgery or hospitalization for Crohn’s disease and Ulcerative colitis

PubMed Central

Ananthakrishnan, Ashwin N.; Gainer, Vivian S.; Cai, Tianxi; Perez, Raul Guzman; Cheng, Su-Chun; Savova, Guergana; Chen, Pei; Szolovits, Peter; Xia, Zongqi; De Jager, Philip L; Shaw, Stanley; Churchill, Susanne; Karlson, Elizabeth W.; Kohane, Isaac; Perlis, Roy H; Plenge, Robert M.; Murphy, Shawn N.; Liao, Katherine P.

2013-01-01

Introduction Psychiatric co-morbidity is common in Crohn’s disease (CD) and ulcerative colitis (UC). IBD-related surgery or hospitalizations represent major events in the natural history of disease. Whether there is a difference in risk of psychiatric co-morbidity following surgery in CD and UC has not been examined previously. Methods We used a multi-institution cohort of IBD patients without a diagnosis code for anxiety or depression preceding their IBD-related surgery or hospitalization. Demographic, disease, and treatment related variables were retrieved. Multivariate logistic regression analysis was performed to individually identify risk factors for depression and anxiety. Results Our study included a total of 707 CD and 530 UC patients who underwent bowel resection surgery and did not have depression prior to surgery. The risk of depression 5 years after surgery was 16% and 11% in CD and UC respectively. We found no difference in the risk of depression following surgery in CD and UC patients (adjusted OR 1.11, 95%CI 0.84 – 1.47). Female gender, co-morbidity, immunosuppressant use, perianal disease, stoma surgery, and early surgery within 3 years of care predicted depression after CD-surgery; only female gender and co-morbidity predicted depression in UC. Only 12% of the CD cohort had ≥ 4 risk factors for depression, but among them nearly 44% were subsequently received a diagnosis code for depression. Conclusion IBD-related surgery or hospitalization is associated with a significant risk for depression and anxiety with a similar magnitude of risk in both diseases. PMID:23337479

Inflammatory bowel disease: A descriptive study of 716 local Chilean patients

PubMed Central

Simian, Daniela; Fluxá, Daniela; Flores, Lilian; Lubascher, Jaime; Ibáñez, Patricio; Figueroa, Carolina; Kronberg, Udo; Acuña, Raúl; Moreno, Mauricio; Quera, Rodrigo

2016-01-01

AIM: To demographically and clinically characterize inflammatory bowel disease (IBD) from the local registry and update data previously published by our group. METHODS: A descriptive study of a cohort based on a registry of patients aged 15 years or older who were diagnosed with IBD and attended the IBD program at Clínica Las Condes in Santiago, Chile. The registry was created in April 2012 and includes patients registered up to October 2015. The information was anonymously downloaded in a monthly report, and the information on patients with more than one visit was updated. The registry includes demographic, clinical and disease characteristics, including the Montreal Classification, medical treatment, surgeries and hospitalizations for crisis. Data regarding infection with Clostridium difficile (C. difficile) were incorporated in the registry in 2014. Data for patients who received consultations as second opinions and continued treatment at this institution were also analyzed. RESULTS: The study included 716 patients with IBD: 508 patients (71%) were diagnosed with ulcerative colitis (UC), 196 patients (27%) were diagnosed with Crohn’s disease (CD) and 12 patients (2%) were diagnosed with unclassifiable IBD. The UC/CD ratio was 2.6/1. The median age was 36 years (range 16-88), and 58% of the patients were female, with a median age at diagnosis of 29 years (range 5-76). In the past 15 years, a sustained increase in the number of patients diagnosed with IBD was observed, where 87% of the patients were diagnosed between the years 2001 and 2015. In the cohort examined in the present study, extensive colitis (50%) and colonic involvement (44%) predominated in the patients with UC and CD, respectively. In CD patients, non-stricturing/non-penetrating behavior was more frequent (80%), and perianal disease was observed in 28% of the patients. There were significant differences in treatment between UC and CD, with a higher use of corticosteroids, and immunosuppressive and biological therapies was observed in the patients with CD (P < 0.05 and P < 0.01). Significant surgical differences were also observed: 5% of the UC patients underwent surgery, whereas 38% of the CD patients required at least one surgery (P < 0.01). The patients with CD were hospitalized more often during their disease course than the patients with UC (55% and 35% of the patients, respectively; P < 0.01). C. difficile infection was acquired by 5% of the patients in each group at some point during the disease course. Nearly half of the patients consulted at the institution for a second opinion, and 32% of these individuals continued treatment at the institution. CONCLUSION: IBD has continued to increase in the study cohort, slowly approaching the level reported in developed countries. PMID:27298570

Health Literacy in Orthopaedic Trauma Patients.

PubMed

Cosic, Filip; Kimmel, Lara; Edwards, Elton

2017-03-01

This study aimed to determine the level of health literacy in a postoperative orthopaedic trauma population and to evaluate the efficacy of a simple predischarge discussion strategy, targeted at improving health literacy. A pre-post intervention study was conducted from April 2014 to January 2015. Academic Level 1 trauma center. One hundred ninety consecutive orthopaedic trauma patients with operatively managed lower limb fractures were recruited. All eligible participants agreed to participate. The first ninety-nine patients received usual care (UC). The following 91 patients received a structured predischarge discussion, including x-rays, written and verbal information, from the orthopaedic staff (DG). Patients were then randomized into health literacy evaluation before first outpatient review or after first outpatient review. The primary outcome measure was a questionnaire determining health literacy. Ninety-six (97%) of the UC patients and 87 (96%) of the discussion patients (DG) completed the interview. UC preoutpatient (n = 46) demonstrated a mean score of 4.67 of a maximum 8. UC postoutpatient (n = 50) demonstrated a mean score of 5.42. DG preoutpatient (n = 47) demonstrated a mean score of 6.70. DG postoutpatient (n = 40) demonstrated a mean score of 7.08. Australian orthopaedic trauma patients demonstrate poor health literacy, with this not showing improvement after their first outpatient follow-up visit. The use of a time efficient, structured predischarge discussion improved patient health literacy. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Integration of pharmacists into patient-centered medical homes in federally qualified health centers in Texas.

PubMed

Wong, Shui Ling; Barner, Jamie C; Sucic, Kristina; Nguyen, Michelle; Rascati, Karen L

To describe the integration and implementation of pharmacy services in patient-centered medical homes (PCMHs) as adopted by federally qualified health centers (FQHCs) and compare them with usual care (UC). Four FQHCs (3 PCMHs, 1 UC) in Austin, TX, that provide care to the underserved populations. Pharmacists have worked under a collaborative practice agreement with internal medicine physicians since 2005. All 4 FQHCs have pharmacists as an integral part of the health care team. Pharmacists have prescriptive authority to initiate and adjust diabetes medications. The PCMH FQHCs instituted co-visits, where patients see both the physician and the pharmacist on the same day. PCMH pharmacists are routinely proactive in collaborating with physicians regarding medication management, compared with UC in which pharmacists see patients only when referred by a physician. Four face-to-face, one-on-one semistructured interviews were conducted with pharmacists working in 3 PCMH FQHCs and 1 UC FQHC to compare the implementation of PCMH with emphasis on 1) structure and workflow, 2) pharmacists' roles, and 3) benefits and challenges. On co-visit days, the pharmacist may see the patient before or after physician consultation. Pharmacists in 2 of the PCMH facilities proactively screen to identify diabetes patients who may benefit from pharmacist services, although the UC clinic pharmacists see only referred patients. Strengths of the co-visit model include more collaboration with physicians and more patient convenience. Payment that recognizes the value of PCMH is one PCMH principle that is not fully implemented. PCMH pharmacists in FQHCs were integrated into the workflow to address specific patient needs. Specifically, full-time in-house pharmacists, flexible referral criteria, proactive screening, well defined collaborative practice agreement, and open scheduling were successful strategies for the underserved populations in this study. However, reimbursement plans and provider status for pharmacists should be established to sustain this model of care. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG).

PubMed

Eriksson, Carl; Marsal, Jan; Bergemalm, Daniel; Vigren, Lina; Björk, Jan; Eberhardson, Michael; Karling, Pontus; Söderman, Charlotte; Myrelid, Pär; Cao, Yang; Sjöberg, Daniel; Thörn, Mari; Karlén, Per; Hertervig, Erik; Strid, Hans; Ludvigsson, Jonas F; Almer, Sven; Halfvarson, Jonas

Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness. Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index <5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index <3 in ulcerative colitis (UC). Two-hundred forty-six patients (147 CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone ≥1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p < .0001 in both groups). Faecal-calprotectin decreased in CD (p < .0001) and in UC (p = .001), whereas CRP decreased in CD (p = .002) but not in UC (p = .11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48). Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

[Treatment adherence and use of complementary and alternative medicine in patients with inflammatory bowel disease].

PubMed

Lakatos, László; Czeglédi, Zsófia; Dávid, Gyula; Kispál, Zsófi; Kiss, Lajos S; Palatka, Károly; Kristóf, Tünde; Molnár, Tamás; Salamon, Agnes; Demeter, Pál; Miheller, Pál; Szamosi, Tamás; Banai, János; Papp, Mária; Bene, László; Kovács, Agota; Rácz, István; Lakatos, Péter László

2010-02-14

Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patients fail to comply with treatment. The aim of our study was to evaluate the prevalence of non-adherence the use of CAM in Hungarian patients with IBD. A total of 655 consecutive IBD patients (Crohn's disease [CD]: 344, age: 38.2 + or - 12.9 years; ulcerative colitis [UC]: 311, age: 44.9 + or - 15.3 years) were interviewed during the visit at specialists by self-administered questionnaire including demographic and disease-related data, as well as items analyzing the extent of non-adherence and CAM use. Patients taking more then 80% of each prescribed medicine were classified as adherent. The overall rate of self reported non-adherence (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use was not different between CD and UC. The most common causes of non-adherence were: forgetfulness (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%) and too frequent dosing. Most common forms of CAM were herbal tee (47.3%), homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease duration, date of last follow-up visit, educational level and previous surgeries were predicting factors for non-adherence. Alternative medicine use was associated in both diseases with younger age, higher educational level and immunosuppressant use. In addition, CAM use in UC was more common in females and in patients with supportive psychiatric/psychological therapy. Non-adherence and CAM use is common in patients with IBD. Special attention should be paid to explore the identified predictive factors during follow-up visits to improve adherence to therapy and improving patient-doctor relationship.

Association of adherence to therapy and complementary and alternative medicine use with demographic factors and disease phenotype in patients with inflammatory bowel disease.

PubMed

Lakatos, Peter Laszlo; Czegledi, Zsofia; David, Gyula; Kispal, Zsofia; Kiss, Lajos S; Palatka, Karoly; Kristof, Tunde; Nagy, Ferenc; Salamon, Agnes; Demeter, Pal; Miheller, Pal; Szamosi, Tamas; Banai, Janos; Papp, Maria; Bene, Laszlo; Kovacs, Agota; Racz, Istvan; Lakatos, Laszlo

2010-09-01

Previous studies have suggested an increasing use of complementary and alternative medicine (CAM) in patients with inflammatory bowel disease (IBD). Furthermore, a significant number of IBD patients fail to comply with treatment. The aim of our study was to evaluate the prevalence of non-adherence and the use of CAM in Hungarian patients with IBD. A total of 655 consecutive IBD patients (CD: 344, age: 38.2 [SD 12.9]years; UC: 311, age: 44.9 [15.3]years) were interviewed during the specialist visit by self-administered questionnaire including demographic and disease-related data as well as items analyzing the extent of non-adherence and CAM use. Patients taking more than 80% of each prescribed medication were classified as adherent. The overall rate of self-reported non-adherence (CD: 20.9%, UC: 20.6%) and CAM (CD: 31.7%, UC: 30.9%) use did not differ between Crohn's disease (CD) and ulcerative colitis (UC). The most common causes of non-adherence were: forgetfulness (47.8%), too many/unnecessary pills (39.7%), being afraid of side effects (27.9%) and too frequent dosing. Most common forms of CAM were herbal tea (47.3%), homeopathy (14.6%), special diet (12.2%), and acupuncture (5.8%). In CD, disease duration, date of last follow-up visit, educational level and previous surgeries were predicting factors for non-adherence. Alternative medicine use was associated in both diseases with younger age, higher educational level, and immunosuppressant use. In addition, CAM use in UC was more common in females and in patients with supportive psychiatric/psychological therapy. Non-adherence and CAM use is common in patients with IBD. Special attention should be paid to explore the identified predictive factors during follow-up visits to improve adherence to therapy and improving patient-doctor relationship. Copyright © 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Results of a prospective randomized control trial comparing hydrophilic to uncoated catheters in children with neurogenic bladder.

PubMed

DeFoor, William; Reddy, Pramod; Reed, Melissa; VanderBrink, Brian; Jackson, Elizabeth; Zhang, Bin; Denlinger, Julie; Noh, Paul; Minevich, Eugene; Sheldon, Curtis

2017-08-01

Children with neurogenic bladder (NGB) often require a lifetime of clean intermittent catheterization (CIC), typically using uncoated catheters (UCs). Hydrophilic catheters (HCs) have lower friction than UCs with reported less damage to the urethra. The purpose of this study is to compare outcomes between these catheters. An investigator-initiated, prospective, randomized clinical trial was conducted to compare HCs versus UCs. Children aged 2-17 years with NGB on CIC were enrolled for 1 year. Block randomization was used. Dexterity scores were obtained in those who perform self-catheterization. Outcomes were UTI, difficulty passing the catheter, urethral injury, and patient satisfaction. Demographic data is presented in the Table. Seventy-eight patients were enrolled. Age and gender were similar between the groups. Fifteen patients in each group performed CIC via an abdominal wall stoma. Eight and 15 patients withdrew from the UC and HC groups, respectively. The HC group overall had more problems with the catheter, mainly difficulty with handling. There were no differences for passing the catheter, pain, hematuria, or urethral injuries. There were two urinary tract infections (UTIs) in two HC patients and 17 UTIs in seven UC patients (p = 0.003). Patients with UTIs in the HC group went from 16% in the previous year to 5% during the study. Three children in the HC group had three or more UTIs in the year before enrollment and none during the study. The patients that completed the study with HC were overall satisfied and many requested to continue with the HC. HCs may decrease the risk of UTI in children with NGB. Urethral complications were low in both groups. Most HC patients were pleased but some found the slippery coating difficult to handle. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis.

PubMed

Sandborn, William J; Regula, Jaroslaw; Feagan, Brian G; Belousova, Elena; Jojic, Njegica; Lukas, Milan; Yacyshyn, Bruce; Krzeski, Piotr; Yeh, Chyon-Hwa; Messer, Christi A; Hanauer, Stephen B

2009-12-01

It is not clear what induction dose of mesalamine is optimal for treating patients with mildly and moderately active ulcerative colitis (UC). This study was conducted to determine the efficacy and safety of mesalamine 4.8 g/day compared with 2.4 g/day for the treatment of moderately active UC. A multicenter, randomized, double-blind, 6-week, active-control study (ASCEND III) was conducted to assess the noninferiority of delayed-release mesalamine 4.8 g/day (Asacol HD, 800-mg tablet; Procter & Gamble, Pharmaceuticals, Inc, Mason, Ohio) with 2.4 g/day (Asacol, 400-mg tablet; Procter & Gamble Pharmaceuticals, Inc) in 772 patients with moderately active UC. The primary endpoint was treatment success (overall improvement) at week 6, defined as improvement in the Physician's Global Assessment (based on clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy), with no worsening in any individual clinical assessment. The primary objective of noninferiority was met. Seventy percent (273 of 389) of patients who received 4.8 g/day of mesalamine achieved treatment success at week 6, compared with 66% (251 of 383) of patients receiving 2.4 g/day (95% confidence interval for 2.4 g/day minus 4.8 g/day, -11.2 to 1.9). In addition, 43% of patients who received 4.8 g/day mesalamine achieved clinical remission at week 6 compared with 35% of patients who received 2.4 g/day (P = .04). A therapeutic advantage for the 4.8 g/day dose was observed among patients previously treated with corticosteroids, oral mesalamines, rectal therapies, or multiple UC medications. Both regimens were well-tolerated with similar adverse events. Delayed-release mesalamine 4.8 g/day (800-mg tablet) is efficacious and well-tolerated in patients with moderately active UC.

Cannabis use amongst patients with inflammatory bowel disease.

PubMed

Lal, Simon; Prasad, Neeraj; Ryan, Manijeh; Tangri, Sabrena; Silverberg, Mark S; Gordon, Allan; Steinhart, Hillary

2011-10-01

Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD). Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions. We aimed to evaluate cannabis use in patients with IBD. One hundred patients with ulcerative colitis (UC) and 191 patients with Crohn's disease (CD) attending a tertiary-care outpatient clinic completed a questionnaire regarding current and previous cannabis use, socioeconomic factors, disease history and medication use, including complimentary alternative medicines. Quality of life was assessed using the short-inflammatory bowel disease questionnaire. A comparable proportion of UC and CD patients reported lifetime [48/95 (51%) UC vs. 91/189 (48%) CD] or current [11/95 (12%) UC vs. 30/189 (16%) CD] cannabis use. Of lifetime users, 14/43 (33%) UC and 40/80 (50%) CD patients have used it to relieve IBD-related symptoms, including abdominal pain, diarrhoea and reduced appetite. Patients were more likely to use cannabis for symptom relief if they had a history of abdominal surgery [29/48 (60%) vs. 24/74 (32%); P=0.002], chronic analgesic use [29/41 (71%) vs. 25/81 (31%); P<0.001], complimentary alternative medicine use [36/66 (55%) vs. 18/56 (32%); P=0.01] and a lower short inflammatory bowel disease questionnaire score (45.1±2.1 vs. 50.3±1.5; P=0.03). Patients who had used cannabis [60/139 (43%)] were more likely than nonusers [13/133 (10%); P<0.001 vs. users] to express an interest in participating in a hypothetical therapeutic trial of cannabis for IBD. Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index. The therapeutic benefits of cannabinoid derivatives in IBD may warrant further exploration.

Differential effects of α4β7 and GPR15 on homing of effector and regulatory T cells from patients with UC to the inflamed gut in vivo.

PubMed

Fischer, Anika; Zundler, Sebastian; Atreya, Raja; Rath, Timo; Voskens, Caroline; Hirschmann, Simon; López-Posadas, Rocío; Watson, Alastair; Becker, Christoph; Schuler, Gerold; Neufert, Clemens; Atreya, Imke; Neurath, Markus F

2016-10-01

Gut homing of lymphocytes via adhesion molecules has recently emerged as new target for therapy in IBDs. We aimed to analyse the in vivo homing of effector (Teff) and regulatory (Treg) T cells to the inflamed gut via α4β7 and G protein receptor GPR15. We assessed the expression of homing receptors on T cells in peripheral blood and inflamed mucosa. We studied the migration pattern and homing of Teff and Treg cells to the inflamed gut using intravital confocal microscopy and FACS in a humanised mouse model in dextran sodium sulfate-treated NSG (NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ) mice. Expression of GPR15 and α4β7 was significantly increased on Treg rather than Teff cells in peripheral blood of patients with UC as compared with Crohn's disease and controls. In vivo analysis in a humanised mouse model showed augmented gut homing of UC Treg cells as compared with controls. Moreover, suppression of UC (but not control) Teff and Treg cell homing was noted upon treatment with the α4β7 antibody vedolizumab. In contrast, siRNA blockade of GPR15 had only effects on homing of Teff cells but did not affect Treg homing in UC. Clinical vedolizumab treatment was associated with marked expansion of UC Treg cells in peripheral blood. α4β7 rather than GPR15 is crucial for increased colonic homing of UC Treg cells in vivo, while both receptors control UC Teff cell homing. Vedolizumab treatment impairs homing of UC Treg cells leading to their accumulation in peripheral blood with subsequent suppression of systemic Teff cell expansion. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Expenditures for Academic Inpatient Care of Inflammatory Bowel Disease Patients Are Almost Double Compared with Average Academic Gastroenterology and Hepatology Cases and Not Fully Recovered by Diagnosis-Related Group (DRG) Proceeds

PubMed Central

Baumgart, Daniel C.; le Claire, Marie

2016-01-01

Background Crohn’s disease (CD) and ulcerative colitis (UC) challenge economies worldwide. Detailed health economic data of DRG based academic inpatient care for inflammatory bowel disease (IBD) patients in Europe is unavailable. Methods IBD was identified through ICD-10 K50 and K51 code groups. We took an actual costing approach, compared expenditures to G-DRG and non-DRG proceeds and performed detailed cost center and type accounting to identify coverage determinants. Results Of all 3093 hospitalized cases at our department, 164 were CD and 157 UC inpatients in 2012. On average, they were 44.1 (CD 44.9 UC 43.3 all 58) years old, stayed 10.1 (CD 11.8 UC 8.4 vs. all 8) days, carried 5.8 (CD 6.4 UC 5.2 vs. all 6.8) secondary diagnoses, received 7.4 (CD 7.7 UC 7 vs. all 6.2) procedures, had a higher cost weight (CD 2.8 UC 2.4 vs. all 1.6) and required more intense nursing. Their care was more costly (means: total cost IBD 8477€ CD 9051€ UC 7903€ vs. all 5078€). However, expenditures were not fully recovered by DRG proceeds (means: IBD 7413€, CD 8441€, UC 6384€ vs all 4758€). We discovered substantial disease specific mismatches in cost centers and types and identified the medical ward personnel and materials budgets to be most imbalanced. Non-DRG proceeds were almost double (IBD 16.1% vs. all 8.2%), but did not balance deficits at total coverage analysis, that found medications (antimicrobials, biologics and blood products), medical materials (mostly endoscopy items) to contribute most to the deficit. Conclusions DRGs challenge sophisticated IBD care. PMID:26784027

Genome-wide association analysis in primary sclerosing cholangitis and ulcerative colitis identifies risk loci at GPR35 and TCF4.

PubMed

Ellinghaus, David; Folseraas, Trine; Holm, Kristian; Ellinghaus, Eva; Melum, Espen; Balschun, Tobias; Laerdahl, Jon K; Shiryaev, Alexey; Gotthardt, Daniel N; Weismüller, Tobias J; Schramm, Christoph; Wittig, Michael; Bergquist, Annika; Björnsson, Einar; Marschall, Hanns-Ulrich; Vatn, Morten; Teufel, Andreas; Rust, Christian; Gieger, Christian; Wichmann, H-Erich; Runz, Heiko; Sterneck, Martina; Rupp, Christian; Braun, Felix; Weersma, Rinse K; Wijmenga, Cisca; Ponsioen, Cyriel Y; Mathew, Christopher G; Rutgeerts, Paul; Vermeire, Séverine; Schrumpf, Erik; Hov, Johannes R; Manns, Michael P; Boberg, Kirsten M; Schreiber, Stefan; Franke, Andre; Karlsen, Tom H

2013-09-01

Approximately 60%-80% of patients with primary sclerosing cholangitis (PSC) have concurrent ulcerative colitis (UC). Previous genome-wide association studies (GWAS) in PSC have detected a number of susceptibility loci that also show associations in UC and other immune-mediated diseases. We aimed to systematically compare genetic associations in PSC with genotype data in UC patients with the aim of detecting new susceptibility loci for PSC. We performed combined analyses of GWAS for PSC and UC comprising 392 PSC cases, 987 UC cases, and 2,977 controls and followed up top association signals in an additional 1,012 PSC cases, 4,444 UC cases, and 11,659 controls. We discovered novel genome-wide significant associations with PSC at 2q37 [rs3749171 at G-protein-coupled receptor 35 (GPR35); P = 3.0 × 10(-9) in the overall study population, combined odds ratio [OR] and 95% confidence interval [CI] of 1.39 (1.24-1.55)] and at 18q21 [rs1452787 at transcription factor 4 (TCF4); P = 2.61 × 10(-8) , OR (95% CI) = 0.75 (0.68-0.83)]. In addition, several suggestive PSC associations were detected. The GPR35 rs3749171 is a missense single nucleotide polymorphism resulting in a shift from threonine to methionine. Structural modeling showed that rs3749171 is located in the third transmembrane helix of GPR35 and could possibly alter efficiency of signaling through the GPR35 receptor. By refining the analysis of a PSC GWAS by parallel assessments in a UC GWAS, we were able to detect two novel risk loci at genome-wide significance levels. GPR35 shows associations in both UC and PSC, whereas TCF4 represents a PSC risk locus not associated with UC. Both loci may represent previously unexplored aspects of PSC pathogenesis. Copyright © 2012 American Association for the Study of Liver Diseases.

[Mechanism of leukocytapheresis effect in the treatment of ulcerative colitis].

PubMed

Sawada, K; Ohnishi, K; Fukunaga, K; Chikano, S; Egashira, A; Satomi, M; Shimoyama, T

1999-12-01

To solve adverse effects of high dose steroid administration for patients with moderately severe and severe ulcerative colitis (UC), additional use of leukocytapheresis (LCAP) was tried to settle colonic inflammation. We evaluated immunological changes in the treatment of LCAP using leukocyte removal filter for UC patients. We then assessed the clinical effectiveness of LCAP compared with that of high dose of steroid therapy. LCAP removed monocytes, granulocytes, and lymphocytes presenting CD 11 b+, CD 11 c+, and HLADR+, selectively from the patients. Proinflammatory cytokine productions measured such as TNF alpha, IL-1 beta, and IL 8 reduced and IL 10 increased immediately after LCAP compared with before perfusion. Improved rate was about 70% for LCAP group and about 40% for high dose steroid group (Refer J Gastroenterol). Selective removal of granulocyte, monocytes, and activated lymphocytes inhibits proinflammatory cytokine production and increases immune modulating cytokine productions (Refer Therapeutic Apheresis). Then quick inhibition of several inflammatory deteriorated factors simultaneously controls the activity and clinical symptoms of UC with less severe adverse effects. It can be considered one option for treatment of UC.

Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update

PubMed Central

Scaldaferri, Franco; Gerardi, Viviana; Mangiola, Francesca; Lopetuso, Loris Riccardo; Pizzoferrato, Marco; Petito, Valentina; Papa, Alfredo; Stojanovic, Jovana; Poscia, Andrea; Cammarota, Giovanni; Gasbarrini, Antonio

2016-01-01

Ulcerative colitis (UC) is a chronic inflammatory disease, whose etiology is still unclear. Its pathogenesis involves an interaction between genetic factors, immune response and the “forgotten organ”, Gut Microbiota. Several studies have been conducted to assess the role of antibiotics and probiotics as additional or alternative therapies for Ulcerative Colitis. Escherichia coli Nissle (EcN) is a nonpathogenic Gram-negative strain isolated in 1917 by Alfred Nissle and it is the active component of microbial drug Mutaflor® (Ardeypharm GmbH, Herdecke, Germany and EcN, Cadigroup, In Italy) used in many gastrointestinal disorder including diarrhea, uncomplicated diverticular disease and UC. It is the only probiotic recommended in ECCO guidelines as effective alternative to mesalazine in maintenance of remission in UC patients. In this review we propose an update on the role of EcN 1917 in maintenance of remission in UC patients, including data about efficacy and safety. Further studies may be helpful for this subject to further the full use of potential of EcN. PMID:27350728

Ultrasonographic assessment of the thyroid gland structure in inflammatory bowel disease patients.

PubMed

Neubauer, Katarzyna; Woźniak-Stolarska, Barbara

2012-01-01

The etiopathogenesis of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is still not fully elucidated and seems to be multifactorial. It has been suggested that genetic, immunological and environmental factors participate in IBD development. IBD extraintestinal manifestations include rheumatic, metabolic, dermatologic, ophthalmologic, hepatobiliary, pancreatic, urologic, pulmonary, neurological, hematological and thromboembolic complications. Thyroid gland diseases have not been confirmed as extraintestinal manifestations of IBD. However, it is known that some thyroid diseases share an immunological background with IBD, and that dysfunction of the thyroid gland may induce gastrointestinal symptoms. Ultrasound examination is the gold standard for evaluation of thyroid gland morphology. This study was designed to assess the prevalence of abnormalities in the structure of the thyroid gland in IBD patients and to compare it to the control group. The study group consisted of 199 consecutive IBD patients (80 CD patients and 119 UC patients) hospitalized at the Department of Gastroenterology and Hepatology of Wroclaw Medical University (Poland). The control group consisted of 42 healthy volunteers and patients with functional gastrointestinal disorders. The most common finding in the ultrasound examination in IBD patients were tumors. Tumors, which were smaller than or equal to 10 mm were present in 11.5% of IBD patients; and tumors larger than 10 mm were present in 13.1%. These results show that small tumors (less than 10 mm in diameter) of the thyroid gland are more frequent among patients with CD and UC compared to the control group (p = 0.0001 and p = 0.001, respectively). Additionally, enlargement of the thyroid gland occurs more often in UC patients compared to the control group (p = 0.003). There was no difference in the frequency of thyroid abnormalities between UC and CD patients. In patients with inflammatory bowel diseases focal lesions relating to tumors of the thyroid gland are more common than in the control group. In patients with ulcerative colitis enlargement of the thyroid gland is more frequent than in the control group. Initial assessments of IBD patients should include ultrasound examinations of the thyroid gland.

Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer.

PubMed

Poort, Hanneke; Verhagen, Constans A H H V M; Peters, Marlies E W J; Goedendorp, Martine M; Donders, A Rogier T; Hopman, Maria T E; Nijhuis-van der Sanden, Maria W G; Berends, Thea; Bleijenberg, Gijs; Knoop, Hans

2017-01-28

Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer. The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14 weeks), and at follow-up assessments (18 and 26 weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue), functional impairments (Sickness Impact Profile total score, EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning) and quality of life (EORTC-QLQ-C30 subscale QoL). Outcomes at 14 weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26 weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants. To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients. NTR3812 ; date of registration: 23/01/2013.

A prospective audit on the effect of training and educational workshops on the incidence of urethral catheterization injuries

PubMed Central

Bhatt, Nikita R.; Davis, Niall F.; Quinlan, Mark R.; Flynn, Robert J.; McDermott, T.E.D.; Manecksha, Rustom P.; Thornhill, John A.

2017-01-01

Introduction The incidence of iatrogenic urethral catheterization (UC) injuries is approximately 0.3%. Resultant complications are associated with patient morbidity and unnecessary healthcare costs. Our aim was to investigate whether educational training workshops decreased the incidence of UC-related injuries. Methods A prospective audit was performed to calculate incidence, morbidity, and costs associated with iatrogenic UC injury from January to July 2015. Educational workshops were then conducted with healthcare staff and training modules for junior doctors. UC-related incidence, morbidity, and costs in the subsequent six-month period were recorded prospectively and compared with the previous data. Results The incidence of iatrogenic UC injuries was reduced from 4.3/1000 catheters inserted to 3.8/1000 catheters after the intervention (p=0.59). Morbidity from UC increased in the second half in the form of increase in cumulative additional inpatient hospital stay (22 to 79 days; p=0.25), incidence of urosepsis (n=2 to n=4), and need for operative intervention (n=1 to n=2). The cost of managing UC injuries almost doubled in the period after the training intervention (€50 449 to €90 100). Conclusions Current forms of educational and training interventions for UC did not significantly change morbidity or cost of iatrogenic UC injuries despite a decrease in incidence. Improved and intensive training protocols are necessary for UC to prevent avoidable iatrogenic complications, as well as a safer urethral catheter design. PMID:28761592

Vedolizumab Treatment for Ulcerative Colitis in an Elderly Multimorbid Patient with Hemophilia A.

PubMed

Schäffler, Holger; Huth, Astrid; Lamprecht, Georg; Anders, Olaf

2017-01-01

The treatment of inflammatory bowel diseases (IBD) can be challenging, especially in elderly multimorbid patients. Since incidence and prevalence rates of IBD are rising steadily, treatment of older patients with relevant and also rare comorbidities will be of increasing relevancy for caregivers. Here we report on a 74-year-old multimorbid patient with severe ulcerative colitis (UC) and hemophilia A. Because of the chronic active disease, therapy with a tumor necrosis factor-α inhibitor was started. He suffered from a severe infectious complication (pneumonia) under therapy with infliximab. The therapy was changed to vedolizumab, with which the patient stayed in long-term clinical and endoscopic remission. Because the patient had a non-ST-segment elevation myocardial infarction in April 2016, he received dual platelet inhibitor therapy with aspirin and clopidogrel. Because of consecutive aspirin intolerance, the therapy was changed to clopidogrel monotherapy. Although the UC was treated appropriately with vedolizumab and the patient was in endoscopic mucosal remission, recurrent bleeding episodes from multiple inflammatory pseudopolyps occurred. The bleeding episodes resolved quickly after immediate treatment with factor VIII (Kogenate®). In conclusion, we describe the first patient in the literature with UC and hemophilia A who stayed in long-term remission under therapy with vedolizumab. From our point of view, vedolizumab can be safely administered in the setting of UC and hemophilia A. Antiplatelet drugs which inhibit primary hemostasis must be used with caution in this setting. Bleeding episodes can be treated safely and effectively with factor VIII (Kogenate®).

Pharmacological intervention based on fecal calprotectin levels in patients with ulcerative colitis at high risk of a relapse: A prospective, randomized, controlled study

PubMed Central

Öhman, Lena; Stotzer, Per-Ove; Isaksson, Stefan; Überbacher, Otto; Ung, Kjell-Arne; Strid, Hans

2015-01-01

Background Targeted therapy, using biomarkers to assess disease activity in ulcerative colitis (UC), has been proposed. Objective The objective of this study was to evaluate whether pharmacological intervention guided by fecal calprotectin (FC) prolongs remission in patients with UC. Methods A total of 91 adults with UC in remission were randomized to an intervention group or a control group. Analysis of FC was performed monthly, during 18 months. A FC value of 300 µg/g was set as the cut-off for intervention, which was a dose escalation of the oral 5-aminosalicylate (5-ASA) agent. The primary study end-point was the number of patients to have relapsed by month 18. Results There were relapses in 18 (35.3%) and 20 (50.0%) patients in the intervention and the control groups, respectively (p = 0.23); and 28 (54.9%) patients in the intervention group and 28 (70.0%) patients in the control group had a FC > 300 µg/g, of which 8 (28.6%) and 16 (57.1%) relapsed, respectively (p < 0.05). Conclusion Active intervention significantly reduced relapse rates, although no significant difference was reached between the groups overall. Thus, FC-levels might be used to identify patients with UC at risk for a flare, and a dose escalation of their 5-ASA agent is a therapeutic option for these patients. PMID:25653861

Vedolizumab: an α4β7 integrin inhibitor for inflammatory bowel diseases.

PubMed

Smith, Michael A; Mohammad, Rima A

2014-12-01

To review the pharmacology, efficacy, and safety of vedolizumab in the treatment of patients with ulcerative colitis (UC) and Crohn's disease (CD). A literature search through clinicialtrials.gov, EMBASE and MEDLINE was conducted (January 1966-June 2014) using the terms vedolizumab and MLN0002. References from retrieved articles were reviewed for any additional material. Additionally, the prescribing information was retrieved. Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of vedolizumab were identified. Vedolizumab, an α4β7 integrin inhibitor, was recently approved for adult patients with moderate to severe active UC or CD who are refractory or intolerant to standard therapies or who are dependent on corticosteroids. Trial data have demonstrated that vedolizumab 300 mg at weeks 0, 2, and 6 followed by every 8 weeks is effective at inducing and maintaining clinical response and remission, improving mucosal appearance, and achieving corticosteroid-free remission in patients with UC. This regimen is also effective at achieving clinical response, remission, and corticosteroid-free remission in patients with CD. Patients treated with vedolizumab, unadjusted for exposure, reported experiencing nasopharyngitis, headache, nausea, arthralgias, pyrexia, upper-respiratory-tract infections, fatigue, and cough. Vedolizumab is an effective agent at inducing and maintaining remission in patients with UC or CD. Vedolizumab is generally well tolerated and has not been associated with progressive multifocal leukoencephalopathy. © The Author(s) 2014.

Estimation of quality of life in Cypriot patients with inflammatory bowel disease.

PubMed

Tsoukka, Maria; Jelastopulu, Eleni; Lavranos, Giagkos; Charalambous, George

2017-01-07

To investigate the health-related quality of life (HRQoL) of patients suffering with idiopathic inflammatory bowel disease (IBD). The Greek validated version of the Short Inflammatory Bowel Disease Questionnaire was used for evaluating the quality of life of IBD patients. The questionnaire was distributed to 100 consecutive patients suffering from IBD and presenting for a clinic appointment at the endoscopy unit of Larnaca General Hospital during the period from October to November 2012. The criteria for participating in this study were constituted by the documented diagnosis of either ulcerative colitis (UC) or Crohn's disease (CD) after endoscopy and histologic examination at least 6 months before the study, adult patients (18 years old or older), the capability of verbal communication and the patient's written consent for attending this study. The majority of the questionnaires were completed by a nurse practitioner who specializes in IBD patient care. Regarding the physical dimension in patients with UC, males scored significantly higher than females (4.2 vs 3.4, P = 0.023). Higher scores were also observed in UC patients younger than 35 or older than 50 years (4.0 and 4.2 vs 3.2, respectively, P = 0.021). The psychological dimension revealed similar results in patients with UC, with males, and older ages scoring higher (5.0 vs 3.0, P = 0.01 and 4.7 vs 2.7, P < 0.5, respectively), whereas regarding CD higher scores were observed in married compared to unmarried (3.83 vs 2.33, P = 0.042). No statistical differences in any parameters in the social dimension were observed. Regarding the treatment of, patients with CD, overall higher scores were observed when treated with biological factors compared to standard therapy in all dimensions but with statistical significant difference in the social dimension (5.00 vs 3.25, P = 0.045). The study reveals a negative impact of IBD on HRQoL. Increased risks are age and gender in patients with UC and family status in patients with CD.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

PubMed

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. We conducted this systematic review to assess the efficacy and safety of FMT in UC. PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis

PubMed Central

Shi, Yanqiang; Dong, Yiwei; Huang, Wenhui; Zhu, Decong; Mao, Hua; Su, Peizhu

2016-01-01

Background Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. Objective We conducted this systematic review to assess the efficacy and safety of FMT in UC. Data Sources PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. Data Extraction and Synthesis We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. Results Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. Conclusion FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition. PMID:27295210

Systematic Review and Meta-analysis: Phenotype and Clinical Outcomes of Older-onset Inflammatory Bowel Disease.

PubMed

Ananthakrishnan, Ashwin N; Shi, Hai Yun; Tang, Whitney; Law, Cindy C Y; Sung, Joseph J Y; Chan, Francis K L; Ng, Siew C

2016-10-01

Little is known of the clinical outcome of patients with older-onset inflammatory bowel disease [IBD]. We performed a systematic review to determine phenotype and outcomes of older-onset IBD compared with younger-onset subjects. A systematic search of Embase and Medline up to June 2015 identified studies investigating phenotype and outcomes of older-onset [diagnosed at age ≥ 50 years] Crohn's disease [CD] and ulcerative colitis [UC] subjects. Pooled analyses of disease phenotype, medication use, and disease-related surgery were calculated. We analysed findings from 43 studies comprising 8274 older-onset and 34641 younger-onset IBD subjects. Compared with younger-onset patients, older-onset CD patients were more likely to have colonic disease (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.88 - 3.48) and inflammatory behaviour [OR 1.19, 95% CI 1.07 - 1.33], and less likely to have penetrating disease or perianal involvement. More older-onset UC patients had left-sided colitis [OR 1.49, 95% CI 1.18 - 1.88]. Although fewer older-onset IBD patients received immunomodulators [CD: OR 0.44; UC: OR 0.60] or biologicals [CD: OR 0.34; UC: OR 0.41], older-onset CD was similar in the need for surgery [OR 0.70, 95% CI 0.40 - 1.22] whereas more older-onset UC patients underwent surgery [OR 1.36, 95% CI 1.18 - 1.57]. Elderly IBD patients present with less complicated disease, but have similar or higher rates of surgery than non-elderly patients. Whether this reflects a non-benign disease course, physicians' reluctance to employ immunomodulators, or both, merits further study which is essential for improving the care of IBD in the elderly. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis

PubMed Central

Alipour, Misagh; Zaidi, Deenaz; Valcheva, Rosica; Jovel, Juan; Martínez, Inés; Sergi, Consolato; Walter, Jens; Mason, Andrew L.; Wong, Gane Ka-Shu; Dieleman, Levinus A.; Carroll, Matthew W.; Huynh, Hien Q.

2016-01-01

Background and Aims: Ulcerative colitis [UC] is associated with colonic mucosa barrier defects and bacterial dysbiosis, but these features may simply be the result of inflammation. Therefore, we sought to assess whether these features are inherently abrogated in the terminal ileum [TI] of UC patients, where inflammation is absent. Methods: TI biopsies from paediatric inflammatory bowel disease [IBD] subsets [Crohn’s disease [CD; n = 13] and UC [n = 10

Dietary protein intakes and risk of ulcerative colitis.

PubMed

Rashvand, Samaneh; Somi, Mohammad Hossein; Rashidkhani, Bahram; Hekmatdoost, Azita

2015-01-01

The incidence of ulcerative colitis (UC) is rising in populations with western-style diet, rich in fat and protein, and low in fruits and vegetables. In the present study, we aimed to evaluate the association between dietary protein intakes and the risk of developing incident UC. Sixty two cases of UC and 124 controls were studied using country-specific food frequency questionnaire (FFQ). Group comparisons by each factor were done using χ2 test, and significance level was set at α= 0.05. Logistic regression adjusted for potential confounding variables was carried out. Univariate analysis suggested positive associations between processed meat, red meat and organ meat with risk of ulcerative colitis. Comparing highest versus lowest categories of consumption, multivariate conditional logistic regression analysis accounting for potential confounding variables indicated that patients who consumed a higher amount of processed meat were at a higher risk for developing UC (P value for trend= 0.02). Similarly, patients who consumed higher amounts of red meat were at a higher risk for UC (P value for trend= 0.01). The highest tertile of intake of organ meat was associated with an increased risk of ulcerative colitis with a statistically significant trend across tertiles (P value for trend= 0.01) when adjusted. In this case-control study we observed that higher consumptions of processed meat, red meat and organ meat were associated with increased risk for UC.

Review article: new drug formulations, chemical entities and therapeutic approaches for the management of ulcerative colitis.

PubMed

Ng, S C; Kamm, M A

2008-10-01

Treatment options for ulcerative colitis (UC) are expanding with the development of novel drug formulations and dosing regimens and new chemical entities. Although the goals of medical therapy for UC remain unchanged, that is to induce and to maintain remission, focus has also centred on improving patient compliance, modifying the natural course of disease and healing the mucosa. To examine novel formulations, new chemical entities and novel therapeutic approaches to the management of UC. Searches for all studies related to UC treatment in Medline and abstracts from major national and international meetings published in the last 10 years. 5-Aminosalicylic acids (5-ASA) remain the standard first-line treatment for patients with mild to moderately active UC. New formulations with altered delivery, and new dosing regimens have demonstrated possible improvements in efficacy compared with historically available preparations and dosing patterns. Once-daily dosing, micropellet formulations,and high-dose tablets offer enhanced efficacy and improved compliance. 5-ASA is now recognized as a ligand for peroxisome proliferator activated receptor-gamma (PPAR-gamma) and it has a role as a chemo-preventive agent in long-standing UC. New colonic release corticosteroid formulations help to limit systemic toxicity; turmeric, tacrolimus and infliximab have shown promising results. New anti-inflammatory targeted therapies include an anti-CD3 antibody, selective integrin blockers, anti-IL-2 antibody and PPAR-gamma agonists. The evolution of novel oral 5-ASA formulations and dosage regimens,and recent development of new molecules have expanded the therapeutic armamentarium of UC.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

PubMed

Uo, Michihide; Hisamatsu, Tadakazu; Miyoshi, Jun; Kaito, Daiki; Yoneno, Kazuaki; Kitazume, Mina T; Mori, Maiko; Sugita, Akira; Koganei, Kazutaka; Matsuoka, Katsuyoshi; Kanai, Takanori; Hibi, Toshifumi

2013-12-01

Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1β (IL-1β), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1β production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

Patients' perceptions on the impact of coffee consumption in inflammatory bowel disease: friend or foe?--a patient survey.

PubMed

Barthel, Christiane; Wiegand, Sandra; Scharl, Sylvie; Scharl, Michael; Frei, Pascal; Vavricka, Stephan R; Fried, Michael; Sulz, Michael Christian; Wiegand, Nico; Rogler, Gerhard; Biedermann, Luc

2015-08-12

Environmental factors are an integral component in the pathogenesis of inflammatory bowel disease (IBD). There is an increasing interest in nutritive components. While the potential disease-modifying role of coffee has been intensively investigated in a variety of gastrointestinal diseases, the data on the potential impact on IBD is very limited. We aimed to determine the patients' perspective on coffee consumption in IBD. We conducted a questionnaire among IBD patients in Switzerland, assessing key questions regarding coffee consumption. Descriptive statistics including chi square testing were used for analysis of questionnaire data. Among a total of 442 patients 73% regularly consume coffee. 96% of patients attributing a positive and 91% of patients attributing no impact of coffee intake on IBD regularly drink coffee and surprisingly even 49% of those patients that assign a negative impact on disease symptoms. Among those patients refraining from regular coffee intake 62% are convinced that coffee adversely influences intestinal symptoms, significantly more in Crohn's disease (CD) than in ulcerative colitis (UC) (76% vs. 44%, p = 0.002). In total, 38% of all study subjects suppose that coffee has an effect on their symptoms of disease, significantly more in CD (54%) compared to UC patients (22%, p < 0.001). Moreover, while 45% of CD patients feel that coffee has a detrimental influence, only 20% of UC patients share this impression (p < 0.001). Two thirds of IBD patients regularly consume coffee. More than twice as many CD compared to UC patients attribute a symptom-modifying effect of coffee consumption, the majority a detrimental one. However, this negative perception does not result in abstinence from coffee consumption.

[Use of allogeneic mesenchymal stem cells in the treatment of intestinal inflammatory diseases].

PubMed

Lazebnik, L B; Konopliannikov, A G; Kniazev, O V; Parfenov, A I; Tsaregorodtseva, T M; Ruchkina, I N; Khomeriki, S G; Rogozina, V A; Konopliannikova, O A

2010-01-01

to determine the whether mesenchymal stem cells (MSC) may be used in the treatment of patients with chrOnic intestinal inflammatory diseases (IID). Thirty-nine patients with ulcerative colitis (UC) (Group 1) and 11 with Crohn's disease (CD) (Group 2) were examined. Comparative groups included 30 patients with UC (Group 2) and 10 with CD (Group 4). Two-three days before MSC administration, immunodepressants were discontinued, the dosage of corticosteroids was reduced to 15-20 mg/day, and that of aminosalicylates remained to be 2 g/day. The results were quantified using the mean values of the Rachmilewich clinical activity index, the Crohn's disease activity index and the Mayo and Gebs scales. The patients were followed up for 4-8 months. Humoral immunological indices (cytokines, autologous antibodies) were determined. Bone marrow cells were obtained from the donor sternum or iliac crest. Cultivation at the end of weeks 5-6 provided a population of allogeneic donor MSC in a quantity of (1.5-2) x 10(8) tells required for transplantation to a patient. MSC cultures were once injected intravenously in a dropwise fashion. A statistically significant decrease in the indices of the clinical and morphological activities of an inflammatory process was noted in 39 patients with UC and in 11 patients with CD as compared with the comporison groups after MSC transplantation. Clinicomorphological remission occurred in 40 patients. Inclusion of MSC into the treatment program was ineffective in 8 patients with UC and in 2 patients with CD. The use of MSC made it possible to discontinue corticosteroids in 34 of the 50 patients with the hormone-dependent and hormone-resistant forms of UC and CD and to reduce the dose of prednisolone to 5 mg/day in 7 patients, by administering 5-aminosalicylic acid only. The use of MSC may be appreciated as a new strategic direction of therapy for IID. The intravenously administered stem cells exert a potent immunomodulatory effect, reduce the activity of autoimmune inflammation, and stimulate a reparative process in the intestinal mucosa.

Curcumin in Combination With Mesalamine Induces Remission in Patients With Mild-to-Moderate Ulcerative Colitis in a Randomized Controlled Trial.

PubMed

Lang, Alon; Salomon, Nir; Wu, Justin C Y; Kopylov, Uri; Lahat, Adi; Har-Noy, Ofir; Ching, Jessica Y L; Cheong, Pui Kuan; Avidan, Benjamin; Gamus, Dorit; Kaimakliotis, Ioannis; Eliakim, Rami; Ng, Siew C; Ben-Horin, Shomron

2015-08-01

The phytochemical compound curcumin was reported to be effective in maintaining remission in patients with ulcerative colitis (UC). We investigated curcumin's efficacy in inducing remission in patients with active mild-to-moderate UC. We performed a multicenter randomized, placebo-controlled, double-blind study of 50 mesalamine-treated patients with active mild-to-moderate UC (defined by the Simple Clinical Colitis Activity Index [SCCAI]) who did not respond to an additional 2 weeks of the maximum dose of mesalamine oral and topical therapy. Patients were randomly assigned to groups who were given curcumin capsules (3 g/day, n = 26) or an identical placebo (n = 24) for 1 month, with continued mesalamine. The primary outcome was the rate of clinical remission (SCCAI ≤2) at week 4. Clinical and endoscopic responses were also recorded. In the intention-to-treat analysis, 14 patients (53.8%) receiving curcumin achieved clinical remission at week 4, compared with none of the patients receiving placebo (P = .01; odds ratio [OR], 42; 95% confidence interval [CI], 2.3-760). Clinical response (reduction of ≥3 points in SCCAI) was achieved by 17 patients (65.3%) in the curcumin group vs. 3 patients (12.5%) in the placebo group (P < .001; OR, 13.2; 95% CI, 3.1-56.6). Endoscopic remission (partial Mayo score ≤1) was observed in 8 of the 22 patients evaluated in the curcumin group (38%), compared with none of 16 patients evaluated in the placebo group (P = .043; OR, 20.7; 95% CI, 1.1-393). Adverse events were rare and comparable between the 2 groups. Addition of curcumin to mesalamine therapy was superior to the combination of placebo and mesalamine in inducing clinical and endoscopic remission in patients with mild-to-moderate active UC, producing no apparent adverse effects. Curcumin may be a safe and promising agent for treatment of UC. Clinicaltrials.gov number: NCT01320436. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Association between Six CETP Polymorphisms and Metabolic Syndrome in Uyghur Adults from Xinjiang, China

PubMed Central

Hou, Huixian; Ma, Rulin; Guo, Heng; He, Jia; Hu, Yunhua; Mu, Lati; Yan, Yizhong; Ma, Jiaolong; Li, Shugang; Zhang, Jingyu; Ding, Yusong; Zhang, Mei; Niu, Qiang; Liu, Jiaming; Guo, Shuxia

2017-01-01

Objective: To explore the association between CETP gene polymorphisms and metabolic syndrome (MS), as well as the relationship between the CETP gene polymorphisms and each component of MS. Methods: A total of 571 individuals which were randomly selected from 5692 Uyghur adults were subdivided into two groups, including 280 patients with MS and 291 control subjects, using the group-matching method after matching for gender. We detected CETP polymorphisms (rs5882, rs1800775, rs3764261, rs12149545, rs711752, and rs708272) by using the Snapshot method. Results: (1) Significant differences were found involving the frequency distribution of genotypes and alleles of rs1800775, rs3764261, rs12149545, rs711752, and rs708272 between the control and MS groups (all p < 0.05). (2) rs1800775, rs3764261, rs12149545, rs711752, and rs708272 polymorphisms were significantly related to the risk of MS (all p < 0.05). (3) The rs1800775 polymorphism was associated with high fasting blood glucose levels and low high density lipoprotein cholesterol (HDL-C); rs3764261 and rs12149545 polymorphisms were associated with all components of MS except high blood pressure; rs711752 and rs708272 polymorphisms were associated with low HDL-C (all p < 0.05). (4) Complete linkage disequilibrium (LD) was identified for two pairs of single nucleotide polymorphisms (SNPs) (rs3764261 and rs12149545 (D’ = 1.000, r2 = 0.931), rs711752 and rs708272 (D’ = 1.000, r2 = 0.996)). (5) The A-G-G-G-C (p = 0.013, odds ratio [OR] = 0.622, 95% confidence interval [95% CI] = 0.427–0.906) and A-T-A-A-T (p < 0.001, OR = 0.519, 95% CI = 0.386–0.697) haplotypes were more frequent in the control group than in the case group. Conclusions: The rs1800775, rs3764261, rs12149545, rs711752, and rs708272 polymorphisms of CETP were associated with MS and its components among the Uyghur ethnic group. Complete LD was found between two pairs of SNPs (rs3764261 and rs12149545, rs711752, and rs708272). The A-G-G-G-C and A-T-A-A-T haplotypes might be protective factors for MS. PMID:28629169

Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.

PubMed

Reinisch, Walter; Panés, Julián; Khurana, Sunil; Toth, Gabor; Hua, Fei; Comer, Gail M; Hinz, Michelle; Page, Karen; O'Toole, Margot; Moorehead, Tara McDonnell; Zhu, Hua; Sun, YanHui; Cataldi, Fabio

2015-06-01

Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. ClinicalTrials.gov number NCT01284062. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Exposure-efficacy Relationships for Vedolizumab Induction Therapy in Patients with Ulcerative Colitis or Crohn's Disease.

PubMed

Rosario, Maria; French, Jonathan L; Dirks, Nathanael L; Sankoh, Serap; Parikh, Asit; Yang, Huyuan; Danese, Silvio; Colombel, Jean-Frédéric; Smyth, Michael; Sandborn, William J; Feagan, Brian G; Reinisch, Walter; Sands, Bruce E; Sans, Miguel; Fox, Irving

2017-08-01

A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [UC] or Crohn's disease [CD] has been reported. Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data. Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated. Exposure-efficacy relationships at Week 6 and potential baseline covariate effects were explored using logistic regression and individual predicted cumulative average concentration through Week 6 [Caverage] as exposure measure. Higher vedolizumab concentrations were associated with higher clinical remission rates; the exposure-efficacy relationship was steeper for UC than CD. Unadjusted analyses overestimated the relationship, more so for CD. From covariate-adjusted models, average probability of remission at Week 6 increased by approximately 15% for UC and 10% for CD between Caverage values of 35 and 84 µg/ml [5th and 95th percentiles, respectively]. On average, patients with higher albumin, lower faecal calprotectin [UC only], lower C-reactive protein [CD only], and no previous tumour necrosis factor-α [TNFα] antagonist use had a higher remission probability. Previous TNFα antagonist use had the greatest impact; remission probability was approximately 10% higher in treatment-naïve patients. Higher vedolizumab serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD. This relationship is affected by several factors, including previous TNFα antagonist use. Prospective studies are needed to assess vedolizumab dose individualisation and optimisation. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

A Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Vedolizumab.

PubMed

Rosario, Maria; Dirks, Nathanael L; Milch, Catherine; Parikh, Asit; Bargfrede, Michael; Wyant, Tim; Fedyk, Eric; Fox, Irving

2017-11-01

Vedolizumab is a humanized anti-α 4 β 7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α 4 β 7 -mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations. At therapeutic concentrations, vedolizumab primarily undergoes linear elimination. From population pharmacokinetic modeling, the vedolizumab terminal elimination half-life (t ½ β) was estimated to be 25.5 days; linear clearance (CL L ) was similar for patients with UC (0.159 L/day) and CD (0.155 L/day). Extreme low albumin concentrations and extreme high body weight values were potentially clinically important predictors of vedolizumab CL L . Other factors, including concomitant therapy use (methotrexate, azathioprine, mercaptopurine, or aminosalicylates) or prior tumor necrosis factor-α (TNF-α) antagonist use, had no clinically relevant effects on CL L . A positive exposure-efficacy relationship for clinical remission and clinical response was apparent for vedolizumab induction therapy in patients with UC or CD. On average, patients with higher albumin, lower fecal calprotectin (UC only), lower C-reactive protein (CD only), and no prior TNF-α antagonist use had a higher probability of remission. Off drug, 10% of patients with UC or CD were positive for anti-drug antibodies. This article provides a comprehensive review of the clinical pharmacokinetics, pharmacodynamics, exposure-efficacy relationships, and immunogenicity of vedolizumab.

Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial

PubMed Central

Bradley Palmer, Jaclyn; Lane, Deforia; Mayo, Diane; Schluchter, Mark; Leeming, Rosemary

2015-01-01

Purpose To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. Patients and Methods Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist-selected recorded music intraoperatively (n = 69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n = 70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n = 68). Results The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P < .001) in anxiety scores preoperatively (mean changes [and standard deviation: −30.9 [36.3], −26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P = .018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. Conclusion Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable. PMID:26282640

Urinary potassium is a potential biomarker of disease activity in Ulcerative colitis and displays in vitro immunotolerant role.

PubMed

Goyal, Sandeep; Rampal, Ritika; Kedia, Saurabh; Mahajan, Sandeep; Bopanna, Sawan; Yadav, Devesh P; Jain, Saransh; Singh, Amit Kumar; Wari, Md Nahidul; Makharia, Govind; Awasthi, Amit; Ahuja, Vineet

2017-12-22

We evaluated the in-vitro effect of potassium on CD4 + T cells and the role of urinary potassium as a potential biomarker of disease activity in patients with ulcerative colitis (UC). This prospective observational cohort study included healthy controls (n = 18) and UC patients [n = 30, median age: 40 (IQR: 28-46) years, 17 males)] with active disease(assessed by Mayo score) from September 2015-May 2016. Twenty-four hours urinary potassium along with fecal calprotectin (FCP) were estimated in UC patients (at baseline and follow-up after 3-6 months) and controls. In healthy volunteers, we also assessed the effect of potassium on CD4 + T cells differentiated in the presence of Th17 polarizing condition. UC patients had significantly higher FCP (368.2 ± 443.04 vs 12.44 ± 27.51, p < 0.001) and significantly lower urinary potassium (26.6 ± 16.9 vs 46.89 ± 35.91, p = 0.01) levels than controls. At follow-up, a significant increase in urinary potassium among patients who had clinical response [n = 22, 21.4 (14.4-39.7) to 36.5 (20.5-61.6), p = 0.04] and remission [n = 12, 18.7 (9.1-34.3) to 36.5 (23.4-70.5), p = 0.05] was accompanied with a parallel decline in FCP. On in-vitro analysis, potassium under Th17 polarizing conditions significantly inhibited IL-17 and interferon-[Formula: see text] expression while favoring the induction of FoxP3 + T cells. Therefore, urinary potassium levels are inversely associated with disease activity in UC with in-vitro data supporting an immune-tolerant role of potassium.

[Expression and clinical significance of 5hmC in bladder urothelial carcinoma].

PubMed

Li, Jie; Xu, Yuqiao; Zhang, Zhiwen; Zhang, Ming; Zhang, Zhekai; Zhang, Feng; Li, Qing

2016-02-01

To investigate the expression of 5-hydroxymethylcytosine (5hmC) in bladder urothelial carcinoma (UC) and its clinical significance. The expression of 5hmC in 21 cases of UC tissues and pericarcinous urinary tract epithelium was detected by immunohistochemical staining. Then the expression of 5hmC in the surgical resection of UC tissues in 92 cases was also surveyed. Non parametric U Mann-Whitney test was used to analyze the correlation between 5hmC expression and clinical data. Single factor survival analysis was performed by Kaplan-Meier test. The expression of 5hmC in normal urinary tract epithelium and UC tissues was significantly different, but there was no significant difference in the expression of 5hmC between low and high grades of UC tissues as well as between different TNM grades. Kaplan-Meier single factor survival analysis showed that there was no significant correlation between the 5hmC expression level and the survival rate or the recurrence-free survival of UC patients. The expression level of 5hmC in UC tissues is significantly lower than that in pericarcinous urinary tract epithelium. There is no correlation between the 5hmC expression and the progression, prognosis and recurrence of UC.

Patients' knowledge and fear of colorectal cancer risk in inflammatory bowel disease.

PubMed

Lopez, Anthony; Collet-Fenetrier, Benjamin; Belle, Arthur; Peyrin-Biroulet, Laurent

2016-06-01

To investigate knowledge and fear of colorectal cancer (CRC) risk in inflammatory bowel disease (IBD) patients. A 12-item self-administered questionnaire, developed after a careful literature review, was administered to all consecutive IBD patients treated with infliximab who were followed up at Nancy University Hospital (Vandoeuvre-lès-Nancy, France) between February and May 2012. Altogether 100 patients including 72 with Crohn's disease (CD) were included. Only 7.0% of patients spontaneously mentioned CRC risk as a main feature of IBD and 37.0% as a potential IBD complication. CRC was the most feared complication by 26 patients [ulcerative colitis (UC) 46.4% vs CD 18.1%, P < 0.01]. Two-thirds of patients knew that IBD increases CRC risk (UC 81.9% vs CD 57.1%, P = 0.02). Their main source of information was their gastroenterologist (52.0%). On the best screening method for CRC, 86.0% of the respondents mentioned colonoscopy. Only 32.0% of patients knew that it has to be performed 10 years after diagnosis. In case of dysplasia, 51.0% of the patients would not undergo colectomy (CD 59.7% vs UC 28.6%, P < 0.01), mainly due to the fear of having ostomy bags. Only one-quarter of UC patients were aware of the chemopreventive effect of 5-aminosalicylates on CRC risk. Two-thirds of IBD patients are aware of the risk of CRC. UC patients have a better knowledge of this risk and are more afraid of this complication. Our results underscore the need for therapeutic education about CRC in IBD patients. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

In Vitro Fertilization in Women With Inflammatory Bowel Disease Is as Successful as in Women From the General Infertility Population

PubMed Central

Oza, Sveta Shah; Pabby, Vikas; Dodge, Laura E.; Moragianni, Vasiliki A.; Hacker, Michele R.; Fox, Janis H.; Correia, Katharine; Missmer, Stacey A.; Ibrahim, Yetunde; Penzias, Alan S.; Burakoff, Robert; Friedman, Sonia; Cheifetz, Adam S.

2015-01-01

BACKGROUND & AIMS Inflammatory bowel disease (IBD) affects women of reproductive age, so there are concerns about its effects on fertility. We investigated the success of in vitro fertilization (IVF) in patients with IBD compared with the general (non-IBD) IVF population. METHODS We conducted a matched retrospective cohort study of female patients with IBD who under-went IVF from 1998 through 2011 at 2 tertiary care centers. Patients were matched 4:1 to those without IBD (controls). The primary outcome was the cumulative rate of live births after up to 6 cycles of IVF. Secondary outcomes included the proportion of patients who became pregnant and the rate of live births for each cycle. RESULTS Forty-nine patients with Crohn’s disease (CD), 71 patients with ulcerative colitis (UC), 1 patient with IBD-unclassified, and 470 controls underwent IVF during the study period. The cumulative rate of live births was 53% for controls, 69% for patients with UC (P = .08 compared with controls), and 57% for patients with CD (P = .87 compared with controls). The incidence of pregnancy after the first cycle of IVF was similar among controls (40.9%), patients with UC (49.3%; P = .18), and patients with CD (42.9%; P = .79). Similarly, the incidence of live births after the first cycle of IVF was similar among controls (30.2%), patients with UC (33.8%; P = .54), and patients with CD (30.6%; P = .95). CONCLUSIONS Based on a matched cohort study, infertile women with IBD achieve rates of live births after IVF that are comparable with those of infertile women without IBD. PMID:25818081

Meta-analysis using individual patient data: efficacy and durability of topical alicaforsen for the treatment of active ulcerative colitis.

PubMed

Vegter, S; Tolley, K; Wilson Waterworth, T; Jones, H; Jones, S; Jewell, D

2013-08-01

The antisense ICAM-1 inhibitor alicaforsen has been studied in four phase 2 studies in ulcerative colitis (UC). Recruited patients varied as to the extent of their colitis and in the severity of disease at entry. To investigate the efficacy of alicaforsen enema in specific UC populations. Efficacy was analysed for short-term (week 6-10) and long-term (week 30) outcomes compared with either placebo or a high-dose mesalazine (mesalamine) enema in patients with disease extent up to 40 cm from the anal verge in patients with moderate or severe disease, and in patients with both of these features. Individual patient data meta-analyses of 200 patients from four phase 2 studies evaluating nightly alicaforsen 240 mg enema and comparators. Patient data were pooled and analysed in a single data set. Continuous outcomes were evaluated using anova; dichotomous outcomes were evaluated using Pearson chi-square or Fisher's exact tests. Alicaforsen showed superior efficacy vs. placebo in: patients with disease extent up to 40 cm, patients with moderate and severe disease and especially when both those conditions were satisfied. In these patient groups, mesalazine also showed short-term efficacy. At week 30, however, the efficacy of mesalazine waned and alicaforsen became significantly more efficacious. This post hoc meta-analysis showed that alicaforsen is effective in patients with active UC, especially in patients with distal disease, which is of moderate/severe activity. The efficacy of alicaforsen was durable in these sub-groups, suggesting a disease-modifying effect. This analysis suggests that alicaforsen enema may offer an effective, potentially durable response in moderate/severe distal active UC. © 2013 John Wiley & Sons Ltd.

New serological markers in pediatric patients with inflammatory bowel disease

PubMed Central

Kovács, Márta; Müller, Katalin Eszter; Papp, Mária; Lakatos, Péter László; Csöndes, Mihály; Veres, Gábor

2014-01-01

The spectrum of serological markers associated with inflammatory bowel disease (IBD) is rapidly growing. Due to frequently delayed or missed diagnoses, the application of non-invasive diagnostic tests for IBD, as well as differentiation between ulcerative colitis (UC) and Crohn’s disease (CD), would be useful in the pediatric population. In addition, the combination of pancreatic autoantibodies and antibodies against Saccharomyces cerevisiae antibodies/perinuclear cytoplasmic antibody (pANCA) improved the sensitivity of serological markers in pediatric patients with CD and UC. Some studies suggested that age-associated differences in the patterns of antibodies may be present, particularly in the youngest children. In CD, most patients develop stricturing or perforating complications, and a significant number of patients undergo surgery during the disease course. Based on recent knowledge, serum antibodies are qualitatively and quantitatively associated with complicated CD behavior and CD-related surgery. Pediatric UC is characterized by extensive colitis and a high rate of colectomy. In patients with UC, high levels of anti-CBir1 and pANCA are associated with the development of pouchitis after ileal pouch-anal anastomosis. Thus, serologic markers for IBD can be applied to stratify IBD patients into more homogeneous subgroups with respect to disease progression. In conclusion, identification of patients at an increased risk of rapid disease progression is of great interest, as the application of early and more aggressive pharmaceutical intervention could have the potential to alter the natural history of IBD, and reduce complications and hospitalizations. PMID:24803798

The challenge of compliance and persistence: focus on ulcerative colitis.

PubMed

Kane, Sunanda V; Brixner, Diana; Rubin, David T; Sewitch, Maida J

2008-01-01

Non-adherence to therapy is a widespread problem, with typical adherence rates for prescribed medications being approximately 50%. An estimated 20% to 50% of patients with ulcerative colitis (UC) do not take their medications as prescribed, resulting in higher disease-recurrence rates and potentially higher health care costs. To characterize the problem of non-adherence in UC, to review the many factors affecting compliance and persistence in this population, and to discuss practical strategies to improve adherence in these patients. Adherence to and persistence with medication are complex and multifactorial behaviors. Factors shown to affect adherence in UC patients include disease extent and duration, cost of medications, fear of adverse effects, individual psychosocial variables, and the patient-physician relationship. In contrast, recent data do not support an important role for treatment-related factors such as daily dose, regimen, and formulation in influencing adherence in this population, particularly with longer duration of use. Strategies to improve adherence should involve the patient, the provider, and the health care delivery system. For UC patients, knowledge and discussion of the rationale for supporting persistence, such as recent data regarding agents that have a potential chemoprotective benefit, may encourage persistence, even during periods of quiescence. The patient-physician relationship is critical in encouraging adherence, particularly with respect to education, open communication, and agreement regarding the value of the assigned treatment. Health care delivery systems can improve adherence by encouraging the participation of multidisciplinary teams, providing reporting and tracking systems, and eliminating financial barriers where possible.

Health utility of patients with Crohn's disease and ulcerative colitis: a systematic review and meta-analysis.

PubMed

Malinowski, Krzysztof Piotr; Kawalec, Paweł

2016-08-01

The aim of this systematic review was to collect and summarize the current data on the utilities of patients with Crohn's disease (CD) and ulcerative colitis (UC). A meta-analysis of the obtained utilities was performed using a random-effects model and meta-regression by the disease type and severity. A bootstrap analysis was performed as it does not require assumption on distribution of the data. The highest utility among patients with CD and UC was observed when the diseases were in remission. The meta-regression analysis showed that both disease severity and an instrument/method/questionnaire used to obtain utilities were significant predictors of utility. Utility was the lowest for severe disease and the highest for disease in remission, the association was more notable in patients with CD compared with UC. Expert commentary: The issue of patients' utility is important for healthcare decision makers but it has not been fully investigated and requires further study.

[Crohns disease and ulcerative colitis - current view on genetic determination, immunopathogenesis and biologic therapy].

PubMed

Buc, M

2017-01-01

Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the intestine, also called inflammatory bowel diseases (IBD), which are not caused by pathogenic microorganisms but result from non-specific inflammatory processes in the bowel. IBD are polygenic diseases, as evidenced by the genome-wide association studies (GWAS), which have discovered more than 200 genes or genetic regions to be associated with IBD. Some of them are specific for CD or UC; however, there are 110 overlapping genes. In the pathogenesis of CD, activation of adaptive immunity mediated by TH1, TH17, or TH1/TH17 cells is induced because of disturbances in the mechanisms of innate immunity and autophagocytosis. By comparison, the major events that trigger autoimmune processes in UC are an increased translocation of commensal bacteria into the submucosa because of loose inter-epithelial connections with subsequent activation of ILC2, TH9, TH2, and NKT cells. Knowledge of the pathogenesis of a disease enables an effective therapy, which is especially true for biological therapy. It is noteworthy that monoclonal antibodies directed against the major protagonists underlying both CD and UC have failed. It points to the complexity of immunopathologic processes that run in both diseases. One can suppose that a blockade of one inflammatory pathway is circumvented by an alternative pathway. TNF is the principal pro-inflammatory cytokine that plays a major role in CD and UC as well. It was therefore decided to treat IBD patients with anti-TNF monoclonal antibodies, infliximab or adalimumab. Approximately one half of the CD patients and one third of the UC patients respond to this treatment.

MICA*A4 protects against ulcerative colitis, whereas MICA*A5.1 is associated with abscess formation and age of onset.

PubMed

Martinez-Chamorro, A; Moreno, A; Gómez-García, M; Cabello, M J; Martin, J; Lopez-Nevot, M Á

2016-06-01

Ulcerative colitis (UC) is one of the two major forms of inflammatory bowel disease, the aetiology of which remains unknown. Several studies have demonstrated the genetic basis of disease, identifying more than 130 susceptibility loci. The major histocompatibility complex class I chain-related gene A (MICA) is a useful candidate to be involved in UC pathogenesis, because it could be important in recognizing the integrity of the epithelial cell and its response to stress. The aim of this study was to analyse the relationship between polymorphisms in the transmembrane domain of MICA and susceptibility to develop UC. A total of 340 patients with UC and 636 healthy controls were genotyped for MICA transmembrane polymorphism using a polymerase chain reaction (PCR) combined with fluorescent technology. Different MICA alleles were determined depending on the PCR product size. The allele MICA*A4 was less frequent in patients than in controls (P = 0·003; OR = 0·643), and this protective role is higher when it forms haplotype with B*27 (P = 0·002; OR = 0·294). The haplotype HLA-B*52/MICA*A6 was also associated with UC [P = 0·001; odds ratio (OR) = 2·914]. No other alleles, genotypes or haplotypes were related with UC risk. Moreover, MICA*A5.1 is associated independently with abscesses (P = 0·002; OR = 3·096) and its frequency is lower in patients diagnosed between ages 17 and 40 years (P = 0·007; OR = 0·633), meaning an extreme age on onset. No association with location, extra-intestinal manifestations or need for surgery was found. © 2016 British Society for Immunology.

Vedolizumab induction therapy for inflammatory bowel disease in clinical practice--a nationwide consecutive German cohort study.

PubMed

Baumgart, D C; Bokemeyer, B; Drabik, A; Stallmach, A; Schreiber, S

2016-05-01

Vedolizumab (VDZ) is a humanised monoclonal IgG1 antibody targeting α4 β7 integrin. To investigate the real-world efficacy of vedolizumab for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). A consecutive cohort of 212 adult IBD patients with active disease (HBI >7/partial Mayo >4) newly receiving VDZ was prospectively recruited from 7 academic and 17 community centres. The primary endpoint was clinical remission (CRM) (CD HBI ≤4, UC pMayo ≤1) in week 14. Secondary endpoints included steroid-free remission (SFCRM), clinical response (CRS) (HBI/pMayo score drop ≥3), vedolizumab impact on CRP, calprotectin and haemoglobin. Data of 97 CD (71.1% female, HBI 11) and 115 UC (42.6% female, pMayo 6) patients were analysed. Only 5.2% CD and 24.3% UC were anti-TNFα naïve. Most had extensive mucosal involvement (Montreal L3 69.1%/E3 53.9%). At week 14, 23.7% vs. 23.5% of CD vs. UC patients achieved CRM, 19.6% vs. 19.1% SFCRM and 60.8% vs. 57.4% CRS, respectively (all based on NRI). Week 14 CRM in CD was significantly associated with no history of extraintestinal manifestations (P = 0.019), no prior adalimumab use (P = 0.011), no hospitalisation in the past 12 months (P = 0.015) and low HBI score (P = 0.02) and in UC with active or previous smoking (P = 0.044/0.028) and no anti-TNFα (P = 0.023) use. Low HBI (P = 0.019) and no hospitalisation in the past 12 months (P = 0.01) predict CD CRM. The three most common AE were joint pain, acne and nasopharyngitis. Vedolizumab is effective in routine use. © 2016 John Wiley & Sons Ltd.

Investigation of multiple susceptibility loci for inflammatory bowel disease in an Italian cohort of patients.

PubMed

Latiano, Anna; Palmieri, Orazio; Latiano, Tiziana; Corritore, Giuseppe; Bossa, Fabrizio; Martino, Giuseppina; Biscaglia, Giuseppe; Scimeca, Daniela; Valvano, Maria Rosa; Pastore, Maria; Marseglia, Antonio; D'Incà, Renata; Andriulli, Angelo; Annese, Vito

2011-01-01

Recent GWAs and meta-analyses have outlined about 100 susceptibility genes/loci for inflammatory bowel diseases (IBD). In this study we aimed to investigate the influence of SNPs tagging the genes/loci PTGER4, TNFSF15, NKX2-3, ZNF365, IFNG, PTPN2, PSMG1, and HLA in a large pediatric- and adult-onset IBD Italian cohort. Eight SNPs were assessed in 1,070 Crohn's disease (CD), 1,213 ulcerative colitis (UC), 557 of whom being diagnosed at the age of ≤16 years, and 789 healthy controls. Correlations with sub-phenotypes and major variants of NOD2 gene were investigated. The SNPs tagging the TNFSF15, NKX2-3, ZNF365, and PTPN2 genes were associated with CD (P values ranging from 0.037 to 7×10(-6)). The SNPs tagging the PTGER4, NKX2-3, ZNF365, IFNG, PSMG1, and HLA area were associated with UC (P values 0.047 to 4×10(-5)). In the pediatric cohort the associations of TNFSF15, NKX2-3 with CD, and PTGER4, NKX2-3, ZNF365, IFNG, PSMG1 with UC, were confirmed. Association with TNFSF15 and pediatric UC was also reported. A correlation with NKX2-3 and need for surgery (P  =  0.038), and with HLA and steroid-responsiveness (P  =  0.024) in UC patients was observed. Moreover, significant association in our CD cohort with TNFSF15 SNP and colonic involvement (P  =  0.021), and with ZNF365 and ileal location (P  =  0.024) was demonstrated. We confirmed in a large Italian cohort the associations with CD and UC of newly identified genes, both in adult and pediatric cohort of patients, with some influence on sub-phenotypes.

Effects of Music Therapy on Anesthesia Requirements and Anxiety in Women Undergoing Ambulatory Breast Surgery for Cancer Diagnosis and Treatment: A Randomized Controlled Trial.

PubMed

Palmer, Jaclyn Bradley; Lane, Deforia; Mayo, Diane; Schluchter, Mark; Leeming, Rosemary

2015-10-01

To investigate the effect of live and recorded perioperative music therapy on anesthesia requirements, anxiety levels, recovery time, and patient satisfaction in women experiencing surgery for diagnosis or treatment of breast cancer. Between 2012 and 2014, 207 female patients undergoing surgery for potential or known breast cancer were randomly assigned to receive either patient-selected live music (LM) preoperatively with therapist-selected recorded music intraoperatively (n=69), patient-selected recorded music (RM) preoperatively with therapist-selected recorded music intraoperatively (n=70), or usual care (UC) preoperatively with noise-blocking earmuffs intraoperatively (n=68). The LM and the RM groups did not differ significantly from the UC group in the amount of propofol required to reach moderate sedation. Compared with the UC group, both the LM and the RM groups had greater reductions (P<.001) in anxiety scores preoperatively (mean changes [and standard deviation: -30.9 [36.3], -26.8 [29.3], and 0.0 [22.7]), respectively. The LM and RM groups did not differ from the UC group with respect to recovery time; however, the LM group had a shorter recovery time compared with the RM group (a difference of 12.4 minutes; 95% CI, 2.2 to 22.5; P=.018). Satisfaction scores for the LM and RM groups did not differ from those of the UC group. Including music therapy as a complementary modality with cancer surgery may help manage preoperative anxiety in a way that is safe, effective, time-efficient, and enjoyable. © 2015 by American Society of Clinical Oncology.

Systemic metabolic signaling in acute and chronic gastrointestinal inflammation of inflammatory bowel diseases.

PubMed

Karrasch, T; Obermeier, F; Straub, R H

2014-06-01

Acute and chronic intestinal inflammation stimulates innate and adaptive immune systems, thereby increasing energy demand of activated immune cells. Energy regulation by systemically released mediators is of critical importance for homeostasis. We wanted to find out how systemic metabolic mediators are affected during intestinal inflammation. A total of 123 patients suffering from Crohn's disease (CD), 76 patients with ulcerative colitis (UC), and 21 healthy controls were recruited. Patients receiving systemic steroids or therapy regimens including biologicals (anti-TNF) were excluded from the study. Serum levels of IL-6, CRP, insulin, glucose, free fatty acid, and RBP-4 were measured by ELISA and RIA. Intestinal inflammation was accompanied by elevated systemic inflammatory para-meters such as IL-6 and CRP in UC and CD and, concomitantly, with elevated insulin levels and increased insulin/glucose ratio in patients with UC. This indicates insulin resistance in liver, muscle, and fat. In addition, intestinal inflammation was associated with elevated levels of circulating free fatty acids in UC and CD, indicating an activation of the organism's appeal for energy-rich substrates (energy appeal reaction). RBP-4 serum levels were also high in acute and chronic intestinal inflammation in UC and CD, which can support insulin resistance. The organism's "energy appeal reaction" in response to acute and chronic inflammation provides free energy in the circulation, which is needed by inflammatory cells. A major mechanism of the redirection program is insulin resistance. New therapeutic strategies might be developed in the future, directly impacting on the storage and utilization of energy-rich fuels. © Georg Thieme Verlag KG Stuttgart · New York.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

PubMed

Costello, S P; Soo, W; Bryant, R V; Jairath, V; Hart, A L; Andrews, J M

2017-08-01

Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods. To determine whether FMT is effective and safe for the induction of remission in active UC. Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs). There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission. Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent. © 2017 John Wiley & Sons Ltd.

Inflammatory Bowel Diseases Can Adversely Impact Domains of Sexual Function Such as Satisfaction with Sex Life.

PubMed

Eluri, Swathi; Cross, Raymond K; Martin, Christopher; Weinfurt, Kevin P; Flynn, Kathryn E; Long, Millie D; Chen, Wenli; Anton, Kristen; Sandler, Robert S; Kappelman, Michael D

2018-06-01

Aspects of sexual health, which can be adversely affected by chronic disease, have been inadequately explored in inflammatory bowel disease (IBD). We evaluated patient-reported interest in sexual activity and satisfaction with sex life in a large cohort of IBD patients. We conducted a cross-sectional study within the Crohn's and Colitis Foundation Partners Internet cohort. Sequential participants completed a 6-question supplemental online survey to examine sexual interest and satisfaction using the Patient-Reported Outcome Measurement Information System ® (PROMIS ® ) Sexual Function and Satisfaction measures. One-sample t tests were used to compare interest and satisfaction scores to general population norms. Among 2569 individuals, 1639 had Crohn's disease (CD), 930 had ulcerative colitis (UC) or indeterminate colitis, and 71% were women. Mean PROMIS scores for sexual interest were comparable to the general US population in men (CD: 49 and UC: 48 vs. population mean 50) and women (CD: 41 and UC: 40 vs. population mean 42). However, sexual satisfaction scores were lower than the US population in men (CD: 48 and UC: 48 vs. 51) and women (CD: 47 and UC: 46 vs. 49), p < 0.01 for both. Older age, disease activity, depression, anxiety, and pain were associated with lower interest and satisfaction and lowered IBD-specific quality of life. IBD patients in a large online survey had similar levels of sexual interest but decreased sexual satisfaction compared to the general population. Exploring these sexual health domains during clinical encounters can aid in improving IBD quality of life.

Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis

PubMed Central

Uygun, Ahmet; Ozturk, Kadir; Demirci, Hakan; Oger, Cem; Avci, Ismail Yasar; Turker, Turker; Gulsen, Mustafa

2017-01-01

Abstract Background: Fecal microbial transplantation (FMT) provides to replace beneficial bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy. Methods: In this prospective and uncontrolled study, 30 patients with UC were included. All medications except mesalazine were stopped 4 weeks before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL extracted fresh fecal suspension was administered into the 30 to 40 cm proximal of terminal ileum of recipients. Results: After FMT, 21 of the (70%) 30 patients showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and endoscopic remission at the week 12. Nine patients (30%) were accepted as a nonresponder at the end of the week 12. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. No adverse events were observed in the majority of patients during FMT and 12 weeks follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea, vomiting, abdominal pain, diarrhea, and fewer after FMT. Conclusion: FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Besides, FMT also appears to be definitely safer and more tolerable than the immunosuppressive therapy in patients with UC (NCT02575040). PMID:28422836

E-health: Web-guided therapy and disease self-management in ulcerative colitis. Impact on disease outcome, quality of life and compliance.

PubMed

Elkjaer, Margarita

2012-07-01

Ulcerative Colitis (UC) together with Crohn's disease (CD) belongs to inflammatory bowel diseases (IBD). IBD is to date as frequent as Insulin Dependent Diabetes (IDDM) and is second to Rheumatoid Arthritis (RA) in its chronicity. The majority (91%) of patients with UC have a mild to moderate disease course eligible for 5-ASA treatment. Poor adherence in UC is a well known phenomenon, which is associated with a 5-fold increased risk of relapse and increased health care costs. Web-based treatment solution with self-initiated 5-ASA treatment in UC based on the patient's pattern recognition of the disease course had not been published previously. The aims of the thesis were: 1) In a European evidence based consensus to assess the IBD patients' need for Quality of Health Care (QoHC); 2) To validate the influence of a Patient Educational Center (PEC) and a web-based treatment solution program, www.constant-care.dk, on patients' disease self-management, adherence, Quality of Life, and disease course after 1 year of self-initiated 5-ASA treatment. UC patients in a conventional out-patient setting were used as controls; 3) To validate two new quantitative rapid tests (RT scanning and HT photo) for Faecal Calprotectin (FC) measurement, and to assess whether HT photo can be useful as a home test to help the patients deciding on self-initiated treatment. The ECCO Consensus found evidence for optimising QoHC by "information"; "education", "benchmarking", and "psychological analysis", which could help to improve patient compliance, QoL, and to decrease depression and anxiety. UC patients, educated in the PEC, significantly improved the level of disease specific knowledge. Patient education and training on www.constant-care.dk, being validated on first 21 Danish patients and subsequently on 233 Danish and 100 Irish patients, showed that the new web guided approach was feasible, safe, and cost effective for the selected group of the patients included in the trial. Use of the web concept increased patients adherence to acute 5-ASA treatment, (p = 0.005) and community effectiveness up to 33%, improved Quality of Life, (p = 0.004), increased patients' ability to sufficient self-initiated treatment and reduce out-patient visits, (p < 0.0001). Patients' morbidity and depression remained unchanged. Median duration of relapse in the web-group was 59 days shorter than in the control-group possibly due to high dose of systemic 5-ASA treatment, (p < 0.0001). We found that the new rapid home test (HT photo) was accurate and comparable with the Enzyme-Linked Immunosorbent Assay (ELISA) with a 90% specificity and a 96% sensitivity. The rapid test can be useful in clinical settings concerning disease self-monitoring at home, which would decrease the use of endoscopy in some cases. The findings corresponded well with action plan for a European e-Health Area and could be a helpful tool to provide more efficient health care for UC patients. Widespread implementation of the "Constant-Care" is possible, but it may require a reshaping of the current health care for IBD patients both legally and economically. It may also empower patients in disease self-management and reduce dependency on doctors. Future long-term studies are needed to investigate, if this concept could possibly change the natural disease course.

Inflammatory bowel disease in Bahrain: single-center experience

PubMed Central

Abdulla, Maheeba; Al Saeed, Mahmood; Fardan, Rawdha Hameed; Alalwan, Hawra Faisal; Ali Almosawi, Zahra S; Almahroos, Amal Fuad; Al Qamish, Jehad

2017-01-01

Purpose The number of newly diagnosed inflammatory bowel disease (IBD) cases such as ulcerative colitis (UC), Crohn’s disease (CD), and indeterminate colitis (IC) is rapidly increasing in Gulf countries and Saudi Arabia. The aim of this study was to investigate the incidence and prevalence of IBD in patients who have attended the Salmaniya Medical Complex, Bahrain, between the years 1984 and 2014. Patients and methods All patients who had attended the Salmaniya Medical Complex, Bahrain, and had been diagnosed with UC, CD, or IC, between the years 1984 and 2014, were included in the analysis. Data collected were: patient demographics, symptoms, clinical signs, complications, surgical interventions, extent of disease, endoscopic findings, histopathology, and lab measurements. Results A total of 187 cases were included; 61 had CD, 123 had UC, and a further 3 cases presented with IC. A clear increase in the incidence and prevalence of IBD can be seen in this cohort. The prevalence of IBD was calculated to be 26.25/105 cases. The average number of IBD cases increased from 3 cases (average for the years 1984–2001) to 12 cases (average for the years 2002–2014). A number of factors correlate positively or negatively with CD and UC. In the current study, a link between gastrointestinal complications in CD cases and the use of steroids as a treatment was noted (p-value −0.02). Age also had a significant influence on the need for surgery in CD cases (p-value −0.04), and a family history of UC was statistically linked to surgical intervention (p-value −0.05). Conclusions IBD can no longer be considered a rare disease in Bahrain. The incidence of both UC and CD is steadily increasing. There is a need for increasing awareness of the Bahraini public to IBD in order for proper medical care to be given. PMID:28765713

Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy.

PubMed

Palagiano, A; Bulletti, C; Pace, M C; DE Ziegler, D; Cicinelli, E; Izzo, A

2004-12-01

Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospective, randomized, double-blind study in one medical center carried out with a parallel trial. The primary objective was to establish the effects of vaginal progesterone (Crinone 8%) in reducing both pain and uterine contractions (UCs). The gel with or without (placebo) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The secondary objective of the study was to evaluate the outcome of the pregnancies. The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration (P < 0.005). The evaluation of the ongoing pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried (P < 0.05). In conclusion, patients with threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain. The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase.

Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries.

PubMed

Kobayashi, Taku; Hisamatsu, Tadakazu; Suzuki, Yasuo; Ogata, Haruhiko; Andoh, Akira; Araki, Toshimitsu; Hokari, Ryota; Iijima, Hideki; Ikeuchi, Hiroki; Ishiguro, Yoh; Kato, Shingo; Kunisaki, Reiko; Matsumoto, Takayuki; Motoya, Satoshi; Nagahori, Masakazu; Nakamura, Shiro; Nakase, Hiroshi; Tsujikawa, Tomoyuki; Sasaki, Makoto; Yokoyama, Kaoru; Yoshimura, Naoki; Watanabe, Kenji; Katafuchi, Miiko; Watanabe, Mamoru; Hibi, Toshifumi

2018-04-01

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Predicting outcomes to optimize disease management in inflammatory bowel disease in Japan: their differences and similarities to Western countries

PubMed Central

Kobayashi, Taku; Suzuki, Yasuo; Ogata, Haruhiko; Andoh, Akira; Araki, Toshimitsu; Hokari, Ryota; Iijima, Hideki; Ikeuchi, Hiroki; Ishiguro, Yoh; Kato, Shingo; Kunisaki, Reiko; Matsumoto, Takayuki; Motoya, Satoshi; Nagahori, Masakazu; Nakamura, Shiro; Nakase, Hiroshi; Tsujikawa, Tomoyuki; Sasaki, Makoto; Yokoyama, Kaoru; Yoshimura, Naoki; Watanabe, Kenji; Katafuchi, Miiko; Watanabe, Mamoru; Hibi, Toshifumi

2018-01-01

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression.

PubMed

Tuygun, Can; Kankaya, Duygu; Imamoglu, Abdurrahim; Sertcelik, Ayse; Zengin, Kursad; Oktay, Murat; Sertcelik, Nurettin

2011-01-01

To investigate the expression of sex-specific hormone receptors in normal bladder urothelium and urothelial carcinomas (UCs) of the bladder, and to analyze clinicopathological features and survival outcomes according to receptor expression. We evaluated the clinical data and tumor specimens of 139 patients with bladder cancer (BC). In addition, 72 samples of normal urothelium were included. Immunohistochemistry was performed using streptavidin-biotin peroxidase method, a monoclonal androgen receptor (AR), and an estrogen receptor-β (ERβ) antibody on paraffin-embedded tissue sections. Expression levels of each receptor were assessed by evaluating 500 tumor cells for each case and the percentage of positively-stained nuclei was recorded. None of the 58 male control cases showed any AR and ERβ expression. Five (35, 71%) of the 14 female control cases expressed ERβ. Of the 139 patients with UCs, 71 (51, 07%) expressed AR (62 male vs. 9 female; P = 0.413) and 44 (31, 65%) (39 male vs. 5 female; P = 0.402) showed ERβ expression (P < 0.001). No significant relationship was found between ERβ expression levels and tumor grades, and stages (P = 0.441; P = 0.247). AR expression was significantly lower in T2-tumors (21%) than in Ta-tumors (60%) and T1-tumors (60%) (P < 0.001). It was significantly higher in low-grade papillary UCs (64%) compared with high-grade papillary UCs (44%) and infiltrative high-grade UCs (17%) (P = 0.039; P < 0.001). Data of 79 patients with noninvasive BC were eligible to present, with a median 29 months follow-up. AR expression level did not influence recurrence-free survival (RFS) and progression-free survival (PFS) (P = 0.095; P = 0.110). No significant association was found between ERβ expression level and RFS (P = 0.293). PFS in patients with lower ERβ-expressing tumors was significantly better than that in patients with higher ERβ-expressing tumors (P = 0.035). Multivariate analysis confirmed this significant influence on PFS (P = 0.025). Although ERβ expression had no impact on histopathological tumor characteristics, decrease in its expression may be associated with better PFS rates in patients with noninvasive BC. Conversely, loss of AR expression was associated with higher grade UCs and invasive UCs, but had no prognostic effect on survival. Finally, sex-specific hormone receptors alone cannot be responsible for gender differences in BC rates because they were expressed in similar rates in both sexes. Copyright © 2011 Elsevier Inc. All rights reserved.

Modelling the cost-effectiveness of pharmacist-managed anticoagulation service for older adults with atrial fibrillation in Singapore.

PubMed

Chua, Wen Bing Brandon; Cheen, Hua Heng McVin; Kong, Ming Chai; Chen, Li Li; Wee, Hwee Lin

2016-10-01

Background Oral anticoagulation with warfarin is the cornerstone therapy in atrial fibrillation (AF) for stroke prevention. Multi-disciplinary anticoagulation management services have been shown to be cost-effective in the United States, Hong Kong and Thailand, but the findings are not readily generalizable to Singapore's healthcare system. Objective This study aimed to evaluate the cost-effectiveness of pharmacist-managed anticoagulation clinic (ACC) compared with usual care (UC) for the management of older adults with AF receiving oral anticoagulation with warfarin. Setting Pharmacist-managed ACC in an academic medical centre. Method A Markov model with 3-month cycle length and 30-year time horizon compared costs and quality-adjusted life-years (QALYs) of ACC and UC from the patient's and healthcare provider's perspectives. Four pathways based on time in therapeutic range (TTR) were: ACC TTR < 70 %, ACC TTR ≥ 70 %, UC TTR < 70 % and UC TTR ≥ 70 %. A hypothetical cohort of 70-year-old Singaporean AF patients receiving warfarin was utilised. Local data from national disease registries, patient surveys and hospital databases were used. When local data was not available, published studies on Asian populations were utilized when available. One-way sensitivity analyses and probabilistic sensitivity analyses were performed to account for uncertainties. Costs and QALYs were discounted annually by 3 %. Main outcome measure Costs and QALYs of ACC and UC. Results Pharmacist-managed ACC was found to dominate UC in all comparisons. It improved effectiveness by 0.19 and 0.13 QALYs at TTR < 70 % and TTR ≥ 70 % respectively compared with UC. From the patient's perspective, ACC reduced costs by SG$1222.67 (€1110.24) for TTR < 70 % and SG$1008.16 (€915.46) for TTR ≥ 70 %. Similar trends were observed from the healthcare provider's perspective, with ACC reducing costs by SG$1444.79 (€1311.94) for TTR < 70 % and SG$1269.17 (€1152.46) for TTR ≥ 70 % compared with UC. The results were robust to variations of the parameters over their plausible ranges in one-way sensitivity analyses. Probabilistic sensitivity analyses demonstrated that ACC was cost-effective more than 79 % of the time from both perspectives at a willingness-to-pay threshold of SG$69,050 (€62,701) per QALY. Conclusion Pharmacist-managed ACC is more effective and less costly compared with UC regardless of the quality of anticoagulation therapy. The findings support the current body of evidence demonstrating the cost-effectiveness of ACC.

[The impact of stress and personality on resilience of patients with ulcerative colitis].

PubMed

Liu, W; Wang, J; Wang, H; Chen, X Y; Li, J S

2018-02-01

Objective: To study relevant factors that influence psychological resilience in patients with ulcerative colitis(UC), especially the role of perceived stress and personality. Methods: Patients with UC were recruited from January 2015 to December 2016 in the First Hospital of Zhengzhou University. Education levels, income, duration of disease, Mayo score and disease phenotype according to Montreal classification were collected. Resilience was measured using Connor-Davidson resilience scale (CD-RISC). Perceived stress was measured by perceived stress scale (PSS). Personality was evaluated using Eysenck personality questionnaire (EPQ). Univariate analyses were conducted to determine the correlation of variables with resilience and thereafter those statistically significant were reanalyzed via a multivariate regression model. Results: A total of 188 patients with UC were finally recruited. Univariate analyses demonstrated resilience was inversely associated with perceived stress, Mayo score and neuroticism. Extraversion, income, college education were positively related to resilience. However, multivariate analyses revealed that perceived stress( OR= 0.901, 95% CI 0.833-0.975), extraversion ( OR= 1.257, 95% CI 1.087-1.454), neuroticism ( OR= 0.818, 95% CI 0.679-0.985), Mayo score ( OR= 0.856, 95% CI 0.742-0.988) and income ( OR= 6.411, 95% CI 2.136-9.244) were significantly related to resilience. Conclusions: Resilience of UC patients is not only associated with disease activity, but also with personality, perceived stress and income.

Nephrogenous Cyclic Adenosine Monophosphate as a Parathyroid Function Test

PubMed Central

Broadus, Arthur E.; Mahaffey, Jane E.; Bartter, Frederic C.; Neer, Robert M.

1977-01-01

Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1°HPT), and 10 patients with chronic hypoparathyroidism. In the group with 1° HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium ≤10.7 mg/dl) or intermittent hypercalcemia, 19 patients with mild renal insufficiency (mean glomerular filtration rate, 64 ml/min), and 10 patients with moderate renal insufficiency (mean glomerular filtration rate, 43 ml/min). Plasma iPTH was increased in 41 patients (73%). The development of a parametric expression for UcAMP was found to be critically important in the clinical interpretation of results for total cAMP excretion. Because of renal impairment in a large number of patients, the absolute excretion rate of cAMP correlated poorly with the hyperparathyroid state. Expressed as a function of creatinine excretion, UcAMP was elevated in 81% of patients with 1° HPT, but the nonparametric nature of the expression led to a number of interpretive difficulties. The expression of cAMP excretion as a function of glomerular filtration rate was developed on the basis of the unique features of cAMP clearance in man, and this expression, which provided elevated values in 51 (89%) of the patients with 1° HPT, avoided entirely the inadequacies of alternative expressions. Results for NcAMP and UcAMP in nonazotemic and azotemic patients with hypoparathyroidism confirmed the validity of the measurements and the expressions employed. PMID:197123

Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib.

PubMed

Winthrop, Kevin L; Melmed, Gil Y; Vermeire, Séverine; Long, Millie D; Chan, Gary; Pedersen, Ronald D; Lawendy, Nervin; Thorpe, Andrew J; Nduaka, Chudy I; Su, Chinyu

2018-05-30

Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Tofacitinib is approved for rheumatoid arthritis and psoriatic arthritis, where it has been shown to increase herpes zoster (HZ) risk. We evaluated HZ risk among UC patients using tofacitinib. HZ cases were identified in tofacitinib phase II/III/ongoing, open-label, long-term extension (OLE) UC trials. We calculated HZ incidence rates (IRs) per 100 patient-years of tofacitinib exposure within phase III maintenance (Maintenance Cohort) and phase II/III/OLE (Overall Cohort) studies, stratified by baseline demographics and other factors. HZ risk factors were evaluated in the Overall Cohort using Cox proportional hazard models. Overall, 65 (5.6%) patients developed HZ. Eleven patients had multidermatomal involvement (2 nonadjacent or 3-6 adjacent dermatomes), and 1 developed encephalitis (resolved upon standard treatment). Five (7.7%) events led to treatment discontinuation. HZ IR (95% confidence interval [CI]) in the Overall Cohort was 4.07 (3.14-5.19) over a mean (range) of 509.1 (1-1606) days, with no increased risk observed with increasing tofacitinib exposure. IRs (95% CI) were highest in patients age ≥65 years, 9.55 (4.77-17.08); Asian patients, 6.49 (3.55-10.89); patients with prior tumor necrosis factor inhibitor (TNFi) failure, 5.38 (3.86-7.29); and patients using tofacitinib 10 mg twice daily, 4.25 (3.18-5.56). Multivariate analysis identified older age and prior TNFi failure as independent risk factors. In tofacitinib-treated UC patients, there was an elevated risk of HZ, although complicated HZ was infrequent. Increased HZ rates occurred in patients who were older, Asian, or had prior TNFi failure (NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612).

Ethnic and socio-cultural specificities in Tunisia have no impact on the prevalence of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients, their relatives or associated clinical factors.

PubMed

Hadrich, Ines; Vandewalle, Peggy; Cheikhrouhou, Fatma; Makni, Fattouma; Krichen, Mohamed Salah; Sendid, Boualem; Standaert-Vitse, Annie; Ayadi, Ali; Poulain, Daniel

2007-06-01

In Western Europe and the USA, the presence of anti-Saccharomyces cerevisiae antibodies (ASCAs) in Crohn's disease (CD) patients and their healthy relatives suggests that ASCAs may be influenced by genetic and/or environmental factors. To assess the prevalence of ASCAs in Tunisian patients with CD or ulcerative colitis (UC), and unaffected family members, in relation to clinical phenotype. Patients and methods. Seventy-seven patients (39 CD, 38 UC), 66 healthy relatives of CD patients, 16 relatives of UC patients and 70 healthy controls were studied. ASCAs were quantified with a new isotype-specific ELISA test involving an antigenic extract from S. cerevisiae strain W303 and by the original test which detects total immunoglobulins against S. cerevisiae Su1 mannan. The specificity of the two tests was identical (91%). The isotype-specific ASCA W303 test was more sensitive than the ASCA Su1 test for immunoglobulin detection, but some CD patients were positive only with this latter test. A high percentage of patients with CD (72%) and their unaffected family members (35%) were ASCA-positive in contrast to UC patients (16%) and their relatives (0%) and controls (8.6%). ASCAs were shown to be independent of rural or urban living, disease activity, but were associated with ileal location. The antigen of S. cerevisiae strain W303 discriminated patients depending on age at onset or location of the disease. This study confirms the antigenic heterogeneity of S. cerevisiae strains in their ability to detect ASCA. It suggests that ASCAs are markers of immunoregulatory disturbance in CD, independently of ethnic/cultural differences between Europe, the USA and North Africa.

Serial semi-quantitative measurement of fecal calprotectin in patients with ulcerative colitis in remission.

PubMed

Garcia-Planella, Esther; Mañosa, Míriam; Chaparro, María; Beltrán, Belén; Barreiro-de-Acosta, Manuel; Gordillo, Jordi; Ricart, Elena; Bermejo, Fernando; García-Sánchez, Valle; Piqueras, Marta; Llaó, Jordina; Gisbert, Javier P; Cabré, Eduard; Domènech, Eugeni

2018-02-01

Fecal calprotectin (FC) correlates with clinical and endoscopic activity in ulcerative colitis (UC), and it is a good predictor of relapse. However, its use in clinical practice is constrained by the need for the patient to deliver stool samples, and for their handling and processing in the laboratory. The availability of hand held devices might spread the use of FC in clinical practice. To evaluate the usefulness of a rapid semi-quantitative test of FC in predicting relapse in patients with UC in remission. Prospective, multicenter study that included UC patients in clinical remission for ≥6 months on maintenance treatment with mesalamine. Patients were evaluated clinically and semi-quantitative FC was measured using a monoclonal immunochromatography rapid test at baseline and every three months until relapse or 12 months of follow-up. One hundred and ninety-one patients had at least one determination of FC. At the end of follow-up, 33 patients (17%) experienced clinical relapse. Endoscopic activity at baseline (p = .043) and having had at least one FC > 60 μg/g during the study period (p = .03) were associated with a higher risk of relapse during follow-up. We obtained a total of 636 semi-quantitative FC determinations matched with a three-month follow-up clinical assessment. Having undetectable FC was inversely associated with early relapse (within three months), with a negative predictive value of 98.6% and a sensitivity of 93.9%. Serial, rapid semi-quantitative measurement of FC may be a useful, easy and cheap monitoring tool for patients with UC in remission.

Preservation of Immune Function in Cervical Cancer Patients during Chemoradiation using a Novel Integrative Approach

PubMed Central

Lutgendorf, Susan K.; Mullen-Houser, Elizabeth; Russell, Daniel; DeGeest, Koen; Jacobson, Geraldine; Hart, Laura; Bender, David; Anderson, Barrie; Buekers, Thomas E.; Goodheart, Michael J.; Antoni, Michael H.; Sood, Anil K.; Lubaroff, David M.

2010-01-01

Patients receiving chemoradiation for cervical cancer are at risk for distress, chemoradiation-related side-effects, and immunosuppression. This prospective randomized clinical trial examined effects of a complementary therapy, Healing Touch (HT), versus relaxation training (RT) and usual care (UC) for 1) supporting cellular immunity, 2) improving mood and quality of life (QOL), and 3) reducing treatment-associated toxicities and treatment delay in cervical cancer patients receiving chemoradiation. Sixty women with stages IB1 to IVA cervical cancer were randomly assigned to receive UC or 4×/weekly individual sessions of either HT or RT immediately following radiation during their 6-week chemoradiation treatment. Patients completed psychosocial assessments and blood sampling before chemoradiation at baseline, weeks 4 and 6. Multilevel regression analyses using orthogonal contrasts tested for differences between treatment conditions over time. HT patients had a minimal decrease in natural killer cell cytotoxicity (NKCC) over the course of treatment whereas NKCC of RT and UC patients declined sharply during chemoradiation (group by time interaction: p=0.018). HT patients showed greater decreases in 2 different indicators of depressed mood (CESD depressed mood subscale and POMS depression scale) compared to RT and UC (group by time interactions: p < 0.05). No between group differences were observed in QOL, treatment delay, or clinically-rated toxicities. HT may benefit cervical cancer patients by moderating effects of chemoradiation on depressed mood and cellular immunity. Effects of HT on toxicities, treatment delay, QOL, and fatigue were not observed. Long-term clinical implications of findings are not known. PMID:20600809

Pectin enhances the effect of fecal microbiota transplantation in ulcerative colitis by delaying the loss of diversity of gut flora.

PubMed

Wei, Yao; Gong, Jianfeng; Zhu, Weiming; Tian, Hongliang; Ding, Chao; Gu, Lili; Li, Ning; Li, Jieshou

2016-11-03

Fecal microbiota transplantation (FMT) induces remission in ulcerative colitis (UC). However, the treatment effect of FMT diminishes over time. Maintaining the diversity of the gut flora for long periods may improve the effects of FMT in UC. Pectin, which can be fermented by gut microbiota into short-chain fatty acids, is postulated to shape the composition and maintain the balance of gut microbiota following transplantation. This study investigated whether pectin could enhance the effects of FMT in UC patients. Three FMT patients and four FMTP patients achieved the primary outcome. The Mayo scores of the FMTP group were lower than those of the FMT group at weeks 4 and 12 (P = 0.042 and P = 0.042, respectively). There were no differences in the diversity of the gut flora between the two groups at weeks 4 and 12; however, the composition of the gut flora of the FMTP group was more similar than the FMT group to that of the donor at all-time points post-treatment. Pectin decreased the Mayo score by preserving the diversity of the gut flora following FMT for UC. Current Controlled Trial NCT02016469 . Registered 10 November 2013.

Blood-based biomarkers used to predict disease activity in Crohn's disease and ulcerative colitis.

PubMed

Burakoff, Robert; Pabby, Vikas; Onyewadume, Louisa; Odze, Robert; Adackapara, Cheryl; Wang, Wei; Friedman, Sonia; Hamilton, Matthew; Korzenik, Joshua; Levine, Jonathan; Makrauer, Frederick; Cheng, Changming; Smith, Hai Choo; Liew, Choong-Chin; Chao, Samuel

2015-05-01

Identifying specific genes that are differentially expressed during inflammatory bowel disease flares may help stratify disease activity. The aim of this study was to identify panels of genes to be able to distinguish disease activity in Crohn's disease (CD) and ulcerative colitis (UC). Patients were grouped into categories based on disease and severity determined by histological grading. Whole blood was collected by PAXgene Blood RNA collection tubes, (PreAnalytiX) and gene expression analysis using messenger RNA was conducted. Logistic regression was performed on multiple combinations of common probe sets, and data were evaluated in terms of discrimination by computing the area under the receiving operator characteristic curve (ROC-AUC). Nine inactive CD, 8 mild CD, 10 moderate-to-severe CD, 9 inactive UC, 8 mild UC, 10 moderate-to-severe UC, and 120 controls were hybridized to Affymetrix U133 Plus 2 microarrays. Panels of 6 individual genes discriminated the stages of disease activity: CD with mild severity {ROC-AUC, 0.89 (95% confidence interval [CI], 0.84%-0.95%)}, CD with moderate-to-severe severity (ROC-AUC 0.98 [95% CI, 0.97-1.0]), UC with mild severity (ROC-AUC 0.92 [95% CI, 0.87-0.96]), and UC with moderate-to-severe severity (ROC-AUC 0.99 [95% CI, 0.97-1.0]). Validation by real-time reverse transcription-PCR confirmed the Affymetrix microarray data. The specific whole blood gene panels reliably distinguished CD and UC and determined the activity of disease, with high sensitivity and specificity in our cohorts of patients. This simple serological test has the potential to become a biomarker to determine the activity of disease.

Alterations in the gut microbiome of children with severe ulcerative colitis

PubMed Central

Michail, Sonia; Durbin, Matthew; Turner, Dan; Griffiths, Anne M; Mack, David R.; Hyams, Jeffrey; Leleiko, Neal; Kenche, Harshavardhan; Stolfi, Adrienne; Wine, Eytan

2011-01-01

Background Although the role of microbes in disease pathogenesis is well established, data describing the variability of the vast microbiome in children diagnosed with ulcerative colitis (UC) are lacking. This study characterizes the gut microbiome in hospitalized children with severe UC and determines the relationship between microbiota and response to steroid therapy. Methods Fecal samples were collected from 26 healthy controls and 27 children hospitalized with severe UC as part of a prospective multi-center study. DNA extraction, PCR amplification of bacterial 16S rRNA, and microarray hybridization were performed. Results were analyzed in Genespring GX 11.0 comparing healthy controls to children with UC, and steroid responsive (n=17) to non-responsive patients (n=10). Results Bacterial signal strength and distribution showed differences between UC and healthy controls (adjusted p<0.05) for Phylum, Class, Order, Family, Genus, and Phylospecies levels with reduction in Clostridia and an increase in Gamma-proteobacteria. The number of microbial phylospecies was reduced in UC (266±69) vs. controls (758±3, p<0.001), as was the Shannon diversity index (6.1±0.23 vs. 6.49±0.04, respectively; p<0.0001). Steroids non-responders harbored less phylospecies than responders (142±49 vs. 338±62, p=0.013). Conclusions Richness, evenness, and biodiversity of the gut microbiome were remarkably reduced in children with UC, compared to healthy controls. Children who did not respond to steroids harbored a microbiome that was even less rich than steroid responders. This study is the first to characterize the gut microbiome in a large cohort of pediatric patients with severe ulcerative colitis and describes changes in the gut microbiome as a potential prognostic feature. PMID:22170749

Once-daily versus multiple-daily mesalamine for patients with ulcerative colitis: a meta-analysis.

PubMed

Tong, Jin Lu; Huang, Mei Lan; Xu, Xi Tao; Qiao, Yu Qi; Ran, Zhi Hua

2012-04-01

To systematically review the efficacy and safety of once-daily (OD) mesalamine for the treatment of ulcerative colitis (UC) compared with multiple-daily (MD) mesalamine. Electronic databases up to July 2011 were searched for related studies evaluating the efficacy of OD vs MD for treatment of UC. Only randomized controlled trials (RCTs) were considered eligible. Remission rates or relapse rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) analysis. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated. Publication bias was assessed with a funnel plot. Overall 10 RCTs including 9 full-text manuscripts and one abstract met the inclusion criteria. OD dosing of mesalamine was shown to be as effective as MD dosing for the maintenance of clinical remission in patients with quiescent UC (RR = 1.00, 95% CI 0.89-1.12) by ITT analysis. For active UC, a mild but significant benefit was achieved by OD dosing compared with MD dosing (RR = 0.80, 95% CI 0.64-0.99). Total adverse events were similar using OD and MD mesalamine in quiescent UC (RR = 1.06, 95% CI 0.93-1.20). Compliance with OD was slightly better than with MD (RR = 0.92, 95% CI 0.82-1.03). OD mesalamine is as effective and has a comparable safety profile as MD regimens for the maintenance treatment of UC, and is even more effective for inducing remission in active UC. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

The polymorphisms K469E and G261R of intercellular adhesion molecule-1 and susceptibility to inflammatory bowel disease: a meta-analysis.

PubMed

Song, Gwan Gyu; Lee, Young Ho

2015-01-01

The aim of this study was to explore whether polymorphisms of intercellular adhesion molecule-1 (ICAM-1) are associated with susceptibility to Crohn's disease (CD) and ulcerative colitis (UC). The authors conducted a meta-analysis on the associations between the polymorphisms K469E and G241R of ICAM-1 and susceptibility to CD and UC. A total of 8 studies with 801 patients with CD, 672 patients with UC, and 1,828 controls were included in the meta-analysis. The meta-analysis revealed no association between CD and the ICAM-1 469E allele among the subjects (OR = 1.175, 95% CI = 0.901-1.533, p = 0.233). However, stratification by ethnicity indicated an association between the ICAM-1 469E allele and CD in Europeans (OR = 1.425, 95% CI = 1.013-2.002, p = 0.042). Meta-analysis using the homozygosity also showed an association with CD in Europeans (OR = 2.054, 95% CI = 1.036-4.073, p = 0.039). The meta-analysis revealed no association between UC and the ICAM-1 K469E polymorphism. No association between CD or UC and the ICAM-1 G241R polymorphism was observed. This meta-analysis demonstrates that the ICAM-1 K469E polymorphism may be associated with susceptibility to CD in Europeans, but no association was found between ICAM-1 K469E and UC. In contrast, the G241R polymorphism was not found to be associated with susceptibility to either CD or UC.

Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis

PubMed Central

Lin, Xue; Chang, Ying; Liu, Jing; Zhou, Rui; Nie, Jia-Yan; Dong, Wei-Guo; Zhao, Qiu; Li, Jin

2017-01-01

The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines. PMID:29228739

A randomized, controlled study to evaluate the role of an in-home asthma disease management program provided by respiratory therapists in improving outcomes and reducing the cost of care.

PubMed

Shelledy, David C; Legrand, Terry S; Gardner, Donna D; Peters, Jay I

2009-03-01

Asthma management programs (AMP) may reduce costs and improve outcomes in patients with moderate to severe asthma. However, it is not known which personnel are best able to deliver such interventions and what settings are most effective. The purpose of this study was to compare the effects of an in-home AMP provided by respiratory therapists (RTs) to an AMP provided by nurses (RNs) and to usual care (UC) provided in physician offices or clinics. Subjects (age 18-64) who had been admitted to the emergency department (ED) or hospital for acute asthma exacerbation were randomized to three groups: AMP-RT, AMP-RN or UC. The AMP groups received five (5) weekly home visits to provide assessment and instruction; the UC group was instructed to return to their physician for routine follow-up. Outcomes assessed at 6 months included hospitalizations, in patient days, hospitalization cost, ED visits and cost, clinic visits, pulmonary function, symptoms, health related quality of life (HRQOL), asthma episode self-management score (AESM), environmental assessment, and patient satisfaction (PS). Variables were compared using ANOVA with a Neuman-Keuls follow-up for multiple comparisons using an intent-to-treat approach. Upon enrollment, (n = 159) there were no differences (p > .05) between groups for age, gender, pulmonary function or HRQOL (SF-36 and St. Georges Respiratory Questionnaire - SGRQ). At 6 months, both AMP groups (AMP-RN n = 54; AMP-RT n = 46) had significantly fewer (p < 0.05) hospitalizations and in-patient days, lower hospitalization costs, and greater HRQOL physical component summary change scores (PCS) and PS than UC (n = 59). AMP-RT also had greater PEFR, SGRQ Total and SGRQ Symptoms change scores when compared to UC and significantly better AESM and PS scores as compared to AMP-RN and UC. An in-home asthma management program can be effectively delivered by respiratory therapists and may reduce hospitalizations, in-patient days, cost and improve measures of HRQOL and PS in a population prone to asthma exacerbation.

Comparison of post-operative intravesical recurrence and oncological outcomes after open versus laparoscopic nephroureterectomy for upper urinary tract urothelial carcinoma.

PubMed

Zou, Lujia; Zhang, Limin; Zhang, Hu; Jiang, Haowen; Ding, Qiang

2014-04-01

To retrospectively evaluate intravesical recurrence and oncological outcomes after open or laparoscopic radical nephroureterectomy (RNU) for the upper urinary tract urothelial carcinoma (UUT-UC). This study comprised 122 patients diagnosed UUT-UC and subsequently nephroureterectomy was performed on. Several clinical and pathological parameters were emphasized for comparison of clinical outcomes. Among 122 patients with UUT-UC, 101 (82.8 %) and 21 (17.2 %) underwent open or laparoscopic radical nephroureterectomy (ONU or LNU), respectively. In univariable and multivariable Cox regression models, the surgical procedure exerted an impact neither on post-operative intravesical recurrence rate (p = 0.179 and 0.213, respectively) nor on cancer-specific mortality rate (p = 0.561 and 0.159, respectively). The 1-, 2- and 5-year cancer-specific survival (CSS) rates of patients undergoing ONU or LNU were 92.1 versus 95.2 %, 87.1 versus 90.5 %, 79.2 versus 85.7 %, respectively, and the Kaplan–Meier plot illustrated that patients from two groups enjoyed an equivalent survival rate (p = 0.559). Moreover, we added that previous history of bladder tumor and pre-operative hydronephrosis was associated with intravesical recurrence, whereas three prognostic factors, including pathological tumor stage, grade, and lymphovascular invasion, showed possibility to be predictors of cancer-specific mortality. There existed no significant difference of intravesical recurrence and CSS between patients after ONU and LNU. Conclusively, laparoscopic radical nephroureterectomy did not present superiority to open management for patients with UUT-UC.

Meta-analysis: effect of preoperative infliximab use on early postoperative complications in patients with ulcerative colitis undergoing abdominal surgery.

PubMed

Yang, Z; Wu, Q; Wang, F; Wu, K; Fan, D

2012-11-01

Infliximab is widely used in severe and refractory ulcerative colitis (UC). The results of clinical studies are inconsistent on whether preoperative infliximab use increases early postoperative complications in UC patients. To determine the clinical safety and efficacy of preoperative infliximab treatment in UC patients with regard to short-term outcomes following abdominal surgery. PubMed, Embase databases were searched for controlled observational studies comparing postsurgical morbidity in UC patients receiving infliximab preoperatively with those not on infliximab. The primary endpoint was total complication rate. Secondary endpoints included the rate of infectious and non-infectious complications. We calculated pooled odds ratios (ORs) with 95% confidence intervals (CIs) as summary measures. A total of 13 studies involving 2933 patients were included in our meta-analysis. There was no significant association between infliximab therapy preoperatively and total (OR = 1.09, 95% CI: 0.87-1.37, P = 0.47), infectious (OR = 1.10, 95% CI: 0.51-2.38, P = 0.81) and non-infectious (OR = 1.10, 95% CI: 0.76-1.59, P = 0.61) postoperative complications respectively. Infliximab might be a protective factor against infection for the use within 12 weeks prior to surgery (OR = 0.43, 95% CI: 0.22-0.83, P = 0.01). No publication bias was found. Preoperative infliximab use does not increase the risk of early postoperative complications in patients with ulcerative colitis undergoing abdominal surgery. © 2012 Blackwell Publishing Ltd.

Mapping of a disease susceptibility locus in chromosome 6p in Japanese patients with ulcerative colitis.

PubMed

Nomura, E; Kinouchi, Y; Negoro, K; Kojima, Y; Oomori, S; Sugimura, M; Hiroki, M; Takagi, S; Aihara, H; Takahashi, S; Hiwatashi, N; Shimosegawa, T

2004-09-01

Ulcerative colitis (UC) is a multifactorial disorder with both genetic and environmental factors. HLA-B*52 and DRB1*1502 are reported to be strongly associated with UC in Japan. However, the actual susceptible gene has not been identified yet. In this study, to map precisely the susceptible locus for UC, we performed association mapping in the chromosome 6p using 24 microsatellite markers distributed over 16 Mb. A total of 183 patients with UC and 186 healthy controls (HC) were included in this study. In all, 15 markers around the human leukocyte antigen (HLA) region showed statistical significance in the genotypic differentiation test concerned with the allelic distribution between the UC and HC. Especially, the markers between the centromeric region of HLA class I and the telomeric region of class III showed remarkably low P-values and the allele239 of C2-4-4 in class I marker showed the strongest association (Pc=2.9 x 10(-9): OR=3.74, 95% CI=2.50-5.60). Furthermore, we found strong linkage disequilibrium (LD) between the allele239 of C2-4-4 and HLA-B*52 in haplotype analysis. These results provide evidence that, in Japanese, important determinants of disease susceptibility to UC may exist in HLA, especially between the centromeric region of class I and the telomeric region of class III, under the strong LD with HLA-B*52.

Genetic characterization of UCS region of Pneumocystis jirovecii and construction of allelic profiles of Indian isolates based on sequence typing at three regions.

PubMed

Gupta, Rashmi; Mirdha, Bijay Ranjan; Guleria, Randeep; Kumar, Lalit; Luthra, Kalpana; Agarwal, Sanjay Kumar; Sreenivas, Vishnubhatla

2013-01-01

Pneumocystis jirovecii is an opportunistic pathogen that causes severe pneumonia in immunocompromised patients. To study the genetic diversity of P. jirovecii in India the upstream conserved sequence (UCS) region of Pneumocystis genome was amplified, sequenced and genotyped from a set of respiratory specimens obtained from 50 patients with a positive result for nested mitochondrial large subunit ribosomal RNA (mtLSU rRNA) PCR during the years 2005-2008. Of these 50 cases, 45 showed a positive PCR for UCS region. Variations in the tandem repeats in UCS region were characterized by sequencing all the positive cases. Of the 45 cases, one case showed five repeats, 11 cases showed four repeats, 29 cases showed three repeats and four cases showed two repeats. By running amplified DNA from all these cases on a high-resolution gel, mixed infection was observed in 12 cases (26.7%, 12/45). Forty three of 45 cases included in this study had previously been typed at mtLSU rRNA and internal transcribed spacer (ITS) region by our group. In the present study, the genotypes at those two regions were combined with UCS repeat patterns to construct allelic profiles of 43 cases. A total of 36 allelic profiles were observed in 43 isolates indicating high genetic variability. A statistically significant association was observed between mtLSU rRNA genotype 1, ITS type Ea and UCS repeat pattern 4. Copyright © 2012 Elsevier B.V. All rights reserved.

Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

PubMed Central

Nagy, Ferenc; Molnár, Tamás; Szepes, Zoltán; Farkas, Klaudia; Nyári, Tibor; Lonovics, János

2008-01-01

AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indices (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA-intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients. PMID:18666323

Clinical Presentation of Ulcerative Colitis in Pakistani Adults.

PubMed

Qureshi, Mustafa; Abbas, Zaigham

2015-01-01

The aim of this study was to determine the clinical presentation and severity of ulcerative colitis (UC) in Pakistani adult patients. An observational study. Data were obtained by reviewing the medical records of patients who visited a gastroenterology clinic between 2008 and 2012. There were 54 patients diagnosed as UC. The male to female ratio was 1:1. Mean age at diagnosis of UC was 38.7 ± 11.8 years (median 36.5, range 18-64). The predominant presenting symptoms were mucus diarrhea in 49 (90.7%), gross blood in stools in 42 (77.8%), abdominal pain or cramps in 40 (74.1%) and weight loss in 15 (27.7%). Left-sided colitis was present in 23 (42.6%), pancolitis in 15 (27.8%), extensive colitis in 11 (20.4%), and proctitis in five (9.2%). The severity of UC as judged by the Mayo scoring system showed that 68.5% were suffering from moderate to severe disease while 31.5% had mild disease. The extra-intestinal manifestation were found only in seven patients; arthritis in five patients and anterior uveitis in two patients. The arthritis was unilateral and the sites were knee joint in three patients and sacroiliac joint in two patients. Ulcerative colitis presents in our adult patients may present at any age with no gender preponderance. The disease severity is moderate to severe in the majority of patients and more than half of them have left-sided colitis or pancolitis at the time of presentation. Extraintestinal manifestations were not common. Qureshi M, Abbas Z. Clinical Presentation of Ulcerative Colitis in Pakistani Adults. Euroasian J Hepato-Gastroenterol 2015;5(2):127-130.

Atezolizumab in Metastatic Urothelial Carcinoma Outside Clinical Trials: Focus on Efficacy, Safety, and Response to Subsequent Therapies.

PubMed

Barata, Pedro C; Gopalakrishnan, Dhrmesh; Koshkin, Vadim S; Mendiratta, Prateek; Karafa, Matt; Allman, Kimberly; Martin, Allison; Beach, Jennifer; Profusek, Pam; Tyler, Allison; Wood, Laura; Ornstein, Moshe; Gilligan, Timothy; Rini, Brian I; Garcia, Jorge A; Grivas, Petros

2018-04-06

Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials. The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials. This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017. Seventy-nine patients, median age 72 years (range 29-93), 71% men and 76% ECOG PS 0-1, were identified. Most patients (79%) had primary cancer in the bladder, 62% had prior surgery, and 75% received at least one prior line of treatment (34 patients had prior cisplatin-based chemotherapy). Best response included 18% partial response, 29% stable disease, and 53% progressive disease. Patients were on atezolizumab for a median of 2.7 months (95%CI, 1.8-3.6) and median PFS was 3.2 months (95%CI, 1.6-4.8). A total of 33 (42%) patients had significant (any cause) AEs, including grade 4 hyperbilirubinemia in two patients; no toxic deaths were reported. At time of data analysis, only 18% of patients received at least one subsequent line of treatment for a median of 1.8 months (95%CI, 0.0-5.0) while 42% were referred to palliative care/hospice or died. Patients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC.

Strategies in maintenance for patients receiving long-term therapy (SIMPLE): a study of MMX mesalamine for the long-term maintenance of quiescent ulcerative colitis.

PubMed

Kane, Sunanda; Katz, Seymour; Jamal, M Mazen; Safdi, Michael; Dolin, Ben; Solomon, Dory; Palmen, Mary; Barrett, Karen

2012-06-01

This was a phase IV, multicenter, open-label, 12-14-month study to assess clinical recurrence in patients with ulcerative colitis (UC) who received maintenance treatment with MMX Multi Matrix System (MMX) mesalamine. A secondary outcome was the relationship between long-term efficacy and adherence. Patients with quiescent UC (no rectal bleeding; 0-1 bowel movements more than normal per day) were enrolled directly into a 12-month maintenance phase of the study during which they received MMX mesalamine 2.4 g/day given once daily (QD). Patients with active, mild-to-moderate UC at screening were enrolled into a 2-month acute phase; those who achieved quiescence could continue into the maintenance phase. The primary endpoint was clinical recurrence at Month 6. Of the 290 patients enrolled, 208 entered the maintenance phase; 152 directly and 56 via the acute phase. Following 6 and 12 months of treatment, 76.5% and 64.4% of evaluable patients, respectively, were recurrence-free. The majority of evaluable patients at Month 6 (81.6%) and Month 12 (79.4%) in the maintenance phase were ≥ 80% adherent to MMX mesalamine. At Month 6, clinical recurrence was observed in 20.6% of patients who were ≥ 80% adherent and 36.1% of patients with <80% adherence (P = 0.05 [post-hoc chi-square analysis]); 31.2% and 52.5% at Month 12 (P = 0.01 [post-hoc chi-square analysis]). MMX mesalamine 2.4 g/day QD is effective for maintaining quiescence in patients with UC. Furthermore, adherence to prescribed treatment yielded lower rates of clinical recurrence. Continued education regarding the importance of long-term 5-aminosalicylic acid therapy is warranted. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases

PubMed Central

Halling, Morten L; Kjeldsen, Jens; Knudsen, Torben; Nielsen, Jan; Hansen, Lars Koch

2017-01-01

AIM To investigate whether immune mediated diseases (IMD) are more frequent in patients with inflammatory bowel disease (IBD). METHODS In this population based registry study, a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16, 2013. Controls were randomly selected from the Danish Civil Registration System (CRS) and matched for sex, age, and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis (UC), Crohn’s disease (CD) and Both the latter referring to those registered with both diagnoses. Subsequently, odds-ratios (OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P-values were estimated using Fisher’s exact test. RESULTS There were significantly more women than men in the registry, and a greater percentage of comorbidity in the IBD groups (P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased (P < 0.00125) for primary sclerosing cholangitis (PSC), celiac disease, type 1 diabetes (T1D), sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis. Restricted to UC (P < 0.00125) were autoimmune hepatitis, primary biliary cholangitis, Grave’s disease, polymyalgia rheumatica, temporal arteritis , and atrophic gastritis. Restricted to CD (P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC (P < 0.00125) were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica. Restricted to women with CD were episcleritis, rheumatoid arthritis, and psoriatic arthritis. The only disease restricted to men (P < 0.00125) was sarcoidosis. CONCLUSION Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways. PMID:28970729

Effect of an extract based on the medicinal mushroom Agaricus blazei Murill on expression of cytokines and calprotectin in patients with ulcerative colitis and Crohn's disease.

PubMed

Førland, D T; Johnson, E; Saetre, L; Lyberg, T; Lygren, I; Hetland, G

2011-01-01

An immunomodulatory extract (AndoSan™) based on the medicinal mushroom Agaricus blazei Murill (AbM) has shown to reduce blood cytokine levels in healthy volunteers after 12 days' ingestion, pointing to an anti-inflammatory effect. The aim was to study whether AndoSan™ had similar effects on cytokines in patients with ulcerative colitis (UC) and Crohn's disease (CD). Calprotectin, a marker for inflammatory bowel disease (IBD), was also measured. Patients with CD (n = 11) and with UC (n = 10) consumed 60 ml/day of AndoSan™. Patient blood plasma was harvested before and after 6 h LPS (1 ng/ml) stimulation ex vivo. Plasma and faecal calprotectin levels were analysed using ELISA and 17 cytokines [IL-2, IFN-γ, IL-12 (Th1), IL-4, IL-5, IL-13 (Th2), IL-7, IL-17, IL-1β, IL-6, TNF-α, IL-8, MIP-1β, MCP-1, G-CSF, GM-CSF and IL-10] by multiplex assay. After 12 days' ingestion of AndoSan™, baseline plasma cytokine levels in UC was reduced for MCP-1 (40%) and in LPS-stimulated blood for MIP-1β (78%), IL-6 (44%), IL-1β (41%), IL-8 (30%), G-CSF (29%), MCP-1 (18%) and GM-CSF (17%). There were corresponding reductions in CD: IL-2 (100%), IL-17 (55%) and IL-8 (29%) and for IL-1β (35%), MIP-1β (30%), MCP-1 (22%), IL-8 (18%), IL-17 (17%) and G-CSF (14%), respectively. Baseline concentrations for the 17 cytokines in the UC and CD patient groups were largely similar. Faecal calprotectin was reduced in the UC group. Ingestion of an AbM-based medicinal mushroom by patients with IBD resulted in interesting anti-inflammatory effects as demonstrated by declined levels of pathogenic cytokines in blood and calprotectin in faeces. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Patients with inflammatory bowel disease have increased risk of autoimmune and inflammatory diseases.

PubMed

Halling, Morten L; Kjeldsen, Jens; Knudsen, Torben; Nielsen, Jan; Hansen, Lars Koch

2017-09-07

To investigate whether immune mediated diseases (IMD) are more frequent in patients with inflammatory bowel disease (IBD). In this population based registry study, a total of 47325 patients with IBD were alive and registered in the Danish National Patient Registry on December 16, 2013. Controls were randomly selected from the Danish Civil Registration System (CRS) and matched for sex, age, and municipality. We used ICD 10 codes to identify the diagnoses of the included patients. The IBD population was divided into three subgroups: Ulcerative colitis (UC), Crohn's disease (CD) and Both the latter referring to those registered with both diagnoses. Subsequently, odds-ratios (OR) and 95%CI were obtained separately for each group and their respective controls. The use of Bonferoni post-test correction adjusted the significance level to P < 0.00125. P -values were estimated using Fisher's exact test. There were significantly more women than men in the registry, and a greater percentage of comorbidity in the IBD groups ( P < 0.05). Twenty different IMDs were all significantly more frequent in the IBD group. Sixteen were associated with UC versus twelve with CD. In both UC and CD ORs were significantly increased ( P < 0.00125) for primary sclerosing cholangitis (PSC), celiac disease, type 1 diabetes (T1D), sarcoidosis, asthma, iridocyclitis, psoriasis, pyoderma gangrenosum, rheumatoid arthritis, and ankylosing spondylitis. Restricted to UC ( P < 0.00125) were autoimmune hepatitis, primary biliary cholangitis, Grave's disease, polymyalgia rheumatica, temporal arteritis , and atrophic gastritis. Restricted to CD ( P < 0.00125) were psoriatic arthritis and episcleritis. Restricted to women with UC ( P < 0.00125) were atrophic gastritis, rheumatoid arthritis, temporal arteritis, and polymyalgia rheumatica. Restricted to women with CD were episcleritis, rheumatoid arthritis, and psoriatic arthritis. The only disease restricted to men ( P < 0.00125) was sarcoidosis. Immune mediated diseases were significantly more frequent in patients with IBD. Our results strengthen the hypothesis that some IMDs and IBD may have overlapping pathogenic pathways.

The relationship among multiple patient-reported outcomes measures for patients with ulcerative colitis receiving treatment with MMX ® formulated delayed-release mesalamine.

PubMed

Yarlas, Aaron; Yen, Linnette; Hodgkins, Paul

2015-03-01

Ulcerative colitis (UC) is associated with impaired health-related quality of life (HRQL) and work-related outcomes (WRO). This analysis examined correspondences among measures of HRQL and WRO in patients with UC, as well as the magnitude of each measure's responsiveness to disease activity and treatment. An open-label, prospective trial of delayed-release mesalamine tablets formulated with MMX(®) technology included 8 weeks of treatment for patients with active mild-to-moderate UC (n = 137) and 12 months of maintenance treatment for patients with quiescent UC (n = 206). Spearman correlations (ρ) measured inter-domain associations across measures of generic HRQL [12-item Short-Form Health Survey (SF-12v2)], disease-specific HRQL [Short Inflammatory Bowel Disease Questionnaire (SIBDQ)], and disease-specific WRO [Work Productivity and Activity Impairment for Specific Health Problems (WPAI:SHP)]. Responsiveness to disease activity and treatment was assessed for each instrument. Changes in scores from baseline to week 8 were moderately correlated across all instrument domains: 65 of 80 (81 %) between-instrument inter-domain correlations were of moderate magnitude (0.30 < ρ < 0.70), with an average magnitude of 0.42 [95 % confidence interval (CI) 0.38-0.46]. Associations between symptom measures were stronger for SIBDQ (|average ρ| = 0.41; 95 % CI 0.34-0.48) and WPAI:SHP (0.40; 0.30-0.47) than SF-12v2 (0.30; 0.27-0.34). SIBDQ was most sensitive to treatment [effect size (d z ) for change from baseline to week 8 = 0.62; 95 % CI 0.35-0.89], followed by WPAI:SHP (d z = 0.43; 0.32-0.54) and SF-12v2 (d z = 0.33; 0.27-0.39). While the SIBDQ showed the greatest overall responsiveness to disease activity and treatment, all three patient-reported outcomes instruments provided complementary interpretive information regarding the impact of UC treatment.

Evaluation of the Risk of Relapse in Ulcerative Colitis According to the Degree of Mucosal Healing (Mayo 0 vs 1): A Longitudinal Cohort Study.

PubMed

Barreiro-de Acosta, Manuel; Vallejo, Nicolau; de la Iglesia, Daniel; Uribarri, Laura; Bastón, Iria; Ferreiro-Iglesias, Rocío; Lorenzo, Aurelio; Domínguez-Muñoz, J Enrique

2016-01-01

Mucosal healing in ulcerative colitis (UC) has become a common endpoint in most clinical trials and a relevant therapeutic goal in clinical practice. Despite important differences between endoscopic Mayo scores 0 and 1, both scores are considered as mucosal healing in most important trials. The aim of the present study was to evaluate the risk of relapse in UC patients according to the degree of mucosal healing (endoscopic Mayo scores of 0 and 1). A prospective longitudinal cohort study was designed. All UC patients who presented with mucosal healing at colonoscopy were consecutively included. Mucosal healing was defined as an endoscopic Mayo score of 0 or 1. Clinical relapse was defined as the need for therapy to induce remission, any treatment escalation, hospitalization or colectomy. All clinical relapses were evaluated at months 6 and 12 after study entry. Results were subjected to unconditional stepwise logistic and Kaplan-Meier regression analysis. One hundred and eighty-seven consecutive UC patients (126 [67.3%] with Mayo score 0 and 61 [32.7%] with Mayo score 1) were included. Of patients with Mayo scores 0 and 1, 9.4 and 36.6% respectively presented a relapse during the first 6 months of follow-up (p < 0.001). The only factor independently associated with UC relapses in the multivariate analysis was an endoscopic Mayo score of 1 (odds ratio 6.27, 95% confidence interval 2.73-14.40, p < 0.001). Patients with an endoscopic Mayo score of 1 have a higher risk of relapse than those with a score of 0. The concept of mucosal healing should be limited to patients with an endoscopic Mayo score of 0. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A content-based image retrieval method for optical colonoscopy images based on image recognition techniques

NASA Astrophysics Data System (ADS)

Nosato, Hirokazu; Sakanashi, Hidenori; Takahashi, Eiichi; Murakawa, Masahiro

2015-03-01

This paper proposes a content-based image retrieval method for optical colonoscopy images that can find images similar to ones being diagnosed. Optical colonoscopy is a method of direct observation for colons and rectums to diagnose bowel diseases. It is the most common procedure for screening, surveillance and treatment. However, diagnostic accuracy for intractable inflammatory bowel diseases, such as ulcerative colitis (UC), is highly dependent on the experience and knowledge of the medical doctor, because there is considerable variety in the appearances of colonic mucosa within inflammations with UC. In order to solve this issue, this paper proposes a content-based image retrieval method based on image recognition techniques. The proposed retrieval method can find similar images from a database of images diagnosed as UC, and can potentially furnish the medical records associated with the retrieved images to assist the UC diagnosis. Within the proposed method, color histogram features and higher order local auto-correlation (HLAC) features are adopted to represent the color information and geometrical information of optical colonoscopy images, respectively. Moreover, considering various characteristics of UC colonoscopy images, such as vascular patterns and the roughness of the colonic mucosa, we also propose an image enhancement method to highlight the appearances of colonic mucosa in UC. In an experiment using 161 UC images from 32 patients, we demonstrate that our method improves the accuracy of retrieving similar UC images.

Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy.

PubMed

Srichomkwun, Panudda; Houngngam, Natnicha; Pasatrat, Sophitsachi; Tharavanij, Thipaporn; Wattanachanya, Lalita; Khovidhunkit, Weerapan

2016-07-01

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.

Chk1 Promotes DNA Damage Response Bypass following Oxidative Stress in a Model of Hydrogen Peroxide-Associated Ulcerative Colitis through JNK Inactivation and Chromatin Binding.

PubMed

Reissig, Kathrin; Silver, Andrew; Hartig, Roland; Schinlauer, Antje; Walluscheck, Diana; Guenther, Thomas; Siedentopf, Sandra; Ross, Jochen; Vo, Diep-Khanh; Roessner, Albert; Poehlmann-Nitsche, Angela

2017-01-01

Dysregulation of c-Jun N -terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases. In both phases, Chk1 was linked to DNA damage response bypass by suppressing JNK activation following oxidative stress, promoting cell cycle progression despite DNA damage. Simultaneously, activated Chk1 was bound to chromatin. This triggered histone acetylation and the binding of histone acetyltransferases and transcription factors to chromatin. Thus, chromatin-immobilized activated Chk1 executed a dual function by suppressing DNA damage response and simultaneously inducing chromatin modulation. This caused undetected DNA damage and increased cellular proliferation through failure to transmit the appropriate DNA damage signal. Findings in vitro were corroborated by chromatin accumulation of activated Chk1, Ac-H3, Ac-H4, and c-Jun in active UC (AUC) in vivo. Targeting chromatin-bound Chk1, GCN5, PCAF, and p300/CBP could be a novel therapeutic strategy to prevent UC-related tumor progression.

Computational Prediction and Validation of BAHD1 as a Novel Molecule for Ulcerative Colitis

NASA Astrophysics Data System (ADS)

Zhu, Huatuo; Wan, Xingyong; Li, Jing; Han, Lu; Bo, Xiaochen; Chen, Wenguo; Lu, Chao; Shen, Zhe; Xu, Chenfu; Chen, Lihua; Yu, Chaohui; Xu, Guoqiang

2015-07-01

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise aetiology of UC remains unknown. In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate the expression profiles of UC patients and small interfering RNA (siRNA)-perturbed cells to predict proteins that might be essential in UC from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those genes predicted to be the most important for UC in dextran sodium sulphate (DSS)-induced colitic mice. We found that bromo-adjacent homology domain (BAHD1), a novel heterochromatinization factor in vertebrates, was the most downregulated gene. We further validated a potential role of BAHD1 as a regulatory factor for inflammation through the TNF signalling pathway in vitro. Our findings indicate that computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases, and BAHD1 might act as an indispensable factor in regulating the cellular inflammatory response in UC.

Second Korean guidelines for the management of ulcerative colitis

PubMed Central

Choi, Chang Hwan; Moon, Won; Kim, You Sun; Kim, Eun Soo; Lee, Bo-In; Jung, Yunho; Yoon, Yong Sik; Lee, Heeyoung; Park, Dong Il

2017-01-01

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the IBD study group of the Korean Association for the Study of Intestinal Diseases established the first Korean guidelines for the management of UC in 2012. This is an update of the first guidelines. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations. PMID:28239313

Genetic characterization of the UCS and Kex1 loci of Pneumocystis jirovecii.

PubMed

Esteves, F; Tavares, A; Costa, M C; Gaspar, J; Antunes, F; Matos, O

2009-02-01

Nucleotide variation in the Pneumocystis jirovecii upstream conserved sequence (UCS) and kexin-like serine protease (Kex1) loci was studied in pulmonary specimens from Portuguese HIV-positive patients. DNA was extracted and used for specific molecular sequence analysis. The number of UCS tandem repeats detected in 13 successfully sequenced isolates ranged from three (9 isolates, 69%) to four (4 isolates, 31%). A novel tandem repeat pattern and two novel polymorphisms were detected in the UCS region. For the Kex1 gene, the wild-type (24 isolates, 86%) was the most frequent sequence detected among the 28 sequenced isolates. Nevertheless, a nonsynonymous (1 isolate, 3%) and three synonymous (3 isolates, 11%) polymorphisms were detected and are described here for the first time.

Bone mineral density in patients with inflammatory bowel disease from north-eastern Romania.

PubMed

Dumitrescu, Gabriela; Mihai, Cătălina; Dranga, Mihaela; Prelipcean, Cristina Cijevschi

2013-01-01

Inflammatory bowel disease (IBD) is associated with increased prevalence of bone demineralization. One of the risk factors for low bone density is the inadequate level of 25-OH vitamin D. To determine the degree of bone demineralization in patients with IBD and the main causes leading to this condition. A prospective study was carried out between April, 2011 and October, 2012 in 143 patients diagnosed with IBD at the Gastroenterology and Hepatology Centre of Iaşi.The IBD diagnosis was made on clinical, biological, and endoscopic criteria and confirmed histologically. The diagnosis of osteopenia/osteoporosis was based on World Health Organization criteria. Osteopenia was found in 48.07% of the patients with ulcerative colits (UC) and in 56.41% of the patients with Crohn's disease (CD); osteoporosis was present in 18.26% of the patients with UC and 15.38% of those with CD. The main causes identified were inadequate vitamin D level, extended high-dose corticotherapy in patients with CD, BMI < 18.5 kg/m2, and smoking, especially in the patients with UC. Bone demineralization and hypovitaminosis D are frequently associated with IBD and require specific treatment.

Characteristics of Fecal and Mucosa-Associated Microbiota in Chinese Patients With Inflammatory Bowel Disease

PubMed Central

Chen, Liping; Wang, Wei; Zhou, Rui; Ng, Siew C.; Li, Jin; Huang, Meifang; Zhou, Feng; Wang, Xin; Shen, Bo; A. Kamm, Michael; Wu, Kaichun; Xia, Bing

2014-01-01

Abstract The intestinal microbiota plays an important role in the pathogenesis of inflammatory bowel disease (IBD), and geographical and genetic backgrounds impact the composition of the intestinal microbiota. However, there is a lack of evidence regarding the overall changes and characteristics of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) in Chinese patients with IBD. We recruited 26 patients with Crohn’s disease (CD), 46 patients with ulcerative colitis (UC), and 21 healthy individuals; we collected matched fresh fecal and mucosal samples from the same subjects. The microbial communities were studied by 454-pyrosequencing. Community-wide changes in FAM and MAM were observed in patients with IBD. The proportion of several butyrate-producing bacteria, such as of the genera Roseburia, Coprococcus, and Ruminococcus were significantly reduced, whereas the pathogens Escherichia-Shigella and Enterococcus were prevalent in patients with IBD. FAM and MAM were similar between CD and UC. FAM differed from MAM in healthy individuals and patients with UC. In conclusion, the compositions of FAM and MAM were altered in patients with IBD. The reduction of butyrate-producing bacteria and the increase in opportunistic pathogens might be associated with the pathogenesis of IBD. PMID:25121355

Diagnostic Potential of Zymogen Granule Glycoprotein 2 Antibodies as Serologic Biomarkers in Chinese Patients With Crohn Disease.

PubMed

Zhang, Shulan; Wu, Ziyan; Luo, Jing; Ding, Xuefeng; Hu, Chaojun; Li, Ping; Deng, Chuiwen; Zhang, Fengchun; Qian, Jiaming; Li, Yongzhe

2015-10-01

The need for reliable biomarkers for distinguishing Crohn disease (CD) from ulcerative colitis (UC) is increasing. This study aimed at evaluating the diagnostic potential of anti-GP2 antibodies as a biomarker in Chinese patients with CD. In addition, a variety of autoantibodies, including anti-saccharomyces cerevisiae antibodies (ASCA), perinuclear anti-neutrophil cytoplasmic antibodies (PANCA), anti-intestinal goblet cell autoantibodies (GAB), and anti-pancreatic autoantibodies (PAB), were evaluated.A total of 91 subjects were prospectively enrolled in this study, including 35 patients with CD, 35 patients with UC, 13 patients with non-IBD gastrointestinal diseases as disease controls (non-IBD DC), and 8 healthy controls (HC). The diagnosis of IBD was determined based on the Lennard-Jones criteria, and the clinical phenotypes of the IBD patients were determined based on the Montreal Classification.Anti-GP2 IgG antibodies were significantly elevated in patients with CD, compared with patients with UC (P = 0.0038), HC (P = 0.0055), and non-IBD DC (P = 0.0063). The prevalence of anti-GP2 IgG, anti-GP2 IgA and anti-GP2 IgA, or IgG antibodies in patients with CD was 40.0%, 37.1%, and 54.3%, respectively, which were higher than those in non-IBD DC (anti-GP2 IgG, 15.4%; anti-GP2 IgA, 7.7%; and anti-GP2 IgA or IgG, 23.1%) and those in patients with UC (anti-GP2 IgG, 11.4%; anti-GP2 IgA, 2.9%; and anti-GP2 IgA or IgG, 14.3%). For distinguishing CD from UC, the sensitivity, specificity, positive predictive value (PPV) and positive likelihood ratios (LR+) were 40%, 88.6%, 77.8%, and 3.51 for anti-GP2 IgG, 37.1%, 97.1%, 92.9%, and 13.0 for anti-GP2 IgA, and 54.3%, 85.3%, 79.2%, and 3.69 for anti-GP2 IgA or IgG. For CD diagnosis, the combination of anti-GP2 antibodies with ASCA IgA increased the sensitivity to 68.6% with moderate loss of specificity to 74.3%. Spearman's rank of order revealed a significantly positive correlation of anti-GP2 IgG with ileocolonic location of disease (L3) (P = 0.043) and a negative correlation of anti-GP2 IgA with biologic therapy (P = 0.012).Our findings suggest that anti-GP2 antibodies could serve as a biomarker for distinguishing patients with CD from patients with UC, and the combination of anti-GP2 antibodies with ASCA IgA may improve the predictive power.

Systematic review: body composition in adults with inflammatory bowel disease.

PubMed

Bryant, R V; Trott, M J; Bartholomeusz, F D; Andrews, J M

2013-08-01

There is a paucity of data on body composition in patients with inflammatory bowel disease (IBD). Alterations of fat and muscle may affect bone health, muscle performance, quality of life (QoL) and overall morbidity. To systematically review the literature on body composition in adults with IBD, and to discuss potential contributory factors and associations. A systematic search was performed in July 2012 of OVID SP MEDLINE, OVID EMBASE and National Library of Medicine's PubMed Central Medline (Limitations: English, humans, from 1992). A total of 19 articles comparing body composition in patients with IBD with healthy age- and sex-matched control populations were included in the primary analysis. A total of 631 patients with Crohn's disease (CD) and 295 with ulcerative colitis (UC), mean age 37.1 (s.d. ± 9.2) years; 485 (52%) female, were reported upon. Data were heterogeneous and methodology varied. Compared with controls, a statistically significant reduction in body mass index (BMI) was reported in 37% of CD and 20% of UC patients; reduced fat-free mass in 28% CD and 13% UC patients, and reduced fat mass in 31% CD and 13% UC patients. There was no consistent association between body composition and disease activity, duration, extent or therapies. BMI did not accurately predict body composition. Current data, although heterogeneous, suggest that many patients with IBD are affected by aberrations in fat and lean mass, which may not be detected during routine clinical assessment. The prevalence and impact of altered body composition amongst this population warrant further investigation. © 2013 John Wiley & Sons Ltd.

High mucosal healing rates in 5-ASA-treated ulcerative colitis patients: results of a meta-analysis of clinical trials.

PubMed

Römkens, Tessa E H; Kampschreur, Milou T; Drenth, Joost P H; van Oijen, Martijn G H; de Jong, Dirk J

2012-11-01

Recently, mucosal healing (MH) is regarded as an important treatment goal in ulcerative colitis (UC). 5-Aminosalicylates (5-ASA) are the standard treatment in mild-to-moderate UC, but the effect on MH is less known. The aim of this study was to systematically review the medical literature in order to compare different preparations of 5-ASA for the effect on MH. We conducted a structured search of PubMed and the Cochrane Central Register of Controlled Trials to identify randomized controlled clinical trials with 5-ASA in UC providing data about MH. We calculated the sample size-weighted pooled proportion of patients with MH, and performed meta-analysis of head-to-head comparisons. Out of 645 hits, we included 90 treatment arms, involving 3977 patients using oral 5-ASA (granulate and tablets) and 2513 patients using rectal 5-ASA (suppositories, enema, and foam). Overall, 43,7% of 5-ASA treated patients achieved MH (oral 36,9%; rectal 50,3%). In oral studies, 49% of patients using granulate (7 treatment-arms) achieved MH compared to 34,9% using tablets (43 treatment-arms). In rectal studies the proportion of MH was 62% for suppositories (eight treatment arms), 51% for foam (nine treatment arms), and 46% for enema (23 treatment arms), respectively. 5-ASA preparations achieved MH in nearly 50% of UC patients. There were no significant differences in MH between the various 5-ASA agents, either in the oral or the rectal treatment groups. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

PubMed

Zampeli, Evanthia; Gizis, Michalis; Siakavellas, Spyros I; Bamias, Giorgos

2014-08-15

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Vedolizumab: An integrin-receptor antagonist for treatment of Crohn's disease and ulcerative colitis.

PubMed

Hahn, Lindsay; Beggs, Ashton; Wahaib, Kristy; Kodali, Leela; Kirkwood, Vanessa

2015-08-01

The pharmacology, pharmacokinetics, safety, efficacy, and dosing recommendations of vedolizumab, an integrin-receptor antagonist for the treatment of Crohn's disease (CD) and ulcerative colitis (UC), are reviewed. Vedolizumab is an integrin-receptor antagonist for the treatment of CD and UC in adults with moderately to severely active disease who have had an inadequate response with, lost response to, or were intolerant to anti-tumor necrosis factor (TNF) agents or immunomodulators or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids. Phase III clinical trials have demonstrated efficacy in achieving remission as induction and maintenance therapy in CD and UC. Remission was also achieved at week 10 in patients with CD in whom previous treatment with anti-TNF agents had failed. Adverse effects of vedolizumab include nasopharyngitis, headache, arthralgia, nausea, pyrexia, upper respiratory tract infection, fatigue, cough, bronchitis, influenza, back pain, rash, pruritus, sinusitis, oropharyngeal pain, and pain in the extremities. To date, no cases of progressive multifocal leukoencephalopathy (PML) have been reported. The recommended dose of vedolizumab in adults with UC or CD is 300 mg administered via intravenous infusion at zero, two, and six weeks, followed by every eight weeks. The average wholesale unit price is $5782.80, but a patient assistance program is available. Vedolizumab is a new alternative for patients with moderate-to-severe UC or CD, as well as patients who have not responded to anti-TNF agents. The current safety profile and lack of reported PML make it a promising addition to the treatment of these conditions. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Comparison of treatment outcomes according to output voltage during shockwave lithotripsy for ureteral calculi: a prospective randomized multicenter study.

PubMed

Park, Jinsung; Kim, Hong-Wook; Hong, Sungwoo; Yang, Hee Jo; Chung, Hong

2015-05-01

To investigate the effect of fixed versus escalating voltage during SWL on treatment outcomes in patients with ureteral calculi (UC). A prospective, randomized, multicenter trial was conducted on 120 patients who were diagnosed with a single radiopaque UC. The patients were randomized into group C (n = 60, constant 13 kV, 3,000 shock wave, 2 Hz) or group E (n = 60, 11.4-12.0-13 kV per 1,000 shock waves, 2 Hz). They were evaluated by plain abdominal radiography and urinalysis at 1 week after a single session of SWL, and repeat SWL was performed if needed. The primary endpoint was stone-free rate at 1 week (SFR1) after SWL. Secondary endpoints were post-SWL visual pain score (VPS), oral analgesic requirements during 1 week, and cumulative SFRs after the second and third sessions of SWL. Groups C and E were well balanced in terms of baseline patients and stone characteristics, including pre-SWL VPS, stone location, and stone size (6.24 ± 1.92 vs. 6.30 ± 2.13 mm). SFR1s were not significantly different between groups C and E (60.0 vs. 68.3%, p = 0.447). Analyses stratified by stone size (<6 vs. ≥6 mm) showed no difference in SFR1 (p = 0.148 vs. 0.808). In the analyses stratified by stone location, group E tended to be more effective in distal UC (81.0 vs. 50.0%, p = 0.052), whereas no difference was seen in proximal UC (p = 0.487). Secondary endpoints were also similar between the two groups. Our results suggest that voltage escalation during SWL in UC may not provide superior stone fragmentation compared to fixed voltage.

Ulcerative colitis-associated hospitalization costs: A population-based study

PubMed Central

Coward, Stephanie; Heitman, Steven J; Clement, Fiona; Hubbard, James; Proulx, Marie-Claude; Zimmer, Scott; Panaccione, Remo; Seow, Cynthia; Leung, Yvette; Datta, Neel; Ghosh, Subrata; Myers, Robert P; Swain, Mark; Kaplan, Gilaad G

2015-01-01

BACKGROUND: Hospitalization costs for ulcerative colitis (UC) following the introduction of infliximab have not been evaluated. OBJECTIVE: To study predictors of costs for UC patients who were hospitalized for a flare or colectomy. METHODS: Population-based surveillance identified adults (≥18 years of age) admitted to hospital for UC flare or colectomy between 2001 and 2009 in the Calgary Health Zone (Alberta). Medical charts were reviewed and patients stratified into three admission types: responsive to inpatient medical therapy (n=307); emergent colectomy (n=227); and elective colectomy (n=208). The annual median cost with interquartile range (IQR) was calculated. Linear regression determined the effect of admission type on hospital charges after adjusting for age, sex, smoking, comorbidities, disease extent, medication use (eg, infliximab) and year. The adjusted cost increase was presented as the percent increase with 95% CIs. Joinpoint analysis assessed for an inflection point in hospital cost after the introduction of infliximab. RESULTS: Median hospitalization cost for UC flare, emergent colectomy and elective colectomy, respectively, were: $5,499 (IQR $3,374 to $8,904), $23,698 (IQR $17,981 to $32,385) and $14,316 (IQR $11,932 to $18,331). Adjusted hospitalization costs increased approximately 6.0% annually (95% CI 4.5% to 7.5%). Adjusted costs were higher for patients who underwent an elective colectomy (percent increase cost 179.8% [95% CI 151.6% to 211.1%]) or an emergent colectomy (percent increase cost 211.1% [95% CI 183.2% to 241.6%]) than medically responsive patients. Infliximab in hospital was an independent predictor of increased costs (percent increase cost 69.5% [95% CI 49.2% to 92.5%]). No inflection points were identified. CONCLUSION: Hospitalization costs for UC increased due to colectomy and infliximab. PMID:26079072

Risk of Colorectal Cancer Among Caucasian and African American Veterans with Ulcerative Colitis

PubMed Central

Hou, Jason K.; Kramer, Jennifer R.; Richardson, Peter; Mei, Minghua; El-Serag, Hashem B.

2014-01-01

Background African Americans are at an increased risk of developing sporadic colorectal cancer (CRC) compared to Caucasians. Ulcerative colitis (UC) is a risk factor for developing CRC; however, risk differences for CRC between African Americans and Caucasians with UC are unknown. Methods We performed a cohort study of patients with a diagnosis of UC during fiscal years 1998 to 2009 using the national Veterans Affairs administrative datasets. Cumulative CRC incidence rates and incidence rate ratios were calculated and Cox proportional hazards models were used to examine the association between race and the CRC risk. Results The cohort comprised of 20,949 patients with UC. A total of 168 incident cases of CRC were identified during 112,243 patient-years (PY) of follow-up; overall CRC incidence rate was 163/100,000 PY (95% confidence interval [CI] 139–187/100,000 PY). The CRC incidence rates were 158/100,000 PY (95% CI 134–181/100,000 PY) and 180/100,000 PY (95% CI 155–205/100,000 PY) in Caucasians and African Americans, respectively, with an incidence rate ratio of 1.17 (95% CI 0.69–1.97). The 3, 5, and 10-year cumulative incidence rates for CRC were 0.36%, 0.76%, 1.79% for African Americans and 0.41%, 0.76%, 1.43% for Caucasians. African Americans were not at an increased risk for CRC (adjusted hazard ratio: 1.10, 95% CI 0.65–1.87) compared to Caucasians. Conclusions In a national cohort of UC patients the risk of developing CRC in African Americans was no higher than in Caucasians. The reasons for lack of racial differences compared to sporadic CRC are not clear; access to care, genetic factors, and molecular pathways require further study. PMID:22334479

Investigation of Crohn’s Disease Risk Loci in Ulcerative Colitis Further Defines Their Molecular Relationship

PubMed Central

ANDERSON, CARL A.; MASSEY, DUNECAN C. O.; BARRETT, JEFFREY C.; PRESCOTT, NATALIE J.; TREMELLING, MARK; FISHER, SHEILA A.; GWILLIAM, RHIAN; JACOB, JEMIMA; NIMMO, ELAINE R.; DRUMMOND, HAZEL; LEES, CHARLIE W.; ONNIE, CLIVE M.; HANSON, CATHERINE; BLASZCZYK, KATARZYNA; RAVINDRARAJAH, RADHI; HUNT, SARAH; VARMA, DHIRAJ; HAMMOND, NAOMI; LEWIS, GREGORY; ATTLESEY, HEATHER; WATKINS, NICK; OUWEHAND, WILLEM; STRACHAN, DAVID; MCARDLE, WENDY; LEWIS, CATHRYN M.; LOBO, ALAN; SANDERSON, JEREMY; JEWELL, DEREK P.; DELOUKAS, PANOS; MANSFIELD, JOHN C.; MATHEW, CHRISTOPHER G.; SATSANGI, JACK; PARKES, MILES

2009-01-01

Background & Aims Identifying shared and disease-specific susceptibility loci for Crohn’s disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. Methods We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. Results Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 × 10-8; odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. Conclusions Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis. PMID:19068216

Mesalamine Dose Escalation Reduces Fecal Calprotectin In Patients With Quiescent Ulcerative Colitis

PubMed Central

Osterman, Mark T.; Aberra, Faten N; Cross, Raymond; Liakos, Steven; McCabe, Robert; Shafran, Ira; Wolf, Douglas; Hardi, Robert; Nessel, Lisa; Brensinger, Colleen; Gilroy, Erin; Lewis, James D.

2014-01-01

Background & Aims Among patients with quiescent ulcerative colitis (UC), lower fecal concentrations of calprotectin are associated with lower rates of relapse. We performed an open-label, randomized, controlled trial to investigate whether increasing doses mesalamine reduce concentrations of fecal calprotectin (FC) in patients with quiescent UC. Methods We screened 119 patients with UC in remission, based on Simple Clinical Colitis Activity Index scores, FC >50 mcg/g, and intake of no more than 3g/day of mesalamine. Participants taking mesalamine formulations other than multimatrix mesalamine were switched to multimatrix mesalamine (2.4 g/day) for 6 weeks; 52 participants were then randomly assigned (1:1) to a group that continued its current dose of mesalamine (controls, n=26) or a group that increased its dose by 2.4 g/day for 6 weeks (n=26). The primary outcome was continued remission with FC<50 mcg/g. Secondary outcomes were continued remission with FC<100 mcg/g or <200 mcg/g (among patients with pre-randomization values above these levels). Results The primary outcome was achieved by 3.8% of controls and 26.9% of the dose escalation group (P=.0496). More patients in the dose escalation group reduced FC to below 100 mcg/g (P=.04) and 200 mcg/g (P=.005). Among the patients who were still in remission after the randomization phase, clinical relapse occurred sooner in patients with FC >200 mcg/g compared to those with FC <200 mcg/g (P=.01). Conclusion Among patients with quiescent UC and increased levels of FC, increasing the dose of mesalamine by 2.4 g/day reduced fecal concentrations of calprotectin to those associated with lower rates of relapse. Clinicaltrials.gov: NCT00652145 PMID:24793028

Body Mass Index Is Associated with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.

PubMed

Dong, Jie; Chen, Yi; Tang, Yuchen; Xu, Fei; Yu, Chaohui; Li, Youming; Pankaj, Prasoon; Dai, Ning

2015-01-01

Prior work suggested that patients with inflammatory bowel diseases (IBD) have lower body mass index (BMI) than controls and patients with lower BMI have more serious complications. The study was aimed to find relationship between BMI in patients with and without IBD, investigate effects of medicine therapy and disease stages on patients' BMI. Potentially eligible studies were identified through searching PubMed, Cochrane and Embase databases. Outcome measurements of mean BMI and the number of patients from each study were pooled by a random-effect model. Publication bias test, sensitivity analysis and subgroup analysis were conducted. A total of 24 studies containing 1442 patients and 2059 controls were included. Main results were as follows: (1) BMI in Crohn's disease (CD) patients was lower than that in health controls (-1.88, 95% CI -2.77 to -1.00, P< 0.001); (2) Medical therapy significantly improved BMI of CD patients (with therapy: -1.58, -3.33 to 0.16; without: -2.09, 95% CI -3.21 to -0.98) while on the contrary not significantly improving BMI of UC patients (with therapy: -0.24, 95% CI -3.68 to 3.20; without: -1.34, 95% CI -2.87 to 0.20, P = 0.57); (3) Both CD and UC patients in active phase showed significantly greater BMI difference compared with controls than those in remission (CD patients: remission: -2.25, 95% CI -3.38 to -1.11; active phase: -4.25, 95% CI -5.58 to -2.92, P = 0.03; UC patients: remission: 0.4, 95% CI -2.05 to 2.84; active phase: -5.38, -6.78 to -3.97, P = 0.001). BMI is lower in CD patients; medical therapy couldn't improve BMI of IBD patients; the state of disease affects BMI of CD patients and UC patients.

Relationship between CATSPERB, NR5A2 gene polymorphisms and Peak Bone Mineral Density in College Students in China

PubMed Central

Zhao, Yuan; Liu, Wenya; HUA, Ma; Shi, Raoni; Wang, Haitao; Yang, Wen

2014-01-01

Abstract Background Peak bone mineral density (PBMD) is influenced by both genetic and environmental factors, genes explains most of variation. As the novel candidate genes CATSPERB and NR5A2 may have been associated with spinal PBMD in adult. This study was to investigate the relationship among these two genes^ PBMD and the life style factors in young female. Methods The rs1298989 single nucleotide polymorphism (SNP) of the CATSPERB gene and the rs3762397 SNP of the NR5A2 gene were genotyped using SNaPshot® in 359 students from Xinjiang. The prospective study included 203 Han and 156 Uyghur subjects. PBMD was measured using quantitative computed tomography (QCT). Calcium, phosphate and alkaline phosphatase were measured by ELISA method. Physical activity, dietary calcium and life styles were assessed by questionnaire. Results Both SNPs showed differences in genotype and allele frequencies (P < 0.05) between the Han and Uyghur subjects. Total calcium intake, energy intake, tea and milk intake were also significantly different between two groups (P < 0.05). Multiple regression analysis showed an association between PBMD and vitamin D intake (P = 0.000), milk (P = 0.000), exercise (P = 0.029), rs1298989 (P = 0.028), energy intake (P = 0.043). Conclusion This study demonstrated the polymorphisms of the rs1298989 and rs3762397 are associated with PBMD both in Han and Uyghur subjects. PBMD, in Xinjiang, appears to be associated with several known factors that are well described in the literature. While the genotypes of rs1298989 and rs3762397 do not appear have a strong effect on the PBMD. PMID:25927035

[Automated Assessment for Bone Age of Left Wrist Joint in Uyghur Teenagers by Deep Learning].

PubMed

Hu, T H; Huo, Z; Liu, T A; Wang, F; Wan, L; Wang, M W; Chen, T; Wang, Y H

2018-02-01

To realize the automated bone age assessment by applying deep learning to digital radiography （DR） image recognition of left wrist joint in Uyghur teenagers, and explore its practical application value in forensic medicine bone age assessment. The X-ray films of left wrist joint after pretreatment, which were taken from 245 male and 227 female Uyghur nationality teenagers in Uygur Autonomous Region aged from 13.0 to 19.0 years old, were chosen as subjects. And AlexNet was as a regression model of image recognition. From the total samples above, 60％ of male and female DR images of left wrist joint were selected as net train set, and 10％ of samples were selected as validation set. As test set, the rest 30％ were used to obtain the image recognition accuracy with an error range in ±1.0 and ±0.7 age respectively, compared to the real age. The modelling results of deep learning algorithm showed that when the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the net train set was 81.4% and 75.6% in male, and 80.5% and 74.8% in female, respectively. When the error range was in ±1.0 and ±0.7 age respectively, the accuracy of the test set was 79.5% and 71.2% in male, and 79.4% and 66.2% in female, respectively. The combination of bone age research on teenagers' left wrist joint and deep learning, which has high accuracy and good feasibility, can be the research basis of bone age automatic assessment system for the rest joints of body. Copyright© by the Editorial Department of Journal of Forensic Medicine.

IBD in the elderly population: results from a population-based study in Western Hungary, 1977-2008.

PubMed

Lakatos, Peter Laszlo; David, Gyula; Pandur, Tunde; Erdelyi, Zsuzsanna; Mester, Gabor; Balogh, Mihaly; Szipocs, Istvan; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos S; Lakatos, Laszlo

2011-02-01

Limited data are available on the incidence and disease course of IBD in the elderly population. Our aim was to analyze the incidence and disease course of IBD according to the age at diagnosis in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008. Data of 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 SD 15.9 years; CD: 506, age at diagnosis: 31.5 SD 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. 106 (11.6%) of UC patients and 21 (4.2%) of CD patients were diagnosed with >60 years of age. In UC, the incidence increased from 1.09 to 10.8/10(5) in the elderly, while CD increased to 3.04/10(5) in 2002-2007. In CD, colonic location (elderly: 61.9% vs. pediatric: 24.3%, p=0.001, and adults: 36.8%, p=0.02) and stenosing disease (elderly: 42.9% vs. pediatric: 14.9%, p=0.005, and adults: 19.5%, p=0.01) were more frequent in the elderly. A change in disease behavior was absent in the elderly, while in pediatric and adult CD population it was 20.3% (p=0.037), 19.8% (p=0.036) after 5 years. In UC, extensive disease was more frequent in pediatric patients compared to the elderly (p=0.003, OR: 2.73, 95%CI: 1.38-5.41). In addition, pediatric (57.3%, p<0.001, OR: 6.58; 95%CI: 3.22-12.9) and adult (39.8%, p<0.001, OR: 3.24; 95%CI: 1.91-5.49) patients required more often systemic steroids during follow-up compared to the elderly (17%). Proximal extension at 10 years was 11.6%, but time to extension was not different according to the age at onset. Elderly patients represent an increasing proportion of the IBD population. Stenosing and colon-only disease were characteristic for elderly CD patients, while the disease course in UC was milder. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery

PubMed Central

Zaharie, Roxana; Zaharie, Florin; Tantau, Marcel; Gheorghe, Liana; Gheorghe, Cristian; Gologan, Serban; Cijevschi, Cristina; Trifan, Anca; Dobru, Daniela; Goldis, Adrian; Constantinescu, Gabriel; Iacob, Razvan; Diculescu, Mircea

2016-01-01

Background: The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. Methods: A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohn’s disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. Results: The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. Conclusions: A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery. PMID:26589956