Surgical management of Crohn's colitis.

PubMed

Moir, Christopher R

2007-08-01

Crohn's disease in childhood is changing. The incidence is increasing, colonic disease is becoming more prevalent in younger children, and colon reconstruction is more acceptable. Genetic phenotypes are influencing decisions for surgery, and targeted immunotherapy has renewed hope for more durable remissions following less extensive resections. The tasks facing the surgeon evaluating a child with Crohn's colitis include confirming the specific diagnostic subtype and selecting the correct procedure. This chapter will review the unique aspects of pediatric Crohn's colitis and the increased complexity of surgical choice for this most challenging presentation. Recent success with less extensive surgery offers renewed hope for children with intractable colonic disease.

Treatment of metastatic cutaneous Crohn disease with certolizumab.

PubMed

Kiuru, Maija; Camp, Brendan; Adhami, Katayun; Jacob, Vinita; Magro, Cynthia; Wildman, Horatio

2015-11-18

Metastatic Crohn disease is a rare cutaneous manifestation of Crohn disease characterized by granulomatous lesions discontinuous with the diseased areas of the gastrointestinal tract. We report a case of a 32-year-old woman with history of Crohn disease who was admitted for treatment of cellulitis after presenting with a tender erythematous plaque of the left calf. Microbiological tests including tissue cultures were negative. A skin biopsy revealed granulomatous dermatitis consistent with metastatic cutaneous Crohn disease. Owing to concomitant perianal fistulas and abscesses and prior infusion reaction to infliximab, the patient was treated with certolizumab, a pegylated tumor necrosis factor (TNF) inhibitor combined with methotrexate resulting in complete resolution of the skin lesion. This case emphasizes the importance of recognizing this rare skin manifestation of Crohn disease and adds certolizumab as one of TNF inhibitors useful in the treatment of metastatic cutaneous Crohn disease.

[New knowledge of the pathogenesis of Crohn's disease].

PubMed

Ambrůzová, B; Rédová, M; Michálek, J; Sachlová, M; Slabý, O

2012-04-01

Crohns disease is a complex chronic inflammatory disease of the gastrointestinal tract with multifactorial pathogenesis. Over the recent years, there has been rather a sharp increase in the incidence of Crohn's disease and, even though this disease had been known for some time, the cause remains unknown. Studies exploring genetic basis of Crohn's disease have provided new knowledge of the pathogenesis of this disease, suggesting that this may be associated with a failure of mechanisms behind symbiosis of gut microflora and intestinal mucosal immune system. Crohn's disease seems to be caused by inadequate immune response to intestinal flora in genetically predisposed individuals. Crohn's disease has been linked to a number of genes. Many of them are related to the modulation of non-specific immune response, defects of which are considered to be key in Crohn's disease pathogenesis. The aim of this review paper is to summarize the new knowledge on the pathogenesis of Crohn's disease at the level of polymorphisms of the NOD2, ATG16L1 genes and the IL23-Th17-lymfocytes signalling pathway genes and to consider further research directions in this disease.

Surgical treatment of complex small bowel Crohn disease.

PubMed

Michelassi, Fabrizio; Sultan, Samuel

2014-08-01

The clinical presentations of Crohn disease of the small bowel vary from low to high complexity. Understanding the complexity of Crohn disease of the small bowel is important for the surgeon and the gastroenterologist caring for the patient and may be relevant for clinical research as a way to compare outcomes. Here, we present a categorization of complex small bowel Crohn disease and review its surgical treatment as a potential initial step toward the establishment of a definition of complex disease. The complexity of small bowel Crohn disease can be sorted into several categories: technical challenges, namely, fistulae, abscesses, bowel or ureteral obstruction, hemorrhage, cancer and thickened mesentery; extensive disease; the presence of short gut; a history of prolonged use of medications, particularly steroids, immunomodulators, and biological agents; and a high risk of recurrence. Although the principles of modern surgical treatment of Crohn disease have evolved to bowel conservation such as strictureplasty techniques and limited resection margins, such practices by themselves are often not sufficient for the management of complex small bowel Crohn disease. This manuscript reviews each category of complex small bowel Crohn disease, with special emphasis on appropriate surgical strategy.

[Crohn's disease surgery].

PubMed

Kala, Zdeněk; Marek, Filip; Válek, Vlastimil A; Bartušek, Daniel

2014-01-01

Surgery of Crohns disease is an important part of the general treatment algorithm. The role of surgery is changing with the development of conservative procedures. The recent years have seen the return to early treatment of patients with Crohns disease. Given the character of the disease and its intestinal symptoms, a specific approach to these patients is necessary, especially regarding the correct choice of surgery. The paper focuses on the luminal damage of the small and large intestine including complications of the disease. We describe the individual indications for a surgical solution, including the choice of anastomosis or multiple / repeated surgeries.

Diagnosis and management of Crohn's disease.

PubMed

Wilkins, Thad; Jarvis, Kathryn; Patel, Jigneshkumar

2011-12-15

Crohn's disease is a chronic inflammatory condition affecting the gastrointestinal tract at any point from the mouth to the rectum. Patients may experience diarrhea, abdominal pain, fever, weight loss, abdominal masses, and anemia. Extraintestinal manifestations of Crohn's disease include osteoporosis, inflammatory arthropathies, scleritis, nephrolithiasis, cholelithiasis, and erythema nodosum. Acute phase reactants, such as C-reactive protein level and erythrocyte sedimentation rate, are often increased with inflammation and may correlate with disease activity. Levels of vitamin B12, folate, albumin, prealbumin, and vitamin D can help assess nutritional status. Colonoscopy with ileoscopy, capsule endoscopy, computed tomography enterography, and small bowel follow-through are often used to diagnose Crohn's disease. Ultrasonography, computed axial tomography, scintigraphy, and magnetic resonance imaging can assess for extraintestinal manifestations or complications (e.g., abscess, perforation). Mesalamine products are often used for the medical management of mild to moderate colonic Crohn's disease. Antibiotics (e.g., metronidazole, fluoroquinolones) are often used for treatment. Patients with moderate to severe Crohn's disease are treated with corticosteroids, azathioprine, 6-mercaptopurine, or anti-tumor necrosis factor agents (e.g., infliximab, adalimumab). Severe disease may require emergent hospitalization and a multidisciplinary approach with a family physician, gastroenterologist, and surgeon.

[Characteristics of Crohn's disease under 
double balloon enteroscopy].

PubMed

Jia, Jia; Liu, Rui; Liu, Xiangjie; Shen, Shourong; Guo, Qin

2018-05-28

To observe ulcer characteristics of Crohn's disease under double balloon enteroscopy, and to evaluate the correlation between endoscopic severity and clinical manifestations.
 Methods: A prospective, observational study from July 2015 to December 2016 in the Third Xiangya Hospital, Central South University, we selected 45 patients with positive double-balloon enteroscopy (DBE) and confirmed Crohn's disease. Two digestive internal physician observed the ulcer characteristics of Crohn's disease under double balloon enteroscopy, and gave a simple endoscopic score for CD (SES-CD). We analyzed the correlation between SES-CD and Crohn's disease activity index (CDAI).
 Results: DBE indicated 24 patient ulcers (53.33%) locating at the end of the ileum, 5 (11.11%) locating at ileocolon, 16 (35.56%) locating at upper gatrointestinal tract and they did not affect the end of the ileum. Among them, 8 cases (17.78%) affected only jejunum. Thirty-two patients with longitudinal ulcers in Crohn's disease, accounting for 71.11%. There was no correlation between SES-CD score and CDAI score (r=0.237, P=0.136).
 Conclusion: The ulcerative appearance in Crohn's disease were diverse under double balloon enteroscopy. Crohn's disease could only affect the upper gastrointestinal tract or jejunum. The unwounded ileum and ileocecal valve couldn't be a sign to exclude Crohn's disease. CDAI score couldn't fully assess the prognosis of Crohn's disease.

Osteomalacia in Crohn's disease.

PubMed

Dedeoglu, Meryem; Garip, Yesim; Bodur, Hatice

2014-01-01

Osteomalacia is a metabolic bone disorder characterized by impaired mineralization of the bone matrix. Vitamin D deficiency due to malabsorption syndromes may cause osteomalacia. This is a case of a patient with a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease who was admitted to our outpatient clinic with symptoms of osteomalacia. Osteomalacia is a metabolic bone disease characterized by an impaired mineralization of the bone matrix, frequently caused by disorders in vitamin D or phosphate metabolism. Vitamin D deficiency due to malabsorption syndromes (e.g., Crohn's disease, ulcerative colitis, celiac disease, and jejuno-ileal bypass for obesity) may cause osteomalacia. A 43-year-old male presented with fatigue, low back pain, and morning stiffness. He had a 6-year history of seronegative spondyloarthropathy associated with Crohn's disease. Laboratory findings revealed low serum calcium, low 25-hydroxy vitamin D3, normal phosphorus, elevated parathyroid hormone, and alkaline phosphatase levels. Radiographs revealed grade IV sacroiliitis and Looser zones. He was diagnosed with osteomalacia due to the malabsorption of vitamin D. His symptoms and signs were relieved with supplements of vitamin D and calcium. Osteomalacia should be considered in differential diagnosis when assessing low back pain in the patients with chronic inflammatory bowel disease. Vitamin D deficiency should be treated with vitamin D supplementation in patients with Crohn's disease to prevent osteomalacia.

Hidradenitis suppurativa and perianal Crohn disease: differential diagnosis.

PubMed

Bassas-Vila, J; González Lama, Y

2016-09-01

The first description of perianal fistulas and complications in Crohn disease was made 75 years ago by Penner and Crohn. Published studies have subsequently confirmed that perianal fistulas are the most common manifestations of fistulising Crohn disease. Hidradenitis suppurativa was described in 1854 by a French surgeon, Aristide Verneuil. It is a chronic, inflammatory, recurrent and debilitating disease of the pilosebaceous follicle, that usually manifests after puberty with deep, painful and inflamed lesions in the areas of the body with apocrine glands, usually the axillary, inguinal and anogenital regions. The differential diagnosis between hidradenitis suppurativa and Crohn disease can be challenging, especially when the disease is primarily perianal. When they occur simultaneously, hidradenitis suppurativa and Crohn disease show severe phenotypes and patients can respond to anti-tumour necrosis factor therapy, although adalimumab is currently the only treatment with demonstrated efficacy in hidradenitis suppurativa and Crohn disease. In addition, there is sometimes a need for different complementary surgical procedures. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

[Medicine and humanism: insights of the Nürnberg city physician Theodericus Ulsenius regarding Morbus Gallicus].

PubMed

Santing, C G

1995-01-01

The Nuremberg physician and humanist Theodericus Ulsenius (c. 1460-1508) was the author of two works on the so-called Morbus Gallicus. In 1496 he published a Vaticinium in epidemicam scabiem, and he also wrote fifty aphorisms, entitled Cura mali francici. In this article I will characterize Ulsenius' ideas and compare these to the measures the Nuremberg town government took to diminish the dangerous effects of the epidemic. In the function of official town physician, Ulsenius was one of the chief advisers and executives of the Nuremberg health policy. As the 'Ratsverlässe' (records of the town-council meetings) give detailed information, the reactions of senate and physicians can be followed from day to day. The Vaticinium a poem of 100 hexameters was printed at the office of Hans Mair and presented as a pamphlet with a woodcut from the workshop of Albrecht Dürer. The verses refer to a dream of the poet, in which the God Apollo addresses him and talks about the terrible disease. The origin and symptoms of the illness are discussed extensively, in accordance with the prevailing medico-astrological conceptions. Nevertheless, the poem ist not a medical piece of work, but a literary-styled and humanistically appropriate description of the recent epidemic, meant for fellow members of the German respublica litteraria. Like most of Ulsenius' writings, the Cura mali francici only survived as a copy made by his colleague Hartmann Schedel. It seems that the author had different types of audience in mind. The aphorisms refer to the Aphorisms of his great example, the famous Ancient medical doctor Hippocrates of Kos. The addresses of the Cura are obviously medical professionals: the physician in the towns harassed by the Morbus Gallicus and especially the medical professors who hat to lecture on the new ailment.

Surgical management of Crohn's disease.

PubMed

Lu, Kim C; Hunt, Steven R

2013-02-01

Although medical management can control symptoms in a recurring incurable disease, such as Crohn's disease, surgical management is reserved for disease complications or those problems refractory to medical management. In this article, we cover general principles for the surgical management of Crohn's disease, ranging from skin tags, abscesses, fistulae, and stenoses to small bowel and extraintestinal disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Crohn's disease in black patients.

PubMed Central

Paul, H.; Barnes, R. W.; Reese, V. E.; Childress, M. H.; Scott, V.; Leffall, L. D.

1990-01-01

Crohn's disease is less prevalent in blacks than in whites. However, when it does occur, it is associated with a high degree of morbidity and is frequently unrecognized at initial presentation. Forty-three patients with Crohn's disease presented to Howard University Hospital between 1965 and 1987. There were 156 hospital admissions, 47 emergency room visits, and 76 clinic visits over this 22-year period. Twenty-eight patients were female and 15 were male. The age of presentation for males ranged from 18 to 63 years and for females, 12 to 74 years. Crohn's disease should be considered in black patients who present with chronic abdominal pain and diarrhea. With correct diagnosis and appropriate medical therapy, patients should have an enhanced quality of life with less morbidity. Images Figure 1 Figure 2 Figure 3 PMID:2280420

Distinct management issues with Crohn's disease of the small intestine.

PubMed

Fong, Steven C M; Irving, Peter M

2015-03-01

Small bowel Crohn's disease can present with clinical challenges that are specific to its location. In this review, we address some of the areas that present particular problems in small bowel Crohn's disease. A key issue specific to small bowel Crohn's disease relates to its diagnosis given that access to the small bowel is limited. Radiological advances, particularly in small bowel ultrasonography and MRI, as well as the introduction of capsule endoscopy and balloon enteroscopy are helping to address this. In addition, our ability to differentiate small bowel Crohn's disease from other causes of inflammation, such as tuberculosis, is improving on the basis of better understanding of the features that differentiate these conditions. It is also becoming apparent that jejunal Crohn's disease represents a distinct disease phenotype with potentially worse clinical outcomes. Finally, because it is a rare complication, our understanding of small bowel cancer associated with Crohn's disease remains limited. Recent publications are, however, starting to improve our knowledge of this condition. Although small bowel Crohn's disease presents specific management issues not seen in patients with Crohn's disease elsewhere in the gastrointestinal tract, our knowledge of how to manage these is improving.

Mycobacterium paratuberculosis as a cause of Crohn's disease

PubMed Central

McNees, Adrienne L.; Markesich, Diane; Zayyani, Najah R.; Graham, David Y.

2016-01-01

SUMMARY Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne’s disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50 to 100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis. PMID:26474349

Capsule endoscopy in the diagnosis of Crohn's disease.

PubMed

Niv, Yaron

2013-01-01

Crohn's disease is a chronic inflammatory disorder affecting any part of the gastrointestinal tract, but frequently involves the small and large bowel. Typical presenting symptoms include abdominal pain and diarrhea. Patients with this disorder may also have extraintestinal manifestations, including arthritis, uveitis, and skin lesions. The PillCam™SB capsule is an ingestible disposable video camera that transmits high quality images of the small intestinal mucosa. This enables the small intestine to be readily accessible to physicians investigating for the presence of small bowel disorders, such as Crohn's disease. Four meta-analyses have demonstrated that capsule endoscopy identifies Crohn's disease when other methods are not helpful. It should be noted that it is the best noninvasive procedure for assessing mucosal status, but is not superior to ileocolonoscopy, which remains the gold standard for assessment of ileocolonic disease. Mucosal healing along the small bowel can only be demonstrated by an endoscopic procedure such as capsule endoscopy. Achievement of long-term mucosal healing has been associated with a trend towards a decreased need for hospitalization and a decreased requirement for corticosteroid treatment in patients with Crohn's disease. Recently, we have developed and validated the Capsule Endoscopy Crohn's Disease Activity Index (also known as the Niv score) for Crohn's disease of the small bowel. The next step is to expand our score to the colon, and to determine the role and benefit of a capsule endoscopy activity score in patients suffering from Crohn's ileocolitis and/or colitis. This scoring system will also serve to improve our understanding of the impact of capsule endoscopy, and therefore treatment, on the immediate outcome of this disorder. As the best procedure available for assessing mucosal status, capsule endoscopy will provide important information about the course and outcome of Crohn's disease.

Ustekinumab in Pediatric Crohn Disease Patients.

PubMed

Bishop, Casey; Simon, Hayley; Suskind, David; Lee, Dale; Wahbeh, Ghassan

2016-09-01

We describe the use of ustekinumab for 4 patients with pediatric Crohn disease treated at the Seattle Children's Hospital Inflammatory Bowel Disease Center. A retrospective chart review was done to identify patients' clinical data, disease phenotype, treatment history, and laboratory and growth parameters before treatment with ustekinumab and at last follow-up. Adverse events while on ustekinumab were also recorded. Four adolescent patients with Crohn disease at our center received ustekinumab. All had previously received corticosteroids, methotrexate, azathioprine/6-mercaptopurine, and both infliximab and adalimumab. Patients had varying disease phenotypes. Ages at ustekinumab initiation were 12, 13, 16, and 17 years. Weight ranged from 40.5 to 57.8 kg, mean 49.5 kg. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy because of continued symptoms and disease complications and required multiple hospitalizations. Ustekinumab was used in 4 children with pediatric Crohn disease with 2 of 4 patients showing clinical response (1 with persistently elevated C-reactive protein). A prospective study is needed to define its efficacy, safety, and placement in managing pediatric Crohn disease in the future.

Nutritional disturbances in Crohn's disease.

PubMed Central

Harries, A. D.; Heatley, R. V.

1983-01-01

A wide range of nutritional disturbances may be found in patients with Crohn's disease. As more sophisticated tests become available to measure vitamin and trace element deficiencies, so these are being recognized as complications of Crohn's disease. It is important to recognize nutritional deficiencies at an early stage and initiate appropriate treatment. Otherwise many patients, experiencing what can be a chronic and debilitating illness, may suffer unnecessarily from the consequences of deprivation of vital nutrients. PMID:6359105

Retinal vasculitis associated with Crohn's disease.

PubMed Central

Garcia-Diaz, M.; Mira, M.; Nevado, L.; Galván, A.; Berenguer, A.; Bureo, J. C.

1995-01-01

Although systemic vasculitis can be a complication of inflammatory bowel disease at several locations (skin, eyes, brain, mesentery, and lung) the association of retinal vasculitis with Crohn's disease is rare. We studied a 26-year-old woman with biopsy-demonstrated Crohn's disease who developed a severe bilateral retinal arteritis and phlebitis, with acute loss of vision. Images Figure 1 Figure 2 PMID:7746779

[A giant field of death: medical and scientific controversies about the cholera morbus epidemic of 1855].

PubMed

Santos, Luciana Dos

2016-01-01

The article examines the cholera morbus epidemic that afflicted the province of Pernambuco, Brazil, in 1855, focusing on the medical and scientific controversies about how the disease spread, which split medical opinion into two camps: contagion and infection. Documents and reports produced by the Society of Medicine of Pernambuco and the General Public Health Board were analyzed, based on which it was possible to describe the official medical and sanitation program, involving engineers, scientists, and physicians, designed to plan a salubrious city - a model of civilization that combined redeveloping the urban space and disseminating new habits amongst the local people. It is essentially an exercise in observing a science and a society as they take shape.

Surgical care of the pediatric Crohn's disease patient.

PubMed

Stewart, Dylan

2017-12-01

Despite the significant advances in the medical management of inflammatory bowel disease over the last decade, surgery continues to play a major role in the management of pediatric Crohn's disease (CD). While adult and pediatric Crohn's disease may share many clinical characteristics, pediatric Crohn's patients often have a more aggressive phenotype, and the operative care given by the pediatric surgeon to the newly diagnosed Crohn's patient is very different in nature to the surgical needs of adult patients after decades of disease progression. Children also have the unique surgical indication of growth failure to consider in the overall clinical decision making. While surgery is never curative in CD, it has the ability to transform the disease process in children, and appropriately timed operations may have tremendous impact on a child's physical and mental maturation. This monograph aims to address the surgical care of Crohn's disease in general, with a specific emphasis on the surgical treatment of small intestinal and ileocecal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

The sensitivity of the sole of the foot in patients with Morbus Parkinson.

PubMed

Prätorius, B; Kimmeskamp, S; Milani, T L

2003-08-07

The sensory input of the foot has an important influence on balance. In patients with Morbus Parkinson (PD-patients) balance control is often impaired. Therefore, the aim of this study was to quantify the sensitivity of the plantar foot in PD-patients. Five sites of the plantar foot were examined in 24 PD-patients and in 20 controls using Semmes-Weinstein Monofilaments for touch pressure and a vibration-exciter (30 Hz) for vibration. The results show significantly higher thresholds in PD-patients. For each tested location (except the heel) the thresholds are at least twice as high as in controls. Moreover, this study proved the correlation between motor and somatosensory systems: the stronger the motor deficiencies in PD-patients (Unified Parkinson's Disease Rating System score) the higher the sensitivity thresholds for vibration. In conclusion, reduced sensitivity of the plantar foot may contribute to impaired balance control.

Guillain-Barré syndrome and Crohn disease: a case report.

PubMed

Yanagida, Hidehiko; Sugimoto, Keisuke; Izu, Akane; Wada, Norihisa; Sakata, Naoki; Takemura, Tsukasa

2014-09-01

Development of both Crohn disease and Guillain-Barré syndrome likely involves autoimmunity associated with excessive inflammatory cytokines. We treated a girl who developed Guillain-Barré syndrome during the course of Crohn disease. Although high-dose γ-globulin therapy administered initially for Guillain-Barré syndrome was ineffective, plasmapheresis ameliorated her acute neuropathic symptoms. Crohn disease was managed with Salazopyrin administration and enteral feeding. Chronic inflammation of the intestinal mucosa caused by Crohn disease can allow presentation of microbial intestinal antigens normally hidden from the immune system. Such presentation could incite an extraintestinal immune response on the basis of molecular mimicry, leading to activation of systemic autoimmunity against the nervous system. Accordingly, concurrence of Guillain-Barré syndrome and Crohn disease in our patient appeared to result from shared autoimmune mechanisms and systemic and local increases in cytokine concentrations. The patient also developed erythema nodosum and gall stones, relatively common complications of Crohn disease. However, Guillain-Barré syndrome is rare. © The Author(s) 2013.

Genetic studies of Crohn's disease: Past, present and future

PubMed Central

Liu, Jimmy Z.; Anderson, Carl A.

2014-01-01

The exact aetiology of Crohn's disease is unknown, though it is clear from early epidemiological studies that a combination of genetic and environmental risk factors contributes to an individual's disease susceptibility. Here, we review the history of gene-mapping studies of Crohn's disease, from the linkage-based studies that first implicated the NOD2 locus, through to modern-day genome-wide association studies that have discovered over 140 loci associated with Crohn's disease and yielded novel insights into the biological pathways underlying pathogenesis. We describe on-going and future gene-mapping studies that utilise next generation sequencing technology to pinpoint causal variants and identify rare genetic variation underlying Crohn's disease risk. We comment on the utility of genetic markers for predicting an individual's disease risk and discuss their potential for identifying novel drug targets and influencing disease management. Finally, we describe how these studies have shaped and continue to shape our understanding of the genetic architecture of Crohn's disease. PMID:24913378

Crohn's disease in adolescence: presentation and treatment.

PubMed

Cullen, Mick; Barnes, Claire

2015-05-13

Crohn's disease is a chronic inflammatory bowel condition that affects more than 115,000 people in the UK. This article focuses on Crohn's disease in adolescents. Management of the condition in this group should address adolescent-specific characteristics and treatment goals. Key elements include optimising growth, pubertal development and social functioning, including education. The condition can affect an individual's mental and emotional wellbeing significantly, as well as their physical health. As adolescence is a time of great change, the additional burden of a chronic illness can prove difficult to manage. The authors provide information on the presentation of Crohn's disease in adolescence and insights into the particular issues encountered by this group.

[Chronic vulvar lymphedema revealing Crohn disease in a teenage girl].

PubMed

Aounallah, A; Ghariani Fetoui, N; Ksiaa, M; Boussofara, L; Saidi, W; Mokni, S; Sriha, B; Belajouza, C; Denguezli, M; Ghariani, N; Nouira, R

2017-04-01

Cutaneous Crohn disease is a rare cutaneous manifestation of Crohn disease in children. Herein is reported a case of persistent vulvar lymphedema revealing Crohn disease in a teenage girl. A 14-year-old girl presented with an 8-month history of persistent vulvar swelling associated with chronic macrocheilia. Dermatologic examination showed an inflammatory vulvar lymphedema, associated with perianal fissures and hypertrophic gingivitis. Vulvar skin biopsy revealed non-necrotizing granulomatous inflammation. Gastrointestinal endoscopy yielded no significant findings. The diagnosis of Crohn disease presenting as vulvar lymphedema was established. Oral metronidazole therapy resulted in partial improvement of cutaneous lesions beginning the 1st week. The originality of this case lies in the presentation of chronic macrocheilia with persistent vulvar lymphedema in a child, revealing Crohn disease without gastrointestinal involvement. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Crohn's disease in Japan: diagnostic criteria and epidemiology.

PubMed

Yao, T; Matsui, T; Hiwatashi, N

2000-10-01

New diagnostic criteria for Crohn's disease and a review of Japanese epidemiologic studies are presented. New diagnostic criteria for Crohn's disease were established by the Research Committee of Inflammatory Bowel Disease, set up by the Japanese Ministry of Health and Welfare. For a definite diagnosis one of the following three conditions is required: 1) longitudinal ulcer or luminal deformity induced by longitudinal ulcer or cobblestone pattern, 2) intestinal small aphthous ulcerations arranged in a longitudinal fashion for at least three months plus noncaseating granulomas, and 3) multiple small aphthous ulcerations in both the upper and lower digestive tract not necessarily with longitudinal arrangement, for at least three months, plus noncaseating granulomas. Moreover, ulcerative colitis, ischemic enterocolitis, and acute infectious enterocolitis should be excluded. Data from the Japanese Ministry of Health and Welfare, in addition to data collected from two study groups, these being the two largest studies in Japan, are reviewed with regard to epidemiology. The number of patients with Crohn's disease has increased remarkably. The prevalence and the annual incidence of patients with Crohn's disease in Japan were estimated to be approximately 2.9 and 0.6 per 10(5) population in 1986, respectively, and 13.5 and 1.2 per 10(5) population in 1998. Characteristic features of Crohn's disease in Japan are that the male-female ratio exceeds 2, and that there is no second peak of incidence in the age group of 55 to 65 years. Clinically, Crohn's disease with only multiple small aphthous ulcerations, which is the earliest stage of the disease that is diagnosable, was found in 5 percent of patients.

Low serum and bone vitamin K status in patients with longstanding Crohn's disease: another pathogenetic factor of osteoporosis in Crohn's disease?

PubMed Central

Schoon, E; Muller, M; Vermeer, C; Schurgers, L; Brummer, R; Stockbrugger, R

2001-01-01

BACKGROUND—A high prevalence of osteoporosis is reported in Crohn's disease. The pathogenesis is not completely understood but is probably multifactorial. Longstanding Crohn's disease is associated with a deficiency of fat soluble vitamins, among them vitamin K. Vitamin K is a cofactor in the carboxylation of osteocalcin, a protein essential for calcium binding to bone. A high level of circulating uncarboxylated osteocalcin is a sensitive marker of vitamin K deficiency.
AIMS—To determine serum and bone vitamin K status in patients with Crohn's disease and to elucidate its relationship with bone mineral density.
METHODS—Bone mineral density was measured in 32 patients with longstanding Crohn's disease and small bowel involvement, currently in remission, and receiving less than 5 mg of prednisolone daily. Serum levels of vitamins D and K, triglycerides, and total immunoreactive osteocalcin, as well as uncarboxylated osteocalcin ("free" osteocalcin) were determined. The hydroxyapatite binding capacity of osteocalcin was calculated. Data were compared with an age and sex matched control population.
RESULTS—Serum vitamin K levels of CD patients were significantly decreased compared with normal controls (p<0.01). "Free" osteocalcin was higher and hydroxyapatite binding capacity of circulating osteocalcin was lower than in matched controls (p<0.05 and p<0.001, respectively), indicating a low bone vitamin K status in Crohn's disease. In patients, an inverse correlation was found between "free" osteocalcin and lumbar spine bone mineral density (r=−0.375, p<0.05) and between "free" osteocalcin and the z score of the lumbar spine (r=−0.381, p<0.05). Multiple linear regression analysis showed that "free" osteocalcin was an independent risk factor for low bone mineral density of the lumbar spine whereas serum vitamin D was not.
CONCLUSIONS—The finding that a poor vitamin K status is associated with low bone mineral density in longstanding Crohn

Septic arthritis as a presentation of Crohn's disease.

PubMed

Zaidi, R; Dala-Ali, B; Dalton, D J N

2011-09-01

A 42-year-old man with colonic Crohn's disease presented to the orthopaedic department with septic arthritis of the knee with frank intra-articular pus, which persisted despite repeated joint washouts. This coincided with a symptomatic flare of his colonic Crohns. Imaging revealed a fistulous connection from the proximal sigmoid colon into the pelvis, a psoas abscess, myositis of the musculature around the left pelvic girdle and left thigh and two focal collections almost surrounding the distal femur. The knee symptoms only settled after laparotomy and resection of the diseased sigmoid colon and fistula. This case report demonstrates an unusual presentation of fistulating Crohns disease as septic arthritis.

Quality of life and uncertainty in Crohn's disease.

PubMed

Niv, Galia; Bar Josef, Simona; Ben Bassat, Ofer; Avni, Irit; Lictenstein, Lev; Niv, Yaron; Barnoy, Sivia

2017-06-01

Crohn's disease impairs patients' perception of health and has a negative impact on health-related quality of life. Although it is apparent that uncertainty is a significant factor that decreases quality of life, it has never been studied in patients with Crohn's disease. The objective of the present study was to examine the association between level of certainty, self-epistemic authority, Internet information gathering habits, and health-related quality of life. A cross-sectional study of 105 Crohn's disease patients was conducted. Data were collected using a questionnaire composed of five parts: (1) demographic and clinical information; (2) health-related quality of life; (3) level of certainty; (4) self-epistemic authority; and (5) Internet information gathering habits regarding Crohn's disease. A significant positive correlation was demonstrated between levels of certainty and health-related quality of life. Self-epistemic authority correlated positively with certainty, while information gathering via the Internet was related to decreased certainty. Multiple regression analysis for factors associated with health-related quality of life showed a positive association with the level of certainty, while negative associations were found between Internet information seeking and disease activity with the quality of life. Level of certainty proved an important variable associated with health-related quality of life in Crohn's disease patients. Improving patients' self-epistemic authority can increase certainty and, thus, improve health-related quality of life.

Cutaneous Manifestations of Crohn Disease.

PubMed

Hagen, Joshua W; Swoger, Jason M; Grandinetti, Lisa M

2015-07-01

Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Epithelioid sarcoma of the plantar fascia mimicking Morbus Ledderhose - A severe pitfall for clinical and histopathological misinterpretation.

PubMed

Toepfer, Andreas; Harrasser, Norbert; Dreyer, Florian; Mogler, Carolin; Walther, Markus; von Eisenhart-Rothe, Rüdiger

2017-12-01

Plantar fibromatosis, also known as Morbus Ledderhose, is a well known and frequently encountered disorder of the planta pedis. When conservative treatment fails, surgical therapy with complete resection is the therapeutical procedure of choice. Soft tissue sarcoma is a heterogeneous and rare malignant disease of the musculoskeletal system with over 50 histopathological subtypes which can potentially arise in any localization but is most commonly found at the extremities. Here, we report the case of an epithelioid sarcoma of the sole of the foot which was initially and repeatedly clinically and histopathologically misinterpreted as plantar fibromatosis, receiving insufficient resection and subsequently ending in amputation of the lower leg. Copyright © 2017 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Crohn disease - children - discharge

MedlinePlus

... 20th ed. Philadelphia, PA: Elsevier; 2016:chap 336. Sands BE, Seigel CA. Crohn's disease. In: Feldman M, ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

Pylephlebitis and Crohn's disease: A rare case of septic shock.

PubMed

Scaringi, Stefano; Giudici, Francesco; Gabbani, Giacomo; Zambonin, Daniela; Morelli, Marco; Carrà, Rossella; Bechi, Paolo

2017-01-01

Troncular pylephlebitis, defined as septic thrombophlebitis of the portal vein, is usually secondary to suppurative infection from the regions drained by the portal system. Therefore, pylephlebitis can occur from the portal vein main tributaries. The occurrence of mesenteric pylephlebitis in Crohn's disease is extremely rare. We describe a case of septic shock due to mesenteric pylephlebitis in a 47 years old male affected with Crohn's disease. The patient was admitted to the emergency department after he had been complained from 3h of a peri-umbilical abdominal pain associated to fever and shivering quickly followed by a severe hypotension. His medical history included histologically confirmed ileal Crohn's disease diagnosed 4 years before and treated with mesalamine only. Computed tomography scan confirmed the mesenteric pylephlebitis diagnosis. After medical therapy with antibiotics and systemic nutrition, the patient was successfully operated to treat his ileal Crohn's disease. In our case, the quick onset of a septic shock was not due to a peritonitis complicating a Crohn's disease, but to a rare condition not needing an urgent surgical resolution. This report shows that, even in Crohn's disease, once diagnosis is performed, antibiotic therapy associated to enteral and parenteral nutrition can lead to a complete clinical remission of mesenteric pylephlebitis, mandatory to perform an elective surgery. This case highlights the importance of promptly considerate and treat mesenteric pylephlebitis in presence of a septic shock in a Crohn's disease patient who is not showing clinical signs of peritonitis. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hla-B genotype in Japanese patients with Crohn's disease.

PubMed

Kinouchi, Yoshitaka; Matsumoto, Keisuke; Negoro, Kenichi; Takagi, Sho; Takahashi, Seiichi; Hiwatashi, Nobuo; Shimosegawa, Tooru

2003-10-01

The HLA-B gene is one of the susceptibility genes for inflammatory bowel disease. Previous association studies of HLA-B showed several associated alleles and haplotypes of HLA-B in patients with ulcerative colitis, and among the associated alleles HLA-B*52 is well known to be strongly associated with ulcerative colitis in Japanese patients. However, there are no convincing reports about HLA-B including the B*52 allele in patients with Crohn's disease. The purpose of this study was to determine if HLA-B, especially the B*52 allele, confers susceptibility to Crohn's disease or determines the disease phenotype of Crohn's disease. A total of 195 patients with Crohn's disease (49 ileitis, 106 ileocolitis, 34 colitis, 6 uncertain) and 185 healthy controls were studied in this case-controlled study. All patients and healthy controls were Japanese. Genotyping of the HLA-B gene was performed by a polymerase chain reaction, sequence-specific primer that can classify the gene into 23 allele groups. Allele frequencies were compared between patients with Crohn's disease and healthy controls with chi-squared test using a 2 x 2 contingency table. P value was corrected by the number of allele groups (n = 23) observed in the Japanese population or the number of clinical subgroups. Corrected P values of <0.05 were considered to be statistically significant. Before the correction for multiple testing, B*4001 and B*44 were associated with patients with Crohn's disease, positively and negatively, respectively. However, after the correction there were no significant differences in any HLA-B alleles between patients with Crohn's disease and healthy controls. In the subgroup analysis according to clinical phenotypes (disease location, anal lesion, age at diagnosis, need for surgery), none of the HLA-B alleles except B*52 showed any disease phenotype-genotype associations. The allele frequency of B*52 in the colitis type (16.2 percent; corrected P = 0.011) was significantly higher than

Potential value of nutrigenomics in Crohn's disease.

PubMed

Ferguson, Lynnette R

2012-03-13

Crohn's disease is a chronic relapsing condition that has no certain cure. Both genetic susceptibility and nutrition have key roles, but their level of involvement varies between patients. Interacting gene pathways influence the probability of disease development, but these are affected by stress and various environmental factors, including diet. In addition, the role of the gut microbiome must not be underestimated, as it is substantially altered in patients with Crohn's disease. Although an elemental diet might lead to disease remission, reintroducing real foods and sustainable diets in patients with Crohn's disease is currently difficult, and would benefit from the sensitivity and rapid feedback provided by the field of nutrigenomics. Nutrigenomics utilizes high-throughput genomics technologies to reveal changes in gene and protein expression that are modulated by the patient's nutrition. The most widely used technique thus far is transcriptomics, which permits measurement of changes in the expression of thousands of genes simultaneously in one sample. Given the volume of numbers generated in such studies, data-basing and bioinformatics are essential to ensure the correct application of nutrigenomics at the population level. These methods have been successfully applied to animal models of Crohn's disease, and the time is right to move them to human studies.

Optimizing biological therapy in Crohn's disease.

PubMed

Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

2016-01-01

Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment.

[Low dose naltrexone for treatment of pain].

PubMed

Plesner, Karin Bruun; Vægter, Henrik Bjarke; Handberg, Gitte

2015-10-09

Recent years have seen an increasing interest in the use of low dose naltrexone (LDN) for off-label treatment of pain in diseases as fibromyalgia, multiple sclerosis and morbus Crohn. The evidence is poor, with only few randomized double-blind placebo-controlled studies. The studies currently available are reviewed in this paper. LDN could be a potentially useful drug in the future for the treatment of pain in fibromyalgia, but more studies are needed to verify that it is superior to placebo, and currently it cannot be recommended as first-line therapy.

[Meckel's diverticulum and enteroliths complicating Crohn's disease].

PubMed

Fernández Salazar, Luis; Alvarez-Quiñones Sanz, María; Sánchez Lite, Israel; Velayos Jiménez, Benito; Legido Morán, Patricia; Macho Conesa, Ana; González Hernández, José Manuel

2013-01-01

We describe the case of a 43-year-old man recently diagnosed with ileal Crohn's disease complicated by a free peritoneal perforation of a Meckel's diverticulum and the presence of enteroliths in the intestinal lumen. The coexistence of Crohńs disease, Meckel's diverticulum and enteroliths has rarely been reported. Meckel's diverticulum can hamper the management of Crohn's disease. Copyright © 2012 Elsevier España, S.L. and AEEH y AEG. All rights reserved.

[Cutaneous involvement in chronic inflammatory bowel disease : Crohn's disease and ulcerative colitis].

PubMed

Richter, L; Rappersberger, K

2016-12-01

Over recent decades, both the incidence and prevalence of chronic inflammatory bowel disease have continued to rise in industrialized countries; the disease is frequently associated with extracutaneous involvement and comorbidity. The purpose of this work was to investigate the frequency and specificity of mucocutaneous manifestations in Crohn's disease (CD) and ulcerative colitis (UC). An extensive search in peer-reviewed journals via PubMed was performed; presented is a summary and analysis of various studies and data, including data of patients treated at our department. CD and UC are frequently associated with mucocutaneous symptoms; however, primary/specific disease-associations are exclusively seen in CD patients. These include peri-anal and -stomal fistulas and ulcerations, "metastatic" Crohn's disease as well as oral granulomatous disease. Moreover, in both CD and UC, there occur several other inflammatory skin conditions such as erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa, chronic oral aphthous disease, Sweet syndrome, pyostomatitis vegetans, and bowel-associated dermatosis-arthritis syndrome. Malnutrition syndromes (zinc and vitamin deficiencies) are only rarely observed. On skin and oral/genital mucous membranes various different inflammatory manifestations may be observed during the course of CD or UC. However, most data about a direct pathogenic relationship of the gastrointestinal and dermatologic disorders are quite heterogeneous or even contradictory. Nevertheless, knowledge of these conditions and their possible association with CD and UC could be crucial for early diagnosis and initiation of an appropriate therapy and thus be essential to prevent secondary tissue damage.

Nutritional therapy in pediatric Crohn disease: the specific carbohydrate diet.

PubMed

Suskind, David L; Wahbeh, Ghassan; Gregory, Nila; Vendettuoli, Heather; Christie, Dennis

2014-01-01

Crohn disease is characterized by chronic intestinal inflammation in the absence of a recognized etiology. Nutritional therapy in the form of exclusive enteral nutrition (EEN) has an established role within pediatric Crohn disease. Following exclusive enteral nutrition's success, many dietary therapies focusing on the elimination of specific complex carbohydrates have been anecdotally reported to be successful. Many of these therapies have not been evaluated scientifically; therefore, we reviewed the medical records of our patients with Crohn disease on the specific carbohydrate diet (SCD). Seven children with Crohn disease receiving the SCD and no immunosuppressive medications were retrospectively evaluated. Duration of the dietary therapy ranged from 5 to 30 months, with an average of 14.6±10.8 months. Although the exact time of symptom resolution could not be determined through chart review, all symptoms were notably resolved at a routine clinic visit 3 months after initiating the diet. Each patient's laboratory indices, including serum albumin, C-reactive protein, hematocrit, and stool calprotectin, either normalized or significantly, improved during follow-up clinic visits. This chart review suggests that the SCD and other low complex carbohydrate diets may be possible therapeutic options for pediatric Crohn disease. Further prospective studies are required to fully assess the safety and efficacy of the SCD, or any other low complex SCDs in pediatric patients with Crohn disease.

Where Are All the Mycobacterium avium Subspecies paratuberculosis in Patients with Crohn's Disease?

PubMed Central

Pierce, Ellen S.

2009-01-01

Mycobacterium avium subspecies paratuberculosis (MAP) causes a chronic granulomatous inflammation of the intestines, Johne's disease, in dairy cows and every other species of mammal in which it has been identified. MAP has been identified in the mucosal layer and deeper bowel wall in patients with Crohn's disease by methods other than light microscopy, and by direct visualization in small numbers by light microscopy. MAP has not been accepted as the cause of Crohn's disease in part because it has not been seen under the microscope in large numbers in the intestines of patients with Crohn's disease. An analysis of the literature on the pathology of Crohn's disease and on possible MAP infection in Crohn's patients suggests that MAP might directly infect endothelial cells and adipocytes and cause them to proliferate, causing focal obstruction within already existing vessels (including granuloma formation), the development of new vessels (neoangiogenesis and lymphangiogenesis), and the “creeping fat” of the mesentery that is unique in human pathology to Crohn's disease but also occurs in bovine Johne's disease. Large numbers of MAP might therefore be found in the mesentery attached to segments of intestine affected by Crohn's disease rather than in the bowel wall, the blood and lymphatic vessels running through the mesentery, or the mesenteric fat itself. The walls of fistulas might result from the neoangiogenesis or lymphangiogenesis that occurs in the bowel wall in Crohn's disease and therefore are also possible sites of large numbers of MAP. The direct visualization of large numbers of MAP organisms in the tissues of patients with Crohn's disease will help establish that MAP causes Crohn's disease. PMID:19325887

Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

PubMed

Labidi, Asma; Serghini, Meriem; Ben Mustapha, Nadia; Fekih, Monia; Boubaker, Jalel; Filali, Azza

2014-11-01

Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies. The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease. Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease. Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial. Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

Perianal Crohn disease.

PubMed

Asma, Sioud Dhrif; Soumaya, Youssef; Kahena, Jaber; Raouf, Dhaoui Mohamed; Nejib, Doss

2006-12-10

Crohn disease is a chronic inflammatory disease characterized by sharply demarcated segments of gastrointestinal involvement from mouth to anus. Its perineal manifestations are among the most devastating and mutilating complications. They occur at any time and may precede the intestinal manifestations. Their most common presentations are perineal ulceration, fistula, and abscess. Proliferative and polypoid morphology of the cutaneous lesions mimicking warts and condyloma are rarely described. We report a 25-year-old woman with a 4-month history of confluent plaques of the perineal region with vegetant surfaces, suspected to be genital warts. The lesions progressed to fistulas, inducing deep ulcerations surrounded by pseudocondylomatous tumors. About 2 months prior to presentation she began to suffer from gastrointestinal symptoms and noted weight loss. Physical examination, endoscopic examination, and pathological interpretation led to the diagnosis of Crohn disease with perineal involvement being the initial presenting sign. Significant improvement was induced with prednisone (45 mg daily) and azathioprine. Our observation is notable for the pseudocondylomatous appearance and the dramatic response to medical treatment despite severe involvement.

Development of CAD prototype system for Crohn's disease

NASA Astrophysics Data System (ADS)

Oda, Masahiro; Kitasaka, Takayuki; Furukawa, Kazuhiro; Watanabe, Osamu; Ando, Takafumi; Goto, Hidemi; Mori, Kensaku

2010-03-01

The purpose of this paper is to present a CAD prototype system for Crohn's disease. Crohn's disease causes inflammation or ulcers of the gastrointestinal tract. The number of patients of Crohn's disease is increasing in Japan. Symptoms of Crohn's disease include intestinal stenosis, longitudinal ulcers, and fistulae. Optical endoscope cannot pass through intestinal stenosis in some cases. We propose a new CAD system using abdominal fecal tagging CT images for efficient diagnosis of Crohn's disease. The system displays virtual unfolded (VU), virtual endoscopic, curved planar reconstruction, multi planar reconstruction, and outside views of both small and large intestines. To generate the VU views, we employ a small and large intestines extraction method followed by a simple electronic cleansing method. The intestine extraction is based on the region growing process, which uses a characteristic that tagged fluid neighbor air in the intestine. The electronic cleansing enables observation of intestinal wall under tagged fluid. We change the height of the VU views according to the perimeter of the intestine. In addition, we developed a method to enhance the longitudinal ulcer on views of the system. We enhance concave parts on the intestinal wall, which are caused by the longitudinal ulcer, based on local intensity structure analysis. We examined the small and the large intestines of eleven CT images by the proposed system. The VU views enabled efficient observation of the intestinal wall. The height change of the VU views helps finding intestinal stenosis on the VU views. The concave region enhancement made longitudinal ulcers clear on the views.

Low dose naltrexone for induction of remission in Crohn's disease.

PubMed

Parker, Claire E; Nguyen, Tran M; Segal, Dan; MacDonald, John K; Chande, Nilesh

2018-04-01

Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. A systematic search of MEDLINE, Embase, PubMed, CENTRAL, and the Cochrane IBD Group Specialized Register was performed from inception to 15 January 2018 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also screened. Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.3.5). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg

Omega-3 fatty acids as adjunctive therapy in Crohns disease.

PubMed

Macdonald, Angie

2006-01-01

Crohns disease is an inflammatory bowel disease that can have a significant impact on the health of those afflicted. The etiology of the disease is unknown, but genetic, environmental, dietary, and immunological factors are thought to be involved. Multiple nutrients can become depleted during active disease due to inadequate intake or malabsorption. Preventing these deficiencies is paramount in the care of those suffering from Crohns disease. Often the traditional treatments (medications) have limited effectiveness and negative side effects that inhibit their use. Enteral nutrition has promising therapeutic benefits, but its use is often limited to the pediatric population due to poor patient acceptability. Omega-3 fatty acids have been investigated for their anti-inflammatory properties as an alternative to traditional care. This article reviews the etiology of Crohns disease, nutritional deficiencies, traditional treatments, and the use of omega-3 fatty acids in the prevention of Crohns recurrence. The results from clinical trials have been conflicting, but a new fish oil preparation that limits the side effects of traditional fish oil therapy shows promise as an adjunctive treatment for Crohns disease. Continued research is needed to validate these findings.

Improvement with Infliximab of a Disseminated Sarcoidosis in a Patient with Crohn's Disease

PubMed Central

Piégay, Fabrice; Traclet, Julie; Mion, François; Mornex, Jean-François

2014-01-01

Sarcoidosis and Crohn's disease are systemic granulomatous disorders affecting the lung and the intestine, respectively, with variable involvement of other organs and are seldom associated. While anti-TNFα is a recognized treatment of Crohn's disease, its usage is discussed in sarcoidosis. A 42-year-old man presented with an 11-year-long history of Crohn's disease; upon discovery of an abnormal chest CT scan the diagnosis of multivisceral sarcoidosis was made and, later, a treatment with an anti-TNFα agent, infliximab, was started, because of worsening Crohn's disease recurrences. CT scan demonstrated net regression of pulmonary opacities and hepatosplenic lesions. Pathologies obtained from the intestinal tract and the bronchi of the patient were, respectively, characteristic of Crohn's disease and sarcoidosis leading to the diagnosis of both diseases. We report a rare case of steroid resistant Crohn's disease associated with multivisceral sarcoidosis, treated successfully by an anti-TNFα agent, infliximab. PMID:24653848

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

PubMed

Khanna, Reena; Bouguen, Guillaume; Feagan, Brian G; DʼHaens, Geert; Sandborn, William J; Dubcenco, Elena; Baker, K Adam; Levesque, Barrett G

2014-10-01

Crohn's disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohn's Disease (SES-CD) are indices with the most extensively described operating properties. Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Granulomatous Tracheo-Bronchitis Associated With Crohn's Disease

PubMed Central

Xia, Kai; Wolf, Jacqueline; Friedman, Sonia

2004-01-01

We report a rare case of diffuse tracheo-bronchitis as a complication of Crohn's disease. A young man with a long-standing history of Crohn's enterocolitis initially presented with epigastric pain and melena. Upper endoscopy revealed erythematous, edematous, and friable mucosa with erosions, particularly in the pyloric channel, causing gastric outlet obstruction, and a nonbleeding ulcer in the corpus of stomach. Biopsy of these lesions showed chronic gastritis and a noncaseating epithelioid granuloma, consistent with active Crohn's disease. The patient was treated with a course of corticosteroids and the gastric symptoms resolved. A few months later, he developed fever, cough, hemoptysis, and rash. Bronchoscopy demonstrated a markedly thickened and very inflamed trachea with extensive friable, whitish lesions and ulcerations. Histology showed severe noncaseating granulomatous inflammation. The patient improved with a 6-week oral, followed by an additional 4-week inhaled, corticosteroid treatment. Since then, he has been doing well without relapse of pulmonary symptoms for 2 years. PMID:15208530

Chronic granulomatous otitis externa as an initial presentation of cutaneous Crohn disease.

PubMed

Raynor, Eileen M

2014-08-01

In the limited number of Crohn disease cases involving the head and neck, there is a predilection for mucosal surfaces and rare reports of involvement in the postauricular region. To our knowledge, in all previously reported cases involving the head and neck, the patients had a known diagnosis of Crohn disease. This case describes a 10-year-old boy with a history of psoriasis and psoriasiform dermatitis who presented with bilateral chronic granulomatous otitis externa, obliteration of the external auditory canal, and fissuring, resulting in separation of the lobule from the preauricular skin. Pathologic examination results were consistent with granulomatous dermatitis concerning for cutaneous Crohn disease, and a subsequent gastroenterologic workup confirmed the diagnosis of Crohn disease. This is a report of chronic granulomatous otitis as the initial presentation of cutaneous Crohn disease in a child.

The surgical treatment for Crohn's disease.

PubMed

Alecu, L; Ursuţ, B; Ursuţ, B; Obrocea, F; Marinescu, E; Sfetea, R; Oproiu, Al; Tulin, A

2013-01-01

Crohn's disease is a chronic idiopathic medical and surgical disease, in which the transmural intestinal inflammatory process frequently leads to complications such as strictures or fistulae. The disease is considered to be the result of an imbalance between the proinflammatory mediators and the anti-inflammatory ones; it can be localized on any segment of the gastrointestinal tract, but it especially affects the terminal ileum. The purpose of the study is to assess Crohn's disease from the point of view of the complications requiring surgical treatment, the manner in which they are solved, as well as the postoperative evolution. we followed retrospectively the patients hospitalized and operated in our department during the period January 2001 - December 2011. We examined the clinical observation charts, the paraclinical investigations, the surgical protocols and the histopathological results. the 11 patients included in the study underwent 13 surgical interventions. Their ages were comprised between 16 and 67, the average age being 42.9. The men women ratio was 7 4 (1.75); the interventions performed were segmental enterectomies, right ileo- hemicolectomy, ileotransverse anastomosis, an exploratory laparotomy and an exploratory laparoscopy. the purpose of the treatment of Crohn's disease is to obtain the best possible clinical, laboratory and paraclinical control of the inflammatory process with the least adverse reactions to the medication. The surgical indications for the treatment of the disease are imposed by severe complications such as perforation, stenosis, fistulisation and even malignancy. Consequently, although Crohn's disease is a chronic disease with many relapses, the correct medical and surgical treatment helps patients to maintain a reasonable quality of life, with a good prognosis and a very low mortality rate. Celsius.

A rolling phenotype in Crohn's disease.

PubMed

Irwin, James; Ferguson, Emma; Simms, Lisa A; Hanigan, Katherine; Carbonnel, Franck; Radford-Smith, Graham

2017-01-01

The Montreal classification of disease behaviour in Crohn's disease describes progression of disease towards a stricturing and penetrating phenotype. In the present paper, we propose an alternative representation of the long-term course of Crohn's disease complications, the rolling phenotype. As is commonly observed in clinical practice, this definition allows progression to a more severe phenotype (stricturing, penetrating) but also, regression to a less severe behaviour (inflammatory, or remission) over time. All patients diagnosed with Crohn's Disease between 01/01/1994 and 01/03/2008, managed at a single centre and observed for a minimum of 5 years, had development and resolution of all complications recorded. A rolling phenotype was defined at each time point based on all observed complications in the three years prior to the time point. Phenotype was defined as B1, B2, B3, or B23 (penetrating and stenotic). The progression over time of the rolling phenotype was compared to that of the cumulative Montreal phenotype. 305 patients were observed a median of 10.0 (Intraquartile range 7.3-13.7) years. Longitudinal progression of rolling phenotype demonstrated a consistent proportion of patients with B1 (70%), B2 (20%), B3 (5%) and B23 (5%) phenotypes. These proportions were observed regardless of initial phenotype. In contrast, the cumulative Montreal phenotype progressed towards a more severe phenotype with time (B1 (39%), B2 (26%), B3(35%) at 10 years). A rolling phenotype provides an alternative view of the longitudinal burden of intra-abdominal complications in Crohn's disease. From this viewpoint, 70% of patients have durable freedom from complication over time (>3 years).

Small-bowel mucosal healing assessment by capsule endoscopy as a predictor of long-term clinical remission in patients with Crohn's disease: a systematic review and meta-analysis.

PubMed

Niv, Yaron

2017-07-01

Capsule endoscopy (CE) may be used for the evaluation and follow-up of patients with Crohn's disease. CE scores correspond to the degree of mucosal inflammation, a major therapeutic target. The aim of this meta-analysis and systematic review was to determine whether mucosal healing assessment by CE may serve as a predictor of clinical remission in patients with Crohn's disease. To identify observational or controlled English-language full-text studies assessing mucosal healing by CE in patients with Crohn's disease up to 30 September 2016, we searched PubMed, Embase, Central, Medline, and Scopus using the key words 'mucosal healing' and 'capsule endoscopy'. A meta-analysis was carried out using 'Comprehensive meta-analysis' software. Pooled odds ratios and 95% confidence intervals were calculated. Five observational studies including 142 patients from five countries fulfilled the inclusion criteria. No publication bias was found by funnel plot. The mucosal healing CE score was found to be significantly associated with improved outcome after a follow-up of 12 weeks to 24 months, with an odds ratio of 11.06 (95% confidence interval: 3.74-32.73, P<0.001). The degree of heterogeneity among the studies was small (Q=2.014, d.f.[Q]=3, P=0.569 and I=0). Endoscopy scores may play a role in the long-term prognostic evaluation of patients with Crohn's disease. Our results may be accepted as proof of concept, but larger studies are needed to corroborate these findings.

Top-down approach to biological therapy of Crohn's disease.

PubMed

Hirschmann, Simon; Neurath, Markus F

2017-03-01

Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.

DWI at MR Enterography for Evaluating Bowel Inflammation in Crohn Disease.

PubMed

Park, Seong Ho

2016-07-01

The purpose of this article is to provide a comprehensive review regarding DWI enterography used for evaluating Crohn disease and to summarize the relevant evidence. Active bowel inflammation in Crohn disease causes restricted diffusion on MR enterography with DWI. Enterographic DWI to evaluate Crohn disease is increasingly drawing attention for both academic research and clinical practice and has shown potential as a quantitative tool for assessing bowel inflammation. DWI enterography also has multiple unresolved issues and limitations.

Partial enteral nutrition with a Crohn's disease exclusion diet is effective for induction of remission in children and young adults with Crohn's disease.

PubMed

Sigall-Boneh, Rotem; Pfeffer-Gik, Tamar; Segal, Idit; Zangen, Tsili; Boaz, Mona; Levine, Arie

2014-08-01

Exclusive enteral nutrition is effective for inducing remission in active pediatric Crohn's disease. Partial enteral nutrition (PEN) with free diet is ineffective for inducing remission, suggesting that the mechanism depends on exclusion of free diet. We developed an alternative diet based on PEN with exclusion of dietary components hypothesized to affect the microbiome or intestinal permeability. Children and young adults with active disease defined as a pediatric Crohn's disease activity index >7.5 or Harvey-Bradshaw index ≥4 received a 6-week structured Crohn's disease exclusion diet that allowed access to specific foods and restricted exposure to all other foods, and up to 50% of dietary calories from a polymeric formula. Remission, C-reactive protien, and erythrocyte sedimentation rate were reevaluated at 6 weeks. The primary endpoint was remission at 6 weeks defined as Harvey-Bradshaw index ≤3 for all patients and pediatric Crohn's disease activity index <7.5 in children. We treated 47 patients (mean age, 16.1 ± 5.6 yr; 34 children). Response and remission were obtained in 37 (78.7%) and 33 (70.2%) patients, respectively. Mean pediatric Crohn's disease activity index decreased from 27.7 ± 9.4 to 5.4 ± 8 (P < 0.001), Harvey-Bradshaw index from 6.4 ± 2.7 to 1.8 ± 2.9 (P < 0.001). Remission was obtained in 70% of children and 69% of adults. Normalization of previously elevated CRP occurred in 21 of 30 (70%) patients in remission. Seven patients used the diet without PEN; 6 of 7 obtained remission. Dietary therapy involving PEN with an exclusion diet seems to lead to high remission rates in early mild-to-moderate luminal Crohn's disease in children and young adults.

Vulvar metastatic Crohn disease: clinical, histopathological and ultrasonographic findings.

PubMed

Pousa-Martínez, María; Alfageme, Fernando; González de Domingo, María Antonia; Suárez-Masa, Dolores; Calvo, Marta; Roustán, Gastón

2017-11-15

Metastatic Crohn disease (MCD) is an unusual type of cutaneous Crohn disease characterized by skin lesions separated from the lesions of the gastrointestinal tract. The diagnosis of MCD is essentially histological,showing noncaseating granulomas in the dermis and subcutaneous fat tissue. We report a case of MCD with vulvar involvement and clinical, histopathological, and ultrasonographic findings of this disease.

Genetics Home Reference: Crohn disease

MedlinePlus

... or indirectly, to abnormal inflammation. However, the exact relationship between these factors and Crohn disease risk remains ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

[NOD2 gene mutation in Moroccan patients with Crohn's disease: prevalence, genotypic study and correlation of NOD2 gene mutation with the phenotype of Crohn's disease].

PubMed

Tamzaourte, Mouna; Errabih, Ikram; Krami, Hayat; Maha, Fadlouallah; Maria, Lahmiri; Benzzoubeir, Nadia; Ouazzani, Laaziza; Sefiani, Ahmed; Ouazzani, Houria

2017-01-01

The aim of this study was to determine the prevalence of NOD2/CARD15 gene mutations in a group of Moroccan patients with Crohn's disease and to study its correlation with genotype-phenotypic expression. We conducted a cross-sectional case-control study over a period of 16 months. 101 patients with Crohn's disease were enrolled between January 2012 and April 2013 as well as a control group of 107 patients. We performed a genetic analysis to identify 3 NOD2 gene variants: p.Arg702Trp, p.Gly908Arg and p.Leu1007fsins. Then we conducted a study of the correlation between genotype and phenotypic expression. The genetic analysis of patients with Crohn's disease highlighted the presence of NOD2 mutation in 14 patients (13.77%) versus 7 patients (6.53%) in the control group. The study of the frequency of different alleles showed p.Gly908Arg mutation in 6.43%, p.Leu1007fsins in 0.99% and p.Arg702Trp in 0.49% versus 2.80%, 0% and 0.46% in the control group respectively. The study of the correlation between genotype and phenotypic expression showed that CARD15 mutation is associated with ileocecal Crohn's disease, with fistulizing and stenosing behavior in Crohn's disease as well as with severe evolution and frequent recourse to surgery and immunosuppressants. The prevalence of NOD2/ CARD15 mutation in our case series is low. This mutation is correlated with severe Crohn's disease.

The TNF-α -308 polymorphism may affect the severity of Crohn's disease

PubMed Central

Santana, Genoile; Bendicho, Maria Teresita; Santana, Tamara Celi; dos Reis, Lidiane Bianca; Lemaire, Denise; Lyra, André Castro

2011-01-01

OBJECTIVE: The goal of this project was to analyze the association between Crohn's disease, its clinical features, and the tumor necrosis factor alpha (TNF-α) -308 polymorphism. METHODS: This is a case-control and cross-sectional study that enrolled 91 patients with Crohn's disease and 91 controls. Patients with Crohn's disease were characterized according to the Montreal Classification, along with their clinical and surgical treatment history. Analysis of the TNF-α -308 polymorphism was performed using a commercial kit. A stratified analysis was applied using an OR (odds ratio) with a 95% confidence interval. The chi-square and Fisher's exact tests were utilized for analysis of the association between the polymorphism and the clinical features of Crohn's disease. RESULTS: The low producer predicted phenotype was present in 76.9% of Crohn's disease cases and 75.8% of controls (OR 0.94 [0.45-1.97]). The TNF2 allele and the high producer predicted phenotype were more frequent among patients with Crohn's disease penetrating behavior (p = 0.004). The TNF2 allele and the high producer predicted phenotype were also associated with a history of colectomy (p = 0.02), and the TNF2 allele was associated with small bowel resection (p = 0.03). CONCLUSIONS: The TNF-α -308 polymorphism appears to affect the severity of the disease. However, TNF-α -308 polymorphism does not appear to be important for the susceptibility in the development of Crohn's disease. PMID:21915486

Filgotinib for the treatment of Crohn's disease.

PubMed

Labetoulle, Remi; Paul, Stephane; Roblin, Xavier

2018-03-01

Inflammatory bowel diseases, such as Crohn's disease (CD) and ulcerative colitis (UC), are widespread diseases (with an estimated 2.2 million Europeans affected), and even populations previously considered 'low risk' (such as Japan and India) are witnessing an increasing incidence. CD is a chronic, progressive immunologically driven disease, with an evolution characterized by succession of periods of progression and remission. New physiopathological pathways are continuously being discovered, the more we understand about how the disease appears and progresses, the more targets become available for the development of novel therapies. Areas covered: Filgotinib is one of these promising new therapies; this article discusses the currently available data. We used an exhaustive search of the PubMed database to corroborate information regarding its chemical characteristics, and the studies evaluating clinical efficacy and safety. Expert opinion: Up to now, the phase-II study evaluating Filgotinib yielded very promising results in moderate to severe CD patients, with good clinical response, mucosal healing, while having few and moderate adverse effects, both in anti-TNF naïve and resistant patients. Phase-III studies are still ongoing and will help decide whether Filgotinib will be a worthwhile drug in the treatment of CD and the best way to use it.

Medical radar considerations for detecting and monitoring Crohn's disease

NASA Astrophysics Data System (ADS)

Smith, Sonny; Narayanan, Ram M.; Messaris, Evangelos

2014-05-01

Crohn's disease is a condition that causes inflammation and associated complications along any section of the digestive tract. Over the years, numerous radiological and endoscopic methods as well as the use of ultrasound have been developed to examine and diagnose inflammatory bowel disorders such as Crohn's disease. While such techniques have much merit, an alternative medical solution that is safe, non-invasive, and inexpensive is proposed in this paper. Reflections from electromagnetic signals transmitted by an ultra-wide band (UWB) radar allow for not only range (or extent) information but also spectral analysis of a given target of interest. Moreover, the radar cross-section (RCS) of an object measures how detectable the electromagnetic return energy of such an object is to the radar. In the preliminary phase of research, we investigate how disparities in the dielectric properties of diseased versus non-diseased portions of the intestines can aid in the detection of Crohn's disease. RCS analysis from finite-difference time-domain (FDTD) method simulations using a simple 3D model of the intestines are presented. The ultimate goal of our research is to design a UWB radar system using a suitable waveform to detect and monitor Crohn's disease.

European evidence based consensus on the diagnosis and management of Crohn's disease: special situations

PubMed Central

Caprilli, R; Gassull, M A; Escher, J C; Moser, G; Munkholm, P; Forbes, A; Hommes, D W; Lochs, H; Angelucci, E; Cocco, A; Vucelic, B; Hildebrand, H; Kolacek, S; Riis, L; Lukas, M; de Franchis, R; Hamilton, M; Jantschek, G; Michetti, P; O'Morain, C; Anwar, M M; Freitas, J L; Mouzas, I A; Baert, F; Mitchell, R; Hawkey, C J

2006-01-01

This third section of the European Crohn's and Colitis Organisation (ECCO) Consensus on the management of Crohn's disease concerns postoperative recurrence, fistulating disease, paediatrics, pregnancy, psychosomatics, extraintestinal manifestations, and alternative therapy. The first section on definitions and diagnosis reports on the aims and methods of the consensus, as well as sections on diagnosis, pathology, and classification of Crohn's disease. The second section on current management addresses treatment of active disease, maintenance of medically induced remission, and surgery of Crohn's disease. PMID:16481630

Facial biometrics of peri-oral changes in Crohn's disease.

PubMed

Zou, L; Adegun, O K; Willis, A; Fortune, Farida

2014-05-01

Crohn's disease is a chronic relapsing and remitting inflammatory condition which affects any part of the gastrointestinal tract. In the oro-facial region, patients can present peri-oral swellings which results in severe facial disfigurement. To date, assessing the degree of facial changes and evaluation of treatment outcomes relies on clinical observation and semi-quantitative methods. In this paper, we describe the development of a robust and reproducible measurement strategy using 3-D facial biometrics to objectively quantify the extent and progression of oro-facial Crohn's disease. Using facial laser scanning, 32 serial images from 13 Crohn's patients attending the Oral Medicine clinic were acquired during relapse, remission, and post-treatment phases. Utilising theories of coordinate metrology, the facial images were subjected to registration, regions of interest identification, and reproducible repositioning prior to obtaining volume measurements. To quantify the changes in tissue volume, scan images from consecutive appointments were compared to the baseline (first scan image). Reproducibility test was performed to ascertain the degree of uncertainty in volume measurements. 3-D facial biometric imaging is a reliable method to identify and quantify peri-oral swelling in Crohn's patients. Comparison of facial scan images at different phases of the disease revealed precisely profile and volume changes. The volume measurements were highly reproducible as adjudged from the 1% standard deviation. 3-D facial biometrics measurements in Crohn's patients with oro-facial involvement offers a quick, robust, economical and objective approach for guided therapeutic intervention and routine assessment of treatment efficacy on the clinic.

Trends in the Surgical Management of Crohn's Disease.

PubMed

Geltzeiler, Cristina B; Hart, Kyle D; Lu, Kim C; Deveney, Karen E; Herzig, Daniel O; Tsikitis, Vassiliki L

2015-10-01

Although medical management of Crohn's disease has changed in recent years, it is unclear whether surgical management has altered. We examined rate changes of surgical interventions, stoma constructions, and subset of ileostomy and colostomy constructions. We reviewed the Nationwide Inpatient Sample database from 1988 to 2011. We examined the number of Crohn's-related operations and stoma constructions, including ileostomies and colostomies; a multivariable logistic regression model was developed. A total of 355,239 Crohn's-related operations were analyzed. Operations increased from 13,955 in 1988 to 17,577 in 2011, p < 0.001. Stoma construction increased from 2493 to 4283, p < 0.001. The subset of ileostomies increased from 1201 to 3169, p < 0.001 while colostomies decreased from 1351 to 1201, p = 0.05. Operation percentages resulting in stoma construction increased from 18 to 24 %, p < 0.001. Weight loss (OR 2.25, 95 % CI 1.88, 2.69) and presence of perianal fistulizing disease (OR 2.91, 95 % CI 2.31, 3.67) were most predictive for requiring stoma construction. Crohn's-related surgical interventions and stoma constructions have increased. The largest predictors for stoma construction are weight loss and perianal fistulizing disease. As a result, nutrition should be optimized and the early involvement of a multidisciplinary team should be considered.

Spheroplastic phase of mycobacteria isolated from patients with Crohn's disease.

PubMed Central

Chiodini, R J; Van Kruiningen, H J; Thayer, W R; Coutu, J A

1986-01-01

Two strains of an unclassified Mycobacterium species were isolated after 18 and 30 months of incubation of media inoculated with resected intestinal tissues from patients with Crohn's disease. These strains represented the third and fourth isolates of this organism from Crohn's disease patients. Ultrastructural examination of this strain and two previously isolated strains revealed the presence of spheroplasts which eventually transformed into the bacillary form of a previously unrecognized Mycobacterium species. These cell wall-deficient forms did not stain with conventional dyes and failed to grow on hypertonic media. Restriction polymorphism of the ribosomal DNA genes was used to determine the relationship between the cell wall-deficient and bacillary forms. Identical restriction patterns of the ribosomal DNA genes were found between the spheroplasts and Mycobacterium sp. isolates with EcoRI, BamHI, and XhoI restriction endonucleases, thus providing definitive evidence of their origin. Unidentified spheroplasts were isolated from an additional 12 patients with Crohn's disease, of which 7 of 10 seroagglutinated with antiserum prepared against the Mycobacterium sp. Spheroplasts were isolated from 16 of 26 (61%) patients with Crohn's disease but not from tissues of 13 patients with ulcerative colitis or 13 patients with other diseases of the bowel. These findings support the role of mycobacteria as etiologic agents in some cases of Crohn's disease. Images PMID:3760132

Janus Kinase Antagonists and Other Novel Small Molecules for the Treatment of Crohn's Disease.

PubMed

Boland, Brigid S; Vermeire, Séverine

2017-09-01

There is an ongoing, unmet need for effective therapies for Crohn's disease. Treatments for Crohn's disease continue to evolve from the traditional biologics to novel small molecules, with targeted mechanisms directed toward pathways that are dysregulated in Crohn's disease. There are multiple emerging mechanisms of action, including Janus kinase inhibition, Smad7 inhibition, and sphingosine-1-phosphate receptor modulators, that are administered as oral medications, and small molecules represent the next generation of therapies for Crohn's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Cryptogenic Organizing Pneumonia With Lung Nodules Secondary to Pulmonary Manifestation of Crohn Disease.

PubMed

Zaman, Taufiq; Watson, Joseph; Zaman, Mohammad

2017-01-01

Crohn disease is an immune-mediated inflammatory condition with gastrointestinal and extraintestinal manifestations in patients. Pulmonary involvement of Crohn disease is one manifestation. There have been case reports which have shown Crohn disease and lung nodules which were noted to be histopathological as cryptogenic organizing pneumonia (COP). In our case, a 22-year-old woman with Crohn disease was seen with complaints of chest pain and cough. Computed tomographic scan of chest showed multiple bilateral lung nodules, for which biopsy was done, which showed COP. The case study is followed by a deeper discussion of COP and the extraintestinal manifestation seen in inflammatory bowel disease.

Perforated Meckel's diverticulitis complicating active Crohn's ileitis: a case report.

PubMed

Schwenter, Frank; Gervaz, Pascal; de Saussure, Philippe; McKee, Thomas; Morel, Philippe

2009-01-13

In Crohn's disease, the extension of active terminal ileitis into a Meckel's diverticulum is possible, but usually has no impact on clinical decision-making. We describe an original surgical approach in a young woman presenting with a combination of perforated Meckel's diverticulitis and active Crohn's ileitis. We report the case of a 22-year-old woman with Crohn's disease, who was admitted for abdominal pain, fever and diarrhoea. CT scan demonstrated active inflammation of the terminal ileum, as well as a fluid collection in the right iliac fossa, suggesting intestinal perforation. Laparoscopy was performed and revealed, in addition to extensive ileitis, a 3 x 3 cm abscess in connection with perforated Meckel's diverticulitis. It was therefore possible to avoid ileocaecal resection by only performing Meckel's diverticulectomy; pathological examination of the surgical specimen revealed the presence of transmural inflammation with granulomas and perforation of the diverticulum at its extremity. Crohn's disease of the ileum may be responsible for Meckel's diverticulitis and cause perforation which, in this case, proved to be a blessing in disguise and spared the patient an extensive small bowel resection.

Postoperative outcomes in vedolizumab-treated Crohn's disease patients undergoing major abdominal operations.

PubMed

Lightner, A L; McKenna, N P; Tse, C S; Raffals, L E; Loftus, E V; Mathis, K L

2018-03-01

Up to 80% of patients with Crohn's disease require an abdominal operation in their lifetime. As the use of vedolizumab is increasing for the treatment of Crohn's disease, it is important to understand its potential association with post-operative complications. We sought to compare 30-day postoperative infectious complication rate among vedolizumab-treated Crohn's disease patients vs those who had received TNFα inhibitors or no biologic therapy. A retrospective review of all Crohn's disease patients who received vedolizumab within 12 weeks of a major abdominal or pelvic operation was performed. Two control cohorts consisted of Crohn's disease patients treated with TNFα inhibitors or no biologic therapy. One hundred Crohn's disease patients received vedolizumab within 12 weeks of an abdominal operation. Vedolizumab-treated patients underwent an equivalent rate of laparoscopic surgery (P = .25), had fewer anastomoses performed (P = .0002), and had equally frequent diversion in the setting of anastomoses (P = .47). Thirty-two vedolizumab-treated patients experienced postoperative infectious complications (32%), 26 of which were surgical site infections (26%). The vedolizumab-treated group experienced no difference in nonsurgical site infections (6% vs 5% anti-TNFα and 2% nonbiologic; P = .34), but significantly higher rates of surgical site infections (26% vs 8% and 11%; P < .001). On univariate and multivariate analysis, exposure to vedolizumab remained a significant predictor of postoperative surgical site infection (P < .001 and P = .002). Twenty-six per cent of Crohn's disease patients who received vedolizumab within 12 weeks prior to a major abdominal operation experienced a 30-day postoperative surgical site infection, significantly higher than that of patients receiving TNFα inhibitors or no biologic therapy. Vedolizumab within 12 weeks of surgery remained a predictor of 30-day postoperative surgical site infection on multivariable

Early bronchopulmonary involvement in Crohn disease: a case report

PubMed Central

Valletta, Enrico; Bertini, Marina; Sette, Luciano; Braggion, Cesare; Pradal, Ugo; Zannoni, Marina

2001-01-01

Background Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. Case presentation A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. Conclusions Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. PMID:11734067

ATG16L1: A multifunctional susceptibility factor in Crohn disease

PubMed Central

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-01-01

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease. PMID:25906181

ATG16L1: A multifunctional susceptibility factor in Crohn disease.

PubMed

Salem, Mohammad; Ammitzboell, Mette; Nys, Kris; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

2015-04-03

Genetic variations in the autophagic pathway influence genetic predispositions to Crohn disease. Autophagy, the major lysosomal pathway for degrading and recycling cytoplasmic material, constitutes an important homeostatic cellular process. Of interest, single-nucleotide polymorphisms in ATG16L1 (autophagy-related 16-like 1 [S. cerevisiae]), a key component in the autophagic response to invading pathogens, have been associated with an increased risk of developing Crohn disease. The most common and well-studied genetic variant of ATG16L1 (rs2241880; leading to a T300A conversion) exhibits a strong association with risk for developing Crohn disease. The rs2241880 variant plays a crucial role in pathogen clearance, resulting in imbalanced cytokine production, and is linked to other biological processes, such as the endoplasmic reticulum stress/unfolded protein response. In this review, we focus on the importance of ATG16L1 and its genetic variant (T300A) within the elementary biological processes linked to Crohn disease.

Pathogenesis: common pathways between hidradenitis suppurativa and Crohn disease.

PubMed

García Martínez, F J; Menchén, L

2016-09-01

Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

Increased levels of circulating platelet derived microparticles in Crohn's disease patients.

PubMed

Tziatzios, Georgios; Polymeros, Dimitrios; Spathis, Aris; Triantafyllou, Maria; Gkolfakis, Paraskevas; Karakitsos, Petros; Dimitriadis, George; Triantafyllou, Konstantinos

2016-10-01

Platelet activation is a consistent feature in inflammatory bowel disease. However, the role of circulating platelet derived microparticles (PDMPs) and the effects of disease activity and treatment on their levels has not been clarified yet in this disorder. Using flow cytometry, we measured platelet derived microparticles and platelet derived microparticles expressing Annexin V in platelet rich plasma from 47 Crohn's disease and 43 ulcerative colitis patients and 24 healthy controls. Crohn's disease patients have greater PDMPs (0.31% ± 0.07% versus 0.14% ± 0.04%, p = 0.02) and PDMPs expressing Annexin V (27% ± 2.6% versus 14.6% ± 2.7%, p = 0.002) levels in comparison with healthy controls; however, both microparticles levels are not related with disease activity. Crohn's disease patients on 5-ASA therapy show lower levels of PDMPs in comparison with those on no 5-ASA (0.30% ± 0.07% versus 0.32% ± 0.09%, p = 0.048). Ulcerative colitis patients have similar PDMPs and PDMPs expressing Annexin V levels, compared to healthy controls (p = 0.06 and p = 0.2, respectively) and there is no correlation of both microparticles expression with disease activity. 5-ASA has no effect on both microparticles levels in ulcerative colitis patients. Anti-TNF-α treatment has no effect on study's microparticles expression in Crohn's and ulcerative colitis patients. Circulating levels of platelet derived microparticles are increased only in Crohn's patients, but they do not correlate with disease activity. 5-ASA treatment is associated with lower levels of PDMPs only in Crohn's, while anti-TNF-α treatment does not influence expression of microparticles in inflammatory bowel disease patients.

Cost of illness of Crohn's disease.

PubMed

Bodger, Keith

2002-01-01

Crohn's disease is a chronic inflammatory bowel disease of unknown aetiology which affects around 35,000 people in the UK (population 56.8 million). The potential for onset in early adult life, disease chronicity and a need for hospitalisation and surgery mean that the disease can be associated with substantial healthcare costs. Cost-of-illness studies focusing on direct medical costs have identified that over half the average costs associated with the disease relate to hospital costs. Estimates of the contribution of drug costs to the total direct economic burden have varied between 4.6 and 25%. Figures for average annual direct costs per patient in the US have been put at between US dollars 6561 (1990 values) and US dollars 12,417 (1994 values), whereas European studies have given much lower cost estimates (US dollars 655, 1994 values). However, all studies have highlighted that much of the total cost of illness relates to extensive interventions required by a small proportion of severely affected individuals. Indirect costs associated with reduced productivity in Crohn's disease can be high, with long periods of absenteeism and early disability. However, most patients (90%) remain in the workforce and life expectancy is relatively normal. A variety of drugs are employed for the treatment of Crohn's disease, both in an attempt to induce clinical remission in active disease and to maintain remission once this has been achieved. Comparative data on cost effectiveness is lacking, though crude estimates based on randomised trials suggest that the frequently prescribed aminosalicylates, which have only modest efficacy, are a relatively costly drug option. The costs associated with adverse drug effects, particularly for corticosteroids, have not been formally quantified. Despite high costs, new drug therapies for more severe disease, such as anti-tumour necrosis factor (TNF-alpha) antibodies, may prove a cost-effective option if the need for hospitalisation is reduced

Fistulizing Crohn's disease: Diagnosis and management.

PubMed

Gecse, Krisztina; Khanna, Reena; Stoker, Jaap; Jenkins, John T; Gabe, Simon; Hahnloser, Dieter; D'Haens, Geert

2013-06-01

Fistulizing Crohn's disease represents an evolving, yet unresolved, issue for multidisciplinary management. Perianal fistulas are the most frequent findings in fistulizing Crohn's disease. While enterocutaneous fistulas are rare, they are associated with considerable morbidity and mortality. Detailed evaluation of the fistula tract by advanced imaging techniques is required to determine the most suitable management options. The fundamentals of perianal fistula management are to evaluate the complexity of the fistula tract, and exclude proctitis and associated abscess. The main goals of the treatment are abscess drainage, which is mandatory, before initiating immunosuppressive medical therapy, resolution of fistula discharge, preservation of continence and, in the long term, avoidance of proctectomy with permanent stoma. The management of enterocutaneous fistulas comprises of sepsis control, skin care, nutritional optimization and, if needed, delayed surgery.

Perforated Meckel's diverticulitis complicating active Crohn's ileitis: a case report

PubMed Central

2009-01-01

Introduction In Crohn's disease, the extension of active terminal ileitis into a Meckel's diverticulum is possible, but usually has no impact on clinical decision-making. We describe an original surgical approach in a young woman presenting with a combination of perforated Meckel's diverticulitis and active Crohn's ileitis. Case presentation We report the case of a 22-year-old woman with Crohn's disease, who was admitted for abdominal pain, fever and diarrhoea. CT scan demonstrated active inflammation of the terminal ileum, as well as a fluid collection in the right iliac fossa, suggesting intestinal perforation. Laparoscopy was performed and revealed, in addition to extensive ileitis, a 3 × 3 cm abscess in connection with perforated Meckel's diverticulitis. It was therefore possible to avoid ileocaecal resection by only performing Meckel's diverticulectomy; pathological examination of the surgical specimen revealed the presence of transmural inflammation with granulomas and perforation of the diverticulum at its extremity. Conclusion Crohn's disease of the ileum may be responsible for Meckel's diverticulitis and cause perforation which, in this case, proved to be a blessing in disguise and spared the patient an extensive small bowel resection. PMID:19144118

Hyaline-Vascular Type Castleman's Disease, Sarcoidosis, and Crohns Disease.

PubMed

Gupta, Arjun; Ayyar, Balaji; Zia, Hamid; Chen, Weina; Harris, Samar; Naina, Harris V

2016-06-01

Sarcoidosis and Crohns disease have been associated with increased long term risk of lymphoproliferative disorders, including lymphomas. Newly developed lymphadenopathy in a patient with these disorders should prompt pathological evaluation. Castleman's disease is a lymphoproliferative disorder characterized by enlarged hyperplastic lymph nodes with regressed follicles surrounded by expanded mantle zones of small lymphocytes, and interfollicular vascular proliferation in the hyaline-vascular type. Similar to sarcoidosis and Crohns disease, its etiology is incompletely understood, although immune dysregulation, genetic factors and infectious and environmental factors are thought to play a role in all three diseases. Interleukin-6 is a possible pathological common factor between these three disease processed. Unicentric, hyaline-vascular type Castleman's disease can be treated successfully with complete surgical resection. We report a patient with long history of sarcoidosis and Crohns disease with newly developed lymphadenopathy which was found to be due to Castleman's disease.

An update on the use of helminths to treat Crohn's and other autoimmunune diseases.

PubMed

Reddy, Aditya; Fried, Bernard

2009-01-01

This review updates our previous one (Reddy and Fried, Parasitol Research 100: 921-927, 2007) on Crohn's disease and helminths. The review considers the most recent literature on Trichuris suis therapy and Crohn's and the significant literature on the use of Necator americanus larvae to treat Crohn's and other autoimmune disorders. The pros and cons of helminth therapy as related to autoimmune disorders are discussed in the review. We also discuss the relationship of the bacterium Campylobacter jejuni and T. suis in Crohn's disease. The significant literature on helminths other than N. americanus and T. suis as related to autoimmune diseases is also reviewed.

Increasing incidence of Crohn's disease in Victorian children.

PubMed

Phavichitr, Nopaorn; Cameron, Donald J S; Catto-Smith, Anthony G

2003-03-01

The incidence of Crohn's disease has been increasing in Western communities, but there are no published studies which have examined this change in children in Australia. The centralization of pediatric gastroenterology services in Victoria provides an opportunity to examine these changes within one state. We undertook a retrospective study over a 31-year period of all children aged 16 years or less initially diagnosed with Crohn's disease at either the Royal Children's Hospital, or Monash Medical Center, Melbourne, Victoria. We identified 351 patients who met the diagnostic criteria between 1971 and 2001. The incidence of Crohn's disease in children aged 16 years or less rose from 0.128 to 2.0 per 100,000 per year over the three decades (r = 0.964, P < 0.01). There was a disproportionate over-representation of children from an urban background (incidence rate ratio 1.66, 95% CI 1.28-2.16). Children currently being diagnosed had on average a lower erythrocyte sedimentation rate (ESR) and higher albumin than in previous decades. The use of flexible endoscopy has increased markedly (1970s: 60%; 1990s: 96%, P < 0.05) and the proportion of children recognized at diagnosis with upper gastrointestinal and colonic involvement has increased significantly. There has been a significant increase in the incidence of Crohn's disease in Victorian children. The pattern of disease has also changed with colonic disease now more frequent, and inflammatory indices less abnormal. The increased use of endoscopy has established the frequent involvement of the upper gastrointestinal tract.

Intestinal tuberculosis masquerading as difficult to treat Crohn disease: a case report.

PubMed

Niriella, Madunil A; Kodisinghe, S Kuleesha; De Silva, Arjuna P; Hewavisenthi, Janaki; de Silva, Hithanadura J

2016-08-24

Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.

Surgical Treatment of Crohn Colitis Involving More Than 2 Colonic Segments

PubMed Central

Lee, Jong Lyul; Yu, Chang Sik; Lim, Seok-Byung; Park, In Ja; Yoon, Yong Sik; Kim, Chan Wook; Yang, Suk-Kyun; Kim, Jin Cheon

2016-01-01

Abstract The incidence of primary Crohn colitis is uncommon and surgical treatment has remained controversial, although most patients with Crohn colitis eventually require surgical intervention. This study aims to compare the operative outcomes of patients who underwent segmental versus either total colectomy or total proctocolectomy for Crohn colitis and to assess potential risk factors associated with clinical and surgical recurrence-free survivals. This is a retrospective study of 116 patients who underwent primary surgery for Crohn colitis between August 1997 and July 2011. Patients were classified based on the type of surgery: segmental colectomy (SC group; n = 71) or either total colectomy or total proctocolectomy (TC group; n = 45). There were no significant differences in postoperative complications or the nutritional state between the SC and TC groups. Patients in TC group had a significantly higher clinical recurrence-free survival (CRFS). Among the 54 patients with multisegmental Crohn colitis, the TC group had a significantly increased CRFS and surgical recurrence-free survival (SRFS), compared with patients in the SC group (5-year CRFS: 82.0% ± 5.8% vs 22.2% ± 13.9%, P = 0.001; 5-year SRFS: 88.1% ± 5.0% vs 44.4% ± 16.6%, P = 0.001). By multivariate analysis of patients with multisegments involved, SC was a risk factor for SRFS and CRFS (hazard ratio [HR] = 4.637, 95% confidence interval [CI] = 1.387–15.509, P = 0.013 and HR = 32.407, 95% CI = 2.873–365.583, P = 0.005). TC patients have significantly increased CRFS and TC in patients with multisegment involvement may affect improved SRFS and CRFS. Among patients with multisegmental Crohn colitis, SC is an independent risk factor for CRFS and SRFS. PMID:27258512

The impact of pregnancy on surgical Crohn disease: an analysis of the Nationwide Inpatient Sample.

PubMed

Hatch, Quinton; Champagne, Bradley J; Maykel, Justin A; Davis, Bradley R; Johnson, Eric K; Bleier, Joshua I; Francone, Todd D; Steele, Scott R

2014-07-01

The impact of pregnancy on the course of Crohn disease is largely unknown. Retrospective surveys have suggested a variable effect, but there are limited population-based clinical data. We hypothesized pregnant women with Crohn disease will have similar rates of surgical disease as a nonpregnant Crohn disease cohort. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify female Crohn patients from all patients admitted using the Nationwide Inpatient Sample (1998-2009). Women were stratified as either pregnant or nonpregnant. We defined Crohn-related surgical disease as peritonitis, gastrointestinal hemorrhage, intra-abdominal abscess, toxic colitis, anorectal suppuration, intestinal-intestinal fistulas, intestinal-genitourinary fistulas, obstruction and/or stricture, or perforation (excluding appendicitis). Of the 92,335 women admitted with a primary Crohn-related diagnosis, 265 (0.3%) were pregnant. Pregnant patients were younger (29 versus 44 y; P<0.001) and had lower rates of tobacco use (6% versus 13%; P<0.001). Pregnant women with Crohn disease had higher rates of intestinal-genitourinary fistulas (23.4% versus 3.0%; P<0.001), anorectal suppuration (21.1% versus 4.1%; P<0.001), and overall surgical disease (59.6% versus 39.2%; P<0.001). On multivariate logistic regression analysis controlling for malnutrition, smoking, age, and prednisone use, pregnancy was independently associated with higher rates of anorectal suppuration (odds ratio [OR], 5.2; 95% confidence interval [CI], 3.8-7.0; P<0.001), intestinal-genitourinary fistulas (OR, 10.4; 95% CI, 7.8-13.8; P<0.001), and overall surgical disease (OR, 2.9; 95% CI, 2.3-3.7; P<0.001). Pregnancy in women with Crohn disease is a significant risk factor for Crohn-related surgical disease, in particular, anorectal suppuration and intestinal-genitourinary fistulas. Published by Elsevier Inc.

Barrier dysfunction and bacterial uptake in the follicle-associated epithelium of ileal Crohn's disease.

PubMed

Keita, Asa V; Söderholm, Johan D

2012-07-01

The ability to control uptake across the mucosa and protect from harmful substances in the gut lumen is defined as intestinal barrier function. The etiology of Crohn's disease is unknown, but genetic, environmental, and immunological factors all contribute. The frontline between these factors lies in the intestinal barrier. The most important inflammation-driving environmental factor in Crohn's disease is the microbiota, where Esherichia coli strains have been assigned a key role. The first observable signs of Crohn's disease are small aphtoid ulcers over Peyer's patches and lymphoid follicles. The overlaying follicle-associated epithelium (FAE) is specialized for luminal sampling and is an entry site for antigens and bacteria. We have demonstrated increased E. coli uptake across the FAE in Crohn's disease, which may initiate inflammation. This short review will discuss barrier dysfunction and bacteria in the context of ileal Crohn's disease, and how the FAE might be the site of initial inflammation. © 2012 New York Academy of Sciences.

Endoscopic Therapy in Crohn's Disease: Principle, Preparation, and Technique.

PubMed

Chen, Min; Shen, Bo

2015-09-01

Stricture and fistula are common complications of Crohn's disease. Endoscopic balloon dilation and needle-knife stricturotomy has become a valid treatment option for Crohn's disease-associated strictures. Endoscopic therapy is also increasingly used in Crohn's disease-associated fistula. Preprocedural preparations, including routine laboratory testing, imaging examination, anticoagulant management, bowel cleansing and proper sedation, are essential to ensure a successful and safe endoscopic therapy. Adverse events, such as perforation and excessive bleeding, may occur during endoscopic intervention. The endoscopist should be well trained, always be cautious, anticipate for possible procedure-associated complications, be prepared for damage control during endoscopy, and have surgical backup ready. In this review, we discuss the principle, preparation, techniques of endoscopic therapy, as well as the prevention and management of endoscopic procedure-associated complications. We propose that inflammatory bowel disease endoscopy may be a part of training for "super" gastroenterology fellows, i.e., those seeking a career in advanced endoscopy or in inflammatory bowel disease.

Restorative Procedures in Colonic Crohn Disease

PubMed Central

Martin, Sean T.; Vogel, Jon D.

2013-01-01

Surgical management for refractory Crohn colitis often involves creation of a temporary or permanent stoma. Traditionally, the procedure of choice has been a total proctocolectomy with permanent ileostomy. However, restorative procedures that help to avoid a permanent stoma are being used with more frequency. In this article, the authors will address these procedures, including colocolonic anastomosis, ileorectal anastomosis, ileal pouch rectal anastomosis, and ileal pouch anal anastomosis. Factors that may influence one's decision to perform these procedures, such as patient age and nutritional status, medical comorbidities, sphincter function, desire to avoid a permanent ostomy, and prior medical therapy, will be discussed. Functional outcomes regarding these procedures will also be described. One should keep in mind that surgery does not cure Crohn disease and that postoperative long-term management is essential in preventing progression or recurrence of disease. PMID:24436657

Can ultrasound be used as the primary imaging in children with suspected Crohn disease?

PubMed

Tsai, Timothy L; Marine, Megan B; Wanner, Matthew R; Cooper, Matthew L; Steiner, Steven J; Ouyang, Fangqian; Gregory Jennings, S; Karmazyn, Boaz

2017-07-01

There is growing literature on the use of ultrasound (US) for evaluation of Crohn disease in adults, but few studies have been conducted on children. Several studies demonstrated high accuracy of US in the diagnosis of Crohn disease. Using US as the primary screening imaging modality for Crohn disease can reduce health care costs, the need for sedation and ionizing radiation exposure. The aim of our study is to determine if US can be used for screening evaluation of pediatric Crohn disease. A prospective cohort study of pediatric patients undergoing MR enterography (MRE) for suspected or known history of Crohn disease was performed, with gray-scale and Doppler US of the terminal ileum done immediately before or after MRE. US images were interpreted by two radiologists (Reader 1 and Reader 2) not involved in image acquisition, in blinded and randomized fashion. US findings of Crohn disease including bowel wall thickening, wall stratification, increased vascularity on Doppler, lymphadenopathy, fat infiltration and extraintestinal complications were evaluated. MRE findings of terminal ileitis were considered the reference standard. Demographic data, body mass index (BMI), symptoms, and laboratory, endoscopic and histopathological data were obtained from electronic medical records. Forty-one patients (mean age: 13.7 years: 4.6-18.9 years) were evaluated. Mean BMI was 21.2 (range: 13-40.2); 10 patients (24.3%) were either overweight or obese. Final diagnoses were Crohn disease (n=24), ulcerative colitis (n=4) and normal/non-inflammatory bowel disease-related diagnoses (n=13). US demonstrated sensitivity of 67% and 78% and specificity of 78% and 83%, by Reader 1 and Reader 2, respectively. MRE sensitivity and specificity were 75% and 100%, respectively, compared to final clinicopathological diagnosis. Interobserver agreement between Reader 1 and Reader 2 was good (0.6< kappa <0.8). In screening for Crohn disease in children, US has limited sensitivity for detecting

Natalizumab for induction of remission in Crohn's disease.

PubMed

Macdonald, J K; McDonald, J W D

2006-07-19

The pathogenesis of Crohn's disease involves migration of leukocytes into gut tissue and subsequent inflammation. Natalizumab (Tysabri, Elan Pharmaceuticals and Biogen Idec) a recombinant humanized IgG4 monoclonal antibody that blocks adhesion and subsequent migration of leukocytes into the gut by binding the alpha4 integrin is a member of a new class of molecules known as selective adhesion molecule (SAM) inhibitors. The results of animal studies suggest that alpha4 integrin blockade could be a useful therapy for inflammatory bowel disease. The results of randomized controlled trials suggest that natalizumab may be an effective therapy for active Crohn's disease. This systematic review summarizes the current evidence on the use of natalizumab for the induction of remission in Crohn's disease. To determine the efficacy and safety of natalizumab for induction of remission in Crohn's disease. A computer assisted search of the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Trials Register, MEDLINE and EMBASE was performed to identify relevant publications between 1966 and June 2005. The medical subject heading (MeSH) terms "Crohn disease" or "inflammatory bowel disease", "Natalizumab" or "Antegren" or "Tysabri" and "Antibodies, Monoclonal" were used to perform key word searches of each database. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed using the computer-assisted search strategy. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Personal contacts, leaders in the field, and the manufacturers were contacted to identify other studies which may not be published. We included only randomized controlled trials comparing natalizumab to a placebo or control therapy for the induction of remission in Crohn

Simultaneous central retinal artery occlusion and optic nerve vasculitis in Crohn disease.

PubMed

Coussa, Razek Georges; Ali-Ridha, Andre; Vila, Natalia; Alshareef, Rayan; Chen, John

2017-04-01

To describe a case of Crohn disease presenting as occlusive vasculitis resulting in a central retinal artery occlusion (CRAO) in one eye and transient ischemic optic neuropathy in the fellow eye. An 18-year-old patient recently diagnosed with biopsy-proven Crohn disease presented with CRAO OD after a previous episode of transient visual loss OS. Extensive workup was negative for other autoimmune or infectious etiologies. The patient was started on intravenous methylprednisolone for 72 h followed by maintenance dose of azathioprine and oral prednisone. Signs of inflammation resolved gradually with some improvement of visual acuity despite developing optic atrophy. To our knowledge, this is the first case of unilateral CRAO and bilateral optic nerve occlusive vasculitis in Crohn disease, which should be considered as an etiology of retinal vascular occlusive disorders especially in young patients. It is important for ophthalmologists to be aware of the ophthalmic risks associated with Crohn disease as aggressive treatment with systemic steroids and immunosuppressive agents is often needed.

Transperineal ultrasonography in perianal Crohn disease: A valuable imaging modality.

PubMed

Wright, Emily K; Novak, Kerri L; Lu, Cathy; Panaccione, Remo; Ghosh, Subrata; Wilson, Stephanie R

2015-01-01

Aims of treatment for Crohn disease have moved beyond the resolution of clinical symptoms to objective end points including endoscopic and radiological normality. Regular re-evaluation of disease status to safely, readily and reliably detect the presence of inflammation and complications is paramount. Improvements in sonographic technology over recent years have facilitated a growing enthusiasm among radiologists and gastroenterologists in the use of ultrasound for the assessment of inflammatory bowel disease. Transabdominal intestinal ultrasound is accurate, affordable and safe for the assessment of luminal inflammation and complications in Crohn disease, and can be performed with or without the use of intravenous contrast enhancement. Perianal fistulizing disease is a common, complex and often treatment-refractory complication of Crohn disease, which requires regular radiological monitoring. Endoanal ultrasound is invasive, uncomfortable and yields limited assessment of the perineal region. Although magnetic resonance imaging of the pelvis is established, timely access may be a problem. Transperineal ultrasound has been described in small studies, and is an accurate, painless and cost-effective method for documenting perianal fluid collections, fistulas and sinus tracts. In the present article, the authors review the literature regarding perineal ultrasound for the assessment of perianal Crohn disease and use case examples to illustrate its clinical utility.

NASPGHAN Clinical Report on Postoperative Recurrence in Pediatric Crohn Disease.

PubMed

Splawski, Judy B; Pffefferkorn, Marian D; Schaefer, Marc E; Day, Andrew S; Soldes, Oliver S; Ponsky, Todd A; Stein, Philip; Kaplan, Jess L; Saeed, Shehzad A

2017-10-01

Pediatric Crohn disease is characterized by clinical and endoscopic relapses. The inflammatory process is considered to be progressive and may lead to strictures, fistulas, and penetrating disease that may require surgery. In addition, medically refractory disease may be treated by surgical resection of inflamed bowel in an effort to reverse growth failure. The need for surgery in childhood suggests severe disease and these patients have an increased risk for recurrent disease and potentially more surgery. Data show that up to 55% of patients had clinical recurrence in the first 2 years after initial surgery. The current clinical report on postoperative recurrence in pediatric Crohn disease reviews the risk factors for early surgery and postoperative recurrence, operative risk factors for recurrence, and prevention and monitoring strategies for postoperative recurrence. We also propose an algorithm for postoperative management in pediatric Crohn disease.

Malignant transformation in perianal fistulas of Crohn's disease: a systematic review of literature.

PubMed

Thomas, Mathew; Bienkowski, Robert; Vandermeer, Thomas J; Trostle, Douglas; Cagir, Burt

2010-01-01

Malignant transformation of perineal fistula in Crohn's disease has rarely been reported. The aim of this study is to define the patient's characteristics and clinical presentation of this rare disease. A systematic review of case series and reports published in English language between 1950 and 2008 was conducted. All cases with malignancy in low pelvic/perineal fistula in patients with Crohn's disease were included. All selected cases were then analyzed with respect to age, gender, duration of Crohn's disease and fistula, location of fistula, presenting symptoms, method of diagnosis, delay in diagnosis, histopathology, treatment, and outcome. Data analyses were done using chi-squared or Fisher's exact test and the Mann-Whitney test. Literature review revealed 61 cases of carcinomas arising in perineal fistulas in Crohn's disease. Sixty-one percent (37) of the patients were females. Females were significantly younger than males at the time of diagnosis of cancer (47 vs. 53 years, P < 0.032). Males were also noted to have significantly longer duration of Crohn's disease compared to females (24 vs. 18 years, P = 0.005). However, females were noted to have the fistula for significantly shorter duration prior to cancer transformation when compared to males (8.3 vs. 16 years, P = 0.0035). On initial examination, malignancy was suspected and proven only in 20% of patients (n = 12). Adenocarcinoma was the most common histology (59%, n = 36), followed by squamous cell carcinoma (31%, n = 19). In most patients (59%, n = 36), the fistula was rectal in origin. A high suspicion for malignancy in chronic perineal fistulas associated with Crohn's disease should be maintained in spite of negative biopsies. Especially in women, the shorter duration of Crohn's fistulas prior to malignant degeneration necessitates an aggressive approach to rule out cancer.

The Mediator Complex Subunits MED14, MED15, and MED16 Are Involved in Defense Signaling Crosstalk in Arabidopsis.

PubMed

Wang, Chenggang; Du, Xuezhu; Mou, Zhonglin

2016-01-01

Mediator is a highly conserved protein complex that functions as a transcriptional coactivator in RNA polymerase II (RNAPII)-mediated transcription. The Arabidopsis Mediator complex has recently been implicated in plant immune responses. Here, we compared salicylic acid (SA)-, methyl jasmonate (MeJA)-, and the ethylene (ET) precursor 1-aminocyclopropane-1-carboxylic acid (ACC)-induced defense and/or wound-responsive gene expression in 14 Arabidopsis Mediator subunit mutants. Our results show that MED14, MED15, and MED16 are required for SA-activated expression of the defense marker gene PATHOEGNESIS-RELATED GENE1 , MED25 is required for MeJA-induced expression of the wound-responsive marker gene VEGATATIVE STORAGE PROTEIN1 ( VSP1 ), MED8, MED14, MED15, MED16, MED18, MED20a, MED25, MED31, and MED33A/B (MED33a and MED33B) are required for MeJA-induced expression of the defense maker gene PLANT DEFENSIN1.2 ( PDF1.2 ), and MED8, MED14, MED15, MED16, MED25, and MED33A/B are also required for ACC-triggered expression of PDF1.2 . Furthermore, we investigated the involvement of MED14, MED15, and MED16 in plant defense signaling crosstalk and found that MED14, MED15, and MED16 are required for SA- and ET-mediated suppression of MeJA-induced VSP1 expression. This result suggests that MED14, MED15, and MED16 not only relay defense signaling from the SA and JA/ET defense pathways to the RNAPII transcription machinery, but also fine-tune defense signaling crosstalk. Finally, we show that MED33A/B contributes to the necrotrophic fungal pathogen Botrytis cinerea- induced expression of the defense genes PDF1.2, HEVEIN-LIKE , and BASIC CHITINASE and is required for full-scale basal resistance to B. cinerea , demonstrating a positive role for MED33 in plant immunity against necrotrophic fungal pathogens.

A Complicated Thread: Abdominal Actinomycosis in a Young Woman with Crohn Disease.

PubMed

Nahum, Ari; Filice, Gregory; Malhotra, Ashish

2017-01-01

Crohn disease is a chronic inflammatory condition that primarily affects the gastrointestinal tract. Typical manifestations include fever, weight loss, fatigue, and abdominal pain, and abdominal abscesses and fistulae are frequent complications. Abdominal actinomycosis is a subacute or indolent disease associated with Actinomyces spp. Symptoms can be very similar to those of Crohn disease, and fistulae are also common. Since ulcerations in the intestinal tract are thought to be caused by Actinomyces escaping from the gut lumen and establishing intra-abdominal infection, it seems likely that abdominal actinomycosis may occur in patients with inflammatory bowel disease. We report a case of abdominal actinomycosis in a woman with active Crohn disease.

Laparoscopic Pancreaticoduodenectomy for the Management of Localized Crohn's Disease of the Duodenum.

PubMed

Xingjun, Guo; Feng, Zhu; Min, Wang; Renyi, Qin

2016-08-01

Crohn's disease of the duodenum is an uncommon condition. Our case was an extremely rare manifestation of Crohn's disease, who presented with obstruction of the pylorus and the first and the second parts of the duodenum. Because of the severity of the obstruction, he underwent laparoscopic pancreaticoduodenectomy. Postoperative pancreatic leakage and bowel fistula were not observed, and there was no morbidity during the follow-up period. There was also no disturbance in digestive function, postoperatively. This is the first case employing laparoscopic pancreaticoduodenectomy to cure benign lesions leading to duodenal obstruction. Minimally invasive laparoscopic pancreaticoduodenectomy technology shows a very big advantage in treating this rare benign Crohn's disease.

Crohn Disease of the Vulva without Gastrointestinal Manifestations in a 16-Year-Old Girl.

PubMed

Zhang, Ai-jun; Zhan, Shu-hui; Chang, Hong; Gao, Yu-qiang; Li, Yan-qing

2015-01-01

Crohn disease of the vulva is a rare disease that is difficult to diagnose. There are limited reports describing treatment of this condition. To describe the diagnosis and treatment of a 16-year-old girl with Crohn disease of the vulva, without onset of intestinal symptoms. Crohn disease was diagnosed by histopathology. The patient was treated with corticosteroids and followed for 1 year. After the final diagnosis, cutaneous lesions responded rapidly to corticosteroid treatment, which was gradually stopped after 6 months. The disease was well controlled at the 1-year follow-up. Crohn disease of the vulva can develop alone without the onset of intestinal symptoms. Diagnosis relies on special pathologic findings. Corticosteroid treatment is effective for this condition. © 2014 Canadian Dermatology Association.

Morbus sacer in Africa: some religious aspects of epilepsy in traditional cultures.

PubMed

Jilek-Aall, L

1999-03-01

Epilepsy when manifested as grand mal seizure provokes strong and ambivalent feelings in those witnessing it. Terms such as morbus sacer, denoting both a sacred and demoniac condition, or folk names indicating divine punishment, have expressed these feelings in European societies from antiquity to the Middle Ages and beyond. An atmosphere of fear, shame and mysticism surrounds epilepsy even in our days in many non-Western and also in Western cultures. In the course of work and studies in Tanzania, where I organized the Mahenge Clinic for Epilepsy in 1960, and in other parts of Africa, I found that epilepsy is conceived of as an "African'' affliction, a manifestation of supernatural forces that makes it difficult to reach epilepsy sufferers with modern medical treatment. Epilepsy is traditionally looked on as caused by ancestral spirits or attributed to possession by evil spirits. It is also thought to be due to witchcraft, and "poisoning," and often taken to be contagious. Epilepsy may, under Christian missionary teaching, have come to be considered as due to demoniac possession or divine punishment for sins, in accordance with biblical examples. In many parts of Africa, syncretic amalgamation of indigenous traditions with Judeo-Christian doctrines influenced popular attitudes toward epilepsy. We demonstrated that persistent efforts at health education in the context of organized treatment of epilepsy can result in a change of popular notions about epilepsy and consequently lead to significant improvement in the quality of life of epilepsy sufferers.

Surgical Treatment of Anorectal Crohn Disease

PubMed Central

Lewis, Robert T.; Bleier, Joshua I. S.

2013-01-01

Crohn disease involves the perineum and rectum in approximately one-third of patients. Symptoms can range from mild, including skin tags and hemorrhoids, to unremitting and severe, requiring a proctectomy in a small, but significant, portion. Fistula-in-ano and perineal sepsis are the most frequent manifestation seen on presentation. Careful diagnosis, including magnetic resonance imaging or endorectal ultrasound with examination under anesthesia and aggressive medical management, usually with a tumor necrosis factor-alpha, is critical to success. Several options for definitive surgical repair are discussed, including fistulotomy, fibrin glue, anal fistula plug, endorectal advancement flap, and ligation of intersphincteric fistula tract procedure. All suffer from decreased efficacy in patients with Crohn disease. In the presence of active proctitis or perineal disease, no surgical therapy other than drainage of abscesses and loose seton placement is recommended, as iatrogenic injury and poor wound healing are common in that scenario. PMID:24436656

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study

PubMed Central

Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

2016-01-01

Summary Background Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34 819 patients (19 713 with Crohn's disease, 14 683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype–phenotype associations across 156 154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. Findings After quality control, the primary analysis included 29 838 patients (16 902 with Crohn's disease, 12 597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for

Human Embryonic Stem Cell Therapy in Crohn's Disease: A Case Report.

PubMed

Shroff, Geeta

2016-02-29

Crohn's disease is a chronic inflammatory disease of the intestines, mainly the colon and ileum, related with ulcers and fistulae. It is estimated to affect 565,000 people in the United States. Currently available therapies, such as antibiotics, thiopurines, and anti-tumor necrosis factor-alpha agents, are only observed to reduce the complications associated with Crohn's disease and to improve quality of life, but cannot cure the disease. Stem cell therapy appears to have certain advantages over conventional therapies. Our study aimed to evaluate the efficacy of human embryonic stem cell therapy in a patient with Crohn's disease. A 21-year-old male with chief complaints of intolerance to specific foods, abdominal pain, and diarrhea underwent human embryonic stem cell therapy for two months. After undergoing human embryonic stem cell therapy, the patient showed symptomatic relief. He had no complaints of back pain, abdominal pain, or diarrhea and had improved digestion. The patient had no signs and symptoms of skin infection, and had improved limb stamina, strength, and endurance. The condition of patient was stable after the therapy. Human embryonic stem cell therapy might serve as a new optimistic treatment approach for Crohn's disease.

Design of a light delivery system for the photodynamic treatment of the Crohn's disease

NASA Astrophysics Data System (ADS)

Gabrecht, Tanja; Borle, Francois; van den Bergh, Hubert; Michetti, Pierre; Ortner, Maria-Anna; Wagnières, Georges

2007-07-01

Crohn's disease is an inflammatory bowel disease originating from an overwhelming response of the mucosal immune system. Low dose photodynamic therapy (PDT) may modify the mucosal immune response and thus serve as a therapy for Crohn's disease. Most patients with Crohn's disease show inflammatory reactions in the terminal ileum or colon where PDT treatment is feasible by low-invasive endoscopic techniques. However, the tube like geometry of the colon, it's folding, and the presences of multiple foci of Crohn's lesions along the colon require the development of adequate light delivery techniques. We present a prototype light delivery system for endoscopic clinical PDT in patients with Crohn's disease. The system is based on a cylindrical light diffuser inserted into a diffusing balloon catheter. Homogenous irradiation is performed with a 4 W diode laser at 635 nm. Light dosimetry is performed using a calibrated integrating sphere. The system can be used with conventional colonoscopes and colonovideoscopes having a 3.8 mm diameter working channel. The feasibility of PDT in colon with our prototype was demonstrated in first clinical trials.

Enterohepatic fistula in a Crohn's disease patient: A case report.

PubMed

Van Backer, Justin T; Lee, Edward C

2017-01-01

Fistulous tracts are a hallmark of Crohn's Disease. However, solid organ to intestinal fistulas are rare with previously few case reports of colosplenic fistulas and one case report of an enterohepatic fistula. We review the available literature and present the first case report of an enterohepatic fistula in a female with Crohn's Disease to be treated operatively. The patient did well postoperatively with complete resolution of her fistula. Crohn's Disease is an inflammatory bowel disease that can present with fistulas. However, a fistula between the liver and bowel is exceedingly rare with only one previous case report. This is the first report of an enteroheptic fistula that has been managed successfully with an operation. Not all enteroenteric fistulas are apparent preoperatively. When discovered, laparoscopic enterohepatic fistula takedown is feasible for this rare disease process manifestation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Which PCDAI Version Best Reflects Intestinal Inflammation in Pediatric Crohn Disease?

PubMed

Turner, Dan; Levine, Arie; Walters, Thomas D; Focht, Gili; Otley, Anthony; López, Victor Navas; Koletzko, Sibylle; Baldassano, Robert; Mack, David; Hyams, Jeffrey; Griffiths, Anne M

2017-02-01

There is increasing interest in measuring mucosal inflammation in Crohn disease (CD), but there are minimal data correlating the Pediatric Crohn's Disease Activity Index (PCDAI) versions (PCDAI, weighted Pediatric Crohn's Disease Activity Index [wPCDAI], abbreviated Pediatric Crohn's Disease Activity Index [abbrPCDAI], and the short Pediatric Crohn's Disease Activity Index [shPCDAI]) with mucosal inflammation. We aimed to compare the 4 PCDAI versions head to head with endoscopic degree of inflammation as measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD), fecal calprotectin, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and to explore cut-off values that are associated with mucosal healing. We used the prospectively collected data from the ImageKids study on 100 children with CD undergoing colonoscopy and from the Growth Relapse and Outcomes with Therapy study (n = 222), in which 145 children had calprotectin data at week 12 after diagnosis. All 4 PCDAI versions had fair correlation with the SES-CD (r = 0.42-0.45, all P < 0.001) and CRP (r = 0.32-0.45, all P < 0.01); the wPCDAI and PCDAI were superior to the shorter versions when comparing the blood tests. All versions had poor correlation with calprotectin, and only the wPCDAI reached significance (r = 0.26, P = 0.002 vs r = 0.15, P = 0.07 for PCDAI; r = 0.08, P = 0.37 for shPCDAI; r = 0.06, P = 0.5 for abbrPCDAI). The best cut-off to identify endoscopic mucosal healing was <12.5 points for the wPCDAI (sensitivity 58% and specificity 84%) and <10 for PCDAI (sensitivity 63% and specificity 77%). The more feasible wPCDAI and the PCDAI had comparable correlation with measures of endoscopic inflammation. These were slightly superior to the other 2 shorter versions, but still none of the PCDAI versions can give a valid assessment of mucosal healing.

Thalidomide induces mucosal healing in Crohn's disease: case report.

PubMed

Leite, Márcio Rios; Santos, Sandra Sousa; Lyra, André Castro; Mota, Jaciane; Santana, Genoile Oliveira

2011-12-07

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract that is defined by relapsing and remitting episodes. Tumor necrosis factor alpha (TNF-α) appears to play a central role in the pathophysiology of the disease. Standard therapies for inflammatory bowel disease fail to induce remission in about 30% of patients. Biological therapies have been associated with an increased incidence of infections, especially infection by Mycobacterium tuberculosis (Mtb). Thalidomide is an oral immunomodulatory agent with anti-TNF-α properties. Recent studies have suggested that thalidomide is effective in refractory luminal and fistulizing Crohn's disease. Thalidomide costimulates T lymphocytes, with greater effect on CD8+ than on CD4+ T cells, which contributes to the protective immune response to Mtb infection. We present a case of Crohn's disease with gastric, ileal, colon and rectum involvement as well as steroid dependency, which progressed with loss of response to infliximab after three years of therapy. The thorax computed tomography scan demonstrated a pulmonary nodule suspected to be Mtb infection. The patient was started on thalidomide therapy and exhibited an excellent response.

Genetic risk variants as therapeutic targets for Crohn's disease.

PubMed

Gabbani, Tommaso; Deiana, Simona; Marocchi, Margherita; Annese, Vito

2017-04-01

The pathogenesis of Inflammatory bowel diseases (IBD) is multifactorial, with interactions between genetic and environmental factors. Despite the existence of genetic factors being largely demonstrated by epidemiological data and several genetic studies, only a few findings have been useful in term of disease prediction, disease progression and targeting therapy. Areas covered: This review summarizes the results of genome-wide association studies in Crohn's disease, the role of epigenetics and the recent discovery by genetic studies of new pathogenetic pathways. Furthermore, it focuses on the importance of applying genetic data to clinical practice, and more specifically how to better target therapy and predict potential drug-related toxicity. Expert opinion: Some genetic markers identified in Crohn`s disease have allowed investigators to hypothesize about, and in some cases, prove the usefulness of new specific therapeutic agents. However, the heterogeneity and complexity of this disease has so far limited the daily clinical use of genetic information. Finally, the study of the implications of genetics on therapy, either to predict efficacy or avoid toxicity, is considered still to be in its infancy.

Effectiveness of infliximab after adalimumab failure in Crohn's disease.

PubMed

Chaparro, María; Andreu, Montserrat; Barreiro-de Acosta, Manuel; García-Planella, Esther; Ricart, Elena; Domènech, Eugeni; Esteve, María; Merino, Olga; Nos, Pilar; Peñalva, Mireia; Gisbert, Javier P

2012-10-07

To evaluate the effectiveness of infliximab as a second-line therapy in Crohn's disease patients after adalimumab failure. A historical cohort study in a community-based gastroenterology practice evaluated Crohn's disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). We included 15 Crohn's disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established.

Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease

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

Willing, B.; Halfvarson, J.; Dicksved, J.

2008-08-15

Large inter-individual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease. To reduce variations in exposure during establishment of the gut flora and influence of genotype, we studied the mucosaassociated microbiota of monozygotic twin pairs that were discordant (n=6) or concordant (n=4) for Crohn's disease. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal-restriction fragment length polymorphism, cloning and sequencing and quantitative real-time PCR. Themore » microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal Crohn's had a dramatically lower abundance (P<0.001) of Faecalibacterium prausnitzii and increased abundance (P<0.03) of Escherichia coli compared to healthy co-twins and those with Crohn's localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal Crohn's disease phenotype, distinct from colonic Crohn's disease and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of Crohn's and eventually customized treatment.« less

Medical Versus Interventional Treatment of Intra-Abdominal Abscess in Patients With Crohn Disease.

PubMed

Graham, Emily; Rao, Krishna; Cinti, Sandro

2017-01-01

Few studies exist to guide the treatment approach to intra-abdominal abscesses in Crohn disease, which can include antimicrobials alone or in conjunction with percutaneous drainage or surgery. The primary aim of this study is to review outcomes from different treatment approaches to intra-abdominal abscess in Crohn disease. Medical records were reviewed for patients admitted to the University of Michigan health care system with Crohn disease and intra-abdominal abscess over a 4-year period. Outcomes were compared among medical and interventional approaches. The χ 2 test was used to test for statistical significance. Of the 33 patients included, 13 were in the medical group and 20 were in the interventional group. Abscess recurrence/nonresolution occurred in 31% of patients in the medical group and 25% of patients in the interventional group ( P = .7). In this study, there was no significant difference in outcome between medical and interventional therapy for intra-abdominal abscess in Crohn disease.

Vedolizumab as a Treatment for Crohn's Disease and Ulcerative Colitis.

PubMed

Ha, Christina; Kornbluth, Asher

2014-12-01

The management of Crohn's disease and ulcerative colitis has become increasingly complex. With the current utilization of immunosuppressive therapies earlier in the disease course for patients presenting with moderate to severe disease, there is a great need for additional biologic agents targeting inflammatory mediators other than anti-tumor necrosis factor-α (anti-TNF) agents. Although anti-TNF agents have positively impacted the treatment of inflammatory bowel disease, many patients can lose their response or develop intolerance to these agents over time through the formation of antidrug antibodies. Furthermore, a sizeable percentage of patients are primary nonresponders to anti-TNF drugs. Vedolizumab (Entyvio, Takeda Pharmaceuticals), a monoclonal antibody to the α4β7 integrin, inhibits gut lymphocyte trafficking and has been demonstrated to be an effective and safe agent for the treatment of both Crohn's disease and ulcerative colitis. This article reviews the clinical trial evidence and rationale for the use of vedolizumab in moderate to severe Crohn's disease and ulcerative colitis.

Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.

PubMed

Cleynen, Isabelle; Boucher, Gabrielle; Jostins, Luke; Schumm, L Philip; Zeissig, Sebastian; Ahmad, Tariq; Andersen, Vibeke; Andrews, Jane M; Annese, Vito; Brand, Stephan; Brant, Steven R; Cho, Judy H; Daly, Mark J; Dubinsky, Marla; Duerr, Richard H; Ferguson, Lynnette R; Franke, Andre; Gearry, Richard B; Goyette, Philippe; Hakonarson, Hakon; Halfvarson, Jonas; Hov, Johannes R; Huang, Hailang; Kennedy, Nicholas A; Kupcinskas, Limas; Lawrance, Ian C; Lee, James C; Satsangi, Jack; Schreiber, Stephan; Théâtre, Emilie; van der Meulen-de Jong, Andrea E; Weersma, Rinse K; Wilson, David C; Parkes, Miles; Vermeire, Severine; Rioux, John D; Mansfield, John; Silverberg, Mark S; Radford-Smith, Graham; McGovern, Dermot P B; Barrett, Jeffrey C; Lees, Charlie W

2016-01-09

Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases. This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile. After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with

Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease.

PubMed

Fischer, Monika; Siva, Shivi; Cook, Gwendolyn K; Jones, David R; Fadda, Hala M

2017-05-01

Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlu n ) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlu n levels were measured in red blood cells (RBCs) using high-performance liquid chromatography-mass spectrometry. No association was observed between RBC individual (MTXGlu n ) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu 3+4+5 ) concentrations compared with those with active disease, a definitive association between RBC MTXGlu 3+4+5 levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlu n levels as indicators of treatment efficacy and clinical outcome. © 2016, The American College of Clinical Pharmacology.

Supplement of a chitosan and ascorbic acid mixture for Crohn's disease: a pilot study.

PubMed

Tsujikawa, Tomoyuki; Kanauchi, Osamu; Andoh, Akira; Saotome, Takao; Sasaki, Masaya; Fujiyama, Yoshihide; Bamba, Tadao

2003-02-01

Although the pathogenesis of Crohn's disease remains unclear, dietary fat is thought to exacerbate intestinal inflammation. Chitosan is a water-insoluble dietary fiber, and a chitosan and ascorbic acid mixture has been shown in rats to increase fecal fat excretion without affecting protein digestibility. However, it remains unclear whether a chitosan and ascorbic acid mixture is safe and effective for patients with Crohn's disease. We designed a pilot trial to investigate the tolerability and amount of fat excretion after the oral administration of a chitosan and ascorbic mixture for inactive Crohn's disease. Eleven outpatients were given seven tablets daily of a chitosan and ascorbic mixture (chitosan was given at 1.05 g/d) for 8 wk. Patients did not interrupt their respective therapies for Crohn's disease. The bowel movements of most patients increased slightly during the study. Nutritional and inflammatory markers in patients did not differ before and after treatment. The chitosan and ascorbic acid mixture significantly increased the fat concentration in the feces during treatment. These results indicated that oral administration of a chitosan and ascorbic acid mixture in patients with Crohn's disease is tolerable and increases fecal fat excretion without affecting disease activity.

Surgical recurrence in Crohn's disease: a comparison between different types of bowel resections.

PubMed

Aaltonen, Gisele; Carpelan-Holmström, Monika; Keränen, Ilona; Lepistö, Anna

2018-04-01

To compare recurrence frequency and location between different types of bowel resections in Crohn's disease patients. This was a retrospective study of consecutive patients undergoing bowel resection for Crohn's disease between 2006 and 2016. Type of primary operation was recorded and grouped as ileocolic resection, small bowel resection, segmental colon resection with colocolic anastomosis or colorectal anastomosis, colectomy with ileorectal anastomosis, or end stoma operation. Binary logistic regression was used to compare surgical recurrence frequency between groups. We also investigated how Crohn's disease location at reoperations was related to the primary bowel resection type. Altogether, 218 patients with a median follow-up of 4.7 years were included in our study. Reoperation was performed in 42 (19.3%) patients. The risk of reoperation using the ileocolic resection group as reference was the following: small bowel resection (odds ratio (OR) 2.95, 95% confidence interval (CI) 1.01-8.66; P = 0.049), segmental colon resection with colocolic or colorectal anastomosis (OR 6.20, 95% CI 2.04-18.87; P = 0.001), colectomy with ileorectal anastomosis (OR 26.57, 95% CI 2.59-273.01; P = 0.006), and end stoma operation (OR 4.62, 95% CI 1.90-11.26; P = 0.001). In case of surgical recurrence, the reoperation type and location correlated with the primary bowel resection type. Reoperation frequency in Crohn's disease is lower after ileocolic resection than after other types of bowel resections. Surgical recurrence in Crohn's disease tends to maintain the disease location of the primary operation. One third of Crohn's patients undergoing an end stoma operation will still need new bowel resections due to recurrence.

Possible association of cutaneous Rosai-Dorfman disease and chronic Crohn disease: a case series report.

PubMed

Salva, Katrin A; Stenstrom, Melissa; Breadon, Jonith Y; Odland, Paul Blair; Bennett, Daniel; Longley, Jack; Wood, Gary S

2014-02-01

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P<.001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease.

Possible Association of Cutaneous Rosai-Dorfman Disease and Chronic Crohn Disease A Case Series Report

PubMed Central

Salva, Katrin A.; Stenstrom, Melissa; Breadon, Jonith Y.; Odland, Paul Blair; Bennett, Daniel; Longley, Jack; Wood, Gary S.

2014-01-01

IMPORTANCE Cutaneous Rosai-Dorfman disease (CRDD), a variant of Rosai-Dorfman disease limited to the skin, has a wide range of clinical presentations. Rosai-Dorfman disease is believed to result from an aberrant response to antigens, caused by immunosuppressive macrophages. Macrophage-mediated immunosuppression is also implicated in the pathogenesis of Crohn disease, linking these otherwise unrelated entities. To our knowledge, the coexistence of these disorders has been described in only 2 cases, 1 of them confined to the skin and soft tissue. OBSERVATIONS We present a series of 3 patients who developed purely CRDD in the context of long-standing Crohn disease. Statistical estimates suggested that the association of these 2 disorders is not due to chance (P < .001). CONCLUSIONS AND RELEVANCE Our case series provides the clinical correlate to the pathogenetic parallels between CRDD and Crohn disease. Crohn disease is frequently complicated by various skin manifestations, which may be mimicked by CRDD. Therefore, it may be prudent for clinicians to include CRDD in the list of differential diagnoses when examining skin lesions in patients with Crohn disease. PMID:24305684

[Strictureplasty in the surgical treatment of complicated Crohn's disease].

PubMed

Sampietro, G M; Sartani, A; Danelli, P; Ghizzoni, M; Sposito, C; Maconi, G; Parente, E; Taschieri, A M

2003-01-01

Crohns disease is a panintestinal chronic inflammatory condition. Its remitting-relapsing behaviour may require in the single patient repeated surgeries, with the aim of resolving the complications of the disease. The awereness that surgery cannot resolve the disease has led, in the last years, to the development of new "conservative surgical techniques", which preserve as much of the intestinal tissue as possible. These techniques are minimal resection and strictureplasty (SP). Aim of the study was to perform a prospective analysis of the long-term outcome of SP in a consecutive series of patients undergoing surgery for complicated Crohns Disease at the Division of general surgery, L. Sacco University Hospital, Milano, Italia. During the period of October 1992 to June 2002, 286 patients underwent surgical procedures for jejunoileal Crohns disease. 116 of them underwent SP resulting in a total of 217 procedures, of which: 111 Heineke-Mikulicz SP (51.2%), 36 ileoileal side-to-side SP (16.6%), 40 ileoceacal SP (18.4%) and the remaining 30 ileocolic SP (13.8%), as previously described by A.M. Taschieri. Fiftyone of the patients (23.5%) had concomitantly a minimal bowel resection. Postoperative mortality was nil, while in 3 cases (2.59%) repeated surgery was necessary due to postsurgical complications. Time-to-event estimates were performed using the Kaplan-Meier function. mortality, morbidity, and long-term results in this population of patients who underwent SP are encouraging and in line with reports in the international literature. It is suggested that SP together with minimal bowel resections, may be considered as first line surgical therapy in patients with Crohns Disease.

Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review.

PubMed

Kawalec, Paweł

2016-04-01

Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem.

Indirect costs of inflammatory bowel diseases: Crohn's disease and ulcerative colitis. A systematic review

PubMed Central

2016-01-01

Introduction Crohn's disease and ulcerative colitis are lifelong illnesses which have a significant impact on quality of life and personal burden through a reduction in the ability to work, sick leave and restrictions of leisure time. The aim of this study was to conduct a systematic review of the indirect costs of Crohn's disease and ulcerative colitis. Material and methods The search was carried out in Medline, EMBASE, the Centre for Reviews and Dissemination, and reference lists of identified articles and reference lists of identified articles were also handsearched. All costs were adjusted to 2013 USD values by using the consumer price index and purchasing power parity. Identified studies were then analysed in order to assess their heterogeneity and possibility of inclusion in the meta-analysis. Results Eleven of the identified publications presented indirect costs of Crohn's disease or ulcerative colitis. The range of estimated yearly indirect costs per patient was large, from $1 159.09 for loss of earnings to $14 135.64 for lost productivity and sick leave for Crohn's disease. The values for ulcerative colitis ranged from $926.49 to $6 583.17. Because of the imprecise definition of methods of indirect cost calculations as well as heterogeneity of indirect cost components, a meta-analysis was not performed. Conclusions The indirect costs of ulcerative colitis seem to be slightly lower than in the case of Crohn's disease. A small number of studies referring to indirect costs of Crohn's disease and ulcerative colitis were identified, which indicates the need to conduct further investigations on this problem. PMID:27186172

A rare complication of CMV infection in Crohn's disease - hemophagocytic syndrome: a case report.

PubMed

Pop, Corina Silvia; Becheanu, Gabriel; Calagiu, Dorina; Jantea, Petruţa-Violeta; Rădulescu, Dragoş Mihai; Pariza, George; Mavrodin, Carmen-Iuliana; Bold, Adriana; Costache, Adrian; Nemeş, Roxana Maria

2015-01-01

We report a case of CMV (cytomegalovirus) infection in a Crohn's disease patient, resulting in severe hemophagocytic syndrome and death. A 63-year-old man with a 10-year history of ileal and colonic Crohn's disease presented with general malaise, loss of appetite and weight loss over the last month. He was in clinical remission for two years, with maintenance therapy 5-Aminosalicylic acid (5-ASA)-derived Mesalamine. The patient had no prior immunomodulators or suppressive treatment. A colonoscopy was performed and we found appearance suggestive of active Crohn's disease, confirmed by histopathological examination. A diagnosis of an exacerbation of Crohn's disease was established. Although the specific treatment was initiated, patient's general condition degraded progressively and diarrheal stools appeared, followed by an episode of massive gastrointestinal bleeding - hematochezia. We performed a new colonoscopy and the pathological examination revealed Crohn's ileocolitis with superimposed CMV infection. Despite the initiation of Ganciclovir alongside with other intensive care measures, he increasingly deteriorated and chest X-ray confirmed multilobar pneumonia. The occurrence of rapidly progressing pancytopenia and evidence for disseminated intravascular coagulopathy as well as hyperferritinemia, raised the suspicion of hemophagocytic syndrome confirmed by bone marrow aspiration. Hence, CMV-associated hemophagocytic syndrome in the context of recent corticotherapy for Crohn's disease was established. There is enough evidence that supports the gravity of the CMV infection in the case of inflammatory bowel disease (IBD) patients, especially the ones on immunomodulator treatment. The hemophagocytic syndrome reactively occurs in patients with infections in cases of immunodeficiency, displaying a hematological aspect of multiple organ dysfunction syndrome.

Risk of early surgery for Crohn's disease: implications for early treatment strategies.

PubMed

Sands, Bruce E; Arsenault, Joanne E; Rosen, Michael J; Alsahli, Mazen; Bailen, Laurence; Banks, Peter; Bensen, Steven; Bousvaros, Athos; Cave, David; Cooley, Jeffrey S; Cooper, Herbert L; Edwards, Susan T; Farrell, Richard J; Griffin, Michael J; Hay, David W; John, Alex; Lidofsky, Sheldon; Olans, Lori B; Peppercorn, Mark A; Rothstein, Richard I; Roy, Michael A; Saletta, Michael J; Shah, Samir A; Warner, Andrew S; Wolf, Jacqueline L; Vecchio, James; Winter, Harland S; Zawacki, John K

2003-12-01

In this study we aimed to define the rate of early surgery for Crohn's disease and to identify risk factors associated with early surgery as a basis for subsequent studies of early intervention in Crohn's disease. We assembled a retrospective cohort of patients with Crohn's disease diagnosed between 1991 and 1997 and followed for at least 3 yr, who were identified in 16 community and referral-based practices in New England. Chart review was performed for each patient. Details of baseline demographic and disease features were recorded. Surgical history including date of surgery, indication, and procedure were also noted. Risk factors for early surgery (defined as major surgery for Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of diagnosis) were identified by univariate analysis. Multiple logistic regression was used to identify independent risk factors. Of 345 eligible patients, 69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients (4.1%) who had major surgery at the time of diagnosis. Overall, the interval between diagnosis and surgery was short; one half of all patients who required surgery underwent operation within 6 months of diagnosis. Risk factors identified by univariate analysis as significantly associated with early surgery included the following: smoking; disease of small bowel without colonic involvement; nausea and vomiting or abdominal pain on presentation; neutrophil count; and steroid use in the first 6 months. Disease localized to the colon only, blood in the stool, use of 5-aminosalicylate, and lymphocyte count were inversely associated with risk of early surgery. Logistic regression confirmed independent associations with smoking as a positive risk factor and involvement of colon without small bowel as a negative risk factor for early surgery. The rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease, particularly in the first 6 months. These results suggest that

Linkage analyses of chromosome 6 loci, including HLA, in familial aggregations of Crohn disease

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

Hugot, J.P.; Laurent-Puig, P.; Gower-Rousseau, C.

1994-08-15

Segregation analyses of familial aggregations of Crohn disease have provided consistent results pointing to the involvement of a predisposing gene with a recessive mode of inheritance. Although extensively investigated, the role played by human leucocyte antigen (HLA) genes in this inflammatory bowel disease remains elusive and the major histocompatibility complex is a candidate region for the mapping of the Crohn disease susceptibility gene. A total of 25 families with multiple cases of Crohn disease was genotyped for HLA DRB1 and for 16 highly polymorphic loci evenly distributed on chromosome 6. The data were subjected to linkage analysis using the lodmore » score method. Neither individual nor combined lod scores for any family and for any locus tested reached values suggesting linkage or genetic heterogeneity. The Crohn disease predisposing locus was excluded from the whole chromosome 6 with lod scores less than -2. It was excluded from the major histocompatibility complex and from 91% of the chromosome 6 genetic map with lod scores less than -4. The major recessive gene involved in genetic predisposition to Crohn disease does not reside on the major histocompatibility complex nor on any locus mapping to chromosome 6. 37 refs., 2 figs., 2 tabs.« less

Bowel Thickening in Crohn's Disease: Fibrosis or Inflammation? Diagnostic Ultrasound Imaging Tools.

PubMed

Coelho, Rosa; Ribeiro, Helena; Maconi, Giovanni

2017-01-01

The high frequency of intestinal strictures in patients with Crohn's disease and the different treatment approaches specific for each type of stenosis make the differentiation between fibrotic and inflammatory strictures crucial in management of the disease. However, there is no standardized approach to evaluate and discriminate intestinal strictures, and until now, there was no established cross-sectional imaging modality to detect fibrosis. New techniques, such as contrast-enhanced ultrasound and sonoelastography allow the assessment of vascularization and mechanical properties of stenotic bowel tissue, respectively. These techniques have shown great potential to characterize strictures in Crohn's disease. The aim of this review is to sum up the current knowledge on bowel ultrasound tools to discriminate inflammatory from fibrotic stenosis in Crohn's disease considering the most recent published studies in the field.

Dietary Fiber Intake is Associated with Increased Colonic Mucosal GPR43+ Polymorphonuclear Infiltration in Active Crohn's Disease.

PubMed

Zhao, Mingli; Zhu, Weiming; Gong, Jianfeng; Zuo, Lugen; Zhao, Jie; Sun, Jing; Li, Ning; Li, Jieshou

2015-07-01

G protein-coupled receptor 43/free fatty acid receptor 2 (GPR43/FFAR2) is essential for polymorphonuclear (PMN) recruitment. We investigated the expression of GPR43/FFAR2 in the colon from Crohn's disease patients and whether dietary fiber in enteral nutrition increases GPR43+ polymorphonuclear infiltration in mucosa. Segments of ascending colon and white blood cells from peripheral blood were obtained from 46 Crohn's disease patients and 10 colon cancer patients. The Crohn's disease patients were grouped by the activity of disease (active or remission) and enteral nutrition with or without dietary fiber. Histological feature, expression and location of GPR43/FFAR2 and level of tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and myeloperoxidase were assessed. The results of hematoxylin-eosin and immunohistochemistry staining revealed that the infiltration of immune cells, including GPR43+ PMN, was more severe in active Crohn's disease patients who consumed normal food or enteral nutrition with dietary fiber than in remission patients and colon cancer patients. This finding was supported by the results of GPR43 and myeloperoxidase expression. Active Crohn's disease (CD) patients who consumed enteral nutrition without dietary fiber exhibited severe immune cell infiltration similar to the other active CD patients, but GPR43+ PMNs were rarely observed. The level of TNF-α mRNA in active Crohn's disease patients was higher than those of the other patients. In conclusion, the use of dietary fiber in enteral nutrition by active Crohn's disease patients might increase GPR43+ PMNs infiltration in colon mucosa. This effect was not observed in Crohn's disease patients in remission.

Deficiency of interstitial cells of Cajal in the small intestine of patients with Crohn's disease.

PubMed

Porcher, Christophe; Baldo, Marjolaine; Henry, Monique; Orsoni, Pierre; Julé, Yvon; Ward, Sean M

2002-01-01

Interstitial cells of Cajal are critical for the generation of electrical slow waves that regulate the phasic contractile activity of the tunica muscularis of the GI tract. Under certain pathophysiological conditions loss of interstitial cells of Cajal may play a role in the generation of certain motility disorders. The aim of the present study was to determine if there is an abnormality in the density or distribution of interstitial cells of Cajal from patients with Crohn's disease. Small intestines from control subjects and patients with Crohn's disease were examined using immunohistochemistry and antibodies against the Kit receptor, which is expressed in interstitial cells of Cajal within the tunica muscularis of the GI tract. The density and distribution of interstitial cells of Cajal were assessed in the longitudinal and circular muscle layers and in the myenteric and deep muscular plexus regions of Crohn's and control tissues. Tissues from Crohn's disease patients showed an almost complete abolition of interstitial cells of Cajal within the longitudinal and circular muscle layers and a significant reduction in numbers at the level of the myenteric and deep muscular plexuses. In tissues from Crohn's disease patients, the density of interstitial cells of Cajal was reduced throughout the tunica muscularis in comparison to control small intestines. The disturbance of intestinal motility that occurs in patients with Crohn's disease may be a consequence of the loss of or defects in specific populations of interstitial cells of Cajal within the tunica muscularis.

The effects of physical exercise on patients with Crohn's disease.

PubMed

Loudon, C P; Corroll, V; Butcher, J; Rawsthorne, P; Bernstein, C N

1999-03-01

Despite the suggested benefits of exercise training in the prevention and management of chronic diseases, few data exist regarding the safety of exercise in Crohn's disease and whether or not exercise may have beneficial effects on patients' health. We performed a pilot study to evaluate the effects of regular light-intensity exercise on sedentary patients with Crohn's disease. Sedentary patients with inactive or mildly active Crohn's disease were eligible for the study. A thrice-weekly, 12-wk walking program was supervised, although if subjects could not attend the group walking sessions they were allowed to walk on their own. Logbooks of performance were maintained, and individual exercise heart rate goals were established. Measures performed at baseline and at study completion included the Inflammatory Bowel Disease Stress Index, the Inflammatory Bowel Disease Quality of Life Score, the Harvey and Bradshaw Simple Index, the Canadian Aerobic Fitness Test, VO2 Max, and body mass index (BMI). Twelve subjects completed the 12-wk exercise program. Subjects walked an average of 2.9 sessions/wk, at an average of 32.6 min/session, and for an average distance of 3.5 km/session. Statistically significant improvements at study end were seen by all measures, with a trend toward reduction in BMI. No patient's disease flared during the study. Sedentary patients with Crohn's disease can tolerate low-intensity exercise of moderate duration without an exacerbation of symptoms. Twelve weeks of walking was adequate to elicit psychological and physical improvements and did not adversely affect disease activity.

Multifocal choroiditis - an unusual finding in Crohns disease.

PubMed

Vianna, R N G; Ozdal, P C; Deschnes, J

To report a patient with Crohns disease and acute decreased vision in one eye secondary to multifocal choroiditis and serous retinal detachment. A complete ocular examination, including fluorescein angiography, was performed. Fundus biomicroscopy disclosed multifocal, deep, discretely elevated yellowish lesions at the posterior pole of the affected eye. Fluorescein angiographic study of these lesions revealed early hypofluorescence followed by late yperfluorescence. Subtenonian injection of corticosteroids rapidly induced remission of the choroidal lesions. Chorioretinal involvement in patients with Crohns disease may or may not be related to reactivation of this disorder. Therefore, even patients without gastrointestinal symptoms who present with posterior segment inflammation must be informed of this. The chorioretinal inflammatory lesions do seem to respond promptly to periocular injection of corticosteroids. (Eur J Ophthalmol 2004; 14: 345-9).

Computed tomography in the evaluation of Crohn disease

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

Goldberg, H.I.; Gore, R.M.; Margulis, A.R.

1983-02-01

The abdominal and pelvic computed tomographic examinations in 28 patients with Crohn disease were analyzed and correlated with conventional barium studies, sinograms, and surgical findings. Mucosal abnormalities such as aphthous lesions, pseudopolyps, and ulcerations were only imaged by conventional techniques. Computed tomography proved superior in demonstrating the mural, serosal, and mesenteric abnormalities such as bowel wall thickening (82%), fibrofatty proliferation of mesenteric fat (39%), mesenteric abscess (25%), inflammatory reaction of the mesentery (14%), and mesenteric lymphadenopathy (18%). Computed tomography was most useful clinically in defining the nature of mass effects, separation, or displacement of small bowel segments seen on smallmore » bowel series. Although conventional barium studies remain the initial diagnostic procedure in evaluating Crohn disease, computed tomography can be a useful adjunct in resolving difficult clinical and radiologic diagnostic problems.« less

Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn's disease: a prospective study.

PubMed

Ryan, B M; Russel, M G V M; Schurgers, L; Wichers, M; Sijbrandij, J; Stockbrugger, R W; Schoon, E

2004-10-15

Patients with Crohn's disease are at increased risk of osteoporosis. Disease activity and circulating proinflammatory cytokines are thought to play a role in this process. Infliximab, a chimaeric antitumour necrosis factor-alpha antibody is effective in the treatment of Crohn's disease. The aim of this study was to investigate the impact of treatment with infliximab on bone turnover in Crohn's disease patients. This was a prospective trial. Twenty-four patients with active Crohn's disease were treated with infliximab (5 mg/kg). Bone markers were assayed pre- and post-treatment. Bone formation was measured using serum bone-specific alkaline phosphatase and total osteocalcin and bone resorption using serum N-telopeptide cross-linked type 1 collagen. Infliximab therapy caused a significant increase in both markers of bone formation in patients with active Crohn's disease. No significant change in the bone resorption marker serum N-telopeptide cross-linked type 1 was found. Infliximab therapy had a significant beneficial effect on bone metabolism in patients with active Crohn's disease. These findings further support the theory that active ongoing inflammation and high levels of circulating cytokines play a pivotal role in the pathogenesis of bone loss in patients with Crohn's disease.

Crohn disease

PubMed Central

Stappenbeck, Thaddeus S.; Rioux, John D.; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J.

2011-01-01

Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract.1 Prevalence in western populations is 100–150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk. PMID:20729636

Small bowel adenocarcinoma in Crohn disease: CT-enterography features with pathological correlation.

PubMed

Soyer, Philippe; Hristova, Lora; Boudghène, Frank; Hoeffel, Christine; Dray, Xavier; Laurent, Valérie; Fishman, Elliot K; Boudiaf, Mourad

2012-06-01

The aim of this study was to analyze the clinical, pathological, and CT-enterography findings of small bowel adenocarcinomas in Crohn disease patients. Clinical, histopathological, and imaging findings were retrospectively evaluated in seven Crohn disease patients with small bowel adenocarcinoma. CT-enterography examinations were reviewed for morphologic features and location of tumor, presence of stratification, luminal stenosis, proximal dilatation, adjacent lymph nodes, and correlated with findings at histological examination. The tumor was located in the terminal (n = 6) or distal (n = 1) ileum. On CT-enterography, the tumor was visible in five patients, whereas two patients had no visible tumor. Four different patterns were individualized including small bowel mass (n = 2), long stenosis with heterogeneous submucosal layer (n = 2), short and severe stenosis with proximal small bowel dilatation (n = 2), and sacculated small bowel loop with irregular and asymmetric circumferential thickening (n = 1). Stratification, fat stranding, and comb sign were present in two, two, and one patients, respectively. Identification of a mass being clearly visible suggests strongly the presence of small bowel adenocarcinoma in Crohn disease patients but adenocarcinoma may be completely indistinguishable from benign fibrotic or acute inflammatory stricture. Knowledge of these findings is critical to help suggest the diagnosis of this rare but severe complication of Crohn disease.

Periodontal disease and anemias associated with Crohn's disease. A case report.

PubMed

Nagpal, Swati; Acharya, Anirudh B; Thakur, Srinath L

2012-03-01

Crohn's disease (CD) is an inflammatory bowel disease with oral findings, including periodontal manifestations. Anemias, such as iron deficiency and anemia of chronic disease (ACD), are the most common hematologic complications of CD. Periodontitis has systemic effects, and may tend toward anemia, which can be explained by depressed erythropoiesis. In the report presented here, the authors review a case of Crohn's disease diagnosed 10 years previous to the patient presenting with a changing anemic profile and periodontal disease. A discussion of patient and disease management is included.

Treatment of Crohn's disease with cannabis: an observational study.

PubMed

Naftali, Timna; Lev, Lihi Bar; Yablecovitch, Doron; Yablekovitz, Doron; Half, Elisabeth; Konikoff, Fred M

2011-08-01

The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn's disease (CD) was ever published. To describe the effects of cannabis use in patients suffering from CD. In this retrospective observational study we examined disease activity, use of medication, need for surgery, and hospitalization before and after cannabis use in 30 patients (26 males) with CD. Disease activity was assessed by the Harvey Bradshaw index for Crohn's disease. Of the 30 patients 21 improved significantly after treatment with cannabis. The average Harvey Bradshaw index improved from 14 +/- 6.7 to 7 +/- 4.7 (P < 0.001). The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use. This is the first report of cannabis use in Crohn's disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.

Pathogenesis of Crohn's disease

PubMed Central

Boyapati, Ray; Satsangi, Jack

2015-01-01

Significant progress in our understanding of Crohn's disease (CD), an archetypal common, complex disease, has now been achieved. Our ability to interrogate the deep complexities of the biological processes involved in maintaining gut mucosal homeostasis is a major over-riding factor underpinning this rapid progress. Key studies now offer many novel and expansive insights into the interacting roles of genetic susceptibility, immune function, and the gut microbiota in CD. Here, we provide overviews of these recent advances and new mechanistic themes, and address the challenges and prospects for translation from concept to clinic. PMID:26097717

Autologous Hematopoetic Stem Cell Transplantation for Refractory Crohn Disease: A Randomized Clinical Trial.

PubMed

Hawkey, Christopher J; Allez, Matthieu; Clark, Miranda M; Labopin, Myriam; Lindsay, James O; Ricart, Elena; Rogler, Gerhard; Rovira, Montserrat; Satsangi, Jack; Danese, Silvio; Russell, Nigel; Gribben, John; Johnson, Peter; Larghero, Jerome; Thieblemont, Catherine; Ardizzone, Sandro; Dierickx, Daan; Ibatici, Adalberto; Littlewood, Timothy; Onida, Francesco; Schanz, Urs; Vermeire, Severine; Colombel, Jean-Frederic; Jouet, Jean-Paul; Clark, Elizabeth; Saccardi, Riccardo; Tyndall, Alan; Travis, Simon; Farge, Dominique

2015-12-15

Case reports and series suggest hematopoietic stem cell transplantation (HSCT) may benefit some patients with Crohn disease. To evaluate the effect of autologous HSCT on refractory Crohn disease. Parallel-group randomized clinical trial conducted in 11 European transplant units from July 2007 to September 2011, with follow-up through March 2013. Patients were aged 18 to 50 years with impaired quality of life from refractory Crohn disease not amenable to surgery despite treatment with 3 or more immunosuppressive or biologic agents and corticosteroids. All patients underwent stem cell mobilization before 1:1 randomization to immunoablation and HSCT (n = 23) or control treatment (HSCT deferred for 1 year [n = 22]). All were given standard Crohn disease treatment as needed. Sustained disease remission at 1 year, a composite primary end point comprising clinical remission (Crohn Disease Activity Index (CDAI) <150 [range, 0-600]), no use of corticosteroids or immunosuppressive or biologic drugs for at least the last 3 months, and no endoscopic or radiological evidence of active (erosive) disease anywhere in the gastrointestinal (GI) tract. Secondary outcomes were individual components of the primary composite outcome and other measures of disease activity, laboratory results, quality of life and functional status, and GI tract imaging. Twenty-three patients underwent HSCT and 22 received standard Crohn disease treatment (controls). Sustained disease remission was achieved in 2 patients undergoing HSCT (8.7%) vs 1 control patient (4.5%) (absolute difference, 4.2% [95% CI, -14.2% to 22.6%]; P = .60). Fourteen patients undergoing HSCT (61%) vs 5 control patients (23%) had discontinued immunosuppressive or biologic agents or corticosteroids for at least 3 months (difference, 38.1% [95% CI, 9.3% to 59.3%]; P = .01). Ten vs 2 patients had a CDAI less than 150 (remission) at the final evaluation, 8 (34.8%) vs 2 (9.1%) for 3 or more months (difference, 25.7% [95

Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn's disease.

PubMed

Lang, B M; Biedermann, L; van Haaften, W T; de Vallière, C; Schuurmans, M; Begré, S; Zeitz, J; Scharl, M; Turina, M; Greuter, T; Schreiner, P; Heinrich, H; Kuntzen, T; Vavricka, S R; Rogler, G; Beerenwinkel, N; Misselwitz, B

2018-01-01

Smoking is a strong environmental factor leading to adverse outcomes in Crohn's disease, but a more benign course in ulcerative colitis. Several single nucleotide polymorphisms (SNPs) are associated with smoking quantity and behaviour. To assess whether smoking-associated SNPs interact with smoking to influence the clinical course of inflammatory bowel diseases. Genetic and prospectively obtained clinical data from 1434 Swiss inflammatory bowel disease cohort patients (821 Crohn's disease and 613 ulcerative colitis) were analysed. Six SNPs associated with smoking quantity and behaviour (rs588765, rs1051730, rs1329650, rs4105144, rs6474412 and rs3733829) were combined to form a risk score (range: 0-12) by adding the number of risk alleles. We calculated multivariate models for smoking, risk of surgery, fistula, Crohn's disease location and ulcerative colitis disease extent. In Crohn's disease patients who smoke, the number of surgeries was associated with the genetic risk score. This translates to a predicted 3.5-fold (95% confidence interval: 2.4- to 5.7-fold, P<.0001) higher number of surgical procedures in smokers with 12 risk alleles than individuals with the lowest risk. Patients with a risk score >7 had a significantly shorter time to first intestinal surgery. The genetic risk score did not predict surgery in ulcerative colitis or occurrence of fistulae in Crohn's disease. SNP rs6265 was associated with ileal disease in Crohn's disease (P<.05) and proctitis in ulcerative colitis (P<.05). SNPs associated with smoking quantity is associated with an increased risk for surgery in Crohn's disease patients who smoke. Our data provide an example of genetics interacting with the environment to influence the disease course of inflammatory bowel disease. © 2017 John Wiley & Sons Ltd.

Crohn's disease of the esophagus: treatment of an esophagobronchial fistula with the novel liquid embolic polymer "onyx".

PubMed

Rieder, F; Hamer, O; Gelbmann, C; Schölmerich, J; Gross, V; Feuerbach, S; Herfarth, H; Rogler, G

2006-07-01

Esophageal involvement in Crohn's disease is very rare. In only a small subgroup of these patients -- up to date fourteen cases have been described in the literature -- the course of the illness may be complicated by esophageal fistula formation. The therapy for fistulizing esophageal Crohn's disease so far has been disappointing, recurrence and progression are likely, and surgery still is the primary treatment modality for refractory patients. We here present a case of severe Crohn's disease with an esophagobronchial fistula and the successful closure of the fistula tract with the novel liquid polymer sealant "Onyx". This approach offers a new option for the treatment of this rare complication of Crohn's disease and should be considered if surgery is not possible.

Measuring patients' satisfaction with their anti-TNF treatment in severe Crohn's disease: scoring and psychometric validation of the Satisfaction for PAtients in Crohn's diseasE Questionnaire (SPACE-Q(©)).

PubMed

Gilet, Hélène; Arnould, Benoit; Fofana, Fatoumata; Clerson, Pierre; Colombel, Jean-Frédéric; D'Hondt, Olivier; Faure, Patrick; Hagège, Hervé; Nachury, Maria; Nahon, Stéphane; Tucat, Gilbert; Vandromme, Luc; Cazala-Telinge, Ines; Thibout, Emmanuel

2014-01-01

Severe Crohn's disease management includes anti-tumor necrosis factor (anti-TNF) drugs that differ from early-stage treatments regarding efficacy, safety, and convenience. This study aimed to finalize and psychometrically validate the Satisfaction for PAtients in Crohn's diseasE Questionnaire (SPACE-Q(©)), developed to measure satisfaction with anti-TNF treatment in patients with severe Crohn's disease. A total of 279 patients with severe Crohn's disease receiving anti-TNF therapy completed the SPACE-Q 62-item pilot version at inclusion and 12 and 13 weeks after first anti-TNF injection. The final SPACE-Q scoring was defined using multitrait and regression analyses and clinical relevance considerations. Psychometric validation included clinical validity against Harvey-Bradshaw score, concurrent validity against Treatment Satisfaction Questionnaire for Medication (TSQM), internal consistency reliability, test-retest reliability, and responsiveness against the patient global impression of change (PGIC). Quality of completion was good (55%-67% of patients completed all items). Four items were removed from the questionnaire. Eleven scores were defined within the final 58-item SPACE-Q: disease control; symptoms, anal symptoms, and quality of life transition scales; tolerability; convenience; expectation confirmation toward efficacy, side effects, and convenience; satisfaction with treatment; and motivation. Scores met standards for concurrent validity (correlation between SPACE-Q satisfaction with treatment and TSQM satisfaction scores =0.59), internal consistency reliability (Cronbach's α=0.67-0.93), test-retest reliability (intraclass correlations =0.62-0.91), and responsiveness (improvement in treatment experience assessed by the SPACE-Q for patients reporting improvement on the PGIC). Significantly different mean scores were observed between groups of patients with different Harvey-Bradshaw disease severity scores. The SPACE-Q is a valid, reliable, and responsive

Comparative studies of mononuclear phagocyte function in patients with Crohn's disease and colon neoplasms.

PubMed Central

Beeken, W L; St Andre-Ukena, S; Gundel, R M

1983-01-01

Phagocytosis and cellular cytotoxicity by mononuclear phagocytes of blood and intestinal mucosa were studied in patients with Crohn's disease and large bowel neoplasms. Antibody coated sheep erythrocytes were used for phagocytic assays and cellular cytotoxicity in vitro was measured by 24 hour isotope release from 75Selenium methionine-labelled RPMI 4788 human cancer cell cultures in the presence of mononuclear phagocyte-enriched effector populations. The mean percent of mononuclear phagocytes in Ficoll-Hypaque purified mononuclear cell suspensions of blood of healthy controls was 25.9 compared with 44.6 in patients with Crohn's disease, 45.6 in patients with colon neoplasms and 11.6 in intestinal mucosa. Phagocytic indices were similar in all groups, but the phagocytic capacity of mucosal macrophages was twice that of blood monocytes. Mean cytotoxicity of monocytes of patients with Crohn's disease was 12.8% compared with 22.9% for monocytes from normal controls, and 29.4% for patients with colon tumours. Mean cytotoxicity by mucosal macrophages was 18.0% compared with 13.2% by mucosal lymphocyte populations. Exposure of monocytes of Crohn's disease patients to bacterial lipopolysaccharide modestly increased cytotoxicity, but exposure did not alter phagocytosis by monocytes of patients or controls. The results indicate that monocytes of patients with Crohn's disease exhibit subnormal in vitro cytotoxicity. Mucosal macrophages from patients with various diseases show enhanced phagocytosis compared with blood monocytes, and they can mediate cellular cytotoxicity in vitro. PMID:6629113

Systematic review: has disease outcome in Crohn's disease changed during the last four decades?

PubMed

Wolters, F L; Russel, M G V M; Stockbrügger, R W

2004-09-01

Disease outcome in Crohn's disease might have changed during the last four decades. Disease outcome measurement in Crohn's disease has methodological difficulties because of patient selection and lack of proper definition of diagnostic and outcome measurement criteria. To assess possible changes in disease outcome in Crohn's disease during the last four decades. A systematic literature search was performed using the MEDLINE search engine and major international conference libraries. Articles and abstracts were selected according to stringent inclusion criteria. Forty articles and nine abstracts complied with the inclusion criteria. Seven studies with a median follow-up time between 11.1 and 17 years showed standard mortality ratios in Crohn's disease ranging between 2.16 and 0.72 with a tendency of decline during the last four decades. One study with 11.4 years mean follow-up time showed a statistically significant increased relative risk for colorectal cancer that was not confirmed by three others. Sixteen publications applied in the disease recurrence category. Probability of first resective surgery ranged between 38 and 96% during the first 15 years after diagnosis. The overall recurrence and surgical recurrence rates after first resective surgery ranged between 50 and 60, and 28 and 45% respectively during the following 15 years without an apparent time trend. This structured literature review provides no hard evidence for change in disease outcome in Crohn's disease during the last four decades. Copyright 2004 Blackwell Publishing Ltd

Pediatric Small Bowel Crohn Disease: Correlation of US and MR Enterography

PubMed Central

Smith, Ethan A.; Sanchez, Ramon J.; DiPietro, Michael A.; DeMatos-Maillard, Vera; Strouse, Peter J.; Darge, Kassa

2015-01-01

Small bowel Crohn disease is commonly diagnosed during the pediatric period, and recent investigations show that its incidence is increasing in this age group. Diagnosis and follow-up of this condition are commonly based on a combination of patient history and physical examination, disease activity surveys, laboratory assessment, and endoscopy with biopsy, but imaging also plays a central role. Ultrasonography (US) is an underutilized well-tolerated imaging modality for screening and follow-up of small bowel Crohn disease in children and adolescents. US has numerous advantages over computed tomographic (CT) enterography and magnetic resonance (MR) enterography, including low cost and no required use of oral or intravenous contrast material. US also has the potential to provide images with higher spatial resolution than those obtained at CT enterography and MR enterography, allows faster examination than does MR enterography, does not involve ionizing radiation, and does not require sedation or general anesthesia. US accurately depicts small bowel and mesenteric changes related to pediatric Crohn disease, and US findings show a high correlation with MR imaging findings in this patient population. ©RSNA, 2015 PMID:25839736

[Current position on Vedolizumab for ulcerative colitis and Crohn's disease].

PubMed

Schreiber, S; Dignass, A U; Hartmann, H; Kruis, W; Rogler, G; Siegmund, B; Stallmach, A; Witte, C; Bokemeyer, B

2015-06-01

Vedolizumab, the first drug in the class of anti-integrin molecules, is newly approved for ulcerative colitis and Crohn's disease and can be prescribed in Germany since mid-2014. By a specific receptor binding a relatively gut-selective mode of action was achieved without the known side effects of the systemic immunosuppression of the anti-TNF-alpha antibodies. According to the present data the safety profile of Vedolizumab appears to be more favorable than that of the anti-TNF- alpha therapy. Vedolizumab is suitable for induction therapy in patients with ulcerative colitis and Crohn's disease, however the kinetic of response compared with the anti-TNF-alpha antibodies seems to be slower. For maintenance therapy the Vedolizumab data show a deep and sustained remission in patients initially responding to induction therapy with a lower loss of efficacy in the long-term treatment known from the anti-TNF-alpha therapy. On the basis of currently available data the efficacy of Vedolizumab in ulcerative colitis appears to be slightly better than in Crohn's disease. © Georg Thieme Verlag KG Stuttgart · New York.

Atorvastatin Reduces Plasma Levels of Chemokine (CXCL10) in Patients with Crohn's Disease

PubMed Central

Grip, Olof; Janciauskiene, Sabina

2009-01-01

Background In Crohn's disease high tissue expression and serum levels of chemokines and their receptors are known to correlate with disease activity. Because statins can reduce chemokine expression in patients with coronary diseases, we wanted to test whether this can be achieved in patients with Crohn's disease. Methodology/Principal Findings We investigated plasma levels of chemokines (CCL2, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26, CXCL8, CXCL10) and endothelial cytokines (sP-selectin, sE-selectin, sICAM-3, thrombomodulin) in ten Crohn's disease patients before and after thirteen weeks' daily treatment with 80 mg atorvastatin. Of the 13 substances investigated, only CXCL10 was found to be significantly reduced (by 34%, p = 0.026) in all of the treated patients. Levels of CXCL10 correlated with C-reactive protein (r = 0.82, p<0.01). Conclusions/Significance CXCL10 is a ligand for the CXCR3 receptor, the activation of which results in the recruitment of T lymphocytes and the perpetuation of mucosal inflammation. Hence the reduction of plasma CXCL10 levels by atorvastatin may represent a candidate for an approach to the treatment of Crohns disease in the future. Trial Registration ClinicalTrials.gov NCT00454545 PMID:19421322

[Environmental risk factors in Crohn's disease and ulcerative colitis (excluding tobacco and appendicectomy)].

PubMed

Jantchou, Prévost; Monnet, Elisabeth; Carbonnel, Franck

2006-01-01

A rapid increase in the incidence of Crohn's disease and ulcerative colitis in developed countries, the occurrence of Crohn's disease in spouses, and a lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Research in the field of environmental factors in IBD is based upon epidemiological (geographical and case-control), clinical and experimental studies. The role of two environmental factors has clearly been established in IBD. Smoking is a risk factor for Crohn's disease and a protective factor for ulcerative colitis; appendectomy is a protective factor for ulcerative colitis. Many other environmental factors for IBD have been investigated, including infectious agents, diet, drugs, stress and social status. They are detailed in the present review. Among them, atypical Mycobacteria, oral contraceptives and antibiotics could play a role in Crohn's disease. To date, three hypotheses associate environmental factors with the pathophysiology of IBD (loss of tolerance of intestinal immune system towards commensal bacterial flora): the hygiene, infection and cold chain hypotheses. Much work remains to be done to identify risk factors for IBD. Research identifying environmental factors that might cause a predisposition to IBD is useful. It may lead to disease prevention in subjects who are genetically predisposed and disease improvement in patients.

Crohns disease: a case report.

PubMed

Adi, Ashindoitiang John; Lloyd, Geoffrey J

2010-01-01

Inflammatory bowel disease (IBD) was previously regarded as a disease of the Western Countries. A number of studies showed a high incidence and prevalence of inflammatory bowel disease in United States, United Kingdom and Northern Europe, whereas it was considered uncommon in Asians population and rare in Africa. To report case of crohns disease that is rare in the tropic like Nigeria so as to create a high index of awareness that inflammatory bowel disease may be present but not correctly diagnosed

The cost of hospitalization in Crohn's disease.

PubMed

Cohen, R D; Larson, L R; Roth, J M; Becker, R V; Mummert, L L

2000-02-01

The aim of this study was to evaluate the demographics, resource use, and costs associated with hospitalization of Crohn's disease patients. All patients hospitalized at our institution from 7/1/96 to 6/30/97 with a primary diagnosis of "Crohn's Disease" were analyzed using a computerized database. Data are presented "per hospitalization." A total of 175 hospitalizations (147 patients) were identified. Mean patient age was 36.5 yr; 61% were female; 82% Caucasian. Payer mix was most commonly contracted (57%), commercial (21%), or Medicare (13%). 57% of hospitalizations had a primary surgical procedure; the remainder were medical. Average length of stay was 8.7 days (surgical, 9.6 days; medical, 7.5 days). The average cost of hospitalization, excluding physician fees, was $12,528 (surgical, $14,409; medical, $10,020), whereas average charges were $35,378 (surgical, $46,354; medical, $20,744), including physician fees, which averaged $7,249 (surgical, $11,217; medical, $1,959). Mean reimbursements were $21,968 (surgical, $28,946; medical, $12,666) with average weighted reimbursement rates of 60.17% of hospital charges, 69.57% of physician fees. The distribution of costs across subcategories was: Surgery (39.6%), Pharmacy (18.6%), Laboratory (3.8%), Radiology (2.1%), Pathology (0.8%), Endoscopy (0.3%), and Other Hospital Costs (34.9%). Of the hospitalizations, 87% included treatment with steroids, 23% with immunomodulators, and 14% with aminosalicylates; 27% included the administration of total parenteral nutrition, which accounted for 63% of the total pharmacy costs. Surgery accounts for the majority of hospitalizations, nearly 40% of their total costs, and 75% of overall charges and reimbursements. Therapy that decreases the number of surgical hospitalizations should substantially reduce inpatient Crohn's disease costs, as well as overall costs.

Colorectal cancer in Crohn's disease--review of a 56-year experience in Karolinska Institute University Hospital.

PubMed

Rubio, Carlos A; Befrits, Ragnar

2008-01-01

We previously reported that the frequency of colorectal carcinomas (CRC) in Crohn's disease (CD) had increased at this hospital between 1951 and May 1996. The aim was to compare the frequency of CRC in CD between June 1996 and September 2007 to that found between 1951 and May 1996. For that purpose colectomy specimens with an IBD-CRC diagnosis filed during the last 11 years were reviewed. It was found that 29 patients with IBD developed a CRC at this hospital: 21 had CD (or 1.91 cases/year) and the remaining eight, ulcerative colitis (or 0.72 cases/year). At this hospital, the number of cases of CRC in Crohn's colitis increased from 0.28/year between 1951 and the end of 1989, to 1.69 patients/year between 1990 and May 1996, and to 1.91 patients/year between June 1996 and September 2007 (present report). The marginal increase number of patients with CRC in Crohn's colitis/year during the last 11 years at this hospital might be only apparent, considering that the incidence of Crohn's disease in the county has dramatically increased, and that the localization of Crohn's disease has changed in later years, with a predilection for the colon and rectum.

Focal enhanced gastritis and macrophage microaggregates in the gastric mucosa: potential role in the differential diagnosis between Crohn's disease and ulcerative colitis.

PubMed

Magalhães-Costa, Marcia Henriques de; Reis, Beatriz Ribeiro dos; Chagas, Vera Lúcia Antunes; Nunes, Tiago; Souza, Heitor Siffert Pereira de; Zaltman, Cyrla

2014-01-01

Focally enhanced gastritis and macrophage microaggregates are found in the upper gastrointestinal involvement of Crohn's disease, and may reflect an underlying defective innate immunity. These features, however, are also described in patients with Helicobacter pylori infection. The role of these gastric abnormalities in the diagnosis of Crohn's disease was assessed in a population with high prevalence of H. pylori infection. Thirty-seven Crohn's disease, 26 ulcerative colitis, and 30 control patients were included. The H. pylori status was evaluated by the rapid urease test and histology. The presence of focally enhanced gastritis and macrophage microaggregates was recorded. Focally enhanced gastritis was present in 24% of Crohn's disease patients, 4% of ulcerative colitis patients and 11.5% of controls, presenting an overall sensitivity and specificity for Crohn's disease of 24% and 88%, respectively. Macrophage microaggregates were found in all groups, but were only detected in ulcerative colitis and controls in association with H. pylori infection, with an overall sensitivity and specificity for Crohn's disease of 61% and 69%, respectively. In the absence of H. pylori infection, focally enhanced gastritis and macrophage microaggregates were significantly associated with Crohn's disease (P<0.02 and P = 0.001 respectively). Focally gastritis and macrophage microaggregates are suggestive of Crohn's disease only in H. pylori-negative specimens.

PubMedReco: A Real-Time Recommender System for PubMed Citations.

PubMed

Samuel, Hamman W; Zaïane, Osmar R

2017-01-01

We present a recommender system, PubMedReco, for real-time suggestions of medical articles from PubMed, a database of over 23 million medical citations. PubMedReco can recommend medical article citations while users are conversing in a synchronous communication environment such as a chat room. Normally, users would have to leave their chat interface to open a new web browser window, and formulate an appropriate search query to retrieve relevant results. PubMedReco automatically generates the search query and shows relevant citations within the same integrated user interface. PubMedReco analyzes relevant keywords associated with the conversation and uses them to search for relevant citations using the PubMed E-utilities programming interface. Our contributions include improvements to the user experience for searching PubMed from within health forums and chat rooms, and a machine learning model for identifying relevant keywords. We demonstrate the feasibility of PubMedReco using BMJ's Doc2Doc forum discussions.

Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial.

PubMed

Sandborn, William J; Rutgeerts, Paul; Enns, Robert; Hanauer, Stephen B; Colombel, Jean-Frédéric; Panaccione, Remo; D'Haens, Geert; Li, Ju; Rosenfeld, Marie R; Kent, Jeffrey D; Pollack, Paul F

2007-06-19

Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent. To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events. 4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005). 52 sites in the United States, Canada, and Europe. 325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn's Disease Activity Index [CDAI] score, 220 to 450 points). Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points. The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured. A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P = 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No

The glucose breath test: a diagnostic test for small bowel stricture(s) in Crohn's disease.

PubMed

Mishkin, Daniel; Boston, Francis M; Blank, David; Yalovsky, Morty; Mishkin, Seymour

2002-03-01

The aim of this study was to determine whether an indirect noninvasive indicator of proximal bacterial overgrowth, the glucose breath test, was of diagnostic value in inflammatory bowel disease. Twenty four of 71 Crohn's disease patients tested had a positive glucose breath test. No statistical conclusions could be drawn between the Crohn's disease activity index and glucose breath test status. Of patients with radiologic evidence of small bowel stricture(s), 96.0% had a positive glucose breath test, while only one of 46 negative glucose breath test patients had a stricture. The positive and negative predictive values for a positive glucose breath test as an indicator of stricture formation were 96.0% and 97.8%, respectively. This correlation was not altered in Crohn's disease patients with fistulae or status postresection of the terminal ileum. The data in ulcerative colitis were nondiagnostic. In conclusion, the glucose breath test appears to be an accurate noninvasive inexpensive diagnostic test for small bowel stricture(s) and secondary bacterial overgrowth in Crohn's disease.

Small bowel carcinomas in celiac or Crohn's disease: distinctive histophenotypic, molecular and histogenetic patterns.

PubMed

Vanoli, Alessandro; Di Sabatino, Antonio; Martino, Michele; Klersy, Catherine; Grillo, Federica; Mescoli, Claudia; Nesi, Gabriella; Volta, Umberto; Fornino, Daniele; Luinetti, Ombretta; Fociani, Paolo; Villanacci, Vincenzo; D'Armiento, Francesco P; Cannizzaro, Renato; Latella, Giovanni; Ciacci, Carolina; Biancone, Livia; Paulli, Marco; Sessa, Fausto; Rugge, Massimo; Fiocca, Roberto; Corazza, Gino R; Solcia, Enrico

2017-10-01

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and

Guidelines for treatment with infliximab for Crohn's disease.

PubMed

Hommes, D W; Oldenburg, B; van Bodegraven, A A; van Hogezand, R A; de Jong, D J; Romberg-Camps, M J L; van der Woude, J; Dijkstra, G

2006-01-01

Infliximab is an accepted induction and maintenance treatment for patients with Crohn's disease. The effectiveness of infliximab has been demonstrated for both active luminal disease and for enterocutaneous fistulisation. In addition, infliximab can be administered for extraintestinal symptoms of Crohn's disease, such as pyoderma gangrenosum, uveitis and arthropathy. Maintenance treatment with infliximab is effective and is regarded as safe as long as the necessary safety measures are heeded. Infusion reactions occur in 3 to 17% of the patients and are associated with the formation of antibodies to infliximab. A reduction in infusion reactions is possible by the concurrent administration of steroids and the use of immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate). Furthermore, immunosuppressants increase the duration of the response to infliximab. For these reasons, the concomitant use of immunosuppressants with infliximab is recommended. Infections and most specifically tuberculosis need to be ruled out before infliximab is administered. Up to now, there are no indications for a connection between an increased risk for malignancies and treatment with infliximab.

Consensus Recommendations for Evaluation, Interpretation, and Utilization of Computed Tomography and Magnetic Resonance Enterography in Patients With Small Bowel Crohn's Disease.

PubMed

Bruining, David H; Zimmermann, Ellen M; Loftus, Edward V; Sandborn, William J; Sauer, Cary G; Strong, Scott A

2018-03-01

Computed tomography and magnetic resonance enterography have become routine small bowel imaging tests to evaluate patients with established or suspected Crohn's disease, but the interpretation and use of these imaging modalities can vary widely. A shared understanding of imaging findings, nomenclature, and utilization will improve the utility of these imaging techniques to guide treatment options, as well as assess for treatment response and complications. Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of Pediatric Radiology, the American Gastroenterological Association, and other experts, systematically evaluated evidence for imaging findings associated with small bowel Crohn's disease enteric inflammation and established recommendations for the evaluation, interpretation, and use of computed tomography and magnetic resonance enterography in small bowel Crohn's disease. This work makes recommendations for imaging findings that indicate small bowel Crohn's disease, how inflammatory small bowel Crohn's disease and its complications should be described, elucidates potential extra-enteric findings that may be seen at imaging, and recommends that cross-sectional enterography should be performed at diagnosis of Crohn's disease and considered for small bowel Crohn's disease monitoring paradigms. A useful morphologic construct describing how imaging findings evolve with disease progression and response is described, and standard impressions for radiologic reports that convey meaningful information to gastroenterologists and surgeons are presented. © 2018, RSNA, AGA Institute, and Society of Abdominal Radiology This article is being published jointly in Radiology and Gastroenterology.

The risk of retention of the capsule endoscope in patients with known or suspected Crohn's disease.

PubMed

Cheifetz, Adam S; Kornbluth, Asher A; Legnani, Peter; Schmelkin, Ira; Brown, Alphonso; Lichtiger, Simon; Lewis, Blair S

2006-10-01

Capsule endoscopy (CE) allows visualization of the mucosa of the entire small bowel and is therefore a potentially important tool in the evaluation of patients with known or suspected Crohn's disease (CD). However, small bowel strictures, which are not uncommon in Crohn's, are considered to be a contraindication to CE for fear of capsule retention. Our goal was to determine the risk of capsule retention in patients with suspected or known CD. We retrospectively reviewed the records of 983 CE cases performed at three private gastroenterology practices between December 2000 and December 2003, and selected those with suspected or proven Crohn's. A total of 102 cases were identified in which CE was used in patients with suspected (N = 64) or known (N = 38) CD. Only one of 64 patients (1.6%) with suspected CD had a retained capsule. However, in five of 38 (13%) patients with known Crohn's, the capsule was retained proximal to a stricture. Of the five cases of retained capsules, three strictures were previously unknown. In four cases, the obstructing lesions were resected without complications, leading to complete resolution of the patient's underlying symptoms. One patient chose not to undergo surgery and has remained without an episode of small bowel obstruction for over 38 months. Capsule retention occurred in 13% (95% CI 5.6%-28%) of patients with known CD, but only in 1.6% (95% CI 0.2%-10%) with suspected Crohn's. A retained capsule may indicate unsuspected strictures in Crohn's that may require an unexpected, but therapeutic, surgical intervention. Patients and physicians should be aware of these potential risks when using CE in CD.

Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

PubMed Central

Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

2016-01-01

Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

Peptide-containing nerve fibres in the gut wall in Crohn's disease.

PubMed Central

Sjölund, K; Schaffalitzky, O B; Muckadell, D E; Fahrenkrug, J; Håkanson, R; Peterson, B G; Sundler, F

1983-01-01

Neurones containing VIP, substance P, or enkephalin were studied by immunocytochemistry in intestinal specimens from 27 patients with Crohn's disease. Also several endocrine cell systems in the gut were examined. The results were compared with those from a control group of 26 patients. The relative frequency of various endocrine cells did not differ overtly from that in controls. Vasoactive intestinal polypeptide and substance P nerve fibres were distributed in all layers of the gut wall, including the submucosal and myenteric plexuses, whereas enkephalin fibres were restricted to the smooth muscle layer and the myenteric plexus. The distribution and frequency of the peptide-containing nerve fibres were the same in Crohn's disease patients as in control patients. A proportion of these nerve fibres, however, were notably coarse in the Crohn's disease patients. This was particularly apparent in the afflicted parts of the intestine although it was noted also in non-afflicted parts. The concentration of VIP and substance P (expressed as pmol/g wet weight) did not, however, exceed that of the control group. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:6192043

Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease

PubMed Central

Peeters, H; Vander, C; Laukens, D; Coucke, P; Marichal, D; Van Den Berghe, M; Cuvelier, C; Remaut, E; Mielants, H; De Keyser, F; Vos, M

2004-01-01

Background: Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases. Objectives: To investigate whether the presence of sacroiliitis in patients with Crohn's disease is linked to the carriage of CARD15 polymorphisms. Methods: 102 consecutive patients with Crohn's disease were clinically evaluated by a rheumatologist. Radiographs of the sacroiliac joints were taken and assessed blindly by two investigators. The RFLP-PCR technique was used to genotype all patients for three single nucleotide polymorphisms (SNP) in the CARD15 gene. Every SNP was verified by direct sequencing. The HLA-B27 phenotype was determined. Results: Radiological evidence of sacroiliitis with or without ankylosing spondylitis was found in 23 patients (23%), of whom only three were HLA-B27 positive. In contrast, 78% of patients with sacroiliitis carried a CARD15 variant v 48% of those without sacroiliitis (p = 0.01; odds ratio 3.8 (95% confidence interval, 1.3 to 11.5)). Multivariate analysis (logistic regression) showed that the association between sacroiliitis and CARD15 polymorphisms was independent of other CARD15 related phenotypes (ileal and fibrostenosing disease, young age at onset of disease, familial Crohn's disease) (p = 0.039). Conclusions: CARD15 variants were identified as genetic predictors of Crohn's disease related sacroiliitis. An association was demonstrated between these polymorphisms and an extraintestinal manifestation of Crohn's disease. PMID:15308523

An international study of agglutinins to Eubacterium, Peptostreptococcus and Coprococcus species in Crohn's disease, ulcerative colitis and control subjects.

PubMed

Wensinck, F; van de Merwe, J P; Mayberry, J F

1983-01-01

The world-wide occurrence of agglutinating antibodies to four coccoid anaerobes belonging to Eubacterium, Peptostreptococcus and Coprococcus spp. was investigated in 937 coded sera from patients suffering from Crohn's disease, ulcerative colitis, various other diseases and from healthy controls. Positive results were found in 59% of patients with Crohn's disease, 29% of patients with ulcerative colitis, and 8% of both diseased and healthy control subjects. Patients with Crohn's disease of the colon had more positive tests (67%) than patients with disease confined to the small bowel (46%). The results show that agglutinating antibodies to the coccoid anaerobes occur more frequently in patients with Crohn's disease than in other subjects in widely varying geographic regions.

PubMedAlertMe - Standalone Windows-based PubMed SDI Software Application

PubMed Central

Ma’ayan, Avi

2008-01-01

PubMedAlertMe is a Windows-based software system for automatically receiving e-mail alert messages about recent publications listed on PubMed. The e-mail messages contain links to newly available abstracts listed on PubMed describing publications that were selectively returned from a specified list of queries. Links are also provided to directly export citations to EndNote, and links are provided to directly forward articles to colleagues. The program is standalone. Thus, it does not require a remote mail server or user registration. PubMedAlertMe is free software, and can be downloaded from: http://amp.pharm.mssm.edu/PubMedAlertMe/PubMedAlertMe_setup.zip PMID:18402930

CT enterography for Crohn's disease: accurate preoperative diagnostic imaging.

PubMed

Vogel, Jon; da Luz Moreira, Andre; Baker, Mark; Hammel, Jeffery; Einstein, David; Stocchi, Luca; Fazio, Victor

2007-11-01

CT enterography (CTE) is a technique that provides detailed images of the small bowel by using a low Hounsfield unit oral contrast media. This study was designed to correlate CTE findings with operative findings in patients with Crohn's disease. We performed a retrospective study of all patients with Crohn's disease of the small bowel or colon, who had CTE and subsequent small bowel or colon surgery within three months after the CT examination. CTE findings of stricture, fistula, inflammatory mass, abscess, and combinations of these abnormalities were compared with operative findings. Specialist radiologists and fellowship-trained colorectal surgeons participated in the study. The Fisher's exact test or chi-squared tests were used with respect to categorical data, and the Wilcoxon's rank-sum test was used for quantitative data. In 36 patients, the presence or absence of stricture, fistula, abscess, or inflammatory mass was correctly determined by CTE in 100, 94, 100, and 97 percent, respectively. The accuracy for stricture or fistula number was 83 and 86 percent, respectively. There were nine patients with multiple disease phenotypes identified on CTE of which eight were confirmed at surgery. CTE overestimated or underestimated the extent of disease in 11 patients (31 percent). CTE is an accurate preoperative diagnostic imaging study for small-bowel Crohn's disease. The ability of this imaging study to detect both luminal and extraluminal pathology is a distinct advantage of CTE compared with small-bowel contrast studies.

Quality of Life Is Related to Fecal Calprotectin Concentrations in Colonic Crohn Disease and Ulcerative Colitis, but not in Ileal Crohn Disease

PubMed Central

Gauss, Annika; Geib, Thomas; Hinz, Ulf; Schaefert, Rainer; Zwickel, Philipp; Zawierucha, Anna; Stremmel, Wolfgang; Klute, Lukas

2016-01-01

Abstract To formulate therapy goals, we aimed to define the relationship between fecal calprotectin and health-related quality of life in inflammatory bowel diseases (IBDs). This retrospective single-center cross-sectional study included ambulatory IBD patients who had completed standardized questionnaires comprising items of health-related quality of life (Short Inflammatory Bowel Disease Questionnaire) and clinical disease activity scores, and who had provided stool samples for calprotectin determination within 30 days of questionnaire completion. Correlation analyses were performed between the indicated parameters. Post hoc analysis was conducted, taking into account only data from patients with fecal calprotectin concentrations measured within 3 days of questionnaire completion. One hundred ninety-seven patients with Crohn disease and 111 patients with ulcerative colitis were enrolled in the study. Lower fecal calprotectin concentrations were associated with better health-related quality of life. The correlations were weak, but stronger if only fecal calprotectin concentrations measured within 3 days of questionnaire completion were included (results for 3 days; Crohn disease: n = 86, rS = −0.419, P < 0.001; ulcerative colitis: n = 43, rS = −0.432, P = 0.004). In Crohn disease, a significant correlation between fecal calprotectin concentration and health-related quality of life was found in patients with colonic involvement (n = 59, rS = −0.470, P < 0.001), but not in patients with purely ileal disease (n = 27, rS = −0.268, P = 0.18). Correlations between fecal calprotectin concentrations and clinical disease activity were also only weak to moderate. Owing to its moderate correlation with fecal calprotectin concentrations in IBD patients with colonic involvement, health-related quality of life should be used in combination with other markers for IBD management. This is even more important in isolated ileal

Quality of Life Is Related to Fecal Calprotectin Concentrations in Colonic Crohn Disease and Ulcerative Colitis, but not in Ileal Crohn Disease.

PubMed

Gauss, Annika; Geib, Thomas; Hinz, Ulf; Schaefert, Rainer; Zwickel, Philipp; Zawierucha, Anna; Stremmel, Wolfgang; Klute, Lukas

2016-04-01

To formulate therapy goals, we aimed to define the relationship between fecal calprotectin and health-related quality of life in inflammatory bowel diseases (IBDs). This retrospective single-center cross-sectional study included ambulatory IBD patients who had completed standardized questionnaires comprising items of health-related quality of life (Short Inflammatory Bowel Disease Questionnaire) and clinical disease activity scores, and who had provided stool samples for calprotectin determination within 30 days of questionnaire completion. Correlation analyses were performed between the indicated parameters. Post hoc analysis was conducted, taking into account only data from patients with fecal calprotectin concentrations measured within 3 days of questionnaire completion. One hundred ninety-seven patients with Crohn disease and 111 patients with ulcerative colitis were enrolled in the study. Lower fecal calprotectin concentrations were associated with better health-related quality of life. The correlations were weak, but stronger if only fecal calprotectin concentrations measured within 3 days of questionnaire completion were included (results for 3 days; Crohn disease: n = 86, rS = -0.419, P < 0.001; ulcerative colitis: n = 43, rS = -0.432, P = 0.004). In Crohn disease, a significant correlation between fecal calprotectin concentration and health-related quality of life was found in patients with colonic involvement (n = 59, rS = -0.470, P < 0.001), but not in patients with purely ileal disease (n = 27, rS = -0.268, P = 0.18). Correlations between fecal calprotectin concentrations and clinical disease activity were also only weak to moderate. Owing to its moderate correlation with fecal calprotectin concentrations in IBD patients with colonic involvement, health-related quality of life should be used in combination with other markers for IBD management. This is even more important in isolated ileal Crohn disease

A family report of Crohn's disease in three children immigrating from Albania to Greece and review of the literature.

PubMed

Katsanos, Konstantinos H; Karetsos, Vasileios; Tsianos, Epameinondas V

2010-11-01

Cases of immigrant families affected by IBD have rarely been reported and seem to be of exceptional interest towards a better understanding of disease aetiopathogenesis. The first case of Crohn's disease in a family of immigrants from Albania to Greece with three offspring is described herein. A family with three children, one 22 year-old male and two 18-year-old twin females immigrated from southern Albania to northwest Greece ten years ago. The whole family lived in the same house and had no previous history of bowel or other chronic diseases. Two years ago the boy complained of diarrhoea, perianal pain and loss of weight. Subsequent investigation revealed ileal and perianal Crohn's disease. One year after Crohn's disease was diagnosed in the boy, one of the twins was diagnosed with ileal Crohn's disease. Six months afterwards, the second twin underwent emergency appendectomy due to acute appendicitis; four months later she was diagnosed with ileal Crohn's disease. Genetically predisposed individuals seem to be vulnerable to a continuous pressure of a still unknown environmental factor(s). In addition, lifestyle modification seems to represent a predisposing factor toward inflammatory bowel disease in immigrants. Copyright © 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Crohn's Disease: Genetics Update.

PubMed

Wang, Ming-Hsi; Picco, Michael F

2017-09-01

Since the discovery of the first Crohn's disease (CD) gene NOD2 in 2001, 140 genetic loci have been found in whites using high-throughput genome-wide association studies. Several genes influence the CD subphenotypes and treatment response. With the observations of increasing prevalence in Asia and developing countries and the incomplete explanation of CD variance, other underexplored areas need to be integrated through novel methodologies. Algorithms that incorporate specific genetic risk alleles with other biomarkers will be developed and used to predict CD disease course, complications, and response to specific therapies, allowing precision medicine to become real in CD. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost effectiveness of alternative imaging strategies for the diagnosis of small-bowel Crohn's disease.

PubMed

Levesque, Barrett G; Cipriano, Lauren E; Chang, Steven L; Lee, Keane K; Owens, Douglas K; Garber, Alan M

2010-03-01

The cost effectiveness of alternative approaches to the diagnosis of small-bowel Crohn's disease is unknown. This study evaluates whether computed tomographic enterography (CTE) is a cost-effective alternative to small-bowel follow-through (SBFT) and whether capsule endoscopy is a cost-effective third test in patients in whom a high suspicion of disease remains after 2 previous negative tests. A decision-analytic model was developed to compare the lifetime costs and benefits of each diagnostic strategy. Patients were considered with low (20%) and high (75%) pretest probability of small-bowel Crohn's disease. Effectiveness was measured in quality-adjusted life-years (QALYs) gained. Parameter assumptions were tested with sensitivity analyses. With a moderate to high pretest probability of small-bowel Crohn's disease, and a higher likelihood of isolated jejunal disease, follow-up evaluation with CTE has an incremental cost-effectiveness ratio of less than $54,000/QALY-gained compared with SBFT. The addition of capsule endoscopy after ileocolonoscopy and negative CTE or SBFT costs greater than $500,000 per QALY-gained in all scenarios. Results were not sensitive to costs of tests or complications but were sensitive to test accuracies. The cost effectiveness of strategies depends critically on the pretest probability of Crohn's disease and if the terminal ileum is examined at ileocolonoscopy. CTE is a cost-effective alternative to SBFT in patients with moderate to high suspicion of small-bowel Crohn's disease. The addition of capsule endoscopy as a third test is not a cost-effective third test, even in patients with high pretest probability of disease. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Normal villous architecture with increased intraepithelial lymphocytes: a duodenal manifestation of Crohn disease.

PubMed

Patterson, Emily R; Shmidt, Eugenia; Oxentenko, Amy S; Enders, Felicity T; Smyrk, Thomas C

2015-03-01

To assess a possible association between inflammatory bowel disease (IBD) and the histologic finding in duodenal biopsy specimens of increased intraepithelial lymphocytes (IELs) with normal villous architecture. We identified all patients with duodenal biopsy specimens obtained between 2000 and 2010 showing increased IELs and normal architecture. Among the 74 such patients who also had IBD, we characterized the clinical features of IBD and reviewed all available upper gastrointestinal biopsy specimens. Fifty-eight patients had Crohn disease, 13 had ulcerative colitis, and three had IBD, type unclassified. No duodenal sample with increased IELs had other histologic features of IBD. Among gastric biopsy specimens from 34 patients with Crohn disease, nearly half (16) had focal gastritis. We propose that Crohn disease be included in the differential diagnosis for increased IELs with normal villous architecture in duodenal biopsy specimens, particularly when gastric biopsy specimens show focal gastritis. Copyright© by the American Society for Clinical Pathology.

Anti-TNF therapy induced immune neutropenia in Crohns disease- report of 2 cases and review of literature.

PubMed

Sebastian, Shaji; Ashton, Katherine; Houston, Yasmine; Diggory, Tina Mary; Dore, Philip

2012-07-01

Transient neutropenia is reported in some patients on biologic therapy. We report two cases of severe neutropenia in patients with Crohn`s disease following treatment with anti-TNF therapy. In both cases neutrophil specific granulocyte autoantibodies were detected during period of neutropenia and disappeared on cessation of anti-TNF therapy. These may indicate that anti-TNF agents may produce autoimmune agranulocytosis by triggering production granulocyte autoantibodies. The long term management strategy for patients with anti-TNF therapy induced autoimmune neutropenia is uncertain. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

The long-term results of resection and multiple resections in Crohn's disease.

PubMed

Krupnick, A S; Morris, J B

2000-01-01

Crohn's disease is a panenteric, transmural inflammatory disease of unknown origin. Although primarily managed medically, 70% to 90% of patients will require surgical intervention. Surgery for small bowel Crohn's is usually necessary for unrelenting stenotic complications of the disease. Fistula, abscess, and perforation can also necessitate surgical intervention. Most patients benefit from resection or strictureplasty with an improved quality of life and remission of disease, but recurrence is common and 33% to 82% of patients will need a second operation, and 22% to 33% will require more than two resections. Short-bowel syndrome is unavoidable in a small percentage of Crohn's patients because of recurrent resection of affected small bowel and inflammatory destruction of the remaining mucosa. Although previously a lethal and unrelenting disease with death caused by malnutrition, patients with short-bowel syndrome today can lead productive lives with maintenance on total parenteral nutrition (TPN). This lifestyle, however, does not come without a price. Severe TPN-related complications, such as sepsis of indwelling central venous catheters and liver failure, do occur. Future developments will focus on more powerful and effective anti-inflammatory medication specifically targeting the immune mechanisms responsible for Crohn's disease. Successful medical management of the disease will alleviate the need for surgical resection and reduce the frequency of short-bowel syndrome. Improving the efficacy of immunosuppression and the understanding of tolerance induction should increase the safety and applicability of small-bowel transplant for those with short gut. Tissue engineering offers the potential to avoid immunosuppression altogether and supplement intestinal length using the patient's own tissues.

Primary Crohn's disease of the appendix: report of 14 cases and review of the literature.

PubMed Central

Yang, S S; Gibson, P; McCaughey, R S; Arcari, F A; Bernstein, J

1979-01-01

Fourteen patients with primary Crohn's disease of the appendix have been seen in a 12 year period. These patients represent 12.8% of the total number undergoing surgical resection because of Crohn's disease. Twenty-three cases of appendiceal Crohn's disease have been previously reported in the literature. A correct preoperative diagnosis is rarely made; the usual diagnosis is that of acute appendicitis or appendiceal abscess. The removed appendix in twelve of our 14 cases had marked thickening of the wall with transmural fibrosis and often with granulomatous inflammation. The enlarged appendix had an external appearance similar to that of ileal Crohn's disease, and we consider a correct surgical diagnosis might be possible with better awareness of its existence. The diagnosis might be suspected earlier when the clinical course of apparent appendicitis is protracted or atypical. Contrary to the previous estimation of high recurrence rate, this series and the cumulative evidence in the literature show a relatively low rate at 14%. The feared fistula formation following the removal of the appendix has not been seen in either our series or the literature. These patients, however, merit long-term follow-up. Images Fig. 7. Fig. 2. Fig. 3. PMID:426564

Conn syndrome and Crohn disease in a pediatric case: an interesting parallel.

PubMed

Rodriguez, Manuel A; Alkhoury, Fuad; Malvezzi, Leopoldo; Diaz, Alejandro

2013-01-01

Conn syndrome is characterized by surreptitious secretion of aldosterone in which patients are found to have hypertension, hypokalemia, and metabolic alkalosis. Although rare, the most common presentation in the pediatric population is bilateral hyperplasia of the adrenal glands as opposed to an adenoma. Crohn disease is part of the spectrum of inflammatory bowel disease, which manifests in children as flare-ups of bloody diarrhea and abdominal pain. The association of concurrent Conn syndrome and Crohn disease has been previously presented in two cases in adults. This is the first pediatric case to be reported in the literature.

Fire in the Belly and the Professionalization of Nurses: A Historical Analysis of Crohn Disease Care

PubMed Central

Brotherton, Carol S.; Taylor, Ann Gill; Keeling, Arlene

2012-01-01

Today professional nurses around the world are stepping up to meet the needs of individuals with Crohn disease using their specialized knowledge and skills that demonstrate areas of expertise that have not always existed. The gastrointestinal-specific knowledge being used by these 21st century nurses exists today because progressive efforts of nurses in previous decades moved the profession of nursing forward. The purpose of this paper is to describe and analyze the development of the role of nurses in responding to new challenges patients with Crohn disease face since the emergence of the disease in the early 1900s. The authors used traditional historic research methods to conduct the study. Primary sources include nursing journals and textbooks published in the 20th and 21st centuries and documents archived at The Mount Sinai Hospital in New York City, where Burrill B. Crohn conducted his seminal work. The significance of the findings is that the changing role of nurses in caring for patients with Crohn disease mirrors the professionalization of nursing during the 20th and early 21st centuries. PMID:23364362

A Qualitative Exploration of the Lived Experiences of Patients Before and After Ileostomy Creation as a Result of Surgical Management for Crohn's Disease.

PubMed

Morris, Andrew; Leach, Bethan

2017-01-01

Patient experiences pre- and post-ileostomy creation as a result of severe Crohn's Disease are underresearched. A qualitative phenomenological design involving a purposeful sampling approach was used to capture the lived physical and psychosocial transition of patients with Crohn's Disease before and after ileostomy formation. Patients were recruited from the membership of the United Kingdom Ileostomy Association; inclusion criteria stipulated participants must speak English and have a diagnosis of Crohn's Disease and subsequent stoma formation. Ten (10) patients (6 women, 4 men, ranging in age from 34 to 83 years with Crohn's Disease and an ileostomy [mean time with stoma 18.3 years, range 3-36 years]) participated in indepth, semistructured interviews with questions on sociodemographic characteristics along with questions informed by the relevant literature regarding life before and after the ileostomy. All interviews were audiorecorded and transcribed verbatim. Interpretative phenomenological analysis was used to examine the data and identify and interpret themes. Participants were asked to comment on these themes to ensure they were a realistic interpretation of their experiences. Two (2) major themes emerged that embodied ileostomy formation: being controlled by Crohn's and transition to a new life with an ileostomy. Crohn's symptoms controlled daily activities such as work and socializing due, in part, to the need to be in close proximity to toilet facilities. The ileostomy facilitated a transition to a new life that allowed patients to re-engage with work and social activities. One minor theme emerged: memories of Crohn's. Participants said their memories of Crohn's affected life with an ileostomy. Where Crohn's controlled every aspect of people's lives pre-ileostomy formation, the creation of the ileostomy was a positive experience because it helped manage Crohn's symptoms. Memories of life pre-ileostomy may affect individuals' behavior post

Clinical course of severe colitis: a comparison between Crohn’s Disease and ulcerative colitis.

PubMed

Sinagra, E; Orlando, A; Mocciaro, F; Criscuoli, V; Oliva, L; Maisano, S; Giunta, M; La Seta, F; Solina, G; Rizzo, A G; Leone, A; Tomasello, G; Cappello, F; Cottone, M

2018-01-01

Few data are available about the clinical course of severe colonic Crohn’s disease (CD). The aim of this study is to describe the clinical course of severe Crohn’s colitis in a patient cohort with isolated colonic or ileocolonic CD, and to compare it with the clinical course of patients with severe ulcerative colitis (UC). Thirty-four patients with severe Crohn’s colitis were prospectively identified in our cohort of 593 consecutive hospitalized patients through evaluation of the Crohn’s Disease Activity Index score and the Harvey-Bradshaw Index. One hundred sixty-nine patients with severe ulcerative colitis were prospectively identified in our cohort of 449 consecutive hospitalized patients through evaluation of the Lichtiger score and the Truelove-Witts score. We evaluated the following data/aspects: response to steroids, response to biologics, colectomy rate in acute, colectomy rate during follow-up, megacolon and cytomegalovirus infection rate. We did not find significant differences in the response to steroids and to biologics, in the percentage of cytomegalovirus infection and of megacolon, while the rate of colectomy in acute turned out to be greater in patients with severe Crohn’s colitis compared to patients with severe UC, and this difference appeared to be the limit of statistical significance (Chi-squared 3.31, p = 0.069, OR 0.39); the difference between the colectomy rates at the end of the follow-up was also not significant. In the whole population, by univariate analysis, according to the linear regression model, a young age at diagnosis is associated with a higher overall colectomy rate (p = 0.024) and a higher elective colectomy rate (p = 0.022), but not with a higher acute colectomy rate, and an elevated ESR is correlated with a higher overall colectomy rate (p = 0.014) and a higher acute colectomy rate (p = 0.032), but not with a higher elective colectomy rate. This correlation was significant on multivariate analysis. The overall rate of

Enterovesical fistulas complicating Crohn's disease: clinicopathological features and management.

PubMed

Yamamoto, T; Keighley, M R

2000-08-01

Enterovesical fistula is a relatively rare condition in Crohn's disease. This study was undertaken to examine clinicopathological features and management of enterovesical fistula complicating Crohn's disease. Thirty patients with enterovesical fistula complicating Crohn's disease, treated between 1970 and 1997, were reviewed. Urological symptoms were present in 22 patients; pneumaturia in 18, urinary tract infection in 7, and haematuria in 2. In 5 patients clinical symptoms were successfully managed by conservative treatment, and they required no surgical treatment for enterovesical fistula. Twenty-five patients required surgery. All the patients were treated by resection of diseased bowel and pinching off the dome of the bladder. No patients required resection of the bladder. The Foley catheter was left in situ for an average of 2 weeks after operation. Three patients developed early postoperative complications; two bowel anastomotic leaks, and one intra-abdominal abscess. All these complications were associated with sepsis and multiple fistulas at the time of laparotomy. After a median follow-up of 13 years, 3 patients having postoperative sepsis (anastomotic leak or abscess) developed a recurrent fistula from the ileocolonic anastomosis to the bladder, which required further surgery. In the other 22 patients without postoperative complications there has been no fistula recurrence. In conclusion, the majority of patients with enterovesical fistula required surgical treatment: resection of the diseased bowel and oversewing the defect in the bladder. The fistula recurrence was uncommon, but the presence of sepsis and multiple fistulas at the time of laparotomy increased the incidence of postoperative complications and fistula recurrence.

Comparison of primary and reoperative surgery in patients with Crohns disease.

PubMed Central

Heimann, T M; Greenstein, A J; Lewis, B; Kaufman, D; Heimann, D M; Aufses, A H

1998-01-01

OBJECTIVE: This study was performed to determine the clinical results of patients with Crohns disease who require surgical resection. The outcome of patients undergoing initial surgery was compared with those having reoperation. METHODS: One hundred sixty-four patients undergoing intestinal resection for Crohns disease at The Mount Sinai Hospital from 1976 to 1989 were studied prospectively. The mean duration of follow-up was 72 months. RESULTS: Ninety patients (55%) underwent initial intestinal resection whereas 74 patients (45%) underwent reoperation for recurrent disease. Patients undergoing reoperation were older (33.4 vs. 38.7 years), had longer durations of disease (8.7 vs. 15.2 years), had shorter resections (60 vs. 46 cm), and were more likely to require ileostomy. Forty-seven percent of the patients with multiple previous resections required an ileostomy. This group also received a mean of 2.3 U blood in the perioperative period and showed a trend to increased symptomatic recurrence (49% vs. 71% at 5 years). CONCLUSIONS: Patients with Crohns disease undergoing first and second reoperation have outcomes similar to those in patients undergoing primary resection. Patients requiring multiple reoperations are more likely to require blood transfusions and permanent ileostomy and to show a greater trend to early symptomatic recurrence. PMID:9563535

Comparison of primary and reoperative surgery in patients with Crohns disease.

PubMed

Heimann, T M; Greenstein, A J; Lewis, B; Kaufman, D; Heimann, D M; Aufses, A H

1998-04-01

This study was performed to determine the clinical results of patients with Crohns disease who require surgical resection. The outcome of patients undergoing initial surgery was compared with those having reoperation. One hundred sixty-four patients undergoing intestinal resection for Crohns disease at The Mount Sinai Hospital from 1976 to 1989 were studied prospectively. The mean duration of follow-up was 72 months. Ninety patients (55%) underwent initial intestinal resection whereas 74 patients (45%) underwent reoperation for recurrent disease. Patients undergoing reoperation were older (33.4 vs. 38.7 years), had longer durations of disease (8.7 vs. 15.2 years), had shorter resections (60 vs. 46 cm), and were more likely to require ileostomy. Forty-seven percent of the patients with multiple previous resections required an ileostomy. This group also received a mean of 2.3 U blood in the perioperative period and showed a trend to increased symptomatic recurrence (49% vs. 71% at 5 years). Patients with Crohns disease undergoing first and second reoperation have outcomes similar to those in patients undergoing primary resection. Patients requiring multiple reoperations are more likely to require blood transfusions and permanent ileostomy and to show a greater trend to early symptomatic recurrence.

Isolated Bilateral Gastrocnemius Myositis in Crohn Disease Successfully Treated with Adalimumab.

PubMed

Vadala di Prampero, Salvatore; Marino, Marco; Toso, Francesco; Avellini, Claudio; Nguyen, Vu; Sorrentino, Dario

2016-01-01

Extraintestinal manifestations are common in inflammatory bowel disease; however, muscular involvement in Crohn disease is rarely reported. We present a case of a 26-year-old male with ileocolonic Crohn disease who developed sudden tenderness in both calves. Doppler ultrasound was negative for deep vein thrombosis. Magnetic resonance imaging of the gastrocnemius muscle showed high intensity signal in the muscle fibers, and muscle biopsy demonstrated nonspecific lymphocytic myositis. Other relevant laboratory results included normal antineutrophil cytoplasmic antibodies and creatine kinase as well as elevated C-reactive protein, erythrocyte sedimentation rate, and anti- Saccharomyces cerevisiae IgG titer. The patient was in clinical remission, being treated with azathioprine 2.5 mg/kg. Prednisone 60 mg/day was initiated with rapid resolution of calf tenderness; however, tenderness soon returned when the dose was tapered to 10 mg/day. Subsequently, prednisone and azathioprine were discontinued, and adalimumab was started at standard induction and maintenance doses. The patient's symptoms resolved shortly after the first induction dose. A repeat magnetic resonance imaging of the calves - 3 months after starting adalimumab - showed complete resolution of muscle inflammation. To our knowledge, this is the first case of gastrocnemius myositis - a rare extraintestinal manifestation of Crohn disease - successfully treated with anti-tumor necrosis factor agents.

Low dose naltrexone for induction of remission in Crohn's disease.

PubMed

Segal, Dan; Macdonald, John K; Chande, Nilesh

2014-02-21

Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy. The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease. A systematic search of MEDLINE, EMBASE, CENTRAL, and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group Specialized Register was performed from inception to February 2013 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also reviewed. Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included. Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.2). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria. Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 1: Diagnosis and Medical Management.

PubMed

Gomollón, Fernando; Dignass, Axel; Annese, Vito; Tilg, Herbert; Van Assche, Gert; Lindsay, James O; Peyrin-Biroulet, Laurent; Cullen, Garret J; Daperno, Marco; Kucharzik, Torsten; Rieder, Florian; Almer, Sven; Armuzzi, Alessandro; Harbord, Marcus; Langhorst, Jost; Sans, Miquel; Chowers, Yehuda; Fiorino, Gionata; Juillerat, Pascal; Mantzaris, Gerassimos J; Rizzello, Fernando; Vavricka, Stephan; Gionchetti, Paolo

2017-01-01

This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016]. 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.

Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT.

PubMed Central

Nyhlin, H; Merrick, M V; Eastwood, M A

1994-01-01

Patients with Crohn's disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn's disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days). Twenty eight per cent of patients with Crohn's disease who had not undergone resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn's disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses. PMID:8307458

Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT.

PubMed

Nyhlin, H; Merrick, M V; Eastwood, M A

1994-01-01

Patients with Crohn's disease who suffer from longstanding diarrhoea that does not respond to conventional treatment pose a common clinical problem. Bile acid malabsorption is a possible cause, although its prevalence and clinical importance is unclear. This paper explores the clinical indications for referring patients with Crohn's disease for bile acid assessment and the extent of bile acid malabsorption in this selected group of patients. The selenium labelled bile acid SeHCAT was used to assess the effect of disease on the integrity of the enterohepatic circulation. Altogether 76% of the patients referred for bile acid assessment had longstanding diarrhoea that had not responded to conventional anti-diarrhoeal treatment or an increase in steroid therapy as their sole or predominant symptom. Ninety per cent of patients with bowel resections, almost exclusively ileocaecal, had abnormal SeHCAT retention (< 5% at seven days). Twenty eight per cent of patients with Crohn's disease who had not undergone resection 28% had a SeHCAT retention < 5%, signifying bile acid malabsorption. Nineteen of 22 patients given cholestyramine treatment subsequent to the SeHCAT test had a good symptomatic response. In conclusion, the prevalence of bile acid malabsorption in this selected group with Crohn's disease is sufficiently high to justify performing the SeHCAT test in order to separate the various differential diagnoses.

Assessment of inflammatory activity in Crohn's disease by means of dynamic contrast-enhanced MRI.

PubMed

Pupillo, V A; Di Cesare, E; Frieri, G; Limbucci, N; Tanga, M; Masciocchi, C

2007-09-01

Our aim was to perform a dynamic study of contrast enhancement of the intestinal wall in patients with Crohn's disease to quantitatively assess local inflammatory activity. We studied a population of 50 patients with histologically proven Crohn's disease. Magnetic resonance imaging (MRI) was performed using a 1.5-T magnet with a phased-array coil and acquisition of T2-weighted single-shot fast spin echo (SSFSE) half Fourier sequences before intravenous administration of gadolinium, and T1-weighted fast spoiled gradient (FSPGR) fat-saturated sequences before and after contrast administration. Before the examination, patents received oral polyethylene glycol (PEG) (1,000 ml for adults; 10 ml/Kg of body weight for children). Regions of interest (ROI) were placed on the normal and diseased intestinal wall to assess signal intensity and rate of increase in contrast enhancement over time. Data were compared with the Crohn's Disease Activity Index (CDAI). The diseased bowel wall showed early and intense uptake of contrast that increases over time until a plateau is reached. In patients in the remission phase after treatment, signal intensity was only slightly higher in diseased bowel loops than in healthy loops. There was a significant correlation between the peak of contrast uptake and CDAI. Dynamic MRI is a good technique for quantifying local inflammatory activity of bowel wall in patients with Crohn's disease.

Pinworm infestation mimicking crohns' disease.

PubMed

Johansson, Joel; Ignatova, Simone; Ekstedt, Mattias

2013-01-01

We here report a case of a young man who presented to his general practitioner with diarrhea. Inflammatory bowel disease was suspected and a colonoscopy showed aphthous lesions suggestive of Crohns' disease but biopsies revealed eggs of Enterobius vermicularis. When treated for this parasite, his symptoms were alleviated and a followup colonoscopy revealed a normal colon and distal ileum. Enterobius vermicularis is the most common parasite worldwide and has been attributed with many different presentations and pathologies. It is therefore necessary to maintain vigilance, even in high-income countries, in order to diagnose patients with one of the many atypical presentations of pinworms.

[Intestinal flora and Crohn's disease].

PubMed

Desreumaux, P; Colombel, J-F

2003-07-01

The pathogenesis of inflammatory bowel diseases (IBD) proceeds through stages of initiation, amplification and healing. Abundant clinical and experimental data incriminate luminal bacteria or bacterial products in both the initiation and perpetuation of chronic intestinal inflammation. Macrophage and T-cell activation with accompanying inflammatory cytokine production appears to be an early event. Studies of lymphocyte responsiveness to autologous and heterologous intestinal bacteria have suggested that this activation may result from a breakdown in tolerance to the enteric flora in IBD. This lack of tolerance might be due to an imbalance between protective and aggressive commensal luminal bacterial species (dysbiosis), a decreased barrier function and/or an impaired mucosal clearance allowing the access of bacteria to the mucosal immune system and lack of regulatory mediators or cells. There is still controversy over whether the virulence traits of bacteria are expressed broadly or just in a small subset of bacteria. Individual bacterial species within the indigenous flora vary in their capacity to drive intestinal inflammation. In experimental models, some bacteria such as Bacteroides vulgatus can cause colitis alone when monoassociated in the HLA-B27 transgenic rat model. Others, including Lactobacillus and Bifidobacterium species have no proinflammatory capacity and have been used as probiotics. In patients with IBD, systematic approach to this issue is hampered by the limited knowledge of intestinal flora. Adherent-invasive Escherichia coli are a possible candidate for the onset and/or persistence of intestinal inflammation in patients with Crohn's disease, since they possess all the virulence factors that allow the bacteria to cross the intestinal barrier, to move to deep tissues, and to continuously activate macrophages. The recent identification of NOD2/CARD15 as a susceptibility gene for Crohn's disease has provided another link between the immune response

On exploration of medical database of Crohn's disease

NASA Astrophysics Data System (ADS)

Manerowska, Anna; Dadalski, Maciej; Socha, Piotr; Mulawka, Jan

2010-09-01

The primary objective of this article is to find a new, more effective method of diagnosis of Crohn's disease. Having created the database on this disease we wanted to find the most suitable classification models. We used the algorithms with their implementations stored in R environment. Having carried out the investigations we have reached results interesting for clinical practice.

Crohn's colitis perforation due to superimposed invasive amebic colitis: a case report.

PubMed

Ozdoğan, Mehmet; Küpelioğlu, Ali

2006-06-01

The clinical and microscopic appearances of inflammatory bowel disease may be very similar to those of amebic colitis. The coexistence of invasive amebiasis with inflammatory bowel disease may have disastrous results. Patients with inflammatory bowel disease have a greater prevalence of amebiasis, but this association is more significant for ulcerative colitis. There have been very few reports in the literature presenting the superimposition of amebiasis on Crohn's disease. In this report, a rare case of Crohn's colitis with superimposed amebiasis resulting in colonic perforation is presented. Patients with inflammatory bowel disease traveling to endemic areas may benefit from receiving a course of prophylactic anti-amebic medication.

Prediction of treatment refractoriness in ulcerative colitis and Crohn's disease--do we have reliable markers?

PubMed

Gelbmann, C M

2000-05-01

Treatment refractoriness is a severe problem in the management of patients with ulcerative colitis and Crohn's disease. Despite some promising new therapeutic approaches, corticosteroids are still the preferential primary treatment for moderate to severe Crohn's disease and of severe ulcerative colitis. However, clinical response to corticosteroids varies, and many patients are resistant to such treatment. Since corticosteroids have frequent and even severe side effects, and toxicity increases with chronic steroid intake, factors predictive of response to such treatment would be very helpful for decisions on further management of these patients. At least in severe attacks of ulcerative colitis, the consensus seems to be that a high frequency of bowel movements as well as a high C-reactive protein and low serum albumin recorded after a few days of intensive medical treatment are important signs for early prediction of treatment failure in the majority of the patients. In Crohn's disease thus far, data on predictive factors are conflicting. No reliable marker with sufficient predictive value for treatment refractoriness could be identified. This might be due to the tremendous heterogeneity of Crohn's disease with many clinical phenotypes, which requires subgroup analysis with sufficient numbers of patients. Corticosteroids as well as other immunomodulating and immunosuppressive medications interfere with the immune system, which plays a central role in the mediation of intestinal inflammation. Treatment refractoriness might have its origin in specific immunological peculiarities eventually reflected in abnormal immunological, biochemical, and clinical parameters. Further exploration of those parameters to predict treatment refractoriness in patients with ulcerative colitis or Crohn's disease is of great clinical importance for safe and efficient management of patients.

Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

PubMed

Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

2016-10-01

Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spontaneous gas gangrene in a patient with Crohn's disease.

PubMed

Vaidya, Yash P; Vaidya, Tanvi P

2012-01-01

Spontaneous gas gangrene is necrosis of muscles in the absence of trauma, causing an acutely painful and potentially fatal condition. However, the occurrence of this condition in Crohn's disease has been very rarely documented. In this extremely rare case we describe an occurrence of spontaneous gas gangrene, in a known case of Crohn's disease. The patient presented with fever and pain in the left arm and abdomen. After admission and initial management with antibiotics, the patient developed crepitus in the arm and myonecrosis necessitating a fasciotomy and later an emergency amputation of his left upper limb. The pathogenesis of gas gangrene in inflammatory bowel disease is not fully understood. Management includes aggressive antibiotic administration followed by amputation of the non-salvageable limb. A high index of suspicion of such rare complications is a must and surgical intervention is life saving; however, the efficacy of anti-gas gangrene serum is controversial. We recommend use of a multipronged approach in such cases with high mortality rates.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

PubMed

Lomer, Miranda C E; Grainger, Stephen L; Ede, Roland; Catterall, Adrian P; Greenfield, Simon M; Cowan, Russell E; Vicary, F Robin; Jenkins, Anthony P; Fidler, Helen; Harvey, Rory S; Ellis, Richard; McNair, Alistair; Ainley, Colin C; Thompson, Richard P H; Powell, Jonathan J

2005-03-01

Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohn's disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohn's disease, in a single-blind, randomized, multi-centre, placebo controlled trial. Eighty-three patients with active Crohn's disease were randomly allocated in a 2 x 2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohn's disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohn's disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohn's disease.

Assessment of Magnetic Resonance Enterography in the Diagnosis of Small Bowel Diseases in Children with Crohn's Disease.

PubMed

Iwańczak, Barbara M; Nienartowicz, Ewa; Krzesiek, Elżbieta

2016-01-01

In pediatric patients Crohn's disease most commonly involves the colon and the ileocecal part of the intestine. MR enterography, a new method of small bowel imaging with magnetic resonance, has been introduced in the last decade. The aim of this study was to assess the usefulness of the MR enterography in the diagnosis of small bowel lesions in children with Crohn's disease. The study included 37 children (18 girls and 19 boys) aged from 5.5 to 18 years (average age, 13.3), diagnosed with Crohn's disease according to the Porto criteria. The disease duration ranged from 1 month to 12 years, on average 3 years. MR eterography was performed according to the Giles et al. protocol. The obtained results were compared with the location and the manifestation of the disease according to the Paris classification. In 13 children (35.1%), the disease began prior to 10 years of age, and in the remaining 24 children (64.9%) between 10 and 17 years of age. The gastrointestinal endoscopy confirmed Crohn's disease in the colon (45.9%) and in the colon and ileum (27.1%). An incomplete colonoscopy examination which did not reveal the location of the disease was conducted in 7 children (18.9%). A comparison of the location of Crohn's disease with the location of lesions in the small bowel as indicated by MR enterography revealed that the most common changes can be found in the final part of ileum, in ileum, and in 4 children in jejunum. MR enterography demonstrated, that 16 children (43.2%) had inflammation, 7 children (18.9%) stenosis, and 14 children (37.8%) had no lesions at all. MR enterography is a non-invasive and safe procedure well tolerated by children that allows the visualization of lesions in the small bowel in children with Crohn's disease.

Mediator Complex Subunits MED2, MED5, MED16, and MED23 Genetically Interact in the Regulation of Phenylpropanoid Biosynthesis.

PubMed

Dolan, Whitney L; Dilkes, Brian P; Stout, Jake M; Bonawitz, Nicholas D; Chapple, Clint

2017-12-01

The phenylpropanoid pathway is a major global carbon sink and is important for plant fitness and the engineering of bioenergy feedstocks. In Arabidopsis thaliana , disruption of two subunits of the transcriptional regulatory Mediator complex, MED5a and MED5b, results in an increase in phenylpropanoid accumulation. By contrast, the semidominant MED5b mutation reduced epidermal fluorescence4-3 ( ref4-3 ) results in dwarfism and constitutively repressed phenylpropanoid accumulation. Here, we report the results of a forward genetic screen for suppressors of ref4-3. We identified 13 independent lines that restore growth and/or phenylpropanoid accumulation in the ref4-3 background. Two of the suppressors restore growth without restoring soluble phenylpropanoid accumulation, indicating that the growth and metabolic phenotypes of the ref4-3 mutant can be genetically disentangled. Whole-genome sequencing revealed that all but one of the suppressors carry mutations in MED5b or other Mediator subunits. RNA-seq analysis showed that the ref4-3 mutation causes widespread changes in gene expression, including the upregulation of negative regulators of the phenylpropanoid pathway, and that the suppressors reverse many of these changes. Together, our data highlight the interdependence of individual Mediator subunits and provide greater insight into the transcriptional regulation of phenylpropanoid biosynthesis by the Mediator complex. © 2017 American Society of Plant Biologists. All rights reserved.

A comparison of abdominal surgical outcomes between African-American and Caucasian Crohn's patients.

PubMed

Griglione, Nicole; Yarandi, Shadi; Srinivasan, Jahnavi; Ahearn, Thomas; Dhere, Tanvi

2014-08-01

Whether race affects the natural history of Crohn's disease is a matter of debate. The aim of the current study was to evaluate the differences in surgical outcomes between African-American (AA) and Caucasian (C) Crohn's patients undergoing surgery at a tertiary care referral center. With Institutional Review Board approval, the medical records of our institution were queried to identify consecutive AA and C patients who underwent surgery for Crohn's disease from December 1, 2009 to December 15, 2011. A retrospective chart review was performed using electronic medical records. A total of 77 patients were included in this study, including 32 AA (41 %) and 45 C (59 %). No significant differences were seen with respect to age, gender, type of insurance, preoperative exposure to immunosuppressives, body mass index, or smoking history between the two populations (p > 0.05). There was a trend toward lower albumin in AAs (p = 0.09). AA and C patients who underwent their first Crohn's disease (CD)-related surgery had similar lag periods between diagnosis and surgery. No significant differences were seen in location of disease, indication for operation, and need for open laparotomy over laparoscopy. No significant differences were seen in need for a repeat operation within 90 days of the original surgery or major postoperative complications. There was a trend toward higher rate of minor complications in the AA group (p = 0.07). No significant differences were noted in the current study in several preoperative variables and surgical outcomes between AA and C.

Inflammatory activity in Crohn disease: ultrasound findings.

PubMed

Migaleddu, Vincenzo; Quaia, Emilio; Scano, Domenico; Virgilio, Giuseppe

2008-01-01

Improvements in the ultrasound examination of bowel disease have registered in the last years the introduction of new technologies regarding high frequency probes (US), highly sensitive color or power Doppler units (CD-US), and the development of new non-linear technologies that optimize detection of contrast agents. Contrast-enhanced ultrasound (CE-US) most importantly increases the results in sonographic evaluation of Crohn disease inflammatory activity. CE-US has become an imaging modality routinely employed in the clinical practice for the evaluation of parenchymal organs due to the introduction of new generation microbubble contrast agents which persist in the bloodstream for several minutes after intravenous injection. The availability of high frequency dedicated contrast-specific US techniques provide accurate depiction of small bowel wall perfusion due to the extremely high sensitivity of non-linear signals produced by microbubble insonation. In Crohn's disease, CE-US may characterize the bowel wall thickness by differentiating fibrosis from edema and may grade the inflammatory disease activity by assessing the presence and distribution of vascularity within the layers of the bowel wall (submucosa alone or the entire bowel wall). Peri-intestinal inflammatory involvement can be also characterized. CE-US can provide prognostic data concerning clinical recurrence of the inflammatory disease and evaluate the efficacy of drugs treatments.

Saccharomyces boulardii does not prevent relapse of Crohn's disease.

PubMed

Bourreille, Arnaud; Cadiot, Guillaume; Le Dreau, Gérard; Laharie, David; Beaugerie, Laurent; Dupas, Jean-Louis; Marteau, Philippe; Rampal, Patrick; Moyse, Dominique; Saleh, Ashraf; Le Guern, Marie-Emmanuelle; Galmiche, Jean-Paul

2013-08-01

Saccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates. We performed a prospective study of 165 patients who achieved remission after treatment with steroids or salicylates; they were randomly assigned to groups given S boulardii (1 g/day) or placebo for 52 weeks. The primary end point was the percentage of patients in remission at week 52. Time to relapse, Crohn's disease activity index scores, and changes in parameters of inflammation were secondary end points. CD relapsed in 80 patients, 38 in the S boulardii group (47.5%) and 42 in the placebo group (53.2%, a nonsignificant difference). The median time to relapse did not differ significantly between patients given S boulardii (40.7 weeks) vs placebo (39.0 weeks). There were no significant differences between groups in mean Crohn's disease activity index scores or erythrocyte sedimentation rates or in median levels of C-reactive protein. In a post hoc analysis, nonsmokers given S boulardii were less likely to experience a relapse of CD than nonsmokers given placebo, but this finding requires confirmation. Although the probiotic yeast S boulardii is safe and well tolerated, it does not appear to have any beneficial effects for patients with CD in remission after steroid or salicylate therapies. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Aminosalicylates for induction of remission or response in Crohn's disease.

PubMed

Lim, Wee-Chian; Hanauer, Stephen

2010-12-08

Controlled clinical trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in patients with mildly to moderately active Crohn's disease. To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease. Separate MEDLINE (1966-July 2010), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 3, 2010) and EMBASE database searches (1985-July 2010) of all relevant English and non-English language articles were performed, followed by manual searches of the reference list from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2010) of the American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG). Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included. Data extraction and assessment of methodological quality of each selected study was independently performed by the investigators and any disagreement was resolved by discussion and consensus. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Nineteen studies met the inclusion criteria and were analyzed. Pooled relative risks (RR) for inducing remission or clinical response and their 95% confidence intervals were calculated (random effects model) where appropriate. Sulfasalazine was more likely to induce remission (RR 1.38; 95% CI

Low dose oral pH modified release budesonide for maintenance of steroid induced remission in Crohn's disease

PubMed Central

Gross, V; Andus, T; Ecker, K; Raedler, A; Loeschke, K; Plauth, M; Rasenack, J; Weber, A; Gierend, M; Ewe, K; Scholmerich, J; Budesonide, S

1998-01-01

Background—The relapse rate after steroid induced remission in Crohn's disease is high. 
Aims—To test whether oral pH modified release budesonide (3 × 1 mg/day) reduces the relapse rate and to identify patient subgroups with an increased risk of relapse. 
Methods—In a multicentre, randomised, double blind study, 179 patients with steroid induced remission of Crohn's disease received either 3 × 1 mg budesonide (n=84) or placebo (n=95) for one year. The primary study aim was the maintenance of remission of Crohn's disease for one year. 
Results—Patient characteristics at study entry were similar for both groups. The relapse rate was 67% (56/84) in the budesonide group and 65% (62/95) in the placebo group. The relapse curves in both groups were similar. The mean time to relapse was 93.5days in the budesonide group and 67.0 days in the placebo group. No prognostic factors allowing prediction of an increased risk for relapse or definition of patient subgroups who derived benefit from low dose budesonide were found. Drug related side effects were mild and no different between the budesonide and the placebo group. 
Conclusion—Oral pH modified release budesonide at a dose of 3 × 1 mg/day is not effective for maintaining steroid induced remission in Crohn's disease. 

 Keywords: budesonide; Crohn's disease; maintenance of remission PMID:9616309

Vedolizumab as induction and maintenance therapy for Crohn's disease.

PubMed

Sandborn, William J; Feagan, Brian G; Rutgeerts, Paul; Hanauer, Stephen; Colombel, Jean-Frédéric; Sands, Bruce E; Lukas, Milan; Fedorak, Richard N; Lee, Scott; Bressler, Brian; Fox, Irving; Rosario, Maria; Sankoh, Serap; Xu, Jing; Stephens, Kristin; Milch, Catherine; Parikh, Asit

2013-08-22

The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but

Detection of longitudinal ulcer using roughness value for computer aided diagnosis of Crohn's disease

NASA Astrophysics Data System (ADS)

Oda, Masahiro; Kitasaka, Takayuki; Furukawa, Kazuhiro; Watanabe, Osamu; Ando, Takafumi; Goto, Hidemi; Mori, Kensaku

2011-03-01

The purpose of this paper is to present a new method to detect ulcers, which is one of the symptoms of Crohn's disease, from CT images. Crohn's disease is an inflammatory disease of the digestive tract. Crohn's disease commonly affects the small intestine. An optical or a capsule endoscope is used for small intestine examinations. However, these endoscopes cannot pass through intestinal stenosis parts in some cases. A CT image based diagnosis allows a physician to observe whole intestine even if intestinal stenosis exists. However, because of the complicated shape of the small and large intestines, understanding of shapes of the intestines and lesion positions are difficult in the CT image based diagnosis. Computer-aided diagnosis system for Crohn's disease having automated lesion detection is required for efficient diagnosis. We propose an automated method to detect ulcers from CT images. Longitudinal ulcers make rough surface of the small and large intestinal wall. The rough surface consists of combination of convex and concave parts on the intestinal wall. We detect convex and concave parts on the intestinal wall by a blob and an inverse-blob structure enhancement filters. A lot of convex and concave parts concentrate on roughed parts. We introduce a roughness value to differentiate convex and concave parts concentrated on the roughed parts from the other on the intestinal wall. The roughness value effectively reduces false positives of ulcer detection. Experimental results showed that the proposed method can detect convex and concave parts on the ulcers.

ACR Appropriateness Criteria Crohn Disease.

PubMed

Kim, David H; Carucci, Laura R; Baker, Mark E; Cash, Brooks D; Dillman, Jonathan R; Feig, Barry W; Fowler, Kathryn J; Gage, Kenneth L; Noto, Richard B; Smith, Martin P; Yaghmai, Vahid; Yee, Judy; Lalani, Tasneem

2015-10-01

Crohn disease is a chronic inflammatory disorder involving the gastrointestinal tract, characterized by episodic flares and times of remission. Underlying structural damage occurs progressively, with recurrent bouts of inflammation. The diagnosis and management of this disease process is dependent on several clinical, laboratory, imaging, endoscopic, and histologic factors. In recent years, with the maturation of CT enterography, and MR enterography, imaging has played an increasingly important role in relation to Crohn Disease. In addition to these specialized examination modalities, ultrasound and routine CT have potential uses. Fluoroscopy, radiography, and nuclear medicine may be less beneficial depending on the clinical scenario. The imaging modality best suited to evaluating this disease may change, depending on the target population, severity of presentation, and specific clinical situation. This document presents seven clinical scenarios (variants) in both the adult and pediatric populations and rates the appropriateness of the available imaging options. They are summarized in a consolidated table, and the underlying rationale and supporting literature are presented in the accompanying narrative. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis.

PubMed

Keulemans, Y C; Mok, K S; Slors, J F; Brink, M A; Gouma, D J; Tytgat, G N; Groen, A K

1999-10-01

Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients. Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.

Malignant peritoneal mesothelioma and Crohn disease.

PubMed

Butnor, Kelly J; Pavlisko, Elizabeth N; Sporn, Thomas A; Roggli, Victor L

2017-03-01

Mesothelial reaction simulating peritoneal diffuse malignant mesothelioma (MM) has been reported in the setting of Crohn ileitis. To our knowledge, peritoneal MM arising in patients with inflammatory bowel disease (IBD) has not been reported. The purpose of this study is to report the clinicopathological characteristics of patients with peritoneal MM and IBD. A database of approximately 3800 MM was reviewed for cases of MM in patients with IBD. Three patients (0.08%) with peritoneal MM and Crohn disease (CD) were identified, including two women and one man ranging in age from 56 to 65 years. All had a long-standing history of diarrhoea and an established diagnosis of CD of 3 years or greater duration. Two had epithelial MM and one had biphasic MM. Only one had documented asbestos exposure. Peritoneal MM occurs rarely in patients with IBD, but interestingly, has only been observed in the setting of CD and not in patients with ulcerative colitis. Chronic inflammation has been associated with the development of MM in rare instances and these three cases suggest that CD with transmural inflammation may also be a precursor. The precise role of CD-related transmural inflammation in the carcinogenesis of peritoneal MM remains to be determined. 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/.

Consensus Recommendations for Evaluation, Interpretation, and Utilization of Computed Tomography and Magnetic Resonance Enterography in Patients With Small Bowel Crohn's Disease.

PubMed

Bruining, David H; Zimmermann, Ellen M; Loftus, Edward V; Sandborn, William J; Sauer, Cary G; Strong, Scott A

2018-03-01

Computed tomography and magnetic resonance enterography have become routine small bowel imaging tests to evaluate patients with established or suspected Crohn's disease, but the interpretation and use of these imaging modalities can vary widely. A shared understanding of imaging findings, nomenclature, and utilization will improve the utility of these imaging techniques to guide treatment options, as well as assess for treatment response and complications. Representatives from the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of Pediatric Radiology, the American Gastroenterological Association, and other experts, systematically evaluated evidence for imaging findings associated with small bowel Crohn's disease enteric inflammation and established recommendations for the evaluation, interpretation, and use of computed tomography and magnetic resonance enterography in small bowel Crohn's disease. This work makes recommendations for imaging findings that indicate small bowel Crohn's disease, how inflammatory small bowel Crohn's disease and its complications should be described, elucidates potential extra-enteric findings that may be seen at imaging, and recommends that cross-sectional enterography should be performed at diagnosis of Crohn's disease and considered for small bowel Crohn's disease monitoring paradigms. A useful morphologic construct describing how imaging findings evolve with disease progression and response is described, and standard impressions for radiologic reports that convey meaningful information to gastroenterologists and surgeons are presented. Copyright © 2018 AGA Institute, RSNA, and Society of Abdominal Radiology. Published by Elsevier Inc. All rights reserved.

Safety and tolerability of low-dose naltrexone therapy in children with moderate to severe Crohn's disease: a pilot study.

PubMed

Smith, Jill P; Field, Douglas; Bingaman, Sandra I; Evans, Robert; Mauger, David T

2013-04-01

There is an unmet need for safe and effective medicines to treat children with Crohn's disease. Recently, investigations have shown an association between endogenous opioid peptides and inflammatory cells. The aims of this study were to evaluate the safety and tolerability of an opioid antagonist, naltrexone, in children with moderate to severe Crohn's disease. A pilot clinical trial was conducted in children with moderate to severe Crohn's disease. Fourteen subjects with a mean age of 12.3 years (range, 8 to 17 y) were enrolled. Children were randomized to placebo or naltrexone (0.1 mg/kg) orally for 8 weeks followed by open-labeled treatment with 8 additional weeks of naltrexone. Safety and toxicity were monitored by physical examinations and blood chemistries. Clinical activity was assessed by the Pediatric Crohn's Disease Activity Index (PCDAI) and Quality of life was monitored by the Impact III survey. Oral naltrexone was well tolerated without any serious adverse events in children with moderate to severe Crohn's disease. PCDAI scores significantly decreased from pretreatment values (34.2±3.3) with an 8-week course of naltrexone therapy (21.7±3.9) (P=0.005). Twenty-five percent of those treated with naltrexone were considered in remission (score ≤10) and 67% had improved with mild disease activity (decrease in PCDAI score by at least 10 points) at the end of the study. Systemic and social quality of life improved with naltrexone treatment (P=0.035). Naltrexone therapy seems safe with limited toxicity when given to children with Crohn's disease and may reduce disease activity.

Metastatic Crohn disease clinically reminiscent of erythema nodosum on the right leg.

PubMed

Park, Hyun C; Kim, Hyun W; Park, Chan G; Ko, Joo Y

2016-09-01

Cutaneous manifestations are well-recognized complications of Crohn disease (CD) that can be divided into disease-specific and reactive conditions. One of the most common reactive conditions is erythema nodosum (EN), which presents as subcutaneous tender nodules most often on the legs. On the other hand, metastatic Crohn disease (MCD) is a rare cutaneous manifestation of CD defined as the presence of noncaseating granulomas that are not contiguous with the gastrointestinal (GI) tract. The clinical presentation of MCD is variable; however, lesions often are located on the legs and genital region. We report the case of a 21-year-old woman with a 6-year history of CD who presented with MCD clinically simulating EN.

A rare case of Crohn's ileitis in a patient with constitutional mismatch repair deficiency.

PubMed

Kaimakliotis, Pavlos; Giardiello, Francis; Eze, Ogechukwu; Truta, Brindusa

2017-01-01

Constitutional mismatch repair deficiency (CMMRD), a variant of Lynch syndrome, is a rare disease characterized by café-au-lait spots, oligopolyposis, glioblastoma and lymphoma. A 24-year-old male, under surveillance for CMMRD, developed Crohn's ileitis after total colectomy with end ileostomy for colorectal cancer and failed to respond to oral corticosteroids. The patient underwent induction and maintenance of remission with vedolizumab infusions. We report the first patient with CMMRD developing Crohn's disease. The choice of immunosuppressive therapy in these patients is challenging and needs to be made according to their risk for malignancy.

Ulcerative Colitis and Crohn's Disease: Implications for College Health Programs

ERIC Educational Resources Information Center

Gelphi, A. P.

1977-01-01

The author reviews clinical patterns of inflammatory bowel disorders, establishes a perspective for recognizing ulcerative colitis, ulcerative proctitis, and Crohn's disease in relation to other bowel inflammations, and suggests some epidemiologic strategies for studying etiology, pathogenesis, and natural history of the diseases. (MJB)

Pinworm Infestation Mimicking Crohns' Disease

PubMed Central

Ignatova, Simone; Ekstedt, Mattias

2013-01-01

We here report a case of a young man who presented to his general practitioner with diarrhea. Inflammatory bowel disease was suspected and a colonoscopy showed aphthous lesions suggestive of Crohns' disease but biopsies revealed eggs of Enterobius vermicularis. When treated for this parasite, his symptoms were alleviated and a followup colonoscopy revealed a normal colon and distal ileum. Enterobius vermicularis is the most common parasite worldwide and has been attributed with many different presentations and pathologies. It is therefore necessary to maintain vigilance, even in high-income countries, in order to diagnose patients with one of the many atypical presentations of pinworms. PMID:23555063

Endoscopy and cross-sectional imaging for assessing Crohn׳s disease activity.

PubMed

Stidham, Ryan W; Cross, Raymond K

2016-07-01

Crohn's disease (CD) is principally characterized by chronic and recurrent inflammation of the gastrointestinal tract, most commonly found in the ileo-colonic region. The chronicity and severity of intestinal inflammation together contribute to progressive, cumulative, deep, transmural intestinal damage, including stricturing, obstruction, abscesses, and fistulae. Both intestinal inflammation and its chronic complications result in a range of symptoms subsequently leading to patient presentations with diarrhea, abdominal pain, and anemia related to intestinal blood loss. Measuring disease activity and severity are essential for decision of treatment intensity early in the disease course and longitudinal monitoring of therapeutic efficacy. This review will summarize the transition from subjective symptoms driving disease activity indices, into increasingly objective and quantitative measures of intestinal injury by direct mucosal assessment (endoscopy), cross-sectional imaging, and surrogate biomarkers. Specific commentary on intestinal stricture and perianal fistula assessment and management are presented in accompanying sections of this series.

The MedDRA paradox.

PubMed

Merrill, Gary H

2008-11-06

MedDRA (the Medical Dictionary for Regulatory Activities Terminology) is a controlled vocabulary widely used as a medical coding scheme. However, MedDRA's characterization of its structural hierarchy exhibits some confusing and paradoxical features. The goal of this paper is to examine these features, determine whether there is a coherent view of the MedDRA hierarchy that emerges, and explore what lessons are to be learned from this for using MedDRA and similar terminologies in a broad medical informatics context that includes relations among multiple disparate terminologies, thesauri, and ontologies.

Infliximab Combined with Enteral Nutrition for Managing Crohn's Disease Complicated with Intestinal Fistulas

PubMed Central

Wu, Xiao-Li; Tao, Li-Ping; Wu, Jian-Sheng; Chen, Xiang-Rong

2016-01-01

Aim. This study was performed to evaluate the additional enteral nutrition (EN) in the efficacy of infliximab (IFX) compared with the conventional therapy in managing Crohn's disease (CD) complicated with intestinal fistulas. Methods. A total of 42 CD with intestinal fistulas were randomly divided into infliximab treatment group (n = 20) and conventional therapy group (n = 22). We evaluated the laboratory indexes, Crohn's disease activity index (CDAI), Crohn's disease simplified endoscopic score (SES-CD), and healing of fistula in the two groups before treatment, at 14 weeks, and at 30 weeks, respectively. Results. In the IFX treatment group, the CDAI score, the SES-CD, erythrocyte sedimentation rate, and C-reactive protein levels were significantly decreased during treatment compared with those before treatment. The body mass index and albumin levels were increased in both groups. Moreover, in the IFX treatment group, fistula healing was found in 8 at the 14th week and 18 at the 30th week, respectively, which was greater than that in the conventional therapy group. Conclusion. Our study suggested that infliximab combined with EN is an effective treatment for CD patients complicated with intestinal fistulas. PMID:27738427

The incidence of Crohn's disease in Cardiff over the last 75 years: an update for 1996-2005.

PubMed

Gunesh, S; Thomas, G A O; Williams, G T; Roberts, A; Hawthorne, A B

2008-02-01

The incidence of Crohn's disease rose rapidly in industralized countries over the past 50 years, but it is unclear whether the incidence is still rising or has reached a plateau. To update the long-term incidence study of Crohn's disease in Cardiff for 1996-2005, to investigate whether incidence is still rising and to study changes in disease characteristics over time. Crohn's cases identified by retrospective analysis of hospital records as in previous studies in Cardiff. Two hundred and twelve cases were identified. Corrected incidence for this decade was 66 x 10(6) per year (95% confidence interval: 58-76), showing a continuing rise compared to previous decades. The proportion with colonic disease at presentation continues to rise (43%) with a corresponding fall in those with terminal ileal disease. There remains a strong female preponderance (F:M 1.6:1) as in previous studies. The incidence in children under age 16 continues to rise, and the median age at diagnosis has fallen slightly. Crohn's disease incidence continues to rise slowly in Cardiff with a continuing increase in those presenting with colonic disease, which is now the commonest disease pattern.

Analysis of PubMed User Sessions Using a Full-Day PubMed Query Log: A Comparison of Experienced and Nonexperienced PubMed Users

PubMed Central

2015-01-01

Background PubMed is the largest biomedical bibliographic information source on the Internet. PubMed has been considered one of the most important and reliable sources of up-to-date health care evidence. Previous studies examined the effects of domain expertise/knowledge on search performance using PubMed. However, very little is known about PubMed users’ knowledge of information retrieval (IR) functions and their usage in query formulation. Objective The purpose of this study was to shed light on how experienced/nonexperienced PubMed users perform their search queries by analyzing a full-day query log. Our hypotheses were that (1) experienced PubMed users who use system functions quickly retrieve relevant documents and (2) nonexperienced PubMed users who do not use them have longer search sessions than experienced users. Methods To test these hypotheses, we analyzed PubMed query log data containing nearly 3 million queries. User sessions were divided into two categories: experienced and nonexperienced. We compared experienced and nonexperienced users per number of sessions, and experienced and nonexperienced user sessions per session length, with a focus on how fast they completed their sessions. Results To test our hypotheses, we measured how successful information retrieval was (at retrieving relevant documents), represented as the decrease rates of experienced and nonexperienced users from a session length of 1 to 2, 3, 4, and 5. The decrease rate (from a session length of 1 to 2) of the experienced users was significantly larger than that of the nonexperienced groups. Conclusions Experienced PubMed users retrieve relevant documents more quickly than nonexperienced PubMed users in terms of session length. PMID:26139516

Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn's Disease.

PubMed

Lewis, James D; Chen, Eric Z; Baldassano, Robert N; Otley, Anthony R; Griffiths, Anne M; Lee, Dale; Bittinger, Kyle; Bailey, Aubrey; Friedman, Elliot S; Hoffmann, Christian; Albenberg, Lindsey; Sinha, Rohini; Compher, Charlene; Gilroy, Erin; Nessel, Lisa; Grant, Amy; Chehoud, Christel; Li, Hongzhe; Wu, Gary D; Bushman, Frederic D

2015-10-14

Abnormal composition of intestinal bacteria--"dysbiosis"-is characteristic of Crohn's disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn's disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.

PubMed

Wright, Emily K; Kamm, Michael A; De Cruz, Peter; Hamilton, Amy L; Selvaraj, Fabiyola; Princen, Fred; Gorelik, Alexandra; Liew, Danny; Prideaux, Lani; Lawrance, Ian C; Andrews, Jane M; Bampton, Peter A; Jakobovits, Simon L; Florin, Timothy H; Gibson, Peter R; Debinski, Henry; Macrae, Finlay A; Samuel, Douglas; Kronborg, Ian; Radford-Smith, Graham; Gearry, Richard B; Selby, Warwick; Bell, Sally J; Brown, Steven J; Connell, William R

2018-05-25

Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

Nutritional supplementation with polymeric diet enriched with transforming growth factor-beta 2 for children with Crohn's disease.

PubMed

Hartman, Corina; Berkowitz, Drora; Weiss, Batia; Shaoul, Ron; Levine, Arie; Adiv, Orly Eshach; Shapira, Riki; Fradkin, Akiva; Wilschanski, Michael; Tamir, Ada; Shamir, Raanan

2008-07-01

A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease. To summarize the experience of several pediatric gastroenterology units in Israel using a TGFbeta2-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease. In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet. The Modulen-treated children showed a significant decrease in PCDAI from 34.3 to 15.7 (P< 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P= 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P= 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group. In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI, suggesting an additional advantage of nutritional therapy in children with this disease.

Magnetic resonance enterography has good inter-rater agreement and diagnostic accuracy for detecting inflammation in pediatric Crohn disease.

PubMed

Church, Peter C; Greer, Mary-Louise C; Cytter-Kuint, Ruth; Doria, Andrea S; Griffiths, Anne M; Turner, Dan; Walters, Thomas D; Feldman, Brian M

2017-05-01

Magnetic resonance enterography (MRE) is increasingly relied upon for noninvasive assessment of intestinal inflammation in Crohn disease. However very few studies have examined the diagnostic accuracy of individual MRE signs in children. We have created an MR-based multi-item measure of intestinal inflammation in children with Crohn disease - the Pediatric Inflammatory Crohn's MRE Index (PICMI). To inform item selection for this instrument, we explored the inter-rater agreement and diagnostic accuracy of individual MRE signs of inflammation in pediatric Crohn disease and compared our findings with the reference standards of the weighted Pediatric Crohn's Disease Activity Index (wPCDAI) and C-reactive protein (CRP). In this cross-sectional single-center study, MRE studies in 48 children with diagnosed Crohn disease (66% male, median age 15.5 years) were reviewed by two independent radiologists for the presence of 15 MRE signs of inflammation. Using kappa statistics we explored inter-rater agreement for each MRE sign across 10 anatomical segments of the gastrointestinal tract. We correlated MRE signs with the reference standards using correlation coefficients. Radiologists measured the length of inflamed bowel in each segment of the gastrointestinal tract. In each segment, MRE signs were scored as either binary (0-absent, 1-present), or ordinal (0-absent, 1-mild, 2-marked). These segmental scores were weighted by the length of involved bowel and were summed to produce a weighted score per patient for each MRE sign. Using a combination of wPCDAI≥12.5 and CRP≥5 to define active inflammation, we calculated area under the receiver operating characteristic curve (AUC) for each weighted MRE sign. Bowel wall enhancement, wall T2 hyperintensity, wall thickening and wall diffusion-weighted imaging (DWI) hyperintensity were most commonly identified. Inter-rater agreement was best for decreased motility and wall DWI hyperintensity (kappa≥0.64). Correlation between MRE

Small-bowel MRI in children and young adults with Crohn disease: retrospective head-to-head comparison of contrast-enhanced and diffusion-weighted MRI.

PubMed

Neubauer, Henning; Pabst, Thomas; Dick, Anke; Machann, Wolfram; Evangelista, Laura; Wirth, Clemens; Köstler, Herbert; Hahn, Dietbert; Beer, Meinrad

2013-01-01

Small-bowel MRI based on contrast-enhanced T1-weighted sequences has been challenged by diffusion-weighted imaging (DWI) for detection of inflammatory bowel lesions and complications in patients with Crohn disease. To evaluate free-breathing DWI, as compared to contrast-enhanced MRI, in children, adolescents and young adults with Crohn disease. This retrospective study included 33 children and young adults with Crohn disease ages 17 ± 3 years (mean ± standard deviation) and 27 matched controls who underwent small-bowel MRI with contrast-enhanced T1-weighted sequences and DWI at 1.5 T. The detectability of Crohn manifestations was determined. Concurrent colonoscopy as reference was available in two-thirds of the children with Crohn disease. DWI and contrast-enhanced MRI correctly identified 32 and 31 patients, respectively. All 22 small-bowel lesions and all Crohn complications were detected. False-positive findings (two on DWI, one on contrast-enhanced MRI), compared to colonoscopy, were a result of large-bowel lumen collapse. Inflammatory wall thickening was comparable on DWI and contrast-enhanced MRI. DWI was superior to contrast-enhanced MRI for detection of lesions in 27% of the assessed bowel segments and equal to contrast-enhanced MRI in 71% of segments. DWI facilitates fast, accurate and comprehensive workup in Crohn disease without the need for intravenous administration of contrast medium. Contrast-enhanced MRI is superior in terms of spatial resolution and multiplanar acquisition.

[The role of infective intestinal complications on the course of Crohn's disease and ulcerative rectocolitis].

PubMed

Romagnoli, A M; Corradini, P; Matergi, M; Schiaroli, G; Moschini, G; Incandela, L; Galassi, L

1993-01-01

The authors studied the incidence of protozoal and bacterial infection in 41 cases of Crohn disease und ulcerative colitis; the effect of anti infective therapy on the clinical course has also been tested. Patients with ulcerative colitis are more frequently involved in this type of complication than those with Crohn disease. Therapy has a positive influence on the course of the disease; therefore systematic study of the faeces for bacteria and parasites is necessary for a correct understanding of chronic inflammatory bowel disease and for specific treatment.

Pachydermoperiostosis in a Patient with Crohn's Disease: Treatment and Literature Review.

PubMed

Mobini, Maryam; Akha, Ozra; Fakheri, Hafez; Majidi, Hadi; Fattahi, Sanam

2018-01-01

Pachydermoperiostosis (PDP) is a rare disorder characterized by pachydermia, digital clubbing, periostitis, and an excess of affected males. It is the primary form of hypertrophic osteoarthropathy (HOA) and there are some rare associations of PDP with other disorders. Here we describe a patient with Crohn's disease associated with PDP. A 26-year-old man, who was a known case of Crohn's disease, referred with diffuse swelling in the upper and lower limbs and cutis verticis gyrata since 7 years ago. PDP was suspected and endocrinological and radiological studies were conducted for the evaluation of underlying disease. He was prescribed celecoxib, low-dose prednisolone, and pamidronate to control the swelling, periostitis, azathiopurine, and mesalazine according to gastrointestinal involvement. In conclusion, it is important to identify this condition since a misdiagnosis might subject the patient to unnecessary investigations.

PubMed-EX: a web browser extension to enhance PubMed search with text mining features.

PubMed

Tsai, Richard Tzong-Han; Dai, Hong-Jie; Lai, Po-Ting; Huang, Chi-Hsin

2009-11-15

PubMed-EX is a browser extension that marks up PubMed search results with additional text-mining information. PubMed-EX's page mark-up, which includes section categorization and gene/disease and relation mark-up, can help researchers to quickly focus on key terms and provide additional information on them. All text processing is performed server-side, freeing up user resources. PubMed-EX is freely available at http://bws.iis.sinica.edu.tw/PubMed-EX and http://iisr.cse.yzu.edu.tw:8000/PubMed-EX/.

Effects of anti-tumour necrosis factor-alpha therapy on the quality of life in Crohn's disease.

PubMed

van Balkom, B P J; Schoon, E J; Stockbrügger, R W; Wolters, F L; van Hogezand, R A; van Deventer, S J H; Oldenburg, B; van Dullemen, H M; Russel, M G V M

2002-06-01

Infusion of anti-tumour necrosis factor-alpha appears to be highly effective in patients with Crohn's disease. To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions. An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified. In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy. Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.

MRI diffusion-weighted imaging (DWI) in pediatric small bowel Crohn disease: correlation with MRI findings of active bowel wall inflammation.

PubMed

Ream, Justin M; Dillman, Jonathan R; Adler, Jeremy; Khalatbari, Shokoufeh; McHugh, Jonathan B; Strouse, Peter J; Dhanani, Muhammad; Shpeen, Benjamin; Al-Hawary, Mahmoud M

2013-09-01

Restricted diffusion on diffusion-weighted imaging (DWI) sequences during magnetic resonance enterography (MRE) has been shown in segments of bowel affected by Crohn disease. However, the exact meaning of this finding, particularly within the pediatric Crohn disease population, is poorly understood. The purpose of this study was to determine the significance of bowel wall restricted diffusion in children with small bowel Crohn disease by correlating apparent diffusion coefficient (ADC) values with other MRI markers of disease activity. A retrospective review of pediatric patients (≤ 18 years of age) with Crohn disease terminal ileitis who underwent MRE with DWI at our institution between May 1, 2009 and May 31, 2011 was undertaken. All of the children had either biopsy-proven Crohn disease terminal ileitis or clinically diagnosed Crohn disease, including terminal ileal involvement by imaging. The mean minimum ADC value within the wall of the terminal ileum was determined for each examination. ADC values were tested for correlation/association with other MRI findings to determine whether a relationship exists between bowel wall restricted diffusion and disease activity. Forty-six MRE examinations with DWI in children with terminal ileitis were identified (23 girls and 23 boys; mean age, 14.3 years). There was significant negative correlation or association between bowel wall minimum ADC value and established MRI markers of disease activity, including degree of bowel wall thickening (R = (-)0.43; P = 0.003), striated pattern of arterial enhancement (P = 0.01), degree of arterial enhancement (P = 0.01), degree of delayed enhancement (P = 0.045), amount of mesenteric inflammatory changes (P < 0.0001) and presence of a stricture (P = 0.02). ADC values were not significantly associated with bowel wall T2-weighted signal intensity, length of disease involvement or mesenteric fibrofatty proliferation. Increasing bowel wall restricted diffusion

Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease.

PubMed

Sands, B E; Bank, S; Sninsky, C A; Robinson, M; Katz, S; Singleton, J W; Miner, P B; Safdi, M A; Galandiuk, S; Hanauer, S B; Varilek, G W; Buchman, A L; Rodgers, V D; Salzberg, B; Cai, B; Loewy, J; DeBruin, M F; Rogge, H; Shapiro, M; Schwertschlag, U S

1999-07-01

Recombinant human interleukin 11 (rhIL-11) is a cytokine with thrombocytopoietic activity and anti-inflammatory and mucosal protective effects. The objectives of this study were to investigate the safety and tolerability of rhIL-11 in patients with Crohn's disease and to explore the effects of dose and schedule on platelet count and Crohn's disease activity. A multicenter, double-masked, placebo-controlled, dose-escalation study of 76 patients with active Crohn's disease was performed. Patients were randomized to receive subcutaneous placebo or rhIL-11 at doses of 5, 16, or 40 microgram. kg-1. wk-1 given 2 or 5 times weekly for 3 weeks. Clinical and laboratory safety data were recorded, and disease activity was measured at each visit. Subcutaneous injection of rhIL-11 generally was well tolerated. Significantly greater increases in platelet counts were found among patients receiving rhIL-11 40 microgram. kg-1. wk-1 as 2 or 5 weekly doses and 16 microgram. kg-1. week-1 as 5 weekly doses compared with patients receiving placebo (P < 0.05). Patients receiving 16 microgram. kg-1. wk-1 had the highest clinical response rates, with a response seen in 42% of patients (5/12) receiving 5 weekly doses and 33% of patients (4/12) receiving 2 weekly doses, compared with 7% of patients (1/15) receiving placebo. Short-term treatment with rhIL-11 is well tolerated in patients with active Crohn's disease. The thrombocytopoietic effect of rhIL-11 seems to be both dose and schedule dependent and may be minimized with retained clinical benefit in Crohn's disease at 16 microgram. kg-1. wk-1 given in 2 equal doses.

Responsiveness of Endoscopic Indices of Disease Activity for Crohn's Disease.

PubMed

Khanna, Reena; Zou, GuangYong; Stitt, Larry; Feagan, Brian G; Sandborn, William J; Rutgeerts, Paul; McDonald, John W D; Dubcenco, Elena; Fogel, Ronald; Panaccione, Remo; Jairath, Vipul; Nelson, Sigrid; Shackelton, Lisa M; Huang, Bidan; Zhou, Qian; Robinson, Anne M; Levesque, Barrett G; D'Haens, Geert

2017-10-01

The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data from a trial of adalimumab, a drug therapy of known efficacy. Paired video recordings (N=112) of colonoscopies (baseline and week 8-12) obtained from patients with CD who participated in a trial of adalimumab therapy were reviewed in random order, in duplicate, by four central readers (56 pairs of videos by 2 groups of readers). Responsiveness of the SES-CD and the CDEIS was evaluated by comparing correlations between the observed and pre-specified predictions of change scores for these endoscopic indices with a global endoscopic evaluation of severity (GELS), a patient reported outcome (PRO2), and the Crohn's disease activity index (CDAI), and by calculation of the standardized effect size, and Guyatt's Responsiveness statistic (GRS) using 2 definitions of change; (1) treatment assignment and (2) an absolute change in total PRO2 of 50. The potential application of effect size estimates was demonstrated by calculating hypothetical sample sizes for comparing two independent groups. The impact of removing stenosis as an index item and adjusting for the number of segments observed was also assessed. Changes in both endoscopic instruments and the GELS were highly correlated. The SES-CD displayed numerically higher effect sizes for both definitions of change. The standardized effect size and GRS estimates (95% confidence interval) for the SES-CD based on treatment assignment were 0.84 (0.53, 1.15) and 0.79 (0.48, 1.09). Corresponding values for the CDEIS were 0.72 (0.42, 1.02) and 0.75 (0.45, 1.06). The standardized effect size and GRS estimates for the SES-CD based on an absolute change in total PRO2 of 50 points or greater were 0.76 (0.49, 1.02) and 0.93 (0.64, 1

Sterile folliculitis as an important diagnostic clue to Crohn's disease.

PubMed

Kempeneers, Céline; Paquot, Isabelle; Philippet, Pierre; Goossens, Annieta; Bernier, Vincent

2013-01-01

Sterile folliculitis is known to be one of the rare cutaneous manifestations of Crohn's disease (CD). To our knowledge it has never been emphasized as a marker of significant diagnostic value, perhaps maybe even more significant than more common cutaneous manifestations such as erythema nodosum (EN). © 2012 Wiley Periodicals, Inc.

Crohn's disease and ulcerative colitis are associated with elevated standardized mortality ratios: a meta-analysis.

PubMed

Bewtra, Meenakshi; Kaiser, Lisa M; TenHave, Tom; Lewis, James D

2013-03-01

Evidence regarding all-cause and cause-specific mortality in inflammatory bowel disease (IBD) is conflicting, and debate exists over appropriate study design to examine these important outcomes. We conducted a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn's disease (CD) and ulcerative colitis (UC), and additionally examined various effects of study design on this outcome. A systematic search of PubMed and EMBASE was conducted to identify studies examining mortality rates relative to the general population. Pooled summary standardized mortality ratios (SMR) were calculated using random effect models. Overall, 35 original articles fulfilled the inclusion and exclusion criteria, reporting all-cause mortality SMRs varying from 0.44 to 7.14 for UC and 0.71 to 3.20 for CD. The all-cause mortality summary SMR for inception cohort and population cohort UC studies was 1.19 (95% confidence interval, 1.06-1.35). The all-cause mortality summary SMR for inception cohort and population cohort CD studies was 1.38 (95% confidence interval, 1.23-1.55). Mortality from colorectal cancer, pulmonary disease, and nonalcoholic liver disease was increased, whereas mortality from cardiovascular disease was decreased. Patients with UC and CD have higher rates of death from all causes, colorectal-cancer, pulmonary disease, and nonalcoholic liver disease.

Analysis of factors affecting the quality of life of those suffering from Crohn's disease.

PubMed

Chrobak-Bień, Joanna; Gawor, Anna; Paplaczyk, Małgorzata; Małecka-Panas, Ewa; Gąsiorowska, Anita

2017-08-31

Crohn's disease is an inflammatory bowel disease of unknown etiology. Its chronic nature, as well as symptoms of intestinal and overall significantly impedes the daily functioning of patients. Alternately occurring periods of exacerbation and remission are the cause of reduced quality of life of patients. Understanding the factors that caused the decrease in the quality of life, it allows us to understand the behavior and the situation of the patient and the ability to cope with stress caused by the disease. The aim of the study was to analyze the factors affecting the quality of life of people with Crohn's disease. The study group consisted of 50 people diagnosed with Crohn's disease. Respondents were treated at the Department of General Surgery and Colorectal Medical University of Lodz and Gastroenterological Clinic at the University Clinical Hospital No. 1 in Lodz. Quality of Life Survey was carried out by a diagnostic survey using a research tool SF-36v2 and surveys of its own design. Analysis of the results demonstrated that the quality of life of patients with Crohn's disease was reduced, especially during exacerbations. Evaluation of the quality of life of respondents in physical terms was slightly higher than in the mental aspect. Higher education subjects and the lack of need for surgical treatment significantly improves the quality of life. The occurrence of chronic disease reduces the quality of life of respondents. Elderly patients are better able to adapt to the difficult situation caused by the disease. The quality of life of women and men is at a similar level and patients in remission of the disease have a better quality of life of patients during exacerbations.

Endoscopic balloon dilatation of Crohn's disease strictures: results from a large United kingdom series.

PubMed

Bhalme, Mahesh; Sarkar, Sanchoy; Lal, Simon; Bodger, Keith; Baker, Rose; Willert, Robert P

2014-02-01

Stricturing is a common complication of Crohn's disease. Endoscopic balloon dilatation (EBD) offers a valuable alternative to surgical intervention, but there are limited data on factors influencing its safety and efficacy. A multicenter retrospective audit across 4 U.K. teaching hospitals was performed on the use of EBD for Crohn's strictures between 1998 and 2011. Demographics, smoking status, medications, C-reactive protein, endoscopic findings, and subsequent surgery at follow-up were recorded. Success of EBD was defined as symptomatic improvement without the need for surgery at follow-up. Seventy-nine patients (47 women; median age, 48 yr) were identified for this study. Forty-eight (61%) patients had ileocolonic anastomotic strictures, whereas the rest had de novo strictures. In total, 191 EBDs (range, 1-11; median 2) were carried out on 93 strictures (range, 1-5; median 1) over a median duration of 12 months (range, 1-84). There were no serious adverse events. Success at index EBD was 34%, with a further 43% achieving long-term benefit from additional EBDs. Eighteen (23%) patients required surgery. Time to surgery after the first EDB was 2.6 to 71.1 months (median, 12.8 mo). Longer Crohn's disease duration (P = 0.03) and high C-reactive protein (P = 0.008) were associated with an increased need for subsequent surgery. EBD was safe and effective in achieving long-term symptom improvement and avoidance of surgery in most patients. Prospective controlled trials are needed to evaluate the effect of other factors, including Crohn's disease phenotype, and the role of concomitant medication to identify those best suited to EBD.

Detecting Microbial Dysbiosis Associated with Pediatric Crohn Disease Despite the High Variability of the Gut Microbiota.

PubMed

Wang, Feng; Kaplan, Jess L; Gold, Benjamin D; Bhasin, Manoj K; Ward, Naomi L; Kellermayer, Richard; Kirschner, Barbara S; Heyman, Melvin B; Dowd, Scot E; Cox, Stephen B; Dogan, Haluk; Steven, Blaire; Ferry, George D; Cohen, Stanley A; Baldassano, Robert N; Moran, Christopher J; Garnett, Elizabeth A; Drake, Lauren; Otu, Hasan H; Mirny, Leonid A; Libermann, Towia A; Winter, Harland S; Korolev, Kirill S

2016-02-02

The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Severe metabolic alkalosis and recurrent acute on chronic kidney injury in a patient with Crohn's disease

PubMed Central

2010-01-01

Background Diarrhea is common in patients with Crohn's disease and may be accompanied by acid base disorders, most commonly metabolic acidosis due to intestinal loss of bicarbonate. Case Presentation Here, we present a case of severe metabolic alkalosis in a young patient suffering from M. Crohn. The patient had undergone multiple resections of the intestine and suffered from chronic kidney disease. He was now referred to our clinic for recurrent acute kidney injury, the nature of which was pre-renal due to profound volume depletion. Renal failure was associated with marked hypochloremic metabolic alkalosis which only responded to high volume repletion and high dose blockade of gastric hypersecretion. Intestinal failure with stomal fluid losses of up to 5.7 litres per day required port implantation to commence parenteral nutrition. Fluid and electrolyte replacement rapidly improved renal function and acid base homeostasis. Conclusions This case highlights the important role of gastrointestinal function to maintain acid base status in patients with Crohn's disease. PMID:20398419

Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease

PubMed Central

Darzi, Youssef; Mongodin, Emmanuel F.; Pan, Chongle; Shah, Manesh; Halfvarson, Jonas; Tysk, Curt; Henrissat, Bernard; Raes, Jeroen; Verberkmoes, Nathan C.; Jansson, Janet K.

2012-01-01

Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers. PMID:23209564

Mild clinical behaviour of Crohn disease in elderly patients in a Latin American country: A case-control study

PubMed Central

Yamamoto-Furusho, Jesús K; Sarmiento-Aguilar, Andrea

2015-01-01

BACKGROUND: Crohn disease is characterized by fluctuating clinical behaviour, which is influenced by various factors. There are no data from Latin America that evaluate the clinical behaviour of Crohn disease in elderly patients. OBJECTIVE: To evaluate the clinical course of elderly onset Crohn disease compared with younger onset in the Mexican population. METHODS: The present analysis was a case-control study that included 132 patients with a histopathological diagnosis of Crohn disease between 1983 and 2013 in an inflammatory bowel disease clinic of a tertiary care centre. Statistical analysis was performed using SPSS version 17 (IBM Corporation, USA) and descriptive statistics, χ2 and Fisher’s exact test for categorical variables and Student’s t test for numerical variables. Univariate and multivariate analysis were performed to identify associated risk factors and OR was calculated. RESULTS: A total of 132 patients (73 men and 59 women) were divided into two groups according to age at diagnosis: 27 cases (>60 years of age) and 105 controls (≤60 years of age). Factors influencing the clinical course of Crohn disease in the elderly were: female sex (OR 2.55 [95% CI 1.06 to 6.10]; P=0.02); colonic location (OR 0.22 [95% CI 0.03 to 0.89]; P=0.02); mild clinical behaviour of disease (OR 10.08 [95% CI 3.74 to 27.17]; P=0.0001); response to medical treatment (OR 2.85 [95% CI 1.08 to 7.48]; P=0.02); frequent use of sulfasalazine (OR 4.46 [95% CI 1.22 to 16.28]; P=0.03); less use of azathioprine (OR 0.38 [95% CI 0.13 to 1.03]; P=0.04); and long-term remission (OR 4.96 [95% CI 1.70 to 14.48]; P=0.002). CONCLUSION: Elderly patients with Crohn disease had a mild clinical course characterized by the lack of escalation to immunosuppressive and anti-tumour necrosis factor therapy, as well as long-term remission. PMID:25996614

Mild clinical behaviour of Crohn disease in elderly patients in a Latin American country: A case-control study.

PubMed

Yamamoto-Furusho, Jesús K; Sarmiento-Aguilar, Andrea

2015-01-01

Crohn disease is characterized by fluctuating clinical behaviour, which is influenced by various factors. There are no data from Latin America that evaluate the clinical behaviour of Crohn disease in elderly patients. To evaluate the clinical course of elderly onset Crohn disease compared with younger onset in the Mexican population. The present analysis was a case-control study that included 132 patients with a histopathological diagnosis of Crohn disease between 1983 and 2013 in an inflammatory bowel disease clinic of a tertiary care centre. Statistical analysis was performed using SPSS version 17 (IBM Corporation, USA) and descriptive statistics, χ2 and Fisher's exact test for categorical variables and Student's t test for numerical variables. Univariate and multivariate analysis were performed to identify associated risk factors and OR was calculated. A total of 132 patients (73 men and 59 women) were divided into two groups according to age at diagnosis: 27 cases (>60 years of age) and 105 controls (≤60 years of age). Factors influencing the clinical course of Crohn disease in the elderly were: female sex (OR 2.55 [95% CI 1.06 to 6.10]; P=0.02); colonic location (OR 0.22 [95% CI 0.03 to 0.89]; P=0.02); mild clinical behaviour of disease (OR 10.08 [95% CI 3.74 to 27.17]; P=0.0001); response to medical treatment (OR 2.85 [95% CI 1.08 to 7.48]; P=0.02); frequent use of sulfasalazine (OR 4.46 [95% CI 1.22 to 16.28]; P=0.03); less use of azathioprine (OR 0.38 [95% CI 0.13 to 1.03]; P=0.04); and long-term remission (OR 4.96 [95% CI 1.70 to 14.48]; P=0.002). Elderly patients with Crohn disease had a mild clinical course characterized by the lack of escalation to immunosuppressive and anti-tumour necrosis factor therapy, as well as long-term remission.

Chronic paracoccidioidmycosis in a woman with Crohn Disease.

PubMed

Tavares Dos Santos, Harim; Augusto Benevenuto de Andrade, Bruno; Fernandes, Darcy; Caxias Travassos, Daphine; Bufalino, Andreia

2017-04-15

We report a rare case of chronic paracoccidioidomycosis(PCM) in a woman with Crohn disease in the setting of treatment with azathioprine and mesalazine. Serum tests for antigens to Paracoccidioides brasiliensis, Histoplasma capsulatum, and Aspergillus fumigatus were negative. An incisional biopsy of an oral lesion with periodic acid-schiff and Grocott-methenamine silver stains revealed chronic granulomatous inflammation with multinucleated giant cells with Paracoccidioides brasiliensis within the cytoplasm, confirming the diagnosis of PCM.

MRI predictors of treatment response for perianal fistulizing Crohn disease in children and young adults.

PubMed

Shenoy-Bhangle, Anuradha; Nimkin, Katherine; Goldner, Dana; Bradley, William F; Israel, Esther J; Gee, Michael S

2014-01-01

Magnetic resonance imaging (MRI) is considered the imaging standard for diagnosis and characterization of perianal complications associated with Crohn disease in children and adults. To define MRI criteria that could act as potential predictors of treatment response in fistulizing Crohn disease in children, in order to guide more informed study interpretation. We performed a retrospective database query to identify all children and young adults with Crohn disease who underwent serial MRI studies for assessment of perianal symptoms between 2003 and 2010. We examined imaging features of perianal disease including fistula number, type and length, presence and size of associated abscess, and disease response/progression on follow-up MRI. We reviewed imaging studies and electronic medical records. Statistical analysis, including logistic regression, was performed to associate MR imaging features with treatment response and disease progression. We included 36 patients (22 male, 14 female; age range 8-21 years). Of these, 32 had a second MRI exam and 4 had clinical evidence of complete response, obviating the need for repeat imaging. Of the parameters analyzed, presence of abscess, type of fistula according to the Parks classification, and multiplicity were not predictors of treatment outcome. Maximum length of the dominant fistula and aggregate fistula length in the case of multiple fistulae were the best predictors of treatment outcome. Maximum fistula length <2.5 cm was a predictor of treatment response, while aggregate fistula length ≥2.5 cm was a predictor of disease progression. Perianal fistula length is an important imaging feature to assess on MRI of fistulizing Crohn disease.

High Risk of Anal and Rectal Cancer in Patients With Anal and/or Perianal Crohn's Disease.

PubMed

Beaugerie, Laurent; Carrat, Fabrice; Nahon, Stéphane; Zeitoun, Jean-David; Sabaté, Jean-Marc; Peyrin-Biroulet, Laurent; Colombel, Jean-Frédéric; Allez, Matthieu; Fléjou, Jean-François; Kirchgesner, Julien; Svrcek, Magali

2018-06-01

Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associé aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29-40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula-related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula-related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1

Upper Gastrointestinal Involvement in Crohn Disease: Histopathologic and Endoscopic Findings.

PubMed

Diaz, Liege; Hernandez-Oquet, Rafael Enrique; Deshpande, Amar R; Moshiree, Baharak

2015-11-01

Studies describing the prevalence of upper gastrointestinal (GI) Crohn disease (CD) and its histopathologic changes have been inconsistent as a result of different definitions used for upper GI involvement, diverse populations, and varying indications for endoscopy. We reviewed the literature describing endoscopic findings and histologic lesions in gastric and duodenal mucosa of patients with established CD. PubMed, EMBASE, and the Cochrane Library were searched for gastroduodenal biopsy findings in patients with CD from 1970 to 2014. We included all retrospective and prospective studies in adults. We calculated the prevalence of the most common endoscopic and histopathological findings among patients with overall CD and upper GI CD. Of the 385 articles identified, 20 eligible studies were included. A total of 2511 patients had CD and 815 had upper GI CD. In the CD group, the most common histopathological finding was nonspecific gastric inflammation in 32% of patients, followed by gastric granuloma in 7.9%. Focal gastritis was prevalent in 30.9% of patients. In the upper GI CD group, gastric inflammation was present in 84% of patients, followed by duodenal inflammation in 28.2% and gastric granuloma in 23.2%. The most common gastric endoscopic finding in patients with CD was erythema in 5.9%, followed by erosions in 3.7%. Duodenal endoscopic findings included ulcers and erythema in 5.3% and 3.0% of patients, respectively. We found a prevalence of 34% for CD involving the upper GI tract across these 20 studies. Routine upper endoscopy with biopsies of the upper GI tract in the diagnostic workup of patients with CD can correctly classify the distribution and extent of the disease.

[CROHN'S DISEASE PATIENTS' SATISFACTION WITH COLONOSCOPY VERSUS ENTERO MAGNETIC RESONANCE IMAGING (MRI)].

PubMed

Cámara Viudez, G; Toro Flores, R; Villafruela Cives, M; Moral Cebrián, I; Tabernero Daveiga, S; Poves Martínez, E

2014-12-01

To evaluate satisfaction and preferences in Crohn's disease patients who have undergone a colonoscopy (CL) and a MRI colonography (MRI). As well as evaluate the effectiveness of the information system to collect the data. A sectional pilot study conducted through a satisfaction survey questionnaire for patients diagnosed with Crohn's disease (CD). Study patients were selected from the Gastroenterology Department in the Principe de Asturias University Hospital, where both the colonoscopy and the entero magnetic resonance imaging tests were done from the 1st of January to the 30th of June 2012. Surveys were conducted during July and August 2012. A total of 48 patients with Crohn's disease participated. Out of these, 24 were women and 24 were men. The mean age was 43 years (SD: 13.8). The worst score was obtained at the time of preparation for both procedures. If patients could choose they would prefer CL 23, 16 MRI and 9 were indifferent. The patients' preference for CL could be due to the administration of sedatives prior to the procedure. A procedure such as the CL which initially may result unpleasant for the patient is tolerated much better as a result of the sedation. In both tests, the preparations prior to the procedures are perceived as unpleasant. We will think about how to improve patients' tolerance to these preparations, maybe by giving more information as patients, because we don't know often how to do it properly, which could magnify this unpleasant perception.

Clinical features of Crohn disease concomitant with ankylosing spondylitis

PubMed Central

Liu, Song; Ding, Jie; Wang, Meng; Zhou, Wanqing; Feng, Min; Guan, Wenxian

2016-01-01

Abstract Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS. We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison. Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (−) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73–0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = −0.73 to −0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = −0.81 to −0.91, P < 0.05). Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected. PMID:27428240

The TB--Crohn's affair--a never ending dilemma.

PubMed

Praveen, S; Razman, J

2008-08-01

An 80 year old lady presented with signs and symptoms of sub-acute intestinal obstruction which failed conservative management. CT scan abdomen revealed circumferential ileum thickening with proximal bowel dilatation. Laparotomy and segmental resection was done. Pathological findings were suggestive of chronic granulomatous ileits with differential of Crohn's disease and gastrointestinal tuberculosis. The patient was presumed to have gastrointestinal tuberculosis and commenced on anti tuberculosis treatment despite inconclusive evidence for confirmation and showed marked clinical improvement.

Effect of exclusive enteral nutrition on health-related quality of life for adults with active Crohn's disease.

PubMed

Guo, Zhen; Wu, Rong; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Li, Yi; Gu, Lili; Li, Ning; Li, Jieshou

2013-08-01

Exclusive enteral nutrition (EEN) is an effective and safe remission induction treatment for Crohn's disease in adults. Its influence on adults' health-related quality of life remains unknown. The aim of this study was to determine the effect of EEN on health-related quality of life in adults with active Crohn's disease. Patients recruited were treated with a polymeric enteral feed that was taken orally in the daytime and via a self-intubated nasogastric tube at night for 4 weeks. Prospective evaluation of disease activity (Crohn's Disease Activity Index, CDAI) and health-related quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ) were performed at enrollment and after 4 weeks of treatment. Patients' feelings about EEN were also investigated through 2 questions. Thirteen patients were treated with 4-week EEN. They had a significant improvement in total IBDQ score (P < .001) and all IBDQ dimensions: bowel symptoms (P < .001), systemic symptoms (P < .001), social function (P = .003), and emotional status (P < .001), with 11 patients (84.6%) achieving clinical remission after treatment. In addition, 8 patients (61.5%) expressed their willingness to receive this 4-week EEN treatment again to induce remission if the disease relapsed. The IBDQ correlated significantly with the CDAI at 4 weeks. A 4-week treatment of EEN improves health-related quality of life significantly in adults with active Crohn's disease and was acceptable by most patients.

Role of percutaneous abscess drainage in the management of young patients with Crohn disease.

PubMed

Pugmire, Brian S; Gee, Michael S; Kaplan, Jess L; Hahn, Peter F; Doody, Daniel P; Winter, Harland S; Gervais, Debra A

2016-05-01

Intra-abdominal abscess is a common complication of Crohn disease in children. Prior studies, primarily in adults, have shown that percutaneous abscess drainage is a safe and effective treatment for this condition; however, the data regarding this procedure and indications in pediatric patients is limited. Our aim was to determine the success rate of percutaneous abscess drainage for abscesses related to Crohn disease in pediatric patients with a focus on treatment endpoints that are relevant in the era of biological medical therapy. We retrospectively reviewed 25 cases of patients ages ≤20 years with Crohn disease who underwent percutaneous abscess drainage. Technical success was defined as catheter placement within the abscess with reduction in abscess size on post-treatment imaging. Clinical success was defined as (1) no surgery within 1 year of drainage or (2) surgical resection following drainage with no residual abscess at surgery or on preoperative imaging. Multiple clinical parameters were analyzed for association with treatment success or failure. All cases were classified as technical successes. Nineteen cases were classified as clinical successes (76%), including 7 patients (28%) who required no surgery within 1 year of percutaneous drainage and 12 patients (48%) who had elective bowel resection within 1 year. There was a statistically significant association between resumption of immunosuppressive therapy within 8 weeks of drainage and both clinical success (P < 0.01) and avoidance of surgery after 1 year (P < 0.01). Percutaneous abscess drainage is an effective treatment for Crohn disease-related abscesses in pediatric patients. Early resumption of immunosuppressive therapy is statistically associated with both clinical success and avoidance of bowel resection, suggesting a role for percutaneous drainage in facilitating prompt initiation of medical therapy and preventing surgical bowel resection.

Induction in rats of serum agglutinins to Eubacterium, Peptostreptococcus and Coprococcus species by the faecal flora from patients with Crohn's disease and healthy subjects.

PubMed

Hazenberg, M P; Van de Merwe, J P; Custers-Van Lieshout, L M; Pennock-Schröder, A M

1984-10-01

Sera from patients with Crohn's disease more often than those from other subjects contain agglutinins against anaerobic coccoid rods, identified as Peptostreptococcus productus, Eubacterium contortum (two strains) and Coprococcus comes. The presence of antigens of the four coccoid rods in faeces of patients with Crohn's disease and healthy subjects was investigated by inoculation of rats with faecal suspensions. Antigens of the coccoid rods were detected in faeces from both patients with Crohn's disease and healthy subjects.

Induction in rats of serum agglutinins to Eubacterium, Peptostreptococcus and Coprococcus species by the faecal flora from patients with Crohn's disease and healthy subjects.

PubMed Central

Hazenberg, M. P.; Van de Merwe, J. P.; Custers-Van Lieshout, L. M.; Pennock-Schröder, A. M.

1984-01-01

Sera from patients with Crohn's disease more often than those from other subjects contain agglutinins against anaerobic coccoid rods, identified as Peptostreptococcus productus, Eubacterium contortum (two strains) and Coprococcus comes. The presence of antigens of the four coccoid rods in faeces of patients with Crohn's disease and healthy subjects was investigated by inoculation of rats with faecal suspensions. Antigens of the coccoid rods were detected in faeces from both patients with Crohn's disease and healthy subjects. PMID:6501880

What Is the Risk of Anastomotic Leak After Repeat Intestinal Resection in Patients With Crohn's Disease?

PubMed

Johnston, W Forrest; Stafford, Caitlin; Francone, Todd D; Read, Thomas E; Marcello, Peter W; Roberts, Patricia L; Ricciardi, Rocco

2017-12-01

Approximately half of Crohn's patients require intestinal resection, and many need repeat resections. The purpose of this study was to evaluate the increased risk of clinical anastomotic leak in patients with a history of previous intestinal resection undergoing repeat resection with anastomosis for Crohn's disease. This was a retrospective analysis of prospectively collected departmental data with 100% capture. The study was conducted at the department of colorectal surgery in a tertiary care teaching hospital between July 2007 and March 2016. A cohort of consecutive patients with Crohn's disease who were treated with intestinal resection and anastomosis, excluding patients with proximal fecal diversion, were included. The cohort was divided into 2 groups, those with no previous resection compared with those with previous resection. Clinical anastomotic leak within 30 days of surgery was measured. Of the 206 patients who met criteria, 83 patients had previous intestinal resection (40%). The 2 groups were similar in terms of patient factors, immune-suppressing medication use, and procedural factors. Overall, 20 clinical anastomotic leaks were identified (10% leak rate). There were 6 leaks (5%) detected in patients with no previous intestinal resection and 14 leaks (17%) detected in patients with a history of previous intestinal resection (p < 0.005). The OR of anastomotic leak in patients with Crohn's disease with previous resection compared with no previous resection was 3.5 (95% CI, 1.3-9.4). Patients with 1 previous resection (n = 53) had a leak rate of 13%, whereas patients with ≥2 previous resections (n = 30) had a leak rate of 23%. The number of previous resections correlated with increasing risk for clinical anastomotic leak (correlation coefficient = 0.998). This was a retrospective study with limited data to perform a multivariate analysis. Repeat intestinal resection in patients with Crohn's disease is associated with an increased rate of anastomotic

Predicting and explaining inflammation in Crohn's disease patients using predictive analytics methods and electronic medical record data.

PubMed

Reddy, Bhargava K; Delen, Dursun; Agrawal, Rupesh K

2018-01-01

Crohn's disease is among the chronic inflammatory bowel diseases that impact the gastrointestinal tract. Understanding and predicting the severity of inflammation in real-time settings is critical to disease management. Extant literature has primarily focused on studies that are conducted in clinical trial settings to investigate the impact of a drug treatment on the remission status of the disease. This research proposes an analytics methodology where three different types of prediction models are developed to predict and to explain the severity of inflammation in patients diagnosed with Crohn's disease. The results show that machine-learning-based analytic methods such as gradient boosting machines can predict the inflammation severity with a very high accuracy (area under the curve = 92.82%), followed by regularized regression and logistic regression. According to the findings, a combination of baseline laboratory parameters, patient demographic characteristics, and disease location are among the strongest predictors of inflammation severity in Crohn's disease patients.

Misbalance in type III collagen formation/degradation as a novel serological biomarker for penetrating (Montreal B3) Crohn's disease.

PubMed

van Haaften, W T; Mortensen, J H; Karsdal, M A; Bay-Jensen, A C; Dijkstra, G; Olinga, P

2017-07-01

Misbalances in extracellular matrix turnover are key factors in the development of stricturing (Montreal B2) and penetrating (Montreal B3) Crohn's disease. To determine whether serological markers for collagen formation and degradation could serve as biomarkers for complications of Crohn's disease. Serum biomarkers for type I, III, V and VI collagen formation (P1NP, Pro-C3, Pro-C5, Pro-C6) and matrix metalloproteinase mediated degradation (C1M, C3M, C5M and C6M) were measured in a retrospective, single centre cohort of 112 patients with Crohn's disease in the terminal ileum (nonstricturing/nonpenetrating: n=40, stricturing: n=55, penetrating: n=17) and 24 healthy controls. Active inflammation was defined as CRP >5 mg/L. C3M and Pro-C5 levels were higher in penetrating vs nonpenetrating/nonstricturing and stricturing disease (33.6±5 vs 25.8±2.2 [P=.004] and 27.2±2.3 [P=.018] nmol/L C3M, 1262.7±259.4 vs 902.9±109.9 [P=.005] and 953.0±106.4 [P=.015] nmol/L Pro-C5). C1M (71.2±26.1 vs 46.2±6.2 nmol/L [P<.001]), C3M (31.6±3.9 vs 26.1±1.6 nmol/L [P=.002] and Pro-C5 levels (1171.7±171.5 vs 909.6±80.4 nmol/L [P=.002]) were higher in patients with active inflammation vs without active inflammation. Pro-C3/C3M-ratios were best to differentiate between penetrating vs nonstricturing/nonpenetrating and stricturing disease with area under the curves of 0.815±0.109 (P<.001) and 0.746±0.114 (P=.002) respectively. Serological biomarkers show that penetrating Crohn's disease is characterised by increased matrix metalloproteinase-9 degraded type III collagen and formation of type V collagen. Active inflammation in Crohn's disease is characterised by increased formation of type V collagen and increased matrix metalloproteinase mediated breakdown of type I, III collagen. Pro-C3/C3M ratios are superior in differentiating between penetrating Crohn's disease vs inflammatory and stricturing Crohn's disease. © 2017 The Authors. Alimentary Pharmacology and Therapeutics

Fluorescence endoscopic imaging study of anastomotic recurrence of Crohn's disease after right ileocolonic resection

NASA Astrophysics Data System (ADS)

Mordon, Serge R.; Maunoury, Vincent; Klein, Olivier; Colombel, Jean-Frederic

1995-12-01

Crohn's disease is an inflammatory bowel disease of unknown etiology. Vasculitis is hypothesized but it was never demonstrated in vivo. This study aimed to evaluate the vascular mucosa perfusion using fluorescence imaging in 13 patients who had previously undergone eileocolonic resection and who agreed to participate in a prospective endoscopic study of anastomotic recurrence. This anastomotic recurrence rate is known to be high (73% after 1 year follow-up) and is characterized by ulcerations. The fluorescence study was started with an I.V. bolus injection of sodium fluorescein. The pre-anastomotic mucosa was endoscopically examined with blue light that stimulates fluorescein fluorescence. Fluorescence emission was recorded with an ultra-high-sensitivity camera connected to the endoscope via an interference filter (520 - 560 nm). A uniform fluorescence was observed a few seconds after the injection and lasted for 15 min in healthy subjects. In case of recurrence, the centers of the ulcerations displayed a very low fluorescence indicating localized ischemia. In contrast, the rims of the ulcers revealed brighter fluorescent images than those of normal mucosa. The anastomotic ulcerations of Crohn's disease recurrence exhibit a high fluorescence intensity at their margins indicating an increased mucosal blood flow and/or enhanced transcapillary diffusion. These findings support the hypothesis of a primary vasculitis in Crohn's disease.

Unique β-Glucuronidase Locus in Gut Microbiomes of Crohn's Disease Patients and Unaffected First-Degree Relatives.

PubMed

Gloux, Karine; Anba-Mondoloni, Jamila

2016-01-01

Crohn's disease, an incurable chronic inflammatory bowel disease, has been attributed to both genetic predisposition and environmental factors. A dysbiosis of the gut microbiota, observed in numerous patients but also in at least one hundred unaffected first-degree relatives, was proposed to have a causal role. Gut microbiota β-D-glucuronidases (EC 3.2.1.33) hydrolyse β-D-glucuronate from glucuronidated compounds. They include a GUS group, that is homologous to the Escherichia coli GusA, and a BG group, that is homologous to metagenomically identified H11G11 BG and has unidentified natural substrates. H11G11 BG is part of the functional core of the human gut microbiota whereas GusA, known to regenerate various toxic products, is variably found in human subjects. We investigated potential risk markers for Crohn's disease using DNA-sequence-based exploration of the β-D-glucuronidase loci (GUS or Firmicute H11G11-BG and the respective co-encoded glucuronide transporters). Crohn's disease-related microbiomes revealed a higher frequency of a C7D2 glucuronide transporter (12/13) compared to unrelated healthy subjects (8/32). This transporter was in synteny with the potential harmful GUS β-D-glucuronidase as only observed in a Eubacterium eligens plasmid. A conserved NH2-terminal sequence in the transporter (FGDFGND motif) was found in 83% of the disease-related subjects and only in 12% of controls. We propose a microbiota-pathology hypothesis in which the presence of this unique β-glucuronidase locus may contribute to an increase risk for Crohn's disease.

Opening (and Swallowing) A Can of Worms to Treat My Crohn's Disease.

PubMed

Ahrens, Sean

2016-07-01

Editor's Note: This article discusses the experience, ingenuity, and determination of Sean Ahrens, a young patient with Crohn's disease who took it upon himself to treat his longstanding, symptomatic Crohn's disease with pig whipworm eggs. Reading this story will make some of you uncomfortable. You might question whether this work belongs in a medical journal or sends the wrong message to readers. However, we recognize that this topic is controversial and that N=1 reports cannot and should not change practice. The purpose of this story is not to encourage the use of pig whipworm or to demonstrate its efficacy (or lack thereof). We firmly believe that patients are uniquely qualified to provide insights into how they view their illnesses, weigh risks and benefits, and ultimately achieve self-efficacy. Stories like this are important for us to acknowledge and understand, even if they do not change our practice.

Comparative Effectiveness of Mesalamine, Sulfasalazine, Corticosteroids, and Budesonide for the Induction of Remission in Crohn's Disease: A Bayesian Network Meta-analysis.

PubMed

Coward, Stephanie; Kuenzig, M Ellen; Hazlewood, Glen; Clement, Fiona; McBrien, Kerry; Holmes, Rebecca; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Rezaie, Ali; Kaplan, Gilaad G

2017-03-01

Induction treatment of mild-to-moderate Crohn's disease is controversial. To compare the induction of remission between different doses of mesalamine, sulfasalazine, corticosteroids, and budesonide for active Crohn's disease. We identified randomized controlled trials from existing Cochrane reviews and an updated literature search in Medline, EMBASE, and CENTRAL to November 2015. We included randomized controlled trials (n = 22) in adult patients with Crohn's disease that compared budesonide, sulfasalazine, mesalamine, or corticosteroids with placebo or each other, for the induction of remission (8-17 wks). Mesalamine (above and below 2.4 g/d) and budesonide (above and below 6 mg/d) were stratified into low and high doses. Our primary outcome was remission, defined as a Crohn's Disease Activity Index score <150. A Bayesian random-effects network meta-analysis was performed on the proportion in remission. Corticosteroids (odds ratio [OR] = 3.80; 95% credible interval [CrI]: 2.48-5.66), high-dose budesonide (OR = 2.96; 95% CrI: 2.06-4.30), and high-dose mesalamine (OR = 2.29; 95% CrI: 1.58-3.33) were superior to placebo. Corticosteroids were similar to high-dose budesonide (OR = 1.21; 95% CrI: 0.84-1.76), but more effective than high-dose mesalamine (OR = 1.83; 95% CrI: 1.16-2.88). Sulfasalazine was not significantly superior to any therapy including placebo. Randomized controlled trials that use a strict definition of induction of remission and disease severity at enrollment to assess effectiveness in treating mild-to-moderate Crohn's disease are limited. Corticosteroids and high-dose budesonide were effective treatments for inducing remission in mild-to-moderate Crohn's disease. High-dose mesalamine is an option among patients preferring to avoid steroids.

Role of magnetic resonance imaging in the management of perianal Crohn's disease.

PubMed

Gallego, Jose C; Echarri, Ana

2018-02-01

Perianal fistulas are a major problem in many patients with Crohn's disease. These are usually complex fistulas that adversely affect patients' quality of life, and their clinical management is difficult. Medical treatment sometimes achieves cessation of discharge and closure of the external opening; however, it is difficult to assess the status of the rest of the fistula tract. Magnetic resonance imaging is the method of choice with which to evaluate the condition of perianal fistulas and allows for assessment of the status of inaccessible areas. Magnetic resonance imaging also allows the clinician to evaluate other perianal manifestations of Crohn's disease that differ from the fistulas. This imaging technique is therefore a fundamental means of patient monitoring. When used in conjunction with assessment of the patient's morphological findings, it provides information that allows for both quantification of disease severity and evaluation of the response to treatment. New types of magnetic resonance sequences are emerging, such as diffusion, perfusion, and magnetisation transfer. These sequences may serve as biomarkers because they provide information reflecting the changes taking place at the molecular level. This will help to shape a new scenario in the early assessment of the response to treatments such as anti-tumour necrosis factor drugs. • MRI is the method of choice with which to evaluate perianal fistulas. • In perianal Crohn's disease, MRI is a fundamental means of patient monitoring. • The usefulness of the Van Assche score for patient monitoring remains unclear. • New MRI sequences' diffusion, perfusion, and magnetisation transfer may serve as biomarkers.

A high-fiber diet may improve bowel function and health-related quality of life in patients with Crohn disease.

PubMed

Brotherton, Carol S; Taylor, Ann Gill; Bourguignon, Cheryl; Anderson, Joel G

2014-01-01

Crohn disease is a chronic disorder characterized by episodes of epithelial inflammation in the gastrointestinal tract for which there is no cure. The prevalence of Crohn disease increased in civilized nations during the time period in which food sources were industrialized in those nations. A characteristic of industrialized diets is the conspicuous absence of cereal fiber. The purpose of this 2-group, randomized, controlled study was to investigate the effects of fiber-related dietary instructions specifying wheat bran consumption on health-related quality of life and gastrointestinal function in individuals diagnosed with Crohn disease, as measured by the Inflammatory Bowel Disease Questionnaire and the partial Harvey Bradshaw Index, respectively. Results demonstrated that consuming a wheat bran-inclusive diet was feasible and caused no adverse effects, and participants consuming whole wheat bran in the diet reported improved health-related quality of life (p = .028) and gastrointestinal function (p = .008) compared to the attention control group. The results of a secondary aim, to investigate differences in measures of systemic inflammation, found no group differences in C-reactive protein or erythrocyte sedimentation rates. This study suggests that diet modification may be a welcomed complementary therapy for individuals suffering gastrointestinal disruption associated with Crohn disease.

Technical development of PubMed Interact: an improved interface for MEDLINE/PubMed searches

PubMed Central

Muin, Michael; Fontelo, Paul

2006-01-01

Background The project aims to create an alternative search interface for MEDLINE/PubMed that may provide assistance to the novice user and added convenience to the advanced user. An earlier version of the project was the 'Slider Interface for MEDLINE/PubMed searches' (SLIM) which provided JavaScript slider bars to control search parameters. In this new version, recent developments in Web-based technologies were implemented. These changes may prove to be even more valuable in enhancing user interactivity through client-side manipulation and management of results. Results PubMed Interact is a Web-based MEDLINE/PubMed search application built with HTML, JavaScript and PHP. It is implemented on a Windows Server 2003 with Apache 2.0.52, PHP 4.4.1 and MySQL 4.1.18. PHP scripts provide the backend engine that connects with E-Utilities and parses XML files. JavaScript manages client-side functionalities and converts Web pages into interactive platforms using dynamic HTML (DHTML), Document Object Model (DOM) tree manipulation and Ajax methods. With PubMed Interact, users can limit searches with JavaScript slider bars, preview result counts, delete citations from the list, display and add related articles and create relevance lists. Many interactive features occur at client-side, which allow instant feedback without reloading or refreshing the page resulting in a more efficient user experience. Conclusion PubMed Interact is a highly interactive Web-based search application for MEDLINE/PubMed that explores recent trends in Web technologies like DOM tree manipulation and Ajax. It may become a valuable technical development for online medical search applications. PMID:17083729

Technical development of PubMed interact: an improved interface for MEDLINE/PubMed searches.

PubMed

Muin, Michael; Fontelo, Paul

2006-11-03

The project aims to create an alternative search interface for MEDLINE/PubMed that may provide assistance to the novice user and added convenience to the advanced user. An earlier version of the project was the 'Slider Interface for MEDLINE/PubMed searches' (SLIM) which provided JavaScript slider bars to control search parameters. In this new version, recent developments in Web-based technologies were implemented. These changes may prove to be even more valuable in enhancing user interactivity through client-side manipulation and management of results. PubMed Interact is a Web-based MEDLINE/PubMed search application built with HTML, JavaScript and PHP. It is implemented on a Windows Server 2003 with Apache 2.0.52, PHP 4.4.1 and MySQL 4.1.18. PHP scripts provide the backend engine that connects with E-Utilities and parses XML files. JavaScript manages client-side functionalities and converts Web pages into interactive platforms using dynamic HTML (DHTML), Document Object Model (DOM) tree manipulation and Ajax methods. With PubMed Interact, users can limit searches with JavaScript slider bars, preview result counts, delete citations from the list, display and add related articles and create relevance lists. Many interactive features occur at client-side, which allow instant feedback without reloading or refreshing the page resulting in a more efficient user experience. PubMed Interact is a highly interactive Web-based search application for MEDLINE/PubMed that explores recent trends in Web technologies like DOM tree manipulation and Ajax. It may become a valuable technical development for online medical search applications.

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

PubMed

Niv, Y; Ilani, S; Levi, Z; Hershkowitz, M; Niv, E; Fireman, Z; O'Donnel, S; O'Morain, C; Eliakim, R; Scapa, E; Kalantzis, N; Kalantzis, C; Apostolopoulos, P; Gal, E

2012-01-01

The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated. © Georg Thieme Verlag KG Stuttgart · New York.

Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study.

PubMed

Kugathasan, Subra; Denson, Lee A; Walters, Thomas D; Kim, Mi-Ok; Marigorta, Urko M; Schirmer, Melanie; Mondal, Kajari; Liu, Chunyan; Griffiths, Anne; Noe, Joshua D; Crandall, Wallace V; Snapper, Scott; Rabizadeh, Shervin; Rosh, Joel R; Shapiro, Jason M; Guthery, Stephen; Mack, David R; Kellermayer, Richard; Kappelman, Michael D; Steiner, Steven; Moulton, Dedrick E; Keljo, David; Cohen, Stanley; Oliva-Hemker, Maria; Heyman, Melvin B; Otley, Anthony R; Baker, Susan S; Evans, Jonathan S; Kirschner, Barbara S; Patel, Ashish S; Ziring, David; Trapnell, Bruce C; Sylvester, Francisco A; Stephens, Michael C; Baldassano, Robert N; Markowitz, James F; Cho, Judy; Xavier, Ramnik J; Huttenhower, Curtis; Aronow, Bruce J; Gibson, Greg; Hyams, Jeffrey S; Dubinsky, Marla C

2017-04-29

Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohn's disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown. We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohn's disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the model's specificity improved to 71%. Our findings support the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, and selection of anti-TNFα therapy. Crohn's and Colitis Foundation of America, Cincinnati

Long-Term Performance of Readers Trained in Grading Crohn Disease Activity Using MRI.

PubMed

Puylaert, Carl A J; Tielbeek, Jeroen A W; Bipat, Shandra; Boellaard, Thierry N; Nio, C Yung; Stoker, Jaap

2016-12-01

We aim to evaluate the long-term performance of readers who had participated in previous magnetic resonance imaging (MRI) reader training in grading Crohn disease activity. Fourteen readers (8 women; 12 radiologists, 2 residents; mean age 40; range 31-59), who had participated in a previous MRI reader training, participated in a follow-up evaluation after a mean interval of 29 months (range 25-34 months). Follow-up evaluation comprised 25 MRI cases of suspected or known Crohn disease patients with direct feedback; cases were identical to the evaluation set used in the initial reader training (of which readers were unaware). Grading accuracy, overstaging, and understaging were compared between training and follow-up using a consensus score by two experienced abdominal radiologists as the reference standard. In the follow-up evaluation, overall grading accuracy was 73% (95% confidence interval [CI]: 62%-81%), which was comparable to reader training grading accuracy (72%, 95% CI: 61%-80%) (P = .66). Overstaging decreased significantly from 19% (95% CI: 12%-27%) to 13% (95% CI: 8%-21%) between training and follow-up (P = .03), whereas understaging increased significantly from 9% (95% CI: 4%-21%) to 14% (95% CI: 7%-26%) (P < .01). Readers have consistent long-term accuracy for grading Crohn disease activity after case-based reader training with direct feedback. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

The MedCLIVAR Network

NASA Astrophysics Data System (ADS)

Lionello, Piero; Medclivar Sc, The

2014-05-01

MedCLIVAR serves as a scientific network to promote interaction among different scientific disciplines and to develop a multidisciplinary vision of the evolution of the Mediterranean climate through studies that integrate atmospheric, marine, and terrestrial climate components at time scales ranging from paleoreconstructions to future climate scenarios. The network deals with scientific issues including past climate variability; connections between the Mediterranean and global climate; the Mediterranean Sea circulation and sea level; feedbacks on the global climate system; and regional responses to greenhouse gas, air pollution, and aerosols. The MedCLIVAR initiative was proposed at the 2003 European Geosciences Union assembly in Nice, France. In 2005, it was endorsed by the International Climate Variability and Predictability (CLIVAR) office. Subsequently, the MedCLIVAR Research Network Project was formally approved by the European Science Foundation and launched in May 2006 for a five year duration. Now MedCLIVAR is continuing with self supporting initiatives, such as the third MedCLIVAR conference, which will be held in June 2014 in Ankara (Turkey) , the publication of a special issue of Regional Environmental Change devoted to the climate of the Mediterranean region, and a newsletter, which is published every six months. More information available in Lionello, P., Gacic, M., Gomis, D., Garcia-Herrera, R., Giorgi, F., Planton, S., Trigo, R., (...), Xoplaki, E. (2012) Program focuses on climate of the Mediterranean region, Eos Trans. AGU 93:105-106

Redox regulation of the MED28 and MED32 mediator subunits is important for development and senescence.

PubMed

Shaikhali, Jehad; Davoine, Céline; Björklund, Stefan; Wingsle, Gunnar

2016-05-01

Mediator is a conserved multi-protein complex that acts as a bridge between promoter-bound transcriptional regulators and RNA polymerase II. While redox signaling is important in adjusting plant metabolism and development, the involvement of Mediator in redox homeostasis and regulation only recently started to emerge. Our previous results show that the MED10a, MED28, and MED32 Mediator subunits form various types of covalent oligomers linked by intermolecular disulfide bonds in vitro. To link that with biological significance we have characterized Arabidopsis med32 and med28 mutants and found that they are affected in root development and senescence, phenotypes possibly associated to redox changes.

Endoscopic fluorescence imaging for early assessment of anastomotic recurrence of Crohn's disease

NASA Astrophysics Data System (ADS)

Mordon, Serge R.; Maunoury, Vincent; Geboes, K.; Klein, Olivier; Desreumaux, P.; Debaert, A.; Colombel, Jean-Frederic

1999-02-01

Crohn's disease is an inflammatory bowel disease of unknown etiology. The mechanism of the initial mucosal alterations is still unclear: ulcerations overlying lymphoid follicles and/or vasculitis have been proposed as the early lesions. We have developed a new and original method combining endoscopy of fluorescence angiography for identifying the early pathological lesions, occurring in the neo-terminal ileum after right ileocolonic resection. The patient population consisted of 10 subjects enrolled in a prospective protocol of endoscopic follow-up at 3 and 12 months after surgery. Fluorescence imaging showed small spots giving a bright fluorescence distributed singly in mucosa which appeared normal in routine endoscopy. Histopathological examination demonstrated that the fluorescence of small spots originated from small, usually superficial, erosive lesions. In several cases, these erosive lesions occurred over lymphoid follicles. Endoscopic fluorescence imaging provides a suitable means of investigating the initial aspect of the Crohn's disease process in displaying some correlative findings between fluorescent aspects and early pathological mucosal alterations.

Ultrasound and MRI predictors of surgical bowel resection in pediatric Crohn disease.

PubMed

Rosenbaum, Daniel G; Conrad, Maire A; Biko, David M; Ruchelli, Eduardo D; Kelsen, Judith R; Anupindi, Sudha A

2017-01-01

Imaging predictors for surgery in children with Crohn disease are lacking. To identify imaging features of the terminal ileum on short-interval bowel ultrasound (US) and MR enterography (MRE) in children with Crohn disease requiring surgical bowel resection and those managed by medical therapy alone. This retrospective study evaluated patients 18 years and younger with Crohn disease undergoing short-interval bowel US and MRE (within 2 months of one another), as well as subsequent ileocecectomy or endoscopy within 3 months of imaging. Appearance of the terminal ileum on both modalities was compared between surgical patients and those managed with medical therapy, with the following parameters assessed: bowel wall thickness, mural stratification, vascularity, fibrofatty proliferation, abscess, fistula and stricture on bowel US; bowel wall thickness, T2 ratio, enhancement pattern, mesenteric edema, fibrofatty proliferation, abscess, fistula and stricture on MRE. A two-sided t-test was used to compare means, a Mann-Whitney U analysis was used for non-parametric parameter scores, and a chi-square or two-sided Fisher exact test compared categorical variables. Imaging findings in surgical patients were correlated with location-matched histopathological scores of inflammation and fibrosis using a scoring system adapted from the Simple Endoscopic Score for Crohn Disease, and a Spearman rank correlation coefficient was used to compare inflammation and fibrosis on histopathology. Twenty-two surgical patients (mean age: 16.5 years; male/female: 13/9) and 20 nonsurgical patients (mean age: 14.8; M/F: 8/12) were included in the final analysis. On US, the surgical group demonstrated significantly increased mean bowel wall thickness (6.1 mm vs. 4.7 mm for the nonsurgical group; P = 0.01), loss of mural stratification (odds ratio [OR] = 6.3; 95% confidence interval [CI]: 1.4-28.4; P = 0.02) and increased fibrofatty proliferation (P = 0.04). On MRE, the

Postoperative therapy with infliximab for Crohn's disease: a 2-year prospective randomized multicenter study in Japan.

PubMed

Fukushima, Kouhei; Sugita, Akira; Futami, Kitaro; Takahashi, Ken-Ichi; Motoya, Satoshi; Kimura, Hideaki; Yoshikawa, Shusaku; Kinouchi, Yoshitaka; Iijima, Hideki; Endo, Katsuya; Hibi, Toshihumi; Watanabe, Mamoru; Sasaki, Iwao; Suzuki, Yasuo

2018-06-01

The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence. We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

Accumulation of mesalazine pills in the medium ileum in a patient with Crohn´s disease.

PubMed

Martínez Huertas, Carmen; Garcia-Villanova Ruiz, Paloma; Pozo Sánchez, José; Dávila Arias, Cristina

2017-03-01

Crohn´s disease is an inflammatory disease that can involve any portion of the gastrointestinal tract, although terminal ileum is the most commonly affected portion. It is characterized by a transmural and discontinuous distribution pattern, with alternating periods of active disease and remission. We present the case of a 23-year-old patient diagnosed with Crohn´s disease, in treatment with extended release Mesalazine and corticoids. The CT Enterography showed activity signs and a great dilatation of medium ileum with lots of Mesalazine pills accumulated inside. Pill accumulation occurred because of stenosis, which did not let the pills at this level progress to distal ileum, and be absorbed.

Altered healing following mucogingival surgery in a patient with Crohn's disease: a literature review and case report.

PubMed

Andersen, Kari M; Selvig, Knut A; Leknes, Knut N

2003-04-01

Crohn's disease is a chronic inflammatory bowel disease characterized by uncertainty in etiology and pathogenesis occasionally with manifestations in oral mucous membranes. This report reviews the literature on Crohn's disease and presents a patient with Crohn's disease on continuous anti-inflammatory and immunosuppressive medication who showed adverse healing response following surgical treatment of gingival recession type defects. A 28-year-old male in generally good health apart from his bowel disease requested treatment of multiple maxillary gingival recessions due to esthetic concerns and root sensitivity. Following oral hygiene instruction, 3 coronally advanced flap procedures were performed in the maxillary anterior region to cover the defects. In 2 of the surgical areas, the exposed root surfaces were treated by ethylenediaminetetraacetic acid (EDTA) in combination with enamel matrix derivative (EMD) before coronally positioning the buccal flap. Postoperatively, chlorhexidine gluconate was used for oral hygiene control. The first surgical procedure, performed as a coronally advanced flap, showed delayed and altered healing. Two weeks postoperatively, the flapped tissue remained intensely red and swollen. In the following 2 surgical sites where EDTA and EMD were applied the healing was uneventful. Differences in immediate tissue response, however, did not influence the 3-month treatment outcome with respect to root coverage. Patients with Crohn's disease on recommended systemic medications may show a delayed and altered wound healing indicating that periodontal surgery must be closely monitored. Treatment planning should take into account the potential wound healing promoting effects of enamel matrix derivative as well as adverse healing effects of chlorhexidine gluconate administration.

NOD2, an Intracellular Innate Immune Sensor Involved in Host Defense and Crohn's Disease

PubMed Central

Strober, Warren; Watanabe, Tomohiro

2013-01-01

Nucleotide binding oligomerization domain 2 (NOD2) is an intracellular sensor for small peptides derived from the bacterial cell wall component, peptidoglycan. Recent studies have uncovered unexpected functions of NOD2 in innate immune responses such as induction of type I IFN and facilitation of autophagy; moreover, they have disclosed extensive cross-talk between NOD2 and Toll-like receptors which plays an indispensable role both in host defense against microbial infection and in the development of autoimmunity. Of particular interest, polymorphisms of CARD15 encoding NOD2 are associated with Crohn's disease and other autoimmune states such as graft versus host disease. In this review, we summarize recent findings regarding normal functions of NOD2 and discuss the mechanisms by which NOD2 polymorphisms associated with Crohn's disease lead to intestinal inflammation. PMID:21750585

Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology

PubMed Central

Roulis, Manolis; Armaka, Maria; Manoloukos, Menelaos; Apostolaki, Maria; Kollias, George

2011-01-01

TNF plays a crucial role in the pathogenesis of Crohn disease. Dysregulated TNF production in mice that bear the genetic deletion of the TNF AU-rich regulatory elements (ARE) (TnfΔARE/+ mice) results in TNF receptor I (TNFRI)-dependent spontaneous Crohn-like pathology. Current concepts consider intestinal epithelial cell (IEC) responses to TNF to be critical for intestinal pathology, but the potential contribution of IEC-derived TNF in disease pathogenesis has not been addressed. In this study we examined whether IEC are sufficient as cellular targets or sources of TNF in the development of intestinal pathology. Using IEC-specific reactivation of a hypomorphic TnfΔAREneo allele in mice, we show that selective chronic overproduction of TNF by IEC suffices to cause full development of Crohn-like pathology. Epithelial TNF overexpression leads to early activation of the underlying intestinal myofibroblast, a cell type previously identified as a sufficient target of TNF for disease development in the TnfΔARE model. By contrast, restricted TNFRI expression on IEC although sufficient to confer IEC apoptosis after acute exogenous TNF administration, fails to induce pathology following chronic specific targeting of IEC by endogenous TNF in TnfΔARE/+ mice. Our results argue against IEC being early and sufficient responders to chronic TNF-mediated pathogenic signals and suggest that proinflammatory aberrations leading to chronic TNF production by IEC may initiate pathology in Crohn disease. PMID:21402942

Prospective Comparison of Magnetic Resonance Imaging, Transrectal and Transperineal Sonography, and Surgical Findings in Complicated Perianal Crohn Disease.

PubMed

Bor, Renáta; Farkas, Klaudia; Bálint, Anita; Szűcs, Mónika; Ábrahám, Szabolcs; Milassin, Ágnes; Rutka, Mariann; Nagy, Ferenc; Milassin, Péter; Szepes, Zoltán; Molnár, Tamás

2016-11-01

Magnetic resonance imaging (MRI) and transrectal sonography are the two accepted imaging modalities for evaluation of perianal fistulas and abscesses. Transperineal sonography is a new technique that is easy to learn and can be performed at any time. The purpose of this study was to prospectively compare the diagnostic accuracy of MRI, transrectal sonography, and transperineal sonography with surgical findings in patients with perianal Crohn disease. All patients with perianal Crohn disease underwent MRI, transrectal sonography, and transperineal sonography within a few days before surgery. Fistulas were classified as simple (43.8%) or complex (52.2%) based on surgical findings. Twenty-three patients with active perianal Crohn disease (12 women and 11 men; mean age, 29.9 years; current therapy: antibiotics, 69.6%; azathioprine, 56.5%; and biologics, 73.9%; previous surgery, 26.1%; and proportion of smokers, 39.1%) were included. Sensitivity values for MRI, transrectal sonography, and transperineal sonography for diagnosis of fistulas were 84.6%, 84.6%, and 100%, respectively. Transperineal sonography was more sensitive for diagnosis of perianal abscesses than MRI and transrectal sonography (100%, 58.8%, and 92.8%). Transperineal sonography is a very accurate diagnostic method with outstanding sensitivity compared with MRI and transrectal sonography for evaluation of complicated perianal Crohn disease. Due to its simplicity and low cost, it is recommended that transperineal sonography be the first diagnostic modality in these cases. © 2016 by the American Institute of Ultrasound in Medicine.

Assessment and classification of fistula-in-ano in patients with Crohn's disease by hydrogen peroxide enhanced transanal ultrasound.

PubMed

Sloots, C E; Felt-Bersma, R J; Poen, A C; Cuesta, M A; Meuwissen, S G

2001-09-01

Crohn's disease is well known for its perianal complications, among which fistulas-in-ano are the most common abnormalities. Fistulas-in-ano in Crohn's disease tend to be complex and have a high recurrence rate. Therefore the role of surgery is generally more conservative. Hydrogen peroxide enhanced transanal ultrasound has proven superior to physical examination, fistulography, computed tomography, and conventional ultrasound in demonstrating the fistula tract. This study examined the fistula tracks in patients with Crohn's disease. Forty-one patients with Crohn's disease and fistula-in-ano were investigated using physical examination, sondage of the fistula, proctoscopy and transanal ultrasound. Hydrogen peroxide was infused via a small catheter into the fistula. The main track and the ramification of the fistula were classified according to the anatomical Parks' classification. Only 9 (22%) patients had a single inter- or transsphincteric fistula. In 5 (12%) patients a single supra- or extrasphincteric fistula (high fistula) was found, in 14 (34%) more than one fistula track (ramified), and in 13 (32%) an anovaginal fistula. Thus 78% of patients had a surgically difficult to treat fistula. In the ramified fistula the main track follows the Parks' classification, but ramifications can have a bizarre pattern which is not in agreement with this classification. Optimal documentation by means of hydrogen peroxide enhanced transanal ultrasound is therefore mandatory before surgery or before other therapies such as anti-tumor necrosis factor treatment.

An engineered human antibody to TNF (CDP571) for active Crohn's disease: a randomized double-blind placebo-controlled trial.

PubMed

Sandborn, W J; Feagan, B G; Hanauer, S B; Present, D H; Sutherland, L R; Kamm, M A; Wolf, D C; Baker, J P; Hawkey, C; Archambault, A; Bernstein, C N; Novak, C; Heath, P K; Targan, S R

2001-05-01

We evaluated CDP571, a humanized antibody to tumor necrosis factor, for the treatment of active Crohn's disease. One hundred sixty-nine patients with moderate-to-severe Crohn's disease were enrolled in a 24-week placebo-controlled trial. Patients were initially randomized to a single dose of 10 or 20 mg/kg CDP571 or placebo to assess dose response. Patients were then retreated with 10 mg/kg CDP571 or placebo every 8 or 12 weeks to assess subsequent dosing intervals. The primary endpoint was clinical response at week 2, defined as a decrease in the Crohn's Disease Activity Index score > or = 70 points. At week 2, clinical response occurred in 45% of CDP571-treated patients compared with 27% of patients in the placebo group (P = 0.023). Patients appeared to benefit from retreatment with CDP571 over 24 weeks, but not all of the results for secondary endpoints were statistically significant. The frequency of severe or serious adverse events was similar among all groups. CDP571 at an initial dose of 10 or 20 mg/kg is safe and effective for treatment of patients with moderate-to-severe Crohn's disease. Preliminary evidence suggests that retreatment with 10 mg/kg CDP571 at dose intervals of 8 or 12 weeks may also be beneficial, but additional studies are needed.

Towards PubMed 2.0.

PubMed

Fiorini, Nicolas; Lipman, David J; Lu, Zhiyong

2017-10-30

Staff from the National Center for Biotechnology Information in the US describe recent improvements to the PubMed search engine and outline plans for the future, including a new experimental site called PubMed Labs.

Endostatin (EntreMed).

PubMed

Grosios, K

2000-07-01

EntreMed has licensed the worldwide rights to the angiogenesis inhibitor Endostatin, a 20 kDa C-terminal fragment of collagen XVIII, from the Children's Hospital of Boston, a teaching affiliate of Harvard Medical School. It is being developed as a potential cancer treatment and may also be useful in certain types of blindness and arthritis [227427]. EntreMed filed an IND for Endostatin in June 1999 [334125] and as of September 1999, phase I trials were underway [341462]. As of April 2000, the company had initiated plans for testing low doses of Endostatin in cancer patients using continuous infusion and sc administration in a further phase I study to be conducted in Europe [361594]. A phase I trial of Endostatin which will evaluate the safety and efficacy of Endostatin at a range of doses in no more than 100 cancer patients has been initiated. The trial will take place at the University of Texas MD Anderson Medical Center and the University of Wisconsin Cancer Center in Madison. The National Cancer Center will be sponsoring the trial, which is expected to be completed in late 2000. As of March 2000, there had been no serious adverse events attributable to Endostatin administration. The first report from this trial is expected in autumn 2000 [341462], [366312]. The mechanism of action for Endostatin remains unclear, although reports from the 91st AACR Meeting in April 2000 showed that recombinant human endostatin bound to a number of tropomyosin cDNAs in a library screen [362039]. In preclinical studies, repeated administration of Endostatin consistently shrank primary tumors and did not produce any drug resistance. In mice, a variety of tumors which had progressed to 1 to 2% of total body weight, regressed to microscopic, dormant lesions following Endostatin treatment [231418], [231470], [270673]. Types of cancers which respond to Endostatin include lung, skin, vascular and fibrosarcomas. Toxicology studies in cynomolgus monkeys showed that bolus injections of

TwiMed: Twitter and PubMed Comparable Corpus of Drugs, Diseases, Symptoms, and Their Relations

PubMed Central

Miyao, Yusuke; Collier, Nigel

2017-01-01

Background Work on pharmacovigilance systems using texts from PubMed and Twitter typically target at different elements and use different annotation guidelines resulting in a scenario where there is no comparable set of documents from both Twitter and PubMed annotated in the same manner. Objective This study aimed to provide a comparable corpus of texts from PubMed and Twitter that can be used to study drug reports from these two sources of information, allowing researchers in the area of pharmacovigilance using natural language processing (NLP) to perform experiments to better understand the similarities and differences between drug reports in Twitter and PubMed. Methods We produced a corpus comprising 1000 tweets and 1000 PubMed sentences selected using the same strategy and annotated at entity level by the same experts (pharmacists) using the same set of guidelines. Results The resulting corpus, annotated by two pharmacists, comprises semantically correct annotations for a set of drugs, diseases, and symptoms. This corpus contains the annotations for 3144 entities, 2749 relations, and 5003 attributes. Conclusions We present a corpus that is unique in its characteristics as this is the first corpus for pharmacovigilance curated from Twitter messages and PubMed sentences using the same data selection and annotation strategies. We believe this corpus will be of particular interest for researchers willing to compare results from pharmacovigilance systems (eg, classifiers and named entity recognition systems) when using data from Twitter and from PubMed. We hope that given the comprehensive set of drug names and the annotated entities and relations, this corpus becomes a standard resource to compare results from different pharmacovigilance studies in the area of NLP. PMID:28468748

Towards PubMed 2.0

PubMed Central

Fiorini, Nicolas; Lipman, David J; Lu, Zhiyong

2017-01-01

Staff from the National Center for Biotechnology Information in the US describe recent improvements to the PubMed search engine and outline plans for the future, including a new experimental site called PubMed Labs. PMID:29083299

Rare Coexistance of Ileal Diverticulosis, Crohn's Disease and Small Bowel Adenocarcinoma: Report of a Case.

PubMed

Spartalis, Eleftherios; Garmpis, Nikolaos; Spartalis, Michael; Damaskos, Christos; Moris, Demetrios; Athanasiou, Antonios; Gkolfakis, Paraskevas; Korkolopoulou, Penelope; Dimitroulis, Dimitrios; Mantas, Dimitrios

2018-01-01

Adenocarcinoma is one of the most common malignant tumors of the small intestine complicating Crohn's disease. However, the coexistence of both conditions with diverticulosis of small bowel in young age makes this coincidence rare and clinical diagnosis very difficult. We report a case of a woman admitted to our Department with acute abdominal pain and fever. The surgical and histological investigation, revealed a rare coexistence that has never been mentioned in the published medical literature. Ileal diverticulosis is not frequent and often asymptomatic as well as adenocarcinoma of the small bowel. In this case, those diseases along with Crohn's disease led the patient to acute symptoms. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The MedCLIVAR Network

NASA Astrophysics Data System (ADS)

Lionello, Piero; Medclivar sg, The

2013-04-01

The MedCLIVAR initiative was first proposed at the 2003 European Geosciences Union assembly in Nice, France. In 2005, it was endorsed by the International Climate Variability and Predictability (CLIVAR) office. Subsequently, the MedCLIVAR Research Network Project was formally approved by the European Science Foundation and launched in May 2006 with the support of funding agencies from 12 countries. Since then, MedCLIVAR has served as a scientific network to promote interaction among different scientific disciplines and to develop a multidisciplinary vision of the evolution of the Mediterranean climate through studies that integrate atmospheric, marine, and terrestrial climate components at time scales ranging from paleoreconstructions to future climate scenarios. Presently, the network continues dealing with scientific issues including past climate variability; connections between the Mediterranean and global climate; the Mediterranean Sea circulation and sea level; feedbacks on the global climate system; and regional responses to greenhouse gas, air pollution, and aerosols. Its present activities include the publication of a newsletter, the organization of the next MedCLIVAR conference in 2014 and the publication of a special issue of Regional Environmental Change devoted to the climate of the Mediterranean region.

The MED-SUV Multidisciplinary Interoperability Infrastructure

NASA Astrophysics Data System (ADS)

Mazzetti, Paolo; D'Auria, Luca; Reitano, Danilo; Papeschi, Fabrizio; Roncella, Roberto; Puglisi, Giuseppe; Nativi, Stefano

2016-04-01

In accordance with the international Supersite initiative concept, the MED-SUV (MEDiterranean SUpersite Volcanoes) European project (http://med-suv.eu/) aims to enable long-term monitoring experiment in two relevant geologically active regions of Europe prone to natural hazards: Mt. Vesuvio/Campi Flegrei and Mt. Etna. This objective requires the integration of existing components, such as monitoring systems and data bases and novel sensors for the measurements of volcanic parameters. Moreover, MED-SUV is also a direct contribution to the Global Earth Observation System of Systems (GEOSS) as one the volcano Supersites recognized by the Group on Earth Observation (GEO). To achieve its goal, MED-SUV set up an advanced e-infrastructure allowing the discovery of and access to heterogeneous data for multidisciplinary applications, and the integration with external systems like GEOSS. The MED-SUV overall infrastructure is conceived as a three layer architecture with the lower layer (Data level) including the identified relevant data sources, the mid-tier (Supersite level) including components for mediation and harmonization , and the upper tier (Global level) composed of the systems that MED-SUV must serve, such as GEOSS and possibly other global/community systems. The Data level is mostly composed of existing data sources, such as space agencies satellite data archives, the UNAVCO system, the INGV-Rome data service. They share data according to different specifications for metadata, data and service interfaces, and cannot be changed. Thus, the only relevant MED-SUV activity at this level was the creation of a MED-SUV local repository based on Web Accessible Folder (WAF) technology, deployed in the INGV site in Catania, and hosting in-situ data and products collected and generated during the project. The Supersite level is at the core of the MED-SUV architecture, since it must mediate between the disparate data sources in the layer below, and provide a harmonized view to

Adolescent "Saxophone Penis" Secondary to Crohn's Disease: Misdiagnosed as Being Posttraumatic.

PubMed

Marshall, Claire; Markiewicz, Dorota; Bewley, Anthony

2016-01-01

We describe a patient with a "saxophone penis" mistakenly diagnosed as having posttraumatic changes. A careful history and attention to blood tests at presentation may have alerted clinicians that there was a nontraumatic cause for our patient's disease. It is essential that clinicians consider "metastatic" anogenital Crohn's disease as a possible cause of "saxophone penis". © 2016 Wiley Periodicals, Inc.

A new rapid test for fecal calprotectin predicts endoscopic remission and postoperative recurrence in Crohn's disease.

PubMed

Lobatón, Triana; López-García, Alicia; Rodríguez-Moranta, Francisco; Ruiz, Alexandra; Rodríguez, Lorena; Guardiola, Jordi

2013-12-01

Fecal calprotectin (FC), as determined by the enzyme-linked immunoassay (ELISA) test, has been proposed as a promising biomarker of endoscopic activity in Crohn's disease (CD). However data on its accuracy in predicting endoscopic remission according to location and postoperative recurrence (POR) is scarce. Our objective was to evaluate the ability of FC determined by a new quantitative point-of-care test (FC-QPOCT) to predict endoscopic remission and POR in CD patients. FC was determined simultaneously by an enzyme-linked immunoassay test (FC-ELISA) and a FC-QPOCT in CD patients undergoing colonoscopy. Clinical disease activity was assessed according to the Crohn's Disease Activity Index (CDAI). Endoscopic results were assessed according to the Crohn's Disease Endoscopic Activity Index of Severity (CDEIS) and postoperative recurrence according to the Rutgeerts' score. A total of 115 ileocolonoscopies were performed (29 on patients with ileocolonic resection). FC levels correlated more closely with the CDEIS than leucocytes, platelets or CRP. The prediction of "endoscopic remission" (CDEIS<3), using FC-QPOCT (cut-off 272 μg/g) and FC-ELISA (cut-off 274 μg/g) presented an AUC of 0.933 and 0.935 respectively. FC-QPOCT results correlated better with endoscopic activity in the ileocolonic location (Pearson's correlation, r=0.879; P<0.001), than the colonic (r=0.725; P<0.001) or the ileal location (r=0.437; P=0.016). Median FC-QPOCT levels discriminated Rutgeerts' score i0-i1 from i2-i4 (98 (range 30-306) μg/g vs. 234.5 (range 100-612) μg/g respectively, P=0.012). FC determined by rapid quantitative test predicts "endoscopic remission" and endoscopic postoperative recurrence in CD patients. Copyright © 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

MR enterography-histology comparison in resected pediatric small bowel Crohn disease strictures: can imaging predict fibrosis?

PubMed

Barkmeier, Daniel T; Dillman, Jonathan R; Al-Hawary, Mahmoud; Heider, Amer; Davenport, Matthew S; Smith, Ethan A; Adler, Jeremy

2016-04-01

Crohn disease is a chronic inflammatory condition that can lead to intestinal strictures. The presence of fibrosis within strictures alters optimal management but is not reliably detected by current imaging methods. To correlate the MRI features of surgically resected small-bowel strictures in pediatric Crohn disease with histological inflammation and fibrosis scoring. We included children with Crohn disease who had symptomatic small-bowel strictures requiring surgical resection and had preoperative MR enterography (MRE) within 3 months of surgery (n = 20). Two blinded radiologists reviewed MRE examinations to document stricture-related findings. A pediatric pathologist scored stricture histological specimens for fibrosis (0-4) and inflammation (0-4). MRE findings were correlated with histological data using Spearman correlation (ρ) and exact logistic regression analysis. There was significant positive correlation between histological bowel wall fibrosis and inflammation in resected strictures (ρ = 0.55; P = 0.01). Confluent transmural histological fibrosis was associated with pre-stricture upstream small-bowel dilatation >3 cm at univariate (odds ratio [OR] = 51.7; 95% confidence interval [CI]: 7.6- > 999.9; P = 0.0002) and multivariate (OR = 43.4; 95% CI: 6.1- > 999.9; P = 0.0006, adjusted for age) analysis. The degree of bowel wall T2-weighted signal intensity failed to correlate with histological bowel wall fibrosis or inflammation (P-values >0.05). There were significant negative correlations between histological fibrosis score and patient age at resection (ρ = -0.48, P = 0.03), and time from diagnosis to surgery (ρ = -0.73, P = 0.0002). Histological fibrosis and inflammation co-exist in symptomatic pediatric Crohn disease small-bowel strictures and are positively correlated. Pre-stenotic upstream small-bowel dilatation greater than 3 cm is significantly associated with confluent transmural fibrosis.

Long-term Outcomes of Infliximab Use for Pediatric Crohn Disease: A Canadian Multicenter Clinical Practice Experience.

PubMed

deBruyn, Jennifer C; Jacobson, Kevan; El-Matary, Wael; Carroll, Matthew; Wine, Eytan; Wrobel, Iwona; Van Woudenberg, Mariel; Huynh, Hien Q

2018-02-01

Data on long-term real-world outcomes of infliximab in pediatric Crohn disease are limited. The aim of the study was to evaluate infliximab optimization and durability in children with Crohn disease. We performed a retrospective review of children with Crohn disease who started infliximab from January 2008 to December 2012 in 4 Canadian tertiary care centers. A priori factors associated with optimization and discontinuation from loss of response were evaluated using logistic regression and Cox proportional hazards model, respectively. One hundred eighty children (54.4% boys) started infliximab; all completed induction. Median age at infliximab start was 14.3 years (Q1, Q3: 12.8, 15.9 years) and median time from diagnosis to infliximab start was 1.5 years (Q1, Q3: 0.6, 3.5 years). At last follow-up, 87.1% were maintained on infliximab (median duration follow-up 85.9 weeks [Q1, Q3: 43.8, 138.8 weeks]). Infliximab optimization occurred in 57.3% (dose escalation 15.2%, interval shortening 3.9%, both 38.2%), primarily due to loss of response. Younger age at diagnosis (<10 years old) and nonstricturing, nonpenetrating behavior were associated with optimization (odds ratio 6.5, 95% confidence interval [CI] 2.0-21.1 and odds ratio 2.1, 95% CI 1.0-4.2, respectively). The 1- and 2-year durability of infliximab (percentage in follow-up who were continuing on infliximab) were 95.5% (95% CI 90.4-98.3) and 91.0% (95% CI 82.4-96.3), respectively. Annual discontinuation due to loss of response occurred at 3.2% per year (95% CI 1.1-5.2). Children with Crohn disease maintain a durable response to infliximab. Optimization occurs frequently and allows for continued use. Younger age at diagnosis and nonstricturing, nonpenetrating behavior are associated with increased need for infliximab optimization.

Discordance between the degree of osteopenia and the prevalence of spontaneous vertebral fractures in Crohn's disease.

PubMed

Stockbrügger, R W; Schoon, E J; Bollani, S; Mills, P R; Israeli, E; Landgraf, L; Felsenberg, D; Ljunghall, S; Nygard, G; Persson, T; Graffner, H; Bianchi Porro, G; Ferguson, A

2002-08-01

A high prevalence of osteoporosis has been noted in Crohn's disease, but data about fractures are scarce. The relationship between low bone mineral density and the prevalence of vertebral fractures was studied in 271 patients with ileo-caecal Crohn's disease in a large European/Israeli study. One hundred and eighty-one currently steroid-free patients with active Crohn's disease (98 completely steroid-naive) and 90 steroid-dependent patients with inactive or quiescent Crohn's disease were investigated by dual X-ray absorptiometry scan of the lumbar spine, a standardized posterior/anterior and lateral X-ray of the thoracic and lumbar spine, and an assessment of potential risk factors for osteoporosis. Thirty-nine asymptomatic fractures were seen in 25 of 179 steroid-free patients (14.0%; 27 wedge, 12 concavity), and 17 fractures were seen in 13 of 89 steroid-dependent patients (14.6%; 14 wedge, three concavity). The prevalence of fractures in steroid-naive patients was 12.4%. The average bone mineral density, expressed as the T-score, of patients with fractures was not significantly different from that of those without fractures (-0.759 vs. -0.837; P=0.73); 55% of patients with fractures had a normal T-score. The bone mineral density was negatively correlated with lifetime steroids, but not with previous bowel resection or current disease activity. The fracture rate was not correlated with the bone mineral density (P=0.73) or lifetime steroid dose (P=0.83); in women, but not in men, the fracture rate was correlated with age (P=0.009). The lack of correlation between the prevalence of fractures on the one hand and the bone mineral density and lifetime steroid dose on the other necessitates new hypotheses for the pathogenesis of the former.

Free-breathing diffusion-weighted imaging for the assessment of inflammatory activity in Crohn's disease.

PubMed

Kiryu, Shigeru; Dodanuki, Keiichi; Takao, Hidemasa; Watanabe, Makoto; Inoue, Yusuke; Takazoe, Masakazu; Sahara, Rikisaburo; Unuma, Kiyohito; Ohtomo, Kuni

2009-04-01

To investigate the application of free-breathing diffusion-weighted MR imaging (DWI) to the assessment of disease activity in Crohn's disease. Thirty-one patients with Crohn's disease were investigated using free-breathing DWI without special patient preparation or IV or intraluminal contrast agent. The bowel was divided into seven segments, and disease activity was assessed visually on DWI. For quantitative analysis, the apparent diffusion coefficient (ADC) was measured in each segment. The findings of a conventional barium study or surgery were regarded as the gold standard for evaluating the diagnostic ability of DWI to assess disease activity. Upon visual assessment, the sensitivity, specificity, and accuracy for the detection of disease-active segments were 86.0, 81.4, and 82.4%, respectively. In the quantitative assessment, the ADC value in the disease-active area was lower than that in disease-inactive area in small and large bowels (1.61 +/- 0.44 x 10(-3) mm(2)/s versus 2.56 +/- 0.51 x 10(-3) mm(2)/s in small bowel and 1.52 +/- 0.43 x 10(-3) mm(2)/s versus 2.31 +/- 0.59 x 10(-3) mm(2)/s in large bowel, respectively, P<0.001). Free-breathing DWI is useful in the assessment of Crohn's disease. The accuracy of DWI is high in evaluating disease activity, especially in the small bowel, and the ADC may facilitate quantitative analysis of disease activity.

Redefining the MED13L syndrome

PubMed Central

Adegbola, Abidemi; Musante, Luciana; Callewaert, Bert; Maciel, Patricia; Hu, Hao; Isidor, Bertrand; Picker-Minh, Sylvie; Le Caignec, Cedric; Delle Chiaie, Barbara; Vanakker, Olivier; Menten, Björn; Dheedene, Annelies; Bockaert, Nele; Roelens, Filip; Decaestecker, Karin; Silva, João; Soares, Gabriela; Lopes, Fátima; Najmabadi, Hossein; Kahrizi, Kimia; Cox, Gerald F; Angus, Steven P; Staropoli, John F; Fischer, Ute; Suckow, Vanessa; Bartsch, Oliver; Chess, Andrew; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M; Kalscheuer, Vera M

2015-01-01

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits. PMID:25758992

Redefining the MED13L syndrome.

PubMed

Adegbola, Abidemi; Musante, Luciana; Callewaert, Bert; Maciel, Patricia; Hu, Hao; Isidor, Bertrand; Picker-Minh, Sylvie; Le Caignec, Cedric; Delle Chiaie, Barbara; Vanakker, Olivier; Menten, Björn; Dheedene, Annelies; Bockaert, Nele; Roelens, Filip; Decaestecker, Karin; Silva, João; Soares, Gabriela; Lopes, Fátima; Najmabadi, Hossein; Kahrizi, Kimia; Cox, Gerald F; Angus, Steven P; Staropoli, John F; Fischer, Ute; Suckow, Vanessa; Bartsch, Oliver; Chess, Andrew; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M; Kalscheuer, Vera M

2015-10-01

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.

Predictors of Depression in Youth With Crohn Disease

PubMed Central

Clark, Jeffrey G.; Srinath, Arvind I.; Youk, Ada O.; Kirshner, Margaret A.; McCarthy, F. Nicole; Keljo, David J.; Bousvaros, Athos; DeMaso, David R.; Szigethy, Eva M.

2014-01-01

Objective The aim of the study was to determine whether infliximab use and other potential predictors are associated with decreased prevalence and severity of depression in pediatric patients with Crohn disease (CD). Methods A total of 550 (n = 550) youth ages 9 to 17 years with biopsy-confirmed CD were consecutively recruited as part of a multicenter randomized controlled trial. Out of the 550, 499 patients met study criteria and were included in the analysis. At recruitment, each subject and a parent completed the Children’s Depression Inventory (CDI). A child or parent CDI score ≥ 12 was used to denote clinically significant depressive symptoms (CSDS). Child and parent CDI scores were summed to form total CDI (CDIT). Infliximab use, demographic information, steroid use, laboratory values, and Pediatric Crohn’s Disease Activity Index (PCDAI) were collected as the potential predictors of depression. Univariate regression models were constructed to determine the relations among predictors, CSDS, and CDIT. Stepwise multivariate regression models were constructed to predict the relation between infliximab use and depression while controlling for other predictors of depression. Results Infliximab use was not associated with a decreased proportion of CSDS and CDIT after adjusting for multiple comparisons. CSDS and CDIT were positively associated with PCDAI, erythrocyte sedimentation rate, and steroid dose (P<0.01) and negatively associated with socioeconomic status (SES) (P<0.001). In multivariate models, PCDAI and SES were the strongest predictors of depression. Conclusions Disease activity and SES are significant predictors of depression in youth with Crohn disease. PMID:24343281

TwiMed: Twitter and PubMed Comparable Corpus of Drugs, Diseases, Symptoms, and Their Relations.

PubMed

Alvaro, Nestor; Miyao, Yusuke; Collier, Nigel

2017-05-03

Work on pharmacovigilance systems using texts from PubMed and Twitter typically target at different elements and use different annotation guidelines resulting in a scenario where there is no comparable set of documents from both Twitter and PubMed annotated in the same manner. This study aimed to provide a comparable corpus of texts from PubMed and Twitter that can be used to study drug reports from these two sources of information, allowing researchers in the area of pharmacovigilance using natural language processing (NLP) to perform experiments to better understand the similarities and differences between drug reports in Twitter and PubMed. We produced a corpus comprising 1000 tweets and 1000 PubMed sentences selected using the same strategy and annotated at entity level by the same experts (pharmacists) using the same set of guidelines. The resulting corpus, annotated by two pharmacists, comprises semantically correct annotations for a set of drugs, diseases, and symptoms. This corpus contains the annotations for 3144 entities, 2749 relations, and 5003 attributes. We present a corpus that is unique in its characteristics as this is the first corpus for pharmacovigilance curated from Twitter messages and PubMed sentences using the same data selection and annotation strategies. We believe this corpus will be of particular interest for researchers willing to compare results from pharmacovigilance systems (eg, classifiers and named entity recognition systems) when using data from Twitter and from PubMed. We hope that given the comprehensive set of drug names and the annotated entities and relations, this corpus becomes a standard resource to compare results from different pharmacovigilance studies in the area of NLP. ©Nestor Alvaro, Yusuke Miyao, Nigel Collier. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 03.05.2017.

Preoperative Nutritional Optimization for Crohn's Disease Patients Can Improve Surgical Outcome.

PubMed

Dreznik, Yael; Horesh, Nir; Gutman, Mordechai; Gravetz, Aviad; Amiel, Imri; Jacobi, Harel; Zmora, Oded; Rosin, Danny

2017-11-01

Preoperative preparation of patients with Crohn's disease is challenging and there are no specific guidelines regarding nutritional support. The aim of this study was to assess whether preoperative nutritional support influenced the postoperative outcome. A retrospective, cohort study including all Crohn's disease patients who underwent abdominal surgery between 2008 and 2014 was conducted. Patients' characteristics and clinical and surgical data were recorded and analyzed. Eighty-seven patients were included in the study. Thirty-seven patients (42.5%) received preoperative nutritional support (mean albumin level 3.14 vs. 3.5 mg/dL in the non-optimized group; p < 0.02) to optimize their nutritional status prior to surgery. Preoperative albumin level, after adequate nutritional preparation, was similar between the 2 groups. The 2 groups differ neither in demographic and surgical data, overall post-op complication (p = 0.85), Clavien-Dindo score (p = 0.42), and length of stay (p = 0.1). Readmission rate was higher in the non-optimized group (p = 0.047). Nutritional support can minimize postoperative complications in patients with low albumin levels. Nutritional status should be optimized in order to avoid hazardous complications. © 2017 S. Karger AG, Basel.

Combined Medical and Surgical Approach Improves Healing of Septic Perianal Crohn's Disease.

PubMed

Choi, Christine S; Berg, Arthur S; Sangster, William; Schieffer, Kathleen M; Harris, Leonard R; Deiling, Sue M; Koltun, Walter A

2016-09-01

Septic perianal Crohn's disease (SPCD) is a treatment challenge in spite of tumor necrosis factor antagonists (anti-TNF). Our aim was to define the success of SPCD management with a combined medical and surgical approach and to identify clinical and genetic factors predictive of healing. A retrospective chart review of patients with SPCD treated at the Penn State Milton S Hershey Medical Center was done. Primary end point was complete healing (ie normal clinical exam and no pain for at least 6 months). Genetic analysis of 185 single nucleotide polymorphisms associated with Crohn's disease was performed in 78 patients. One hundred and thirty-five episodes of SPCD were identified in 114 patients with a mean follow-up of 77 ± 7.4 months. Overall, 80 of 135 episodes healed (59.3%) and did not differ between those receiving anti-TNF and not (60.4% vs 56.8%). There appeared to be a consistent improved heal rate in each subcategory of surgically managed patients that received anti-TNF. Female sex was significantly predictive of healing in only those receiving anti-TNF agents (63.6% vs 25.0%; p = 0.0005). Twenty-two (19.3%) patients ultimately received a permanent diversion with either a total proctocolectomy or completion proctectomy. Multivariate analysis suggested several single nucleotide polymorphisms in Crohn's disease-associated genes to be possibly associated with healing, but lost significance after Bonferroni correction. Overall, there is an approximate 60% rate of healing SPCD using a combined medical and surgical approach. About 20% of SPCD patients will require a permanent stoma. There were no clear genetic predictors of healing SPCD. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Value of dual-energy CT enterography in the analysis of pathological bowel segments in patients with Crohn's disease.

PubMed

Villanueva Campos, A M; Tardáguila de la Fuente, G; Utrera Pérez, E; Jurado Basildo, C; Mera Fernández, D; Martínez Rodríguez, C

To analyze whether there are significant differences in the objective quantitative parameters obtained in the postprocessing of dual-energy CT enterography studies between bowel segments with radiologic signs of Crohn's disease and radiologically normal segments. This retrospective study analyzed 33 patients (16 men and 17 women; mean age 54 years) with known Crohn's disease who underwent CT enterography on a dual-energy scanner with oral sorbitol and intravenous contrast material in the portal phase. Images obtained with dual energy were postprocessed to obtain color maps (iodine maps). For each patient, regions of interest were traced on these color maps and the density of iodine (mg/ml) and the fat fraction (%) were calculated for the wall of a pathologic bowel segment with radiologic signs of Crohn's disease and for the wall of a healthy bowel segment; the differences in these parameters between the two segments were analyzed. The density of iodine was lower in the radiologically normal segments than in the pathologic segments [1.8 ± 0.4mg/ml vs. 3.7 ± 0.9mg/ml; p<0.05]. The fat fraction was higher in the radiologically normal segments than in the pathologic segments [32.42% ± 6.5 vs. 22.23% ± 9.4; p<0.05]. There are significant differences in the iodine density and fat fraction between bowel segments with radiologic signs of Crohn's disease and radiologically normal segments. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

PubMed Informer: Monitoring MEDLINE/PubMed through E-mail Alerts, SMS, PDA downloads and RSS feeds

PubMed Central

Muin, Michael; Fontelo, Paul; Ackerman, Michael

2005-01-01

Summary PubMed Informer is a Web-based monitoring tool for topics of interest from MEDLINE/PubMed primarily designed for healthcare professionals. Five tracking methods are available: Web access, e-mail, Short Message Service (SMS), PDA downloads and RSS feeds. PubMed Informer delivers focused search updates and specific information to users with varying information-seeking practices. PMID:16779344

Indian Society of Gastroenterology consensus statements on Crohn's disease in India.

PubMed

Ramakrishna, Balakrishnan S; Makharia, Govind K; Ahuja, Vineet; Ghoshal, Uday C; Jayanthi, Venkataraman; Perakath, Benjamin; Abraham, Philip; Bhasin, Deepak K; Bhatia, Shobna J; Choudhuri, Gourdas; Dadhich, Sunil; Desai, Devendra; Goswami, Bhaba Dev; Issar, Sanjeev K; Jain, Ajay K; Kochhar, Rakesh; Loganathan, Goundappa; Misra, Sri Prakash; Ganesh Pai, C; Pal, Sujoy; Philip, Mathew; Pulimood, Anna; Puri, Amarender S; Ray, Gautam; Singh, Shivaram P; Sood, Ajit; Subramanian, Venkatraman

2015-01-01

In 2012, the Indian Society of Gastroenterology's Task Force on Inflammatory Bowel Diseases undertook an exercise to produce consensus statements on Crohn's disease (CD). This consensus, produced through a modified Delphi process, reflects our current recommendations for the diagnosis and management of CD in India. The consensus statements are intended to serve as a reference point for teaching, clinical practice, and research in India.

Guillain-Barré syndrome during adalimumab therapy for Crohn´s disease: coincidence or consequence?

PubMed

Cançado, Guilherme Grossi Lopes; Vilela, Eduardo Garcia

2017-04-01

We report the case of a 64-year-old patient diagnosed with extensive ileal Crohn´s disease who developed Guillain-Barré syndrome after starting biological therapy with adalimumab. Neurologic involvement associated with inflammatory bowel diseases is recognized as an extra-intestinal manifestation. After the breakthrough of antitumor necrosis factor alpha (anti-TNF-α) agents, an increasing number of cases of acute inflammatory demyelinating polyneuropathies have been reported; however, only one case has been described in a patient with Crohn´s disease. Although a causal relationship between Guillain-Barré syndrome and TNF-α antagonist therapy cannot be proven, this report emphasizes the need to monitor for neurologic signs and symptoms in patients with inflammatory bowel diseases, with or without biological therapy, to avoid severe and irreversible complications associated with demyelinating diseases.

Pub-Med-dot-com, here we come!

PubMed

Pulst, Stefan M

2016-08-01

As of April 8, 2016, articles in Neurology® Genetics can be searched using PubMed. Launched in 1996, PubMed is a search engine that accesses citations and abstracts of more than 26 million articles. Its primary sources include the MEDLINE database, which was started in the 1960s, and biomedical and life sciences journal articles that date back to 1946. In addition, PubMed accesses other sources, for example, citations to those life sciences journals that submit full-text articles to PubMed Central (PMC). PubMed Central was launched in 2000 as a free archive of biomedical and life science journals.

Medical Management of Crohn Disease

PubMed Central

Scott, Frank I.; Osterman, Mark T.

2013-01-01

Crohn disease (CD) is one of the major subtypes of inflammatory bowel disease and can occur in any segment of the alimentary tract. There have been significant advances in the medical therapy of CD over the past several decades. For mild CD, the oral corticosteroid derivative budesonide has demonstrated superior efficacy compared with traditional therapies such as 5-aminosalicylic acid, and can be used concurrently with these agents. For the management of moderate to severe disease, the immunomodulators azathioprine, 6-mercaptopurine, and methotrexate, as well as the antitumor necrosis factor-alpha (TNF-α) agents infliximab, adalimumab, and certolizumab pegol, have become the mainstay of therapy, with growing interest in combining these agents for maximal effect. Immunomodulators and anti-TNF-α agents have also demonstrated benefit in fistulizing CD. There has been growing evidence suggesting that both of these agents, along with the antibiotics metronidazole and ornidazole, are also effective in preventing postoperative recurrence of CD. PMID:24436652

Model for Postgraduate Medical Education: Study of Crohn's Disease in New Mexico

ERIC Educational Resources Information Center

Gregory, Daniel H.; And Others

1974-01-01

The purpose of this study is to introduce a model system for the continuous retrieval, storage, and dissemination of relevant clinical information that has proven to be an effective resource of real-life data. Patients with Crohn's disease from a geographic area served as the population base for 2 groups of physicians, one group practicing in the…

Factors affecting poor nutritional status after small bowel resection in patients with Crohn disease.

PubMed

Jang, Ki Ung; Yu, Chang Sik; Lim, Seok-Byung; Park, In Ja; Yoon, Yong Sik; Kim, Chan Wook; Lee, Jong Lyul; Yang, Suk-Kyun; Ye, Byong Duk; Kim, Jin Cheon

2016-07-01

In Crohn disease, bowel-preserving surgery is necessary to prevent short bowel syndrome due to repeated operations. This study aimed to determine the remnant small bowel length cut-off and to evaluate the clinical factors related to nutritional status after small bowel resection in Crohn disease.We included 394 patients (69.3% male) who underwent small bowel resection for Crohn disease between 1991 and 2012. Patients who were classified as underweight (body mass index < 17.5) or at high risk of nutrition-related problems (modified nutritional risk index < 83.5) were regarded as having a poor nutritional status. Preliminary remnant small bowel length cut-offs were determined using receiver operating characteristic curves. Variables associated with poor nutritional status were assessed retrospectively using Student t tests, chi-squared tests, Fisher exact tests, and logistic regression analyses.The mean follow-up period was 52.9 months and the mean patient ages at the time of the last bowel surgery and last follow-up were 31.2 and 35.7 years, respectively. The mean remnant small bowel length was 331.8 cm. Forty-three patients (10.9%) underwent ileostomy, 309 (78.4%) underwent combined small bowel and colon resection, 111 (28.2%) had currently active disease, and 105 (26.6%) underwent at least 2 operations for recurrent disease. The mean body mass index and modified nutritional risk index were 20.6 and 100.8, respectively. The independent factors affecting underweight status were remnant small bowel length ≤240 cm (odds ratio: 4.84, P < 0.001), ileostomy (odds ratio: 4.70, P < 0.001), and currently active disease (odds ratio: 4.16, P < 0.001). The independent factors affecting high nutritional risk were remnant small bowel length ≤230 cm (odds ratio: 2.84, P = 0.012), presence of ileostomy (odds ratio: 3.36, P = 0.025), and currently active disease (odds ratio: 4.90, P < 0.001).Currently active disease, ileostomy, and remnant small

Clinical experience of the use of adalimumab in the management of hidradenitis suppurativa. Comparison of response rates with Crohn disease.

PubMed

Moyano, B; Clemente, A; Marín-Jiménez, I; Martorell, A

2016-09-01

The recent approval of adalimumab as the first treatment to be approved for the management of hidradenitis suppurativa has represented a before and after in the control of this chronic inflammatory disease. Given the inflammatory burden of this cutaneous disease, in the last few years hidradenitis suppurativa has been compared with inflammatory bowel disease, particularly with Crohn disease, to the point of considering hidradenitis suppurativa as "Crohn disease of the skin". These two chronic inflammatory diseases show sufficient similarities to consider whether treatment response based on the inflammatory load could also be similar. The present article aims to analyse the efficacy of adalimumab in hidradenitis suppurativa in comparison with a truly comparable disease, Crohn disease, with a view to evaluating therapeutic response rates and to drawing conclusions on the therapeutic success obtained in this disabling cutaneous disease. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

The Arabidopsis mediator complex subunits MED16, MED14, and MED2 regulate mediator and RNA polymerase II recruitment to CBF-responsive cold-regulated genes.

PubMed

Hemsley, Piers A; Hurst, Charlotte H; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R; De Cothi, Elizabeth A; Steele, John F; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation-induced freezing tolerance. In addition, these three subunits are required for low temperature-induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced.

Management of post-operative Crohn's disease in 2017: where do we go from here?

PubMed

Nguyen, Vu; Kanth, Rajan; Gazo, Joshua; Sorrentino, Dario

2016-11-01

Postoperative recurrence (POR) of Crohn's disease is common after surgical resection. How to best manage POR remains uncertain. Areas covered: In this review, we will first describe the natural course and the best modalities to diagnose this surgical sequela. We will then focus on the potential risk factors for relapse and highlight the main shortcomings in the current study designs and endoscopic and clinical scoring systems, which may partly explain the unexpected outcomes of recent clinical trials. Finally, we will propose a strategy to address the management of POR. Expert commentary: Anti-tumor necrosis factor (Anti-TNF) agents are the most effective therapy to prevent POR in Crohn's disease. Patient risk stratification and active monitoring with scheduled ileocolonoscopy are cornerstones of optimal POR management. Further studies are needed to address areas of uncertainty including timing and duration of therapy and the role of therapeutic drug monitoring in this setting.

JTF CapMed Warrior Transition Division

DTIC Science & Technology

2011-01-25

The Quadruple Aim: Working Together, Achieving Success 2011 Military Health System Conference JTF CapMed Warrior Transition Division 25 January 2011...Colonel Julia Adams 1 Military Health System Conference Joint Task Force National Capital Region Medical (JTF CapMed ) Report Documentation Page Form...DATES COVERED 00-00-2011 to 00-00-2011 4. TITLE AND SUBTITLE JTF CapMed Warrior Transition Division 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

Stress, coping and support needs of patients with ulcerative colitis or Crohn's disease: a qualitative descriptive study.

PubMed

Larsson, Kjerstin; Lööf, Lars; Nordin, Karin

2017-03-01

To examine disease-related stress, coping strategies and the need for information and support in patients with inflammatory bowel disease (ulcerative colitis or Crohn's disease). Psychological stress is an important factor in ulcerative colitis and Crohn's disease, and therefore, coping strategies and support needs should be considered in routine clinical practice. This is a qualitative study using a descriptive interview-based approach. Fifteen patients with ulcerative colitis (n = 7) or Crohn's disease (n = 8) were interviewed. The interviews were analysed with content analysis. The informants largely focused on disease-related stress (e.g. access to a toilet, symptoms and worries) and relations to other people (various reactions from others and social situations). Behavioural strategies (i.e. taking actions and the need for making plans, prepare and adapt), social strategies (seeking help and information and sharing feelings about the disease with others) and emotional strategies (distraction, positive attitude and acceptance) were adopted to cope with the stress associated with the disease. The need for information and support concerned instrumental support (disease-related information) and emotional support (to talk about disease management). Faecal urgency and the fear of losing bowel control are important stressors for patients with inflammatory bowel disease. The patients handle this problem using various coping strategies depending on the type of stressful events. Both instrumental and emotional support were requested which primarily occurred at the time of diagnosis and disease flare-ups. Patients with ulcerative colitis or Crohn's disease ask for information and psychosocial support that are tailored to their individual needs and at different stages in the disease trajectory to improve everyday life and strengthen self-management strategies. © 2016 John Wiley & Sons Ltd.

Changes in Crohn's disease phenotype over time in the Chinese population: validation of the Montreal classification system.

PubMed

Chow, Dorothy K L; Leong, Rupert W L; Lai, Larry H; Wong, Grace L H; Leung, Wai-Keung; Chan, Francis K L; Sung, Joseph J Y

2008-04-01

Phenotypic evolution of Crohn's disease occurs in whites but has never been described in other populations. The Montreal classification may describe phenotypes more precisely. The aim of this study was to validate the Montreal classification through a longitudinal sensitivity analysis in detecting phenotypic variation compared to the Vienna classification. This was a retrospective longitudinal study of consecutive Chinese Crohn's disease patients. All cases were classified by the Montreal classification and the Vienna classification for behavior and location. The evolution of these characteristics and the need for surgery were evaluated. A total of 109 patients were recruited (median follow-up: 4 years, range: 6 months-18 years). Crohn's disease behavior changed 3 years after diagnosis (P = 0.025), with an increase in stricturing and penetrating phenotypes, as determined by the Montreal classification, but was only detected by the Vienna classification after 5 years (P = 0.015). Disease location remained stable on follow-up in both classifications. Thirty-four patients (31%) underwent major surgery during the follow-up period with the stricturing [P = 0.002; hazard ratio (HR): 3.3; 95% CI: 1.5-7.0] and penetrating (P = 0.03; HR: 5.8; 95% CI: 1.2-28.2) phenotypes according to the Montreal classification associated with the need for major surgery. In contrast, colonic disease was protective against a major operation (P = 0.02; HR: 0.3; 95% CI: 0.08-0.8). This is the first study demonstrating phenotypic evolution of Crohn's disease in a nonwhite population. The Montreal classification is more sensitive to behavior phenotypic changes than is the Vienna classification after excluding perianal disease from the penetrating disease category and was useful in predicting course and the need for surgery.

Perspectives of IBD China: Is Crohn's and Colitis Foundation Model a Solution to Health Care Issues for the Country?

PubMed

Chen, Yan

2018-04-21

The success of the Crohn's and Colitis Foundation of America (CCFA), now Crohn's and Colitis Foundation (CCF) has established a role model for developing countries with an increasing incidence of inflammatory bowel disease (IBD), including China. While there are shared etiopathogenetic pathways and clinical features in IBD between Eastern and Western countries, patients with IBD as well as health care professionals in China are facing distinctive challenges, including the fragmented and inconsistent health insurance, social support system, and three-tiered health care service. Financial burden remains to be a tremendous obstacle to the management of IBD. In addition, poor rapport between patients and clinicians, and the lack of properly trained IBD specialists makes a noticeable gap in the management of IBD between China and Western countries. The China Crohn's &Colitis Foundation (CCCF), closely following the successful model of CCF, was established under the same doctrine, and served as a non-profit, volunteer-driven organization dedicated to improving quality of life of patients in by IBD through education and training.

An Evil Backstage Manipulator: Psychological Factors Correlated with Health-Related Quality of Life in Chinese Patients with Crohn's Disease

PubMed Central

Liu, Song; Hong, Zhiwu; Li, Xiaoting; Yao, Min; Yan, Dongsheng; Ren, Huajian; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Xia, Qiuyuan; Han, Gang; Li, Jieshou

2013-01-01

Health-related quality of life (HRQoL) is recommended as one of essential parameters to evaluate treatment effect and clinical outcome in patients with Crohn's disease (CD). Recent studies reported that psychological factors might play a role in HRQoL in Western and American CD patients. Sufficient evidences in Chinese CD patients are still unavailable. This study is dedicated to investigate the correlation of various psychological factors with HRQoL in Chinese CD patients. We prospectively collected 40 active and 40 quiescent CD patients in China and found that psychological factors, especially neuroticism and anxiety, significantly correlate with and affect HRQoL in both active and quiescent CD groups. This is the first report revealing correlation between psychological factors and HRQoL in Chinese CD patients. Therefore, we assume that our results can contribute to a better understanding of etiology and tailoring of management in Chinese patients with Crohn's disease and are beneficial to our colleagues to compare the heterogeneous characteristics of Crohn's disease in different ethnic groups. PMID:24453858

Certolizumab pegol: new drug. As a last resort in Crohn's disease: continue to use other TNF alpha inhibitors.

PubMed

2009-06-01

(1) Infliximab and adalimumab, two TNF alpha-inhibitor immunosuppressants, are both available for use as a last resort in Crohn's disease. They are effective in about one in two patients but they carry a risk of serious infections, lymphoma and aggravation of heart failure; (2) Certolizumab is a new TNF alpha-inhibitor monoclonal antibody. It is pegylated to prolong its action, hence the name certolizumab pegol; (3) Certolizumab is sold in the United States for the treatment of Crohn's disease, after failure of conventional treatments. However, the European authorities issued a negative opinion on this drug, and the European Commission refused to grant marketing authorization on 21 May 2008. It is nonetheless available for named-patient compassionate use in France; (4) Certolizumab pegol has not been compared directly with infliximab or adalimumab; (5) In a double-blind placebo-controlled trial including 662 adults with an exacerbation of Crohn's disease, a 6-month course of certolizumab pegol reduced symptom intensity in slightly more patients than placebo (23% versus 16%). However, the rate of clinical remissions was similar (about 12% of patients overall); (6) In a placebo-controlled trial in 428 patients with an initial critical response to certolizumab pegol, maintaining this treatment for 6 months was more effective than switching to placebo. Clinical remissions were obtained at the end of treatment in respectively 48% and 29% of patients; (7) These short-term trials showed a higher frequency of infections with certolizumab pegol than with placebo; these infections ranged from mild respiratory tract infections to fatal tuberculosis. Some patients also developed autoantibodies and anti-certolizumab pegol antibodies, but the clinical implications are unclear. There is also evidence of an excess risk of haemorrhage. The risk of long-term adverse effects remains to be determined; (8) Certolizumab pegol is injected subcutaneously, once a month, on an outpatient

Crohn's disease management after intestinal resection: a randomised trial.

PubMed

De Cruz, Peter; Kamm, Michael A; Hamilton, Amy L; Ritchie, Kathryn J; Krejany, Efrosinia O; Gorelik, Alexandra; Liew, Danny; Prideaux, Lani; Lawrance, Ian C; Andrews, Jane M; Bampton, Peter A; Gibson, Peter R; Sparrow, Miles; Leong, Rupert W; Florin, Timothy H; Gearry, Richard B; Radford-Smith, Graham; Macrae, Finlay A; Debinski, Henry; Selby, Warwick; Kronborg, Ian; Johnston, Michael J; Woods, Rodney; Elliott, P Ross; Bell, Sally J; Brown, Steven J; Connell, William R; Desmond, Paul V

2015-04-11

Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm

The Molecular Chaperone HSP70 Binds to and Stabilizes NOD2, an Important Protein Involved in Crohn Disease*

PubMed Central

Mohanan, Vishnu; Grimes, Catherine Leimkuhler

2014-01-01

Microbes are detected by the pathogen-associated molecular patterns through specific host pattern recognition receptors. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor that recognizes fragments of the bacterial cell wall. NOD2 is important to human biology; when it is mutated it loses the ability to respond properly to bacterial cell wall fragments. To determine the mechanisms of misactivation in the NOD2 Crohn mutants, we developed a cell-based system to screen for protein-protein interactors of NOD2. We identified heat shock protein 70 (HSP70) as a protein interactor of both wild type and Crohn mutant NOD2. HSP70 has previously been linked to inflammation, especially in the regulation of anti-inflammatory molecules. Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments. In addition, an HSP70 inhibitor, KNK437, was capable of decreasing NOD2-mediated NF-κB activation in response to bacterial cell wall stimulation. We found HSP70 to regulate the half-life of NOD2, as increasing the HSP70 level in cells increased the half-life of NOD2, and down-regulating HSP70 decreased the half-life of NOD2. The expression levels of the Crohn-associated NOD2 variants were less compared with wild type. The overexpression of HSP70 significantly increased NOD2 levels as well as the signaling capacity of the mutants. Thus, our study shows that restoring the stability of the NOD2 Crohn mutants is sufficient for rescuing the ability of these mutations to signal the presence of a bacterial cell wall ligand. PMID:24790089

Secondary Loss of Response to Infliximab in Pediatric Crohn Disease: Does It Matter How and When We Start?

PubMed

Bolia, Rishi; Rosenbaum, Jeremy; Schildkraut, Vered; Hardikar, Winita; Oliver, Mark; Cameron, Donald; Alex, George

2018-04-01

A significant proportion of children with Crohn disease develop a secondary loss of response (LOR) to infliximab. Our aim was to study the impact of initial treatment strategies on secondary LOR. We reviewed the medical records of children with Crohn disease who received scheduled maintenance infliximab therapy for at least 12 months. We compared children who developed LOR with those who did not; with regards to their clinical and laboratory parameters, disease phenotype, and treatment strategy before developing LOR. A total of 73 children (median age at diagnosis 11 (2-16) years, 41 boys) who had received a median duration of 33 (13-110) months of infliximab therapy were included in the final analysis. LOR was seen in 25(34.2%). Demographic variables, disease phenotype (age, disease location, and behavior), inflammatory parameters, and pediatric Crohn disease activity index at induction with infliximab were similar between both groups. Children with LOR had a significantly greater number of flares of the disease when compared to those who did not have LOR (4 [1-8] vs 2 [1-5] P = 0.03). The choice of the concomitant immunomodulator-methotrexate (11/29 [37.9%]) versus azathioprine (11/36 [30.5%]) (P = 0.6) did not affect LOR rates. The median time-lag between diagnosis and induction with infliximab was significantly longer in children with LOR as compared to those who did not have an LOR (28 [4-90] months vs 12.5 [1-121] months, P = 0.004). Early use of infliximab in pediatric Crohn disease is associated with a decrease in secondary LOR. The type of concomitant immunomodulator used does not make a difference to LOR rates.

Accuracy of magnetic resonance enterography in the preoperative assessment of patients with Crohn's disease of the small bowel.

PubMed

Pous-Serrano, S; Frasson, M; Palasí Giménez, R; Sanchez-Jordá, G; Pamies-Guilabert, J; Llavador Ros, M; Nos Mateu, P; Garcia-Granero, E

2017-05-01

To assess the accuracy of magnetic resonance enterography in predicting the extension, location and characteristics of the small bowel segments affected by Crohn's disease. This is a prospective study including a consecutive series of 38 patients with Crohn's disease of the small bowel who underwent surgery at a specialized colorectal unit of a tertiary hospital. Preoperative magnetic resonance enterography was performed in all patients, following a homogeneous protocol, within the 3 months prior to surgery. A thorough exploration of the small bowel was performed during the surgical procedure; calibration spheres were used according to the discretion of the surgeon. The accuracy of magnetic resonance enterography in detecting areas affected by Crohn's disease in the small bowel was assessed. The findings of magnetic resonance enterography were compared with surgical and pathological findings. Thirty-eight patients with 81 lesions were included in the study. During surgery, 12 lesions (14.8%) that were not described on magnetic resonance enterography were found. Seven of these were detected exclusively by the use of calibration spheres, passing unnoticed at surgical exploration. Magnetic resonance enterography had 90% accuracy in detecting the location of the stenosis (75.0% sensitivity, 95.7% specificity). Magnetic resonance enterography did not precisely diagnose the presence of an inflammatory phlegmon (accuracy 46.2%), but it was more accurate in detecting abscesses or fistulas (accuracy 89.9% and 98.6%, respectively). Magnetic resonance enterography is a useful tool in the preoperative assessment of patients with Crohn's disease. However, a thorough intra-operative exploration of the entire small bowel is still necessary. Colorectal Disease © 2017 The Association of Coloproctology of Great Britain and Ireland.

High-output stoma after small-bowel resections for Crohn's disease.

PubMed

Tsao, Stephen K K; Baker, Melanie; Nightingale, Jeremy M D

2005-12-01

A 56-year-old Caucasian woman with a history of Crohn's disease and multiple bowel resections resulting in a loop jejunostomy was referred to our Nutritional Unit from a neighboring district general hospital for further management. She was first seen in October 2001, and initial assessment indicated that she was malnourished with fluid depletion, evidenced by the high volume of stomal fluid produced. There had been no sudden change in her medication, her Crohn's disease was quiescent and there was no evidence of any intra-abdominal sepsis. Despite a high calorific intake through her diet, she continued to lose weight. Serum urea and electrolytes; magnesium; C-reactive protein; full blood count; urinary spot sodium; anthropometric measurements. High-output stoma with malabsorption as a consequence of repeated small-bowel surgery. The patient was treated with oral hypotonic fluid restriction (0.5 l/day), 2 l of oral glucose-saline solution per day, high-dose oral antimotility agents (loperamide and codeine phosphate), a proton-pump inhibitor (omeprazole) and oral magnesium replacement. A year later, the patient's loop jejunostomy was closed and an end ileostomy fashioned, bringing an additional 35 cm of small bowel into continuity; macronutrient absorption improved but her problem of dehydration was only slightly reduced. She was stabilized on a twice-weekly subcutaneous magnesium and saline infusion and daily oral 1alpha-hydroxycholecalciferol.

Genome analysis of E. coli isolated from Crohn's disease patients.

PubMed

Rakitina, Daria V; Manolov, Alexander I; Kanygina, Alexandra V; Garushyants, Sofya K; Baikova, Julia P; Alexeev, Dmitry G; Ladygina, Valentina G; Kostryukova, Elena S; Larin, Andrei K; Semashko, Tatiana A; Karpova, Irina Y; Babenko, Vladislav V; Ismagilova, Ruzilya K; Malanin, Sergei Y; Gelfand, Mikhail S; Ilina, Elena N; Gorodnichev, Roman B; Lisitsyna, Eugenia S; Aleshkin, Gennady I; Scherbakov, Petr L; Khalif, Igor L; Shapina, Marina V; Maev, Igor V; Andreev, Dmitry N; Govorun, Vadim M

2017-07-19

Escherichia coli (E. coli) has been increasingly implicated in the pathogenesis of Crohn's disease (CD). The phylogeny of E. coli isolated from Crohn's disease patients (CDEC) was controversial, and while genotyping results suggested heterogeneity, the sequenced strains of E. coli from CD patients were closely related. We performed the shotgun genome sequencing of 28 E. coli isolates from ten CD patients and compared genomes from these isolates with already published genomes of CD strains and other pathogenic and non-pathogenic strains. CDEC was shown to belong to A, B1, B2 and D phylogenetic groups. The plasmid and several operons from the reference CD-associated E. coli strain LF82 were demonstrated to be more often present in CDEC genomes belonging to different phylogenetic groups than in genomes of commensal strains. The operons include carbon-source induced invasion GimA island, prophage I, iron uptake operons I and II, capsular assembly pathogenetic island IV and propanediol and galactitol utilization operons. Our findings suggest that CDEC are phylogenetically diverse. However, some strains isolated from independent sources possess highly similar chromosome or plasmids. Though no CD-specific genes or functional domains were present in all CD-associated strains, some genes and operons are more often found in the genomes of CDEC than in commensal E. coli. They are principally linked to gut colonization and utilization of propanediol and other sugar alcohols.

PubMedMiner: Mining and Visualizing MeSH-based Associations in PubMed.

PubMed

Zhang, Yucan; Sarkar, Indra Neil; Chen, Elizabeth S

2014-01-01

The exponential growth of biomedical literature provides the opportunity to develop approaches for facilitating the identification of possible relationships between biomedical concepts. Indexing by Medical Subject Headings (MeSH) represent high-quality summaries of much of this literature that can be used to support hypothesis generation and knowledge discovery tasks using techniques such as association rule mining. Based on a survey of literature mining tools, a tool implemented using Ruby and R - PubMedMiner - was developed in this study for mining and visualizing MeSH-based associations for a set of MEDLINE articles. To demonstrate PubMedMiner's functionality, a case study was conducted that focused on identifying and comparing comorbidities for asthma in children and adults. Relative to the tools surveyed, the initial results suggest that PubMedMiner provides complementary functionality for summarizing and comparing topics as well as identifying potentially new knowledge.

Age-related differences in the clinical course of Crohns disease in an Asian population: a retrospective cohort review.

PubMed

Law, Siu-Tong; Li, Kin Kong

2013-12-01

The aim of this study was to compare the clinical characteristics and treatment outcomes of patients with young and adult onset Crohns disease. Among 79 consecutive Crohns disease patients (11 (13.92%) with onset =16 years old), young onset Crohns disease was significantly associated with fever (36.36 vs. 14.71%, P 0.041), weight loss (72.7 vs. 29.4%, P 0.003), isolated abdominal pain (45.45 vs. 16.18%, P 0.013), lower body mass index ( 17.32 vs. 21.29 kgm2, P 0.019), and extraintestinal manifestation, particularly oral (45.5% vs. 22.1%, P 0.049) and perianal lesion (63.6% vs. 36.8%, P 0.046). In both groups, ileocolonic disease and inflammatory lesion were the most prevalent site of involvement and dominant disease behavior respectively. Their complication and bowel resection rate were similar but the former took a longer period of time to develop in the young onset group (84 vs. 24 month, P 0.018). Cox proportional hazard regression analysis revealed that active smoking and delayed use of immunosuppressive therapy were the only independent risk factors associated with increased risk of complications.

Is there a benefit from the concomitant use of immunosupression with anti-TNF in Crohn's disease; heads or tails?

PubMed

Lakatos, Peter Laszlo

2009-09-01

Over the last some years the increasing knowledge on the pathogenesis of Crohn's disease led to the development of a number of biological agents targeting specific molecules involved in gut inflammation, first of all TNF-alpha and its receptors. Infliximab, adalimumab and certolizumab have been successful in inducing and maintaining remission in Crohn's disease at both short and long term. This was recently confirmed by a Cochrane meta-analysis and also open label extension follow-up and cohort studies. Emerging new data however indicate that combination therapy with infliximab-azathioprine appears to have added benefit in inducing steroid-free remission and mucosal healing than either infliximab or azathioprine alone in azathioprine-naïve patients with early disease. Similarly the combination of steroids induction and infliximab was efficacious in luminal Crohn's disease. In contrast, there seems to be no synergism between methotrexate and infliximab. It is also less clear whether it is beneficial to use short or long-term infliximab-azathioprine combination in patients who previously failed therapy with azathioprine. In contrast, combination may potentially be associated with increased risk for infection and cancer. In case control-studies, especially the combination of steroids and anti-TNF and older age increased the risk for infectious complications, while scattered case reports point to the potentially increased risk of a rare form of non-Hodgkin's lymphoma (Hepatosplenic T cell lymphoma) with the use of azathioprine-anti-TNF combination. The aim of this review is to summarize the benefits and risks for the use combination therapy with TNF-alpha inhibitors in the treatment of Crohn's disease.

[Adalimumab for the treatment of adult Crohn's disease--update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology].

PubMed

Novacek, G; Haas, T; Knoflach, P; Petritsch, W; Tilg, H; Vogelsang, H; Reinisch, W

2013-09-01

TNF alpha antibodies have clearly improved the outcome of moderate to severe Crohn's disease. Adalimumab is the first fully human, monoclonal TNF alpha antibody, which can be self-administered subcutaneously. Since August 2012 adalimumab is approved for the treatment of moderately to severely active Crohn's disease, in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant or who are intolerant to or have medical contraindications for such therapies. Compared to placebo adalimumab can induce significantly more often steroid-free remission and mucosal healing in patients with moderate to severe Crohn's disease, reduce the rate of Crohn's disease-related hospitalisations and surgery and improve health-related quality of life. Adalimumab is clinically efficacious both in patients with Crohn's disease naïve to previous exposure to TNF-alpha antibodies and in those previously exposed with a rapid onset of action within days and confirmed maintenance performance over 3 years. The safety profile of adalimumab is comparable to those of other TNF alpha inhibitors. Due to its low immunogenicity allergic reactions are rare. The update of a consensus report by the Working Group Inflammatory Bowel Disease of the Austrian Society of Gastroenterology and Hepatology presents the existing evidence on adalimumab for the treatment of Crohn's disease and is aimed to assist as a code of practice in its applications. © Georg Thieme Verlag KG Stuttgart · New York.

Overview of the MEDLI Project

NASA Technical Reports Server (NTRS)

Gazarik, Michael J.; Hwang, Helen; Little, Alan; Cheatwood, Neil; Wright, Michael; Herath, Jeff

2007-01-01

The Mars Science Laboratory Entry, Descent, and Landing Instrumentation (MEDLI) Project's objectives are to measure aerothermal environments, sub-surface heatshield material response, vehicle orientation, and atmospheric density for the atmospheric entry and descent phases of the Mars Science Laboratory (MSL) entry vehicle. The flight science objectives of MEDLI directly address the largest uncertainties in the ability to design and validate a robust Mars entry system, including aerothermal, aerodynamic and atmosphere models, and thermal protection system (TPS) design. The instrumentation suite will be installed in the heatshield of the MSL entry vehicle. The acquired data will support future Mars entry and aerocapture missions by providing measured atmospheric data to validate Mars atmosphere models and clarify the design margins for future Mars missions. MEDLI thermocouple and recession sensor data will significantly improve the understanding of aeroheating and TPS performance uncertainties for future missions. MEDLI pressure data will permit more accurate trajectory reconstruction, as well as separation of aerodynamic and atmospheric uncertainties in the hypersonic and supersonic regimes. This paper provides an overview of the project including the instrumentation design, system architecture, and expected measurement response.

[Effect of promoter polymorphism of organic cation transporter OCTN1/2 on the susceptibility to Crohns disease: a Meta-analysis].

PubMed

Ma, Mu-yuan; Ma, Zhi-bin; Xu, Hong-yu; Zhao, Jing-bo; Li, Ying; Gao, Meng

2013-03-01

To investigate the associations between polymorphisms of organic cation transporter OCTN1/2 (organic cation transporter 1/2) and the susceptibility of Crohn's disease (CD) through a meta-analysis. Databases of PubMed, EMBASE, MedLine, and CNKI (Chinese), Wanfang (Chinese) were searched for published case control studies on the association between polymorphisms of OCTN1/2 gene and the susceptibility of CD which were published before September 2012. The meta-analysis was applied with Review Manager 4.2 software and Stata 10.0 software. Nineteen eligible studies, including 14 from Europeans, 3 from Asians, 1 from Oceania, and 1 from the US were included in the meta-analysis. In total, significant associations were found between OCTN1/2 polymorphisms and the susceptibility of CD for all genetic models. In subgroup analyses, significant associations were found in the European population for OCTN1/2. Associations were not significant in the non-European population for OCTN1 (TT vs. CT: OR = 1.25, 95%CI: 0.75 - 1.98, P = 0.34; TT vs. CC + CT: OR = 1.48, 95%CI: 0.95 - 2.29, P = 0.08) and for OCTN2 (CC vs. GC: OR = 1.03, 95%CI: 0.68 - 1.56, P = 0.89; CC vs. GG + GC: OR = 1.23, 95%CI: 0.83 - 1.82, P = 0.31). However, there were significant associations found between OCTN1/2 (TT vs. CC, TT + CT vs. CC, CC vs. GG, CC + GC vs. GG) polymorphisms and the susceptibility of CD found in the non-European population. Results from this meta-analysis suggested that OCTN1/2 polymorphisms were associated with the susceptibility of CD in the European population. Associations between OCTN1/2 polymorphisms and the susceptibility of CD in the non-European population required searching for large samples to confirm the findings.

Bones and Crohn's: estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density.

PubMed

Klaus, J; Reinshagen, M; Adler, G; Boehm, Bo; von Tirpitz, C

2008-10-23

Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis. To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers. 111 male CD patients underwent osteodensitometry (DXA) of the spine (L1-L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls. Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD. We found an altered hormonal status--i.e. E2 and, to a lesser extent T deficiency--in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.

LactMed: Drugs and Lactation Database

MedlinePlus

... App LactMed Record Format Database Creation & Peer Review Process Help Fact Sheet Sample Record TOXNET FAQ Glossary Selected References About Dietary Supplements Breastfeeding Links Get LactMed Widget Contact Us Email: tehip@ ...

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease

PubMed Central

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-01-01

Abstract This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity. We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters. Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016). E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD. PMID:27684872

Increased Enterococcus faecalis infection is associated with clinically active Crohn disease.

PubMed

Zhou, Youlian; Chen, Huiting; He, Hanchang; Du, Yanlei; Hu, Jiaqi; Li, Yingfei; Li, Yuyuan; Zhou, Yongjian; Wang, Hong; Chen, Ye; Nie, Yuqiang

2016-09-01

This study was performed to investigate the relationship between the abundance of pathogenic gut microbes in Chinese patients with inflammatory bowel disease (IBD) and disease severity.We collected clinical data and fecal samples from 47 therapy-naive Chinese patients with ulcerative colitis (UC), 67 patients with Crohn disease (CD), and 48 healthy volunteers. Bacteria levels of Fusobacterium species (spp), enterotoxigenic Bacteroides fragilis (B fragilis), enteropathogenic Escherichia coli (E coli), and Enterococcus faecalis (E faecalis) were assessed by quantitative real-time PCR (qRT-PCR). Spearman correlation coefficients were calculated to test associations between bacterial content and clinical parameters.Compared to healthy controls, the levels of both Fusobacterium spp and E faecalis were significantly increased in the feces of patients with IBD (P < 0.01). B fragilis levels were higher (P < 0.05) and E faecalis levels lower (P < 0.05) in patients with CD compared to those with UC. Increased E faecalis colonization in CD associated positively with disease activity (P = 0.015), Crohn disease activity index (CDAI; R = 0.3118, P = 0.0108), and fecal calprotectin (P = 0.016).E faecalis and Fusobacterium spp are significantly enriched in patients with IBD, and increased E faecalis infection is associated with clinically active CD.

Histoplasma meets Crohn's disease: a rare case of new-onset ascites.

PubMed

Bosshardt, Charles Robert; Gnann, John; Lodhia, Nilesh

2018-04-17

A 53-year-old man with Crohn's disease treated with adalimumab was hospitalised with abdominal pain, fatigue, fever and chills. CT scan of the abdomen showed chronic thickening of the terminal ileum and cecum and new-onset ascites. Further studies revealed weakly positive urine and serum histoplasma antigen. Laparoscopy revealed metastatic caking of the omentum and abdominal wall; peritoneal biopsy demonstrated organisms morphologically consistent with Histoplasma capsulatum No dissemination outside of the peritoneal cavity was evident. The patient completed 2 weeks of liposomal amphotericin B followed by oral itraconazole for 1 year. Adalimumab therapy was held for 10 weeks, then restarted. Presenting symptoms resolved following initiation of antifungal therapy. Follow-up MRI of his abdomen demonstrated resolution of ascites. To our knowledge, this is the first reported case of histoplasmosis presenting as peritonitis in a patient with Crohn's disease receiving antitumour necrosis factor-alpha (TNF-α) therapy. Many clinicians are aware that patients receiving anti-TNF-α therapy are at increased risk for histoplasmosis, but may fail to consider the diagnosis in the absence of lung involvement. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Anti-TNFα therapy early improves hemodynamics in local intestinal and extraintestinal circulations in active Crohn's disease.

PubMed

Bonnin, Philippe; Coelho, Jessica; Pocard, Marc; Levy, Bernard I; Marteau, Philippe

2013-07-01

Active Crohn's disease affects intestine but may alter other locations as eyes vasculature. Previous studies provide evidence of elevated blood flow velocities (BFv) and volume (BFV) in superior mesenteric artery (SMA). We prospectively studied hemodynamics in feeding arteries of bowel and eyes before and 2 weeks after treatment induction with anti-TNFα. Fifteen patients (5 females, 10 males, 35.4 ± 9.0 years, mean ± SD) with active Crohn's disease for 7.5 ± 7.7 years were enrolled. Ultrasound imaging was performed before and 2 weeks after treatment in SMA and retrobulbar arteries: central retinal (CRA), temporal posterior ciliary (TPCA) and ophthalmic (OA) arteries. Serum markers of inflammation (CRP and fibrinogen), arterial blood pressures (ABP) and skin flow-mediated dilation (sFMD) were measured and patients were compared to 10 control age- and sex-matched subjects. Before treatment, CRP and fibrinogen plasma concentrations, SMA BFV (339 ± 100 mL/min) were higher in patients than in controls by 8.5-fold (p<0.001), 1.4-fold (p<0.01) and 1.5-fold, respectively (p<0.01). BFv in CRA (3.5 ± 0.7 cm/s) and TPCA (4.4 ± 1.0 cm/s), sFMD (371 ± 469%) were significantly lower than in controls by 83%, 73% and 52% respectively (p<0.05). Two weeks after treatment, CRP and fibrinogen decreased, SMA BFV was normalized (230 ± 39L/min, p<0.01), BFv in CRA, TPCA and OA increased respectively to 4.0 ± 1.1 (p<0.05), 5.2 ± 1.4 (p<0.001), 8.9 ± 3 cm/s (p<0.05). ABP and sFMD remained unchanged. In active Crohn's disease, a first anti-TNFα administration rapidly normalized concomitantly plasma inflammatory markers and blood-flows in the mesenteric and retrobulbar arteries without affecting blood pressure and endothelial function. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Assessment of the Quality of Patient-Orientated Information on Surgery for Crohn's Disease on the Internet.

PubMed

Yeung, Trevor M; Sacchi, Matteo; Mortensen, Neil J; Spinelli, Antonino

2015-09-01

The Internet is a vast resource for patients to search for health information on the treatment of Crohn's disease. This study examines the quality of Web sites that provide information to adults regarding Crohn's disease, including treatment options and surgery. Two search engines (Google and Yahoo) and the search terms "surgery for Crohn's disease" were used. The first 50 sites of each search were assessed. Sites that fulfilled the inclusion criteria were evaluated for content and scored by using the DISCERN instrument, which evaluates the quality of health information on treatment choices. One hundred sites were examined, of which 13 were duplicates. Sixty-two sites provided patient-orientated information. The other sites included 7 scientific articles, 3 blogs, 2 links, 6 forums, 3 video links, and 4 dead links. Of the 62 Web sites that provided patient information for adults, only 15 (24.2%) had been updated within the past 2 years. Only 9 (14.5%) were affiliated with hospitals and clinics. The majority of sites (33, 53.2%) were associated with private companies with commercial interests. Only half of the Web sites provided details on treatment options, and most Web sites did not provide any information on symptoms and procedure details. Just 5 Web sites (8.1%) described the risks of surgery, and only 7 (11.3%) provided any information on the timescale for recovery. Overall, only 1 Web site (1.6%) was identified as being "good" or "excellent" with the use of the DISCERN criteria. Although the internet is constantly evolving, this study captures data at a specific time point. Search results may vary depending on geographical location. This study only assessed English language websites. The quality of patient information on surgery for Crohn's disease is highly variable and generally poor. There is potential for the Internet to provide valuable information, and clinicians should identify high-quality Web sites to guide their patients.

Non perianal fistulas in Crohn's disease and short bowel syndrome: what we can do?

PubMed

Zildzic, Muharem; Alibegovic, Ervin

2009-01-01

Crohn's disease (CD) is a lifelong disease arising from an interaction between genetic and environmental factors, but seen predominantly in the developed countries of the world. The precise etiology is unknown and therefore a causal treatment is not yet available. Fistulating Crohn's disease includes fistulas arising in the perianal area, together with those communicating between the intestine and other organs or the abdominal wall. Non perianal fistulas include fistulas communicating with other viscera (urinary bladder, vagina), loops of intestine (enteroenteral fistulas) or the abdominal wall (enterocutaneus fistulas). The diagnostic approach is a crucial aspect in the management of fistulating CD as the findings influence the therapeutic strategy. Short bowel syndrome caused by extensive bowel resection should be initially treated with nutritional support and can caused serious treatment and reevaluating problems. We review this uncommon manifestation in a high risk patient after multiple operations and severely shortened bowel and also with non perianal fistulating CD.

Recurrent Hepatocellular Carcinoma in Patient with Crohn's Disease: Incidental or Expected Outcome of Azathioprine?

PubMed Central

Botros, Youssef; Mathews, Mary; Patel, Hiren; Shah, Nihar; Baddoura, Walid; de la Torre, Andrew

2015-01-01

Hepatocellular carcinoma (HCC) usually occurs in patients with underlying risk factors such as liver cirrhosis and chronic hepatitis B. Although patients with Crohn's disease (CD) are at an increased risk to develop malignancies such as colon cancer, the incidence of HCC in this population is extremely rare. We report a case of 62-year-old male with long history of CD treated with azathioprine (AZA) and aminosalicylic acid (ASA) who was incidentally diagnosed with HCC, for which left hepatectomy was done. Four years later during routine follow-up, patient had another hepatic lesion and underwent resection of the mass. The mechanism of occurrence of HCC in patient with CD is still controversial and may include immune mediated changes and medication related complications. AZA was reported in all case reports of CD that developed HCC. Through this report we hope to explore the complex pathophysiological mechanisms contributing to the development of HCC in the Crohn's disease patient population. PMID:26788381

Vitamin D-mediated calcium absorption in patients with clinically stable Crohn's disease: a pilot study

USDA-ARS?s Scientific Manuscript database

Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's ...

Laparoscopic approach is feasible in Crohn's complex enterovisceral fistulas: a case-match review.

PubMed

Beyer-Berjot, Laura; Mancini, Julien; Bege, Thierry; Moutardier, Vincent; Brunet, Christian; Grimaud, Jean-Charles; Berdah, Stéphane

2013-02-01

Complex enterovisceral fistulas are internal fistulas joining a "diseased" organ to any intra-abdominal "victim" organ, with the exception of ileoileal fistulas. Few publications have addressed laparoscopic surgery for complex fistulas in Crohn's disease. The aim of this study was to evaluate the feasibility of such an approach. This study is a retrospective, case-match review. This study was conducted at a tertiary academic hospital. : All patients who underwent a laparoscopic ileocecal resection for complex enterovisceral fistulas between January 2004 and August 2011 were included. They were matched to a control group undergoing operation for nonfistulizing Crohn's disease according to age, sex, nutritional state, preoperative use of steroids, and type of resection performed. Matching was performed blind to the peri- and postoperative results of each patient. The 2 groups were compared in terms of operative time, conversion to open surgery, morbidity and mortality rates, and length of stay. Eleven patients presenting with 13 complex fistulas were included and matched with 22 controls. Group 1 contained 5 ileosigmoid fistulas (38%), 3 ileotransverse fistulas (23%), 3 ileovesical fistulas (23%), 1 colocolic fistula (8%), and 1 ileosalpingeal fistula (8%). There were no significant differences between the groups in terms of operative time (120 (range, 75-270) vs 120 (range, 50-160) minutes, p = 0.65), conversion to open surgery (9% vs 0%, p = 0.33), stoma creation (9% vs 14%, p = 1), global postoperative morbidity (18% vs 32%, p = 0.68), and major complications (Dindo III: 0% vs 9%, p = 0.54; Dindo IV: 0% vs 0%, p = 1), as well as in terms of length of stay (8 (range, 7-32) vs 9 (range, 5-17) days, p = 0.72). No patients died. This is a retrospective review with a small sample size. A laparoscopic approach for complex fistulas is feasible in Crohn's disease, with outcomes similar to those reported for nonfistulizing forms.

Accuracy of CT enterography and magnetic resonance enterography imaging to detect lesions preoperatively in patients undergoing surgery for Crohn's disease.

PubMed

Seastedt, Kenneth P; Trencheva, Koiana; Michelassi, Fabrizio; Alsaleh, Doaa; Milsom, Jeffrey W; Sonoda, Toyooki; Lee, Sang W; Nandakumar, Govind

2014-12-01

CT enterography and magnetic resonance enterography have emerged as first-line imaging technologies for the evaluation of the gastrointestinal tract in Crohn's disease. The purpose of this work was to evaluate the accuracy of these imaging modalities to identify Crohn's disease lesions preoperatively. This was a retrospective chart review. The study was conducted at a single institution. Seventy-six patients with Crohn's disease with preoperative CT enterography and/or magnetic resonance enterography were included in the study. The number of stenoses, fistulas, and abscesses on CT enterography and/or magnetic resonance enterography before surgery were compared with operative findings. Forty patients (53%) were women, 46 (60%) underwent surgery for recurrent Crohn's disease, and 46 (57%) had previous abdominal surgery. Thirty-six (47%) had a preoperative CT enterography and 43 (57%) had a preoperative magnetic resonance enterography. CT enterography sensitivity was 75% for stenosis and 50% for fistula. MRE sensitivity was 68% for stenosis and 60% for fistula. The negative predictive values of CT enterography and magnetic resonance enterography for stenosis were very low (54% and 65%) and were 85% and 81% for fistula. CT enterography had 76% accuracy for stenosis and 79% for fistula; magnetic resonance enterography had 78% accuracy for stenosis and 85% for fistula. Both were accurate for abscess. False-negative rates for CT enterography were 50% for fistula and 25% for stenosis. False-negative rates for magnetic resonance enterography were 40% for fistula and 32% for stenosis. Unexpected intraoperative findings led to modification of the planned surgical procedure in 20 patients (26%). This study was limited by its small sample size, its retrospective nature, and that some studies were performed at outside institutions. CT enterography and magnetic resonance enterography in patients with Crohn's disease were accurate for the identification of abscesses but not for

Surgical Management in Enterovesical Fistula in Crohn Disease at a Single Medical Center

PubMed Central

Su, Yann-Rong; Shih, I-Lun; Tai, Huai-Ching; Wei, Shu-Chen; Lin, Been-Ren; Yu, Hong-Jeng; Huang, Chao-Yuan

2014-01-01

Crohn disease is a chronic, transmural, inflammatory disease of the gastrointestinal tract with unknown etiology. It can affect any part of the gastrointestinal tract and may cause fistula, stricture, or abscess formation with disease progression. The preoperative diagnosis and definite management of this rare complication are challenges for physicians, urologists, and surgeons. PMID:24670020

Effect of thalidomide on clinical remission in children and adolescents with refractory Crohn disease: a randomized clinical trial.

PubMed

Lazzerini, Marzia; Martelossi, Stefano; Magazzù, Giuseppe; Pellegrino, Salvatore; Lucanto, Maria Cristina; Barabino, Arrigo; Calvi, Angela; Arrigo, Serena; Lionetti, Paolo; Lorusso, Monica; Mangiantini, Francesca; Fontana, Massimo; Zuin, Giovanna; Palla, Gabriella; Maggiore, Giuseppe; Bramuzzo, Matteo; Pellegrin, Maria Chiara; Maschio, Massimo; Villanacci, Vincenzo; Manenti, Stefania; Decorti, Giuliana; De Iudicibus, Sara; Paparazzo, Rossella; Montico, Marcella; Ventura, Alessandro

2013-11-27

Pediatric-onset Crohn disease is more aggressive than adult-onset disease, has high rates of resistance to existing drugs, and can lead to permanent impairments. Few trials have evaluated new drugs for refractory Crohn disease in children. To determine whether thalidomide is effective in inducing remission in refractory pediatric Crohn disease. Multicenter, double-blind, placebo-controlled, randomized clinical trial of 56 children with active Crohn disease despite immunosuppressive treatment, conducted August 2008-September 2012 in 6 pediatric tertiary care centers in Italy. Thalidomide, 1.5 to 2.5 mg/kg per day, or placebo once daily for 8 weeks. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for an additional minimum 52 weeks. Primary outcomes were clinical remission at week 8, measured by Pediatric Crohn Disease Activity Index (PCDAI) score and reduction in PCDAI by ≥25% or ≥75% at weeks 4 and 8. Primary outcomes during the open-label follow-up were clinical remission and 75% response. Twenty-eight children were randomized to thalidomide and 26 to placebo. Clinical remission was achieved by significantly more children treated with thalidomide (13/28 [46.4%] vs 3/26 [11.5%]; risk ratio [RR], 4.0 [95% CI, 1.2-12.5]; P = .01; number needed to treat [NNT], 2.86). Responses were not different at 4 weeks, but greater improvement was observed at 8 weeks in the thalidomide group (75% response, 13/28 [46.4%] vs 3/26 [11.5%]; RR, 4.0 [95% CI, 1.2-12.5]; NNT = 2.86; P = .01; and 25% response, 18/28 [64.2%] vs 8/26 [30.8%]; RR, 2.1 [95% CI, 1.1-3.9]; NNT = 2.99; P = .01). Of the nonresponders to placebo who began receiving thalidomide, 11 of 21 (52.4%) subsequently reached remission at week 8 (RR, 4.5 [95% CI, 1.4-14.1]; NNT = 2.45; P = .01). Overall, 31 of 49 children treated with thalidomide (63.3%) achieved clinical remission, and 32 of 49

Crohn's disease-associated interstitial lung disease mimicking sarcoidosis: a case report and review of the literature.

PubMed

Thao, Choua; Lagstein, Amir; Allen, Tadashi; Dincer, Huseyin Erhan; Kim, Hyun Joo

2016-10-07

Respiratory involvement in Crohn's disease (CD) is a rare manifestation known to involve the large and small airways, lung parenchyma, and pleura. The clinical presentation is nonspecific, and diagnostic tests can mimic other pulmonary diseases, posing a diagnostic challenge and delay in treatment. We report a case of a 60-year-old female with a history of CD and psoriatic arthritis who presented with dyspnea, fever, and cough with abnormal radiological findings. Diagnostic testing revealed an elevated CD4:CD8 ratio in the bronchoalveolar lavage fluid, and cryoprobe lung biopsy results showed non-necrotizing granulomatous inflammation. We describe here the second reported case of pulmonary involvement mimicking sarcoidosis in Crohn's disease and a review of the literature on the approaches to making a diagnosis of CD-associated interstitial lung disease.

Predicting clicks of PubMed articles.

PubMed

Mao, Yuqing; Lu, Zhiyong

2013-01-01

Predicting the popularity or access usage of an article has the potential to improve the quality of PubMed searches. We can model the click trend of each article as its access changes over time by mining the PubMed query logs, which contain the previous access history for all articles. In this article, we examine the access patterns produced by PubMed users in two years (July 2009 to July 2011). We explore the time series of accesses for each article in the query logs, model the trends with regression approaches, and subsequently use the models for prediction. We show that the click trends of PubMed articles are best fitted with a log-normal regression model. This model allows the number of accesses an article receives and the time since it first becomes available in PubMed to be related via quadratic and logistic functions, with the model parameters to be estimated via maximum likelihood. Our experiments predicting the number of accesses for an article based on its past usage demonstrate that the mean absolute error and mean absolute percentage error of our model are 4.0% and 8.1% lower than the power-law regression model, respectively. The log-normal distribution is also shown to perform significantly better than a previous prediction method based on a human memory theory in cognitive science. This work warrants further investigation on the utility of such a log-normal regression approach towards improving information access in PubMed.

Decreased number of steroid receptors of circulating lymphocytes in Crohn's disease and ulcerative colitis.

PubMed

Krasznai, A; Krajcsi, P; Arányi, P; Mészáros, K; Horváth, I

1986-01-01

The number of steroid receptors of circulating lymphocytes was determined in 13 patients with inflammatory bowel disease and in controls. Marked reduction of the number of receptors was observed both in Crohn's disease and in ulcerative colitis; no receptors were detected by radioactive hormone binding assay in 4 cases.

Overview of the MEDLI Project

NASA Technical Reports Server (NTRS)

Gazarik, Michael J.; Little, Alan; Cheatwood, F. Neil; Wright, Michael J.; Herath, Jeff A.; Martinez, Edward R.; Munk, Michelle; Novak, Frank J.; Wright, Henry S.

2008-01-01

The Mars Science Laboratory Entry, Descent, and Landing Instrumentation (MEDLI) Project s objectives are to measure aerothermal environments, sub-surface heatshield material response, vehicle orientation, and atmospheric density for the atmospheric entry and descent phases of the Mars Science Laboratory (MSL) entry vehicle. The flight science objectives of MEDLI directly address the largest uncertainties in the ability to design and validate a robust Mars entry system, including aerothermal, aerodynamic and atmosphere models, and thermal protection system (TPS) design. The instrumentation suite will be installed in the heatshield of the MSL entry vehicle. The acquired data will support future Mars entry and aerocapture missions by providing measured atmospheric data to validate Mars atmosphere models and clarify the design margins for future Mars missions. MEDLI thermocouple and recession sensor data will significantly improve the understanding of aeroheating and TPS performance uncertainties for future missions. MEDLI pressure data will permit more accurate trajectory reconstruction, as well as separation of aerodynamic and atmospheric uncertainties in the hypersonic and supersonic regimes. This paper provides an overview of the project including the instrumentation design, system architecture, and expected measurement response.

The molecular chaperone HSP70 binds to and stabilizes NOD2, an important protein involved in Crohn disease.

PubMed

Mohanan, Vishnu; Grimes, Catherine Leimkuhler

2014-07-04

Microbes are detected by the pathogen-associated molecular patterns through specific host pattern recognition receptors. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is an intracellular pattern recognition receptor that recognizes fragments of the bacterial cell wall. NOD2 is important to human biology; when it is mutated it loses the ability to respond properly to bacterial cell wall fragments. To determine the mechanisms of misactivation in the NOD2 Crohn mutants, we developed a cell-based system to screen for protein-protein interactors of NOD2. We identified heat shock protein 70 (HSP70) as a protein interactor of both wild type and Crohn mutant NOD2. HSP70 has previously been linked to inflammation, especially in the regulation of anti-inflammatory molecules. Induced HSP70 expression in cells increased the response of NOD2 to bacterial cell wall fragments. In addition, an HSP70 inhibitor, KNK437, was capable of decreasing NOD2-mediated NF-κB activation in response to bacterial cell wall stimulation. We found HSP70 to regulate the half-life of NOD2, as increasing the HSP70 level in cells increased the half-life of NOD2, and down-regulating HSP70 decreased the half-life of NOD2. The expression levels of the Crohn-associated NOD2 variants were less compared with wild type. The overexpression of HSP70 significantly increased NOD2 levels as well as the signaling capacity of the mutants. Thus, our study shows that restoring the stability of the NOD2 Crohn mutants is sufficient for rescuing the ability of these mutations to signal the presence of a bacterial cell wall ligand. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Carcinoma of the small intestine and colon as a complication of Crohn disease: radiologic manifestation

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

Kerber, G.W.; Frank, P.H.

1984-03-01

Barium examinations of the large and small bowel were analyzed in six of seven patients who had adenocarcinoma in areas of the intestine affected with Crohn disease; radiographic changes were correlated with clinical, surgical, and pathologic findings. Radiographic examinations were available in five of these patients at the time of diagnosis of tumor. Two of the five patients demonstrated classic radiographic changes associated with carcinoma. In the other three cases, the radiographic changes were atypical for carcinoma and demonstrated progression of disease over time to include more portions of the bowel and presence of fistulas, strictures, and obstruction. The mostmore » frequent clinical presentation of adenocarcinoma in these patients was a recrudescence of symptoms after a long quiescent period. In patients with long-standing Crohn disease plus these clinical features and the above radiographic findings, the diagnosis of a coexisting carcinoma should be considered.« less

Long-term Efficacy of Vedolizumab for Crohn's Disease.

PubMed

Vermeire, Severine; Loftus, Edward V; Colombel, Jean-Frédéric; Feagan, Brian G; Sandborn, William J; Sands, Bruce E; Danese, Silvio; D'Haens, Geert R; Kaser, Arthur; Panaccione, Remo; Rubin, David T; Shafran, Ira; McAuliffe, Megan; Kaviya, Arpeat; Sankoh, Serap; Mody, Reema; Abhyankar, Brihad; Smyth, Michael

2017-04-01

Vedolizumab is a gut-selective α4β7 integrin antagonist therapy for ulcerative colitis and Crohn's disease. The GEMINI long-term safety [LTS] trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn's disease. Patients from the C13004, GEMINI 2 and GEMINI 3 studies and vedolizumab-naïve patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks. Data were collected from May 22, 2009 to June 27, 2013. Outcomes of clinical response and remission, defined by the Harvey-Bradshaw Index, and health-related quality of life [HRQL] were assessed for up to 152 weeks of treatment in the efficacy population. Among patients with response at week 6 in GEMINI 2 who received vedolizumab continuously, 83% [n=100/120] and 89% [n=62/70] of patients with available data were in remission after 104 and 152 weeks, respectively. Increased dosing frequency from every 8 weeks [GEMINI 2] to every 4 weeks [GEMINI LTS] improved outcomes in patients who had withdrawn early from GEMINI 2, with 47% [n=27/57] experiencing clinical response and 32% [n=18/57] in remission at week 52 of GEMINI LTS [up from 39% and 4% before the dose increase]. Similar improvements were observed regardless of prior tumour necrosis factor [TNF] antagonist exposure. Long-term benefits of HRQL were also observed. The clinical benefits of vedolizumab continued with long-term treatment regardless of prior TNF antagonist exposure. Increased dosing frequency might improve outcomes in patients who lose response to conventional 8-weekly dosing. 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

Crohn's disease of the vulva.

PubMed

Barret, Maximilien; de Parades, Vincent; Battistella, Maxime; Sokol, Harry; Lemarchand, Nicolas; Marteau, Philippe

2014-07-01

Crohn's disease (CD) of the vulva is a rare, yet under recognized condition. Fistulae arising from the digestive tract account for the greater part of genital lesions in CD. However, cutaneous so-called metastatic lesions of the vulva have been reported in the literature. They are clinically challenging for gastroenterologists as well as for gynecologists, with numerous differential diagnoses, especially among venereal diseases, and require a multidisciplinary approach. The most frequently observed features of the disease are labial swelling, vulvar ulcers, and hypertrophic lesions. Biopsy samples for histological study are mandatory, in order to establish the diagnosis of vulvar CD. Treatment options include oral prolonged courses of metronidazole and systemic immunosuppressive therapy such as corticosteroids and azathioprine, with promising data published on the efficacy of infliximab. Surgery remains restricted to medical treatment failures or resection of unsightly lesions. Prospective studies or case series with long follow-up data are still missing to guide the treatment of this condition. © 2013. Published by Elsevier B.V. All rights reserved.

Vedolizumab: a review of its use in adult patients with moderately to severely active ulcerative colitis or Crohn's disease.

PubMed

Garnock-Jones, K P

2015-02-01

Vedolizumab (Entyvio™) is a humanized monoclonal antibody α4β7 integrin-receptor antagonist indicated for the treatment of adult patients with moderately to severely active ulcerative colitis or Crohn's disease. This article reviews the pharmacological properties of intravenous infusions of vedolizumab and its clinical efficacy in adult patients with these diseases. In phase III clinical trials, patients with ulcerative colitis had significantly higher rates of clinical response and clinical remission when treated with vedolizumab than when receiving placebo at both 6 and 52 weeks. However, outcomes with vedolizumab in patients with Crohn's disease were mixed. In a study that evaluated both clinical remission rate and CDAI-100 response rate as primary endpoints, only the clinical remission rate at 6 weeks was significantly higher with vedolizumab than placebo. In another trial, there was no significant between-group difference in the clinical remission rate in TNF-antagonist failure patients at 6 weeks (primary endpoint), although there was a significant difference at 10 weeks. In the Crohn's disease study that included maintenance treatment, vedolizumab was significantly more effective at 52 weeks than placebo in both endpoints (clinical remission was the only primary endpoint in the maintenance study). Vedolizumab was generally well tolerated in these trials. As vedolizumab is a specific α4β7 integrin antagonist, with gut-specific effects, it is unlikely to be associated with the development of progressive multifocal leukoencephalopathy, a risk observed with the less selective α4β7/α4β1 integrin antagonist natalizumab. Vedolizumab is a useful addition to the treatment options available for patients with moderately to severely active ulcerative colitis and Crohn's disease.

MED-SUV final strategic issues

NASA Astrophysics Data System (ADS)

Spampinato, Letizia; Puglisi, Giuseppe; Sangianantoni, Agata

2016-04-01

Aside the scientific, technical and financial aspects managed by the "Project Management" Work Package (WP1), the great challenge and more time consuming task of this WP has surely been the definition and application of some strategic guidelines crucial to trace the project right path to its final success and for the project outcome sustainability after month 36. In particular, given that one of the main objectives of MED-SUV is that to be compliant with the GEO initiative, particularly concerning the data sharing, great efforts have been made by WP1 at first to define the MED-SUV Data Policy Guidelines, and currently to make it suitable for the EU Supersites. At present, WP1 is also dealing with the exploitation of the achieved foreground among the project's participant and to define a Memorandum of Understanding to sustain the monitoring systems and e-infrastructure developed in the project framework. Whilst the Data Policy guidelines document was implemented in the first year of MED-SUV, WP1 is now focused on the last deliverable 'Strategic and Legal deliverables', which includes the remaining issues. To the aim, WP1 has strategically separated the Exploitation of Foreground document preparation from the Memorandum of Understanding definition. The Exploitation of Foreground process has regarded the identification of Foreground, the exploitable results, the purpose of such Foreground, the collection of information from either the scientific community of MED-SUV or industrial participants; to this aim WP1 circulated an ad hoc questionnaire to put together information on (the) every kind of MED-SUV outcome, on their owners, on the kind of ownership (single/joint), on the outcome exploitation, and on proposals for its sustainability. While the first information will allow us to prepare the final Exploitation Agreement among the project's participant, the information on the exploitation of the outcome and likely sustainability proposals will contribute to the

Complete Genome Sequence of the Crohn's Disease-Associated Adherent-Invasive Escherichia coliStrain HM605▿

PubMed Central

Clarke, David J.; Chaudhuri, Roy R.; Martin, Helen M.; Campbell, Barry J.; Rhodes, Jonathan M.; Constantinidou, Chrystala; Pallen, Mark J.; Loman, Nicholas J.; Cunningham, Adam F.; Browning, Douglas F.; Henderson, Ian R.

2011-01-01

Adherent-invasive Escherichia colistrains are increasingly being associated with intestinal pathologies. Here we present the genome sequence of E. coliHM605, a strain isolated from colonic biopsy specimens of a patient with Crohn's disease. PMID:21705601

A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

NASA Astrophysics Data System (ADS)

Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

2014-02-01

Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

The cost-effectiveness of infliximab in Crohn's disease.

PubMed

Smart, Claire; Selinger, Christian P

2014-10-01

Crohn's disease (CD) is a chronic inflammatory condition that can affect any part of the gastrointestinal tract. It leads to severe symptoms and reduced quality of life. Infliximab is a monoclonal antibody against TNF-α and is effective in treating moderate to severe CD. It is associated with high treatment costs, but subsequent reductions in hospitalisation and surgery have been reported. This review examines the evidence for the cost-effectiveness of infliximab for the treatment of CD. Studies have been found to be very heterogeneous depending on setting, costs assumed and clinical data. Within the UK setting infliximab has been found to be cost effective with increased costs of around £25,000 per quality adjusted life year gained.

Predicting clicks of PubMed articles

PubMed Central

Mao, Yuqing; Lu, Zhiyong

2013-01-01

Predicting the popularity or access usage of an article has the potential to improve the quality of PubMed searches. We can model the click trend of each article as its access changes over time by mining the PubMed query logs, which contain the previous access history for all articles. In this article, we examine the access patterns produced by PubMed users in two years (July 2009 to July 2011). We explore the time series of accesses for each article in the query logs, model the trends with regression approaches, and subsequently use the models for prediction. We show that the click trends of PubMed articles are best fitted with a log-normal regression model. This model allows the number of accesses an article receives and the time since it first becomes available in PubMed to be related via quadratic and logistic functions, with the model parameters to be estimated via maximum likelihood. Our experiments predicting the number of accesses for an article based on its past usage demonstrate that the mean absolute error and mean absolute percentage error of our model are 4.0% and 8.1% lower than the power-law regression model, respectively. The log-normal distribution is also shown to perform significantly better than a previous prediction method based on a human memory theory in cognitive science. This work warrants further investigation on the utility of such a log-normal regression approach towards improving information access in PubMed. PMID:24551386

Pediatric Crohn Disease Clinical Outcome Assessments and Biomarkers: Current State and Path Forward for Global Collaboration.

PubMed

Sun, Haihao; Vesely, Richard; Lee, Kerry Jo; Klein, Agnes; Ikima, Mutsuhiro; Mulberg, Andrew E

2017-03-01

There is a pressing need for drug development in pediatric Crohn disease (CD). Our aim was to provide strategic approaches toward harmonization of current thinking about clinical outcome assessments (COAs) and biomarkers to facilitate drug development in pediatric CD. Scientists from the United States Food and Drug Administration, European Medicines Agency, Health Canada, and the Pharmaceuticals and Medical Devices Agency of Japan had monthly teleconferences from January 2014 through May 2015. A literature review was conducted to assess the measurement properties of all existing COA tools and to evaluate the current landscape of biomarkers used in pediatric CD. Based on the findings of literature review, we reached the consensus on the strategic approaches for evaluating outcomes in pediatric CD trials. The pediatric Crohn's Disease Activity Index, Crohn's Disease Activity Index, and Harvey-Bradshaw's index were used in pediatric CD clinical studies. But they lack adequate measurement properties (validity, reliability, and ability to detect change of the treatment) that are required to support approval of products intended to treat pediatric CD. Biomarkers (ie, fecal lactoferrin, osteoprotegerin, and calprotectin) have shown some promise for their potential as noninvasive surrogate endpoints in CD. Lack of well-defined and reliable COAs presents a hurdle for global drug development in pediatric CD. It is essential to develop well-defined and reliable COAs that can measure meaningful clinical benefit for patients in terms of how they feel, function, and survive. Development of noninvasive biomarkers as reliable surrogate endpoints needs to be further explored.

Further confirmation of the MED13L haploinsufficiency syndrome.

PubMed

van Haelst, Mieke M; Monroe, Glen R; Duran, Karen; van Binsbergen, Ellen; Breur, Johannes M; Giltay, Jacques C; van Haaften, Gijs

2015-01-01

MED13L haploinsufficiency syndrome has been described in two patients and is characterized by moderate intellectual disability (ID), conotruncal heart defects, facial abnormalities and hypotonia. Missense mutations in MED13L are linked to transposition of the great arteries and non-syndromal intellectual disability. Here we describe two novel patients with de novo MED13L aberrations. The first patient has a de novo mutation in the splice acceptor site of exon 5 of MED13L. cDNA analysis showed this mutation results in an in-frame deletion, removing 15 amino acids in middle of the conserved MED13L N-terminal domain. The second patient carries a de novo deletion of exons 6-20 of MED13L. Both patients show features of the MED13L haploinsufficiency syndrome, except for the heart defects, thus further confirming the existence of the MED13L haploinsufficiency syndrome.

Human melioidosis reported by ProMED.

PubMed

Nasner-Posso, Katherinn Melissa; Cruz-Calderón, Stefania; Montúfar-Andrade, Franco E; Dance, David A B; Rodriguez-Morales, Alfonso J

2015-06-01

There are limited sources describing the global burden of emerging diseases. A review of human melioidosis reported by ProMED was performed and the reliability of the data retrieved assessed in comparison to published reports. The effectiveness of ProMED was evaluated as a source of epidemiological data by focusing on melioidosis. Using the keyword 'melioidosis' in the ProMED search engine, all of the information from the reports and collected data was reviewed using a structured form, including the year, country, gender, occupation, number of infected individuals, and number of fatal cases. One hundred and twenty-four entries reported between January 1995 and October 2014 were identified. A total of 4630 cases were reported, with death reported in 505 cases, suggesting a misleadingly low overall case fatality rate (CFR) of 11%. Of 20 cases for which the gender was reported, 12 (60%) were male. Most of the cases were reported from Australia, Thailand, Singapore, Vietnam, and Malaysia, with sporadic reports from other countries. Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided good information about melioidosis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Temporal Change in Phenotypic Behaviour in Patients with Crohn's Disease: Do Indian Patients Behave Differently from Western and Other Asian Patients?

PubMed

Kalaria, Rishikesh; Desai, Devendra; Abraham, Philip; Joshi, Anand; Gupta, Tarun; Shah, Sudeep

2016-03-01

In Western studies, one-third of patients with Crohn's disease have stricturing or penetrating disease at presentation and one-half will progress to complicated disease in 20 years. Asian studies indicate that the Asian disease phenotype may be different. Our aim was to study the disease behaviour in Indian patients with Crohn's disease. In this hospital-based study, we analysed [Montreal classification] disease phenotype, presence of perianal disease, need for intestinal surgery, and changes in the Montreal classification over time in Crohn's disease patients from our database. In the 178 patients (median age 35, interquartile range [IQR] 21 years; 97 males) with Crohn's disease, the proportion of various features was as follows. More patients had ileo-colonic[L3: 43.8%] than ileal[L1: 27.5%] or colonic[L2: 28.7%] disease. Perianal disease was seen in 11.8% at baseline. Non-stricturing, non-fistulising disease[B1] was seen in 74.7%, 65.7%, 50%, and 44.4% at baseline, at 5, 10 and 15 years, respectively. Stricturing disease[B2] was seen in 21.4%, 21.9%, 28.9%, and 33.3%; penetrating disease[B3] in 3.9%, 11.4%, 21%, and 16.7%; and intestinal surgery was required in 10.7%, 20%, 34.2%, and 55.5%, respectively. KaplanMeier analysis showed no association between progression of disease and patient age or the location of the disease. Gender distribution and predominant ileo-colonic location of disease were similar to earlier Asian reports on Crohn's disease. Perianal disease was less frequent than reported in Western and other Asian studies. One-fourth of Indian patients had aggressive disease at diagnosis, but the tendency to progress towards aggressive disease over time was less pronounced than in Western 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.

MED-SUV Data Life Cycle

NASA Astrophysics Data System (ADS)

Sangianantoni, Agata; Puglisi, Giuseppe; Spampinato, Letizia; Tulino, Sabrina

2015-04-01

The MED-SUV project aims to implement a digital e-infrastructure for data access in order to promote the monitoring and study of key volcanic regions prone to volcanic hazards, and thus improve hazard assessment, according to the rationale of Supersite GEO initiative to Vesuvius- Campi Flegrei and Mt Etna, currently identified as Permanent Supersites. The present study focuses on the life cycle of MED-SUV data generated in the first period of the project and highlights the managing approach, as well as the crucial steps to be implemented for ensuring that data will be properly and ethically managed and can be used and accessed from both MED-SUV and the external community. The process is conceived outlining how research data being handled as the project progresses, describing what data are collected, processed or generated and how these data are going to be shared and made available through Open Access. Data cycle begins with their generation and ends with the deposit in the digital infrastructure, its key series of stages through which MED-SUV data passes are Collection, Data citation, Categorization of data, Approval procedure, Registration of datasets, Application of licensing models, and PID assignment. This involves a combination of procedures and practices taking into account the scientific core mission and the priorities of the project as well as the potential legal issues related to the management and protection of the Intellectual Property. We believe that the implementation of this process constitutes a significant encouragement in MED-SUV data sharing and as a consequence a better understanding on the volcanic processes, hazard assessment and a better integration with other Supersites projects.

Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers.

PubMed

Aguilar, Claire; Lenoir, Christelle; Lambert, Nathalie; Bègue, Bernadette; Brousse, Nicole; Canioni, Danielle; Berrebi, Dominique; Roy, Maryline; Gérart, Stéphane; Chapel, Helen; Schwerd, Tobias; Siproudhis, Laurent; Schäppi, Michela; Al-Ahmari, Ali; Mori, Masaaki; Yamaide, Akiko; Galicier, Lionel; Neven, Bénédicte; Routes, John; Uhlig, Holm H; Koletzko, Sibylle; Patel, Smita; Kanegane, Hirokazu; Picard, Capucine; Fischer, Alain; Bensussan, Nadine Cerf; Ruemmele, Frank; Hugot, Jean-Pierre; Latour, Sylvain

2014-11-01

Crohn disease is an inflammatory bowel disease (IBD) with a complex mode of inheritance. Although nucleotide binding and oligomerization domain containing 2 (NOD2) is the strongest risk factor, the cause of Crohn disease remains unknown in the majority of the cases. X-linked inhibitor of apoptosis (XIAP) deficiency causes X-linked lymphoproliferative syndrome type 2. IBD has been reported in some XIAP-deficient patients. We characterize the IBD affecting a large cohort of patients with mutations in XIAP and examine the possible pathophysiologic mechanisms. We performed a phenotypical and histologic analysis of the IBD affecting 17 patients with hemizygous mutations in XIAP, including 3 patients identified by screening 83 patients with pediatric-onset IBD. The X chromosome inactivation was analyzed in female carriers of heterozygous XIAP mutations, including 2 adults with IBD. The functional consequences of XIAP deficiency were analyzed. Clinical presentation and histology of IBD in patients with XIAP deficiency overlapped with those of patients with Crohn disease. The age at onset was variable (from 3 months to 41 years), and IBD was severe and difficult to treat. In 2 patients hematopoietic stem cell transplantation fully restored intestinal homeostasis. Monocytes of patients had impaired NOD2-mediated IL-8 and monocyte chemoattractant protein 1 (MCP-1) production, as well as IL-10, in response to NOD2 and Toll-like receptor 2/4 costimulation. Nucleotide binding and oligomerization domain containing 1 (NOD1)-mediated IL-6 and IL-8 production was defective in fibroblasts from XIAP-deficient patients. The 2 heterozygous female carriers of XIAP mutations with IBD displayed abnormal expression of the XIAP mutated allele, resulting in impaired activation of the NOD2 pathway. IBD in patients with XIAP deficiency is similar to Crohn disease and is associated with defective NOD2 function in monocytes. Importantly, we report that it is not restricted to male patients

Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management.

PubMed

Johnson, F Reed; Hauber, Brett; Özdemir, Semra; Siegel, Corey A; Hass, Steven; Sands, Bruce E

2010-10-01

Crohn's disease is a serious and debilitating gastrointestinal disorder with a high, unmet need for new treatments. Biologic agents have the potential to alter the natural course of Crohn's disease but present known risks of potential serious adverse events (SAEs). Previous studies have shown that patients are willing to accept elevated SAE risks in exchange for clinical efficacy. Gastroenterologists and patients may have similar goals of maximizing treatment benefit while minimizing risk; however, gastroenterologists may assess the relative importance of risk differently than patients. To (a) understand how gastroenterologists caring for patients with Crohn's disease balance benefits and risks in their treatment decisions and (b) compare their treatment preferences with those of adult patients with Crohn's disease. Both patient and gastroenterologist treatment preferences were elicited using a web-based, choice-format conjoint survey instrument. The conjoint questions required subjects to choose between 2 hypothetical treatment options with differing levels of treatment attributes. Patients evaluated the treatment options for themselves, and gastroenterologists evaluated the treatment options for each of 3 hypothetical patient types: (a) female aged 25 years with no history of Crohn's disease surgery (young), (b) male aged 45 years with 1 Crohn's disease surgery (middleaged), and (c) female older than 70 years with 4 Crohn's disease surgeries (older). Treatment attributes represented the expected outcomes of treatment: severity of daily symptoms, frequency of flare-ups, serious disease complications, oral steroid use, and the risks of 3 potentially fatal SAEs - lymphoma, serious or opportunistic infections, and progressive multifocal leukoencephalopathy (PML) - during 10 years of treatment. Maximum acceptable risk (MAR), defined as the highest level of SAE risk that subjects would accept in return for a given improvement in efficacy (i.e., the increase in

The Arabidopsis Mediator Complex Subunits MED16, MED14, and MED2 Regulate Mediator and RNA Polymerase II Recruitment to CBF-Responsive Cold-Regulated Genes[C][W][OPEN

PubMed Central

Hemsley, Piers A.; Hurst, Charlotte H.; Kaliyadasa, Ewon; Lamb, Rebecca; Knight, Marc R.; De Cothi, Elizabeth A.; Steele, John F.; Knight, Heather

2014-01-01

The Mediator16 (MED16; formerly termed SENSITIVE TO FREEZING6 [SFR6]) subunit of the plant Mediator transcriptional coactivator complex regulates cold-responsive gene expression in Arabidopsis thaliana, acting downstream of the C-repeat binding factor (CBF) transcription factors to recruit the core Mediator complex to cold-regulated genes. Here, we use loss-of-function mutants to show that RNA polymerase II recruitment to CBF-responsive cold-regulated genes requires MED16, MED2, and MED14 subunits. Transcription of genes known to be regulated via CBFs binding to the C-repeat motif/drought-responsive element promoter motif requires all three Mediator subunits, as does cold acclimation–induced freezing tolerance. In addition, these three subunits are required for low temperature–induced expression of some other, but not all, cold-responsive genes, including genes that are not known targets of CBFs. Genes inducible by darkness also required MED16 but required a different combination of Mediator subunits for their expression than the genes induced by cold. Together, our data illustrate that plants control transcription of specific genes through the action of subsets of Mediator subunits; the specific combination defined by the nature of the stimulus but also by the identity of the gene induced. PMID:24415770

Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease.

PubMed

Lee, James C; Biasci, Daniele; Roberts, Rebecca; Gearry, Richard B; Mansfield, John C; Ahmad, Tariq; Prescott, Natalie J; Satsangi, Jack; Wilson, David C; Jostins, Luke; Anderson, Carl A; Traherne, James A; Lyons, Paul A; Parkes, Miles; Smith, Kenneth G C

2017-02-01

For most immune-mediated diseases, the main determinant of patient well-being is not the diagnosis itself but instead the course that the disease takes over time (prognosis). Prognosis may vary substantially between patients for reasons that are poorly understood. Familial studies support a genetic contribution to prognosis, but little evidence has been found for a proposed association between prognosis and the burden of susceptibility variants. To better characterize how genetic variation influences disease prognosis, we performed a within-cases genome-wide association study in two cohorts of patients with Crohn's disease. We identified four genome-wide significant loci, none of which showed any association with disease susceptibility. Conversely, the aggregated effect of all 170 disease susceptibility loci was not associated with disease prognosis. Together, these data suggest that the genetic contribution to prognosis in Crohn's disease is largely independent of the contribution to disease susceptibility and point to a biology of prognosis that could provide new therapeutic opportunities.

Diagnostic Accuracy of CT Enterography for Active Inflammatory Terminal Ileal Crohn Disease: Comparison of Full-Dose and Half-Dose Images Reconstructed with FBP and Half-Dose Images with SAFIRE.

PubMed

Gandhi, Namita S; Baker, Mark E; Goenka, Ajit H; Bullen, Jennifer A; Obuchowski, Nancy A; Remer, Erick M; Coppa, Christopher P; Einstein, David; Feldman, Myra K; Kanmaniraja, Devaraju; Purysko, Andrei S; Vahdat, Noushin; Primak, Andrew N; Karim, Wadih; Herts, Brian R

2016-08-01

Purpose To compare the diagnostic accuracy and image quality of computed tomographic (CT) enterographic images obtained at half dose and reconstructed with filtered back projection (FBP) and sinogram-affirmed iterative reconstruction (SAFIRE) with those of full-dose CT enterographic images reconstructed with FBP for active inflammatory terminal or neoterminal ileal Crohn disease. Materials and Methods This retrospective study was compliant with HIPAA and approved by the institutional review board. The requirement to obtain informed consent was waived. Ninety subjects (45 with active terminal ileal Crohn disease and 45 without Crohn disease) underwent CT enterography with a dual-source CT unit. The reference standard for confirmation of active Crohn disease was active terminal ileal Crohn disease based on ileocolonoscopy or established Crohn disease and imaging features of active terminal ileal Crohn disease. Data from both tubes were reconstructed with FBP (100% exposure); data from the primary tube (50% exposure) were reconstructed with FBP and SAFIRE strengths 3 and 4, yielding four datasets per CT enterographic examination. The mean volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) at full dose were 13.1 mGy (median, 7.36 mGy) and 15.9 mGy (median, 13.06 mGy), respectively, and those at half dose were 6.55 mGy (median, 3.68 mGy) and 7.95 mGy (median, 6.5 mGy). Images were subjectively evaluated by eight radiologists for quality and diagnostic confidence for Crohn disease. Areas under the receiver operating characteristic curves (AUCs) were estimated, and the multireader, multicase analysis of variance method was used to compare reconstruction methods on the basis of a noninferiority margin of 0.05. Results The mean AUCs with half-dose scans (FBP, 0.908; SAFIRE 3, 0.935; SAFIRE 4, 0.924) were noninferior to the mean AUC with full-dose FBP scans (0.908; P < .003). The proportion of images with inferior quality was significantly higher with all

Apparent discrimination in the provision of biologic therapy to patients with Crohn's disease according to ethnicity.

PubMed

Farrukh, A; Mayberry, J F

2015-05-01

The objective of the study was to investigate whether patients from a South Asian ethnic background who had Crohn's disease received equivalent access to therapy with biologics compared to patients with an English background. The study was retrospective and covered the period 2008 to 2012. It was based on a register of all patients with Crohn's disease in Leicestershire who are treated with biologics. The prevalence of Crohn's disease in Leicestershire amongst South Asian and English patients was known from earlier studies and from these data it was possible to make corrections to allow for the difference in frequency of the condition between the two communities. All adult patients who received biologics for treatment of Crohn's disease in Leicestershire between 2008 and 2012 were reviewed and their gender and ethnicity noted as well as whether they had received infliximab or adalumimab. The expected numbers of patients who should have received these therapies were calculated in two ways: One hundred and twenty six patients with Crohn's disease who received treatment with biologics were European and 13 South Asian. The patients' gender was also noted and 67 European patients (53%) were female as were six Asians (46%). Based on prevalence data, the expected distribution of the treatment would have been for 97 of the patients to have been European and 42 to have been South Asian. If 126 European patients warranted treatment, on this basis the expected number of South Asian patients in need of biologic therapy would have been 55. Based on the smaller predicted number of South Asian patients (42) the difference is significant at P < 0.0001 [Proportion difference=0.69 (95% confidence interval=0.539278-0.809576]. For the difference to be extinguished the number of English patients who should have received biologic therapy would have been as low as between 30 and 39 cases (based on the calculated proportion of 97 and the actual figure of 126 European patients

The MedAustron project

NASA Astrophysics Data System (ADS)

Griesmayer, E.; Schreiner, T.; Pavlovič, M.

2007-05-01

The Austrian government has approved its financial contribution to the MedAustron project in October 2004. MedAustron, the Austrian ion therapy and cancer research centre, should be set into operation in 2010. MedAustron combines medical cancer treatment and cancer research and non-clinical research. For medical treatment and cancer research active scanning of a proton and a carbon-ion beam is provided. The beam energy must correspond to the desirable penetration range of the beam in the patient body, which translates into the energy interval of 60-220 MeV protons and 120-400 MeV per nucleon carbon ions. The intensity of extracted beam is 1010 protons per spill and four times 108 carbon ions per spill. Spill duration can be varied from 1 s to 10 s. For a spill lasting 1 s the beam intensity is equivalent to an electrical beam current of 1.6 nA for protons and 0.38 nA for carbon ions. Although the machine parameters must be optimised for therapy needs, additional beam features can be offered by a modern medical accelerator for non-clinical research. Various ions with energies up to 400 MeV per nucleon can be used for irradiation purposes. For synchrotrons such as proposed in the Design Study the magnetic rigidity would allow to accelerate protons up to 1.18 GeV when using an appropriate RF-system. Two beam lines are proposed for non-clinical research, such as biomedicine, medical physics, physics or industrial technological research. The experimental facility of MedAustron will be offered to research institutes and to industry on an international level.

Clinical features of Crohn disease concomitant with ankylosing spondylitis: A preliminary single-center study.

PubMed

Liu, Song; Ding, Jie; Wang, Meng; Zhou, Wanqing; Feng, Min; Guan, Wenxian

2016-07-01

Extraintestinal manifestations (EIMs) cause increased morbidity and decreased quality of life in Crohn disease (CD). Ankylosing spondylitis (AS) belongs to EIMs. Very little is known on the clinical features of CD concomitant with AS. This study is to investigate the clinical features of CD patients with AS.We retrospectively collected all CD patients with AS in our hospital, and established a comparison group (CD without AS) with age, sex, and duration of Crohn disease matched. Clinical information was retrieved for comparison.Eight CD + AS patients were identified from 195 CD patients. Sixteen CD patients were randomly selected into comparison group. All CD + AS patients were male, HLA-B27 (+), and rheumatoid factor (-) with an average age of 40.8 ± 4.52 years. Significant correlation between disease activity of CD and AS was revealed (r = 0.857, P = 0.011). Significant correlation between disease activity of CD and functional limitation associated with AS was identified (r = 0.881, P < 0.01). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and globulin were positively correlated to Crohn disease activity index (CDAI), Bath AS disease activity index, and Bath AS functional index(BASFI) scores (r = 0.73-0.93, P < 0.05). Albumin was negatively associated with CDAI and BASFI (r = -0.73 to -0.91, P < 0.05). The ratio of albumin to globulin (Alb/Glo) was significantly related to all 3 scores (r = -0.81 to -0.91, P < 0.05).Male predominance with a 4.12% concomitant incidence of AS is observed in CD patients. Disease activity of CD correlates with disease activity of AS and functional limitation caused by AS. CRP, ESR, and Alb/Glo may serve as biomarkers for disease activity and functional limitation in CD patients concomitant with AS, although future studies are expected.

Pharmacokinetic and pharmacodynamic model for analysis of adalimumab administered for Crohn's disease.

PubMed

Kimura, Koji; Yoshida, Atsushi; Takayanagi, Risa; Yamada, Yasuhiko

2018-05-23

Adalimumab (ADA) is used as a therapeutic agent for Crohn's disease (CD). Although that dosage regimen has been established through clinical trial experience, it has not been analyzed theoretically. In the present study, we analyzed of sequential changes of the Crohn's disease activity index (CDAI) after repeated administrations of ADA using a pharmacokinetic and pharmacodynamic model. In addition, we analyzed the validity of the dosage regimen, and potential efficacy gained by increasing the dose and reducing the interval of administration. The sequential changes in CDAI values obtained with our model were in good agreement with observed CDAI values, which was considered to show the validity of our analysis. We considered that our results showed the importance of the loading dose of ADA to obtain remission in an early stage of active CD. In addition, we showed that patients who have an incomplete response to ADA can obtain similar efficacy from increasing the dose and reducing the dose interval. In conclusion, our results showed that the present model may be applied to predict the CDAI values of ADA for CD. They indicated the validity of the dosage regimen, as well as the efficacy of increasing the dose and reducing the dose interval. This article is protected by copyright. All rights reserved.

Dietary fiber information for individuals with Crohn disease: reports of gastrointestinal effects.

PubMed

Brotherton, Carol S; Taylor, Ann Gill

2013-01-01

The experiences of individuals with Crohn disease before and after receiving dietary fiber information have not been described in the literature. This article offers findings from a study that used four semistructured audiorecorded interviews during a 4-week time period for the purpose of exploring the experiences of 11 individuals before and after receiving dietary fiber information from a healthcare professional. The first and second interviews occurred immediately before and after the presentation of information. Follow-up interviews occurred at 2-week intervals. Thematic analysis of the baseline interviews revealed 2 themes: (a) accepting a redefined (lower expectations) definition of normal quality of life and (b) continuing to look for answers. Three themes emerged from the follow-up interviews at Week 4: (a) reevaluating old diet-related concepts, (b) enjoying a healthier lifestyle at a self-set pace, and (c) enjoying positive physical effects of wheat bran consumption. This article examines the 3rd postintervention theme, "enjoying physical effects of wheat bran consumption." The relevance of this research is that nurses equipped with dietary fiber information may be better able to help some individuals with Crohn disease to explore the potential benefits of a well-rounded nutritious pattern of eating that includes wheat bran cereal.

Use of antibiotics in patients with Crohn's disease: a systematic review and meta-analysis.

PubMed

Su, Jie Wen; Ma, Jing Jing; Zhang, Hong Jie

2015-02-01

Some studies have suggested that antibiotic treatment might be efficient for patients with active Crohn's disease (CD). However, the results are conflicting. The aim of this study was to summarize the available evidence on the efficacy of antibiotics, especially ciprofloxacin, in treating patients with CD. A literature search was conducted on the PubMed, Medline, Web of Science and Excerpta Medica Database (EMBASE) for manuscripts published until March 2014. Randomized controlled trials that mainly evaluated the efficacy of antibiotic treatment in patients with CD using clinical remission or response as the key outcome of interest were included. Intention-to-treat analyses were used to evaluate the relative risk (RR) and 95% confidence intervals (CI). In all, 15 randomized placebo-controlled clinical trials involving 1407 participants were included in the meta-analysis. A pooled analysis revealed that compared with placebo, antibiotics benefited CD patients to a certain extent (RR 1.33, 95% CI 1.17-1.51, P < 0.00001). The random-effects model showed that there was no significant difference between patients treated with ciprofloxacin and placebo (combined RR 1.35, 95% CI 0.92-1.97, P = 0.12). However, ciprofloxacin exhibited significant clinical benefits in patients with perianal fistulas (RR 1.64, 95% CI 1.16-2.32, P = 0.005). The utility of antibiotics was beneficial for patients with CD. Nevertheless, subgroup analyses indicated that treatment with ciprofloxacin alone was significantly efficient for CD patients with perianal fistulas. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Clinical status, quality of life, and work productivity in Crohn's disease patients after one year of treatment with adalimumab.

PubMed

Saro, Cristina; Ceballos, Daniel; Muñoz, Fernando; de la Coba, Cristóbal; Aguilar, María Dolores; Lázaro, Pablo; García-Sánchez, Valle; Hernández, Mariola; Barrio, Jesús; de Francisco, Ruth; Fernández, Luis I; Barreiro-de Acosta, Manuel

2017-02-01

Clinical trials have shown the efficacy of adalimumab in Crohn's disease, but the outcome in regular practice remains unknown. The aim of the study was to examine clinical status, quality of life, and work productivity of Crohn's disease patients receiving adalimumab for one year in the context of usual clinical practice. This was a prospective, observational study with a one-year follow-up. After baseline, Crohn's disease patients were evaluated at 1, 3, 6, 9, and 12 months after starting treatment with adalimumab. Outcome variables included: clinical status (measured with CDAI), quality of life (measured with EuroQoL-5D and IBDQ), and work productivity (measured with WPAI questionnaire). These outcome variables were compared using the Student's t test or Wilcoxon test for paired comparison data according to the data distribution. Statistical significance was set at two-sided p < 0.05. The sample was composed of 126 patients (age [mean] 39.1 ± [standard deviation] 13.8 years; 51% male). Significant changes were observed during the follow-up period: CDAI decreased from [median] 194 ([25-75 percentiles] 121-269) to 48.2 (10.1-122.0) (p < 0.05); the EuroQoL-5D increased from 0.735 (0.633-0.790) to 0.797 (0.726-1.000) (p < 0.05); the EuroQoL-5D visual analogue scale increased from 50.0 (40-70) to 80.0 (60-90); (p < 0.05) and the IBDQ increased from 56.7 (51.6-61.5) to 67.5 (60.1-73.6) (p < 0.05). The total work productivity impact decreased from 53% to 24% (p < 0.05). In regular practice, adalimumab is clinically effective in the treatment of Crohn's disease patients and results in a significant improvement in quality of life and work productivity.

OvidSP Medline-to-PubMed search filter translation: a methodology for extending search filter range to include PubMed's unique content.

PubMed

Damarell, Raechel A; Tieman, Jennifer J; Sladek, Ruth M

2013-07-02

PubMed translations of OvidSP Medline search filters offer searchers improved ease of access. They may also facilitate access to PubMed's unique content, including citations for the most recently published biomedical evidence. Retrieving this content requires a search strategy comprising natural language terms ('textwords'), rather than Medical Subject Headings (MeSH). We describe a reproducible methodology that uses a validated PubMed search filter translation to create a textword-only strategy to extend retrieval to PubMed's unique heart failure literature. We translated an OvidSP Medline heart failure search filter for PubMed and established version equivalence in terms of indexed literature retrieval. The PubMed version was then run within PubMed to identify citations retrieved by the filter's MeSH terms (Heart failure, Left ventricular dysfunction, and Cardiomyopathy). It was then rerun with the same MeSH terms restricted to searching on title and abstract fields (i.e. as 'textwords'). Citations retrieved by the MeSH search but not the textword search were isolated. Frequency analysis of their titles/abstracts identified natural language alternatives for those MeSH terms that performed less effectively as textwords. These terms were tested in combination to determine the best performing search string for reclaiming this 'lost set'. This string, restricted to searching on PubMed's unique content, was then combined with the validated PubMed translation to extend the filter's performance in this database. The PubMed heart failure filter retrieved 6829 citations. Of these, 834 (12%) failed to be retrieved when MeSH terms were converted to textwords. Frequency analysis of the 834 citations identified five high frequency natural language alternatives that could improve retrieval of this set (cardiac failure, cardiac resynchronization, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and LV dysfunction). Together these terms reclaimed

[Natalizumab for the treatment of Crohn’s disease: Report of three cases].

PubMed

Fluxá, Daniela; Ibáñez, Patricio; Flores, Lilian; Figueroa, Carolina; Lubascher, Jaime; Kronberg, Udo; Simian, Daniela; Pizarro, Gonzalo; Toche, Paola; Quera, Rodrigo

2017-04-01

Anti-tumor necrosis factor-α (TNF) agents have dramatically changed the management of Crohn’s Disease (CD). However, a significant number of these patients do not respond at all or cease to respond to antibodies against TNF. In this clinical situation, the options include intensification of anti-TNF therapy by either increasing the dose or by shortening the administration interval, the use of a second anti-TNF or medications with a different mechanism of action. Among the later, Natalizumab, a humanized IgG4 monoclonal antibody against α4β1 and α4β7 integrins, is safe and effective in inducing and maintaining remission in active CD patient’s refractory to anti-TNF. In spite of this, Natalizumab use has been limited because of an increased risk of progressive multifocal leukoencephalophaty which results from reactivation of the John Cunningham (JC) virus. However, the presence of antibodies against JC virus in serum can be used to reduce the risk for this complication. We report three patients with Crohn’s disease refractory to treatment with infliximab, who responded successfully to the use of Natalizumab.

Cannabis finds its way into treatment of Crohn's disease.

PubMed

Schicho, Rudolf; Storr, Martin

2014-01-01

In ancient medicine, cannabis has been widely used to cure disturbances and inflammation of the bowel. A recent clinical study now shows that the medicinal plant Cannabis sativa has lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases. In a prospective placebo-controlled study, it has been shown what has been largely anticipated from anecdotal reports, i.e. that cannabis produces significant clinical benefits in patients with Crohn's disease. The mechanisms involved are not yet clear but most likely include peripheral actions on cannabinoid receptors 1 and 2, and may also include central actions. © 2013 S. Karger AG, Basel.

MED COMMITTEE STRUCTURE

EPA Science Inventory

It is beneficial to share good Diversity-related practices with other NHEERL Divisions. Sharing of this information will help MED showcase the many activities that are in place for Diversity that we are using to help us become a level 4 organization.

PubMed Medical publications from Libya

PubMed Central

Bakoush, O; Al-Tubuly, AA; Ashammakhi, N; Elkhammas, EA

2007-01-01

Medical research and publications are the back-bone for advancing the medical field. We identified the Pubmed medical publications that are affiliated with Libya to shed some light on the contribution of this country's medical community to the PubMed database. All publications affiliated with Libya in the PubMed were counted over a five year period ending December 2006. We also used the same method to obtain data on the PubMed medical publications from Tunisia, Morocco and Yemen. Tunisia had the largest number of PubMed publications among the studied countries: 20.4 publications per million population per year and 7.2 publications per year per one billion US$ GDP. Libya had much fewer publications: 2.4 publications per million population per year and 0.4 publications per one billion US$ GDP. The citation frequency for Libyan published research was very low compared to Tunisian and Moroccan related research. Conclusion: This preliminary analysis shows that medical research output in Libya is about twenty times less than in other countries with similar backgrounds, and that it needs to be enhanced. PMID:21503210

Host Defense Peptide Resistance Contributes to Colonization and Maximal Intestinal Pathology by Crohn's Disease-Associated Adherent-Invasive Escherichia coli

PubMed Central

McPhee, Joseph B.; Small, Cherrie L.; Reid-Yu, Sarah A.; Brannon, John R.; Le Moual, Hervé

2014-01-01

Host defense peptides secreted by colonocytes and Paneth cells play a key role in innate host defenses in the gut. In Crohn's disease, the burden of tissue-associated Escherichia coli commonly increases at epithelial surfaces where host defense peptides concentrate, suggesting that this bacterial population might actively resist this mechanism of bacterial killing. Adherent-invasive E. coli (AIEC) is associated with Crohn's disease; however, the colonization determinants of AIEC in the inflamed gut are undefined. Here, we establish that host defense peptide resistance contributes to host colonization by Crohn's-associated AIEC. We identified a plasmid-encoded genomic island (called PI-6) in AIEC strain NRG857c that confers high-level resistance to α-helical cationic peptides and α- and β-defensins. Deletion of PI-6 sensitized strain NRG857c to these host defense molecules, reduced its competitive fitness in a mouse model of infection, and attenuated its ability to induce cecal pathology. This phenotype is due to two genes in PI-6, arlA, which encodes a Mig-14 family protein implicated in defensin resistance, and arlC, an OmpT family outer membrane protease. Implicit in these findings are new bacterial targets whose inhibition might limit AIEC burden and disease in the gut. PMID:24866805

Adalimumab for maintenance therapy for one year in Crohn's disease: results of a Latin American single-center observational study.

PubMed

Kotze, Paulo Gustavo; Abou-Rejaile, Vinícius Rezende; Uiema, Luciana Aparecida; Olandoski, Marcia; Sartor, Maria Cristina; Miranda, Eron Fábio; Kotze, Lorete Maria da Silva; Saad-Hossne, Rogério

2014-01-01

Adalimumab is a fully-human antibody that inhibits TNF alpha, with a significant efficacy for long-term maintenance of remission. Studies with this agent in Latin American Crohn's disease patients are scarce. The objective of this study was to outline clinical remission rates after 12 months of adalimumab therapy for Crohn's disease patients. Retrospective, single-center, observational study of a Brazilian case series of Crohn's disease patients under adalimumab therapy. Variables analyzed: demographic data, Montreal classification, concomitant medication, remission rates after 1, 4, 6 and 12 months. Remission was defined as Harvey-Bradshaw Index ≤ 4, and non-responder-imputation and last-observation-carried-forward analysis were used. The influence of infliximab on remission rates was analyzed by Fischer and Chi-square tests (P<0.05). Fifty patients, with median age of 35 years at therapy initiation, were included. Remission rates after 12 months of therapy were 54% under non-responder-imputation and 88% under last-observation-carried-forward analysis. After 12 months, remission on patients with previous infliximab occurred in 69.23% as compared to 94.59% in infliximab-naïve patients (P = 0.033). Adalimumab was effective in maintaining clinical remission after 12 months of therapy, with an adequate safety profile, and was also more effective in infliximab naïve patients.

PubMed searches: overview and strategies for clinicians.

PubMed

Lindsey, Wesley T; Olin, Bernie R

2013-04-01

PubMed is a biomedical and life sciences database maintained by a division of the National Library of Medicine known as the National Center for Biotechnology Information (NCBI). It is a large resource with more than 5600 journals indexed and greater than 22 million total citations. Searches conducted in PubMed provide references that are more specific for the intended topic compared with other popular search engines. Effective PubMed searches allow the clinician to remain current on the latest clinical trials, systematic reviews, and practice guidelines. PubMed continues to evolve by allowing users to create a customized experience through the My NCBI portal, new arrangements and options in search filters, and supporting scholarly projects through exportation of citations to reference managing software. Prepackaged search options available in the Clinical Queries feature also allow users to efficiently search for clinical literature. PubMed also provides information regarding the source journals themselves through the Journals in NCBI Databases link. This article provides an overview of the PubMed database's structure and features as well as strategies for conducting an effective search.

Endoscopic Scores for Evaluation of Crohn's Disease Activity at Small Bowel Capsule Endoscopy: General Principles and Current Applications.

PubMed

Rosa, Bruno; Pinho, Rolando; de Ferro, Susana Mão; Almeida, Nuno; Cotter, José; Saraiva, Miguel Mascarenhas

2016-01-01

The small bowel is affected in the vast majority of patients with Crohn's Disease (CD). Small bowel capsule endoscopy (SBCE) has a very high sensitivity for the detection of CD-related pathology, including early mucosal lesions and/or those located in the proximal segments of the small bowel, which is a major advantage when compared with other small bowel imaging modalities. The recent guidelines of European Society of Gastrointestinal Endoscopy (ESGE) and European Crohn's and Colitis Organisation (ECCO) advocate the use of validated endoscopic scoring indices for the classification of inflammatory activity in patients with CD undergoing SBCE, such as the Lewis Score or the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI). These scores aim to standardize the description of lesions and capsule endoscopy reports, contributing to increase inter-observer agreement and enabling a stratification of the severity of the disease. On behalf of the Grupo de Estudos Português do Intestino Delgado (GEPID) - Portuguese Small Bowel Study Group, we aimed to summarize the general principles and clinical applications of current endoscopic scoring systems for SBCE in the setting of CD, covering the topic of suspected CD as well as the evaluation of disease extent (with potential prognostic and therapeutic impact), evaluation of mucosal healing in response to treatment and evaluation of post-surgical recurrence in patients with previously established diagnosis of CD.

A study on PubMed search tag usage pattern: association rule mining of a full-day PubMed query log.

PubMed

Mosa, Abu Saleh Mohammad; Yoo, Illhoi

2013-01-09

The practice of evidence-based medicine requires efficient biomedical literature search such as PubMed/MEDLINE. Retrieval performance relies highly on the efficient use of search field tags. The purpose of this study was to analyze PubMed log data in order to understand the usage pattern of search tags by the end user in PubMed/MEDLINE search. A PubMed query log file was obtained from the National Library of Medicine containing anonymous user identification, timestamp, and query text. Inconsistent records were removed from the dataset and the search tags were extracted from the query texts. A total of 2,917,159 queries were selected for this study issued by a total of 613,061 users. The analysis of frequent co-occurrences and usage patterns of the search tags was conducted using an association mining algorithm. The percentage of search tag usage was low (11.38% of the total queries) and only 2.95% of queries contained two or more tags. Three out of four users used no search tag and about two-third of them issued less than four queries. Among the queries containing at least one tagged search term, the average number of search tags was almost half of the number of total search terms. Navigational search tags are more frequently used than informational search tags. While no strong association was observed between informational and navigational tags, six (out of 19) informational tags and six (out of 29) navigational tags showed strong associations in PubMed searches. The low percentage of search tag usage implies that PubMed/MEDLINE users do not utilize the features of PubMed/MEDLINE widely or they are not aware of such features or solely depend on the high recall focused query translation by the PubMed's Automatic Term Mapping. The users need further education and interactive search application for effective use of the search tags in order to fulfill their biomedical information needs from PubMed/MEDLINE.

Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

PubMed

Colombel, Jean-Frederic; Panaccione, Remo; Bossuyt, Peter; Lukas, Milan; Baert, Filip; Vaňásek, Tomas; Danalioglu, Ahmet; Novacek, Gottfried; Armuzzi, Alessandro; Hébuterne, Xavier; Travis, Simon; Danese, Silvio; Reinisch, Walter; Sandborn, William J; Rutgeerts, Paul; Hommes, Daniel; Schreiber, Stefan; Neimark, Ezequiel; Huang, Bidan; Zhou, Qian; Mendez, Paloma; Petersson, Joel; Wallace, Kori; Robinson, Anne M; Thakkar, Roopal B; D'Haens, Geert

2018-12-23

Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (<70 kg or ≥70 kg), and disease duration (≤2 years or >2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of <70 points compared with baseline or CDAI >200; clinical management group after random assignment: CDAI decrease of <100 points compared with baseline or

Mars 2020 Entry, Descent and Landing Instrumentation (MEDLI2)

NASA Technical Reports Server (NTRS)

Bose, Deepak; Wright, Henry; White, Todd; Schoenenberger, Mark; Santos, Jose; Karlgaard, Chris; Kuhl, Chris; Oishi, TOmo; Trombetta, Dominic

2016-01-01

This paper will introduce Mars Entry Descent and Landing Instrumentation (MEDLI2) on NASA's Mars2020 mission. Mars2020 is a flagship NASA mission with science and technology objectives to help answer questions about possibility of life on Mars as well as to demonstrate technologies for future human expedition. Mars2020 is scheduled for launch in 2020. MEDLI2 is a suite of instruments embedded in the heatshield and backshell thermal protection systems of Mars2020 entry vehicle. The objectives of MEDLI2 are to gather critical aerodynamics, aerothermodynamics and TPS performance data during EDL phase of the mission. MEDLI2 builds up the success of MEDLI flight instrumentation on Mars Science Laboratory mission in 2012. MEDLI instrumentation suite measured surface pressure and TPS temperature on the heatshield during MSL entry into Mars. MEDLI data has since been used for unprecedented reconstruction of aerodynamic drag, vehicle attitude, in-situ atmospheric density, aerothermal heating, transition to turbulence, in-depth TPS performance and TPS ablation. [1,2] In addition to validating predictive models, MEDLI data has highlighted extra margin available in the MSL forebody TPS, which can potentially be used to reduce vehicle parasitic mass. MEDLI2 expands the scope of instrumentation by focusing on quantities of interest not addressed in MEDLI suite. The type the sensors are expanded and their layout on the TPS modified to meet these new objectives. The paper will provide key motivation and governing requirements that drive the choice and the implementation of the new sensor suite. The implementation considerations of sensor selection, qualification, and demonstration of minimal risk to the host mission will be described. The additional challenges associated with mechanical accommodation, electrical impact, data storage and retrieval for MEDLI2 system, which extends sensors to backshell will also be described.

Vedolizumab Compared with Certolizumab in the Therapy of Crohn Disease: A Systematic Review and Indirect Comparison.

PubMed

Kawalec, Paweł; Moćko, Pawel; Pilc, Andrzej; Radziwon-Zalewska, Maria; Malinowska-Lipień, Iwona

2016-08-01

The increasing prevalence of Crohn disease (CD) underscores the need to identify new effective drugs, which is particularly important for patients who do not respond or do not tolerate standard biologic therapies. The purpose of this analysis was to compare the efficacy and safety of vedolizumab and certolizumab pegol in patients with active moderate to severe CD. This analysis was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search of Medline (PubMed), Embase, and the Cochrane Library was conducted through March 5, 2016. Studies included were randomized controlled trials (RCTs) that enrolled patients treated for CD with vedolizumab or certolizumab pegol. All studies were critically appraised; indirect comparison was performed with the Bucher method. Eight RCTs were identified, and four were homogeneous enough to be included in the indirect comparison of the induction phase of treatment. No statistically significant differences were found in clinical response (relative risk [RR] 1.23, 95% confidence interval [CI] 0.81-1.88) or remission (RR 1.35, 95% CI 0.89-2.07) between vedolizumab and certolizumab pegol in the overall population. Similar nonstatistically significant differences in response and remission were noted in a subgroup analysis of anti-tumor necrosis factor-naive patients (RR 1.10, 95% CI 0.72-1.66 and RR 1.98, 95% CI 0.95-4.11, respectively). In addition, there were no statistically significant differences in safety profiles. This indirect comparison analysis demonstrated no statistically significant differences in efficacy and safety between vedolizumab and certolizumab pegol. © 2016 Pharmacotherapy Publications, Inc.

Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.

PubMed

Hazlewood, Glen S; Rezaie, Ali; Borman, Meredith; Panaccione, Remo; Ghosh, Subrata; Seow, Cynthia H; Kuenzig, Ellen; Tomlinson, George; Siegel, Corey A; Melmed, Gil Y; Kaplan, Gilaad G

2015-02-01

There is controversy regarding the best treatment for patients with Crohn's disease because of the lack of direct comparative trials. We compared therapies for induction and maintenance of remission in patients with Crohn's disease, based on direct and indirect evidence. We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central databases, through June 2014. We identified randomized controlled trials (N = 39) comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies with placebo or an active agent for induction and maintenance of remission in adult patients with Crohn's disease. Pairwise treatment effects were estimated through a Bayesian random-effects network meta-analysis and reported as odds ratios (OR) with a 95% credible interval (CrI). Infliximab, the combination of infliximab and azathioprine (infliximab + azathioprine), adalimumab, and vedolizumab were superior to placebo for induction of remission. In pair-wise comparisons of anti-tumor necrosis factor agents, infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1; 95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All treatments were superior to placebo for maintaining remission, except for the combination of infliximab and methotrexate. Adalimumab, infliximab, and infliximab + azathioprine were superior to azathioprine/6-mercaptopurine: adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5), infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of remission. Adalimumab and infliximab + azathioprine were superior to certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab + azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab (OR, 2.4; 95% CrI, 1.2-4.6). Based on a network meta-analysis, adalimumab and infliximab + azathioprine are the most effective therapies for induction and maintenance of

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease

PubMed Central

Canavan, James B; Scottà, Cristiano; Vossenkämper, Anna; Goldberg, Rimma; Elder, Matthew J; Shoval, Irit; Marks, Ellen; Stolarczyk, Emilie; Lo, Jonathan W; Powell, Nick; Fazekasova, Henrieta; Irving, Peter M; Sanderson, Jeremy D; Howard, Jane K; Yagel, Simcha; Afzali, Behdad; MacDonald, Thomas T; Hernandez-Fuentes, Maria P; Shpigel, Nahum Y; Lombardi, Giovanna; Lord, Graham M

2016-01-01

Background and aim Thymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn's disease (CD). However, barriers exist to this approach. The stability of Tregs expanded from Crohn's blood is unknown. The potential for adoptively transferred Tregs to express interleukin-17 and exacerbate Crohn's lesions is of concern. Mucosal T cells are resistant to Treg-mediated suppression in active CD. The capacity for expanded Tregs to home to gut and lymphoid tissue is unknown. Methods To define the optimum population for Treg cell therapy in CD, CD4+CD25+CD127loCD45RA+ and CD4+CD25+CD127loCD45RA− Treg subsets were isolated from patients’ blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. Results Tregs can be expanded from the blood of patients with CD to potential target dose within 22–24 days. Expanded CD45RA+ Tregs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA− Tregs. CD45RA+ Tregs highly express α4β7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA+ Tregs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA+ Tregs. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn's mucosa. Conclusions CD4+CD25+CD127loCD45RA+ Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials. PMID:25715355

[Benign multicystic peritoneal mesothelioma in a patient with Crohn disease].

PubMed

Fluxá, Daniela; Kronberg, Udo; Lubascher, Jaime; O'Brien, Andrés; Las Heras, Facundo; Ibáñez, Patricio; Quera, Rodrigo

2016-12-01

Benign multicystic peritoneal mesothelioma is an uncommon lesion arising from the peritoneal mesothelium. It is asymptomatic or presents with unspecific symptoms. Imaging techniques may reveal it, however the final diagnosis can only be made by histopathology. Surgery is the only effective treatment considering its high recurrence rate. We report a 19 years old male with Crohn’s disease. Due to persistent abdominal pain, an abdominal magnetic resonance imaging was performed, showing a complex cystic mass in the lower abdomen. The patient underwent surgery and the lesion was completely resected. The pathological study reported a benign multicystic peritoneal mesothelioma.

Decision-making in ileocecal Crohn's disease management: surgery versus pharmacotherapy.

PubMed

Eshuis, Emma J; Stokkers, Pieter Cf; Bemelman, Willem A

2010-04-01

Ileocecal Crohn's disease (CD) can be treated medically as well as surgically. Both treatment modalities have been improved markedly in the last two decades, making CD more manageable. However, multidisciplinary research, addressing issues such as timing of surgery or medical treatment versus surgery, is scarce. Particularly in limited ileocecal CD, ileocolic resection might be a good alternative to long-term medical therapy. This review discusses the evidence on medical and surgical treatment options for ileocecal CD. It provides an aid in decision-making by discussing a treatment algorithm that can be used until further evidence on treatment is available.

Thalidomide induces mucosal healing in postoperative Crohn disease endoscopic recurrence

PubMed Central

Hu, Huiqin; Wang, Xinying; Liu, Side

2016-01-01

Abstract Background: Thalidomide has been successful use in patients with refractory Crohn disease (CD) in recent years. Methods: We collected the data of a postoperative CD patient who was prescribed thalidomide to induce remission and reviewed the relevant literatures. Results: A 51-year-old female was diagnosed as CD after an urgent terminal intestinal resection and presented endoscopic recurrence despite the prophylactic treatment with azathioprine (AZA). Fortunately, she achieved mucosal healing (MH) at a low dose of thalidomide for 15 months. Conclusion: Thalidomide is effective to induce MH in the postoperative CD endoscopic recurrence. PMID:27603389

Mesalamine-induced myopericarditis in a paediatric patient with Crohn's disease.

PubMed

Nair, Asha G; Cross, Russell R

2015-04-01

Mesalamine-containing products are considered first-line treatment for inflammatory bowel disease. Myocarditis is recognised as a very rare possible side effect of these medications, but has not often been described in the paediatric population. We present a case of an adolescent with Crohn's disease who presented with myopericarditis after recent initiation of Pentasa. Once identified as the causative agent, the drug was discontinued, with subsequent normalisation of troponin and improvement of function. This case identifies the importance of prompt evaluation, diagnosis, and treatment of paediatric patients receiving mesalamine-containing medications that present with significant cardiovascular symptoms.

An Atypical Eating Disorder with Crohn's Disease in a Fifteen-Year-Old Male: A Case Study.

ERIC Educational Resources Information Center

Holaday, Margot; And Others

1994-01-01

Discusses how 6 months after psychological intervention for an eating disorder, a 15-year-old male was diagnosed with Crohn's disease, a chronic inflammatory bowel disease. Addresses need for additional training for those from traditional school and counseling psychology programs. Advocates a team approach and consultations. (RJM)

Molecular reclassification of Crohn's disease: a cautionary note on population stratification.

PubMed

Maus, Bärbel; Jung, Camille; Mahachie John, Jestinah M; Hugot, Jean-Pierre; Génin, Emmanuelle; Van Steen, Kristel

2013-01-01

Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals.

College adjustment in University of Michigan students with Crohn's and colitis.

PubMed

Adler, Jeremy; Raju, Sheela; Beveridge, Allison S; Wang, Sijian; Zhu, Ji; Zimmermann, Ellen M

2008-09-01

Adjustment to college is critical for academic success. Poor college adjustment correlates with poor academic performance, low graduation rates, and poor success later in life. Limited data are available on the effects of inflammatory bowel disease (IBD) on college adjustment. We hypothesize that disease activity negatively impacts on QOL, and adversely affects college adjustment. Undergraduate students (6 Crohn's disease [CD], 12 ulcerative colitis [UC], 19 healthy controls) completed a standardized college adjustment survey (SACQ) and QOL instrument (SF-12). Where appropriate, disease specific activity and QOL indices were obtained (HBI, SCCAI, SIBDQ). There was an inverse correlation between disease activity and college adjustment in CD and UC (R = -0.6554, p = 0.0032). IBD students had lower physical QOL (SF-12) than controls (p = 0.0009). Emotional domain of college adjustment correlated best with SIBDQ (R = 0.8228, p < 0.0001), and correlated better in CD (R = 0.8619) than UC (R = 0.7946). Mental QOL (SF-12) was worse in CD than UC (p = 0.0211), but neither differed from controls (p = 0.4, p = 0.6). Students with active Crohn's and colitis adjust less well to college life. Physical and emotional factors likely contribute. More aggressive medical therapy and better emotional support before and during college may result in happier and healthier college students, leading to higher graduation rates and future success. Interventions resulting in better disease control and support systems may improve college performance and provide long-term benefits to young adults with IBD.

ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients and show no influence of food and time of food intake on bioavailability.

PubMed

Maurer, J M; Schellekens, R C A; van Rieke, H M; Stellaard, F; Wutzke, K D; Buurman, D J; Dijkstra, G; Woerdenbag, H J; Frijlink, H W; Kosterink, J G W

2013-12-28

ColoPulse tablets are an innovative development in the field of oral drug delivery and are characterized by a colon-specific release. Until now ColoPulse dosage forms (only capsules) have been studied in healthy volunteers having a standardized breakfast three hours after administration but not in specific patient groups and not with a shorter interval between administration and breakfast. Information on bioavailability and release characteristics of ColoPulse tablets in Crohn's patients and the influence of food and time of food intake is a prerequisite to properly design future clinical studies with active substances in these patients. In the current cross-over study bioavailability and drug release characteristics of ColoPulse tablets were compared in healthy volunteers and in Crohn's patients in remission. Furthermore the influence of food and time of food intake on the in vivo drug release behavior of ColoPulse tablets was investigated. In this study the dual label isotope strategy was used which means that a ColoPulse tablet containing (13)C-urea and an uncoated, immediate release tablet containing (15)N2-urea were taken simultaneously. Breath and urine samples were collected during the test day for isotope analysis. The appearance of the stable isotopes in breath and/or urine provides information on the site of release from the dosage form, release characteristics and bioavailability. Both tablets were administered on two different days in a cross-over design: the first day with a breakfast (non-standardized) one hour after administration and the second day with a standardized breakfast three hours after administration of the tablets. There was no difference in instructions for administration between both days. Results of 16 healthy volunteers and 14 Crohn's patients were evaluated. At least 86% (51 out of 59) of all ColoPulse tablets administered in this study released their contents at the desired intestinal region. There was no significant difference in

3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations.

PubMed

Gionchetti, Paolo; Dignass, Axel; Danese, Silvio; Magro Dias, Fernando José; Rogler, Gerhard; Lakatos, Péter Laszlo; Adamina, Michel; Ardizzone, Sandro; Buskens, Christianne J; Sebastian, Shaji; Laureti, Silvio; Sampietro, Gianluca M; Vucelic, Boris; van der Woude, C Janneke; Barreiro-de Acosta, Manuel; Maaser, Christian; Portela, Francisco; Vavricka, Stephan R; Gomollón, Fernando

2017-02-01

This paper is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease [CD] and concerns the surgical management of CD as well as special situations including management of perianal CD and extraintestinal manifestations. Diagnostic approaches and medical management of CD of this ECCO Consensus are covered in the first paper [Gomollon et al JCC 2016]. 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.

Systematic review with meta-analysis: breastfeeding and the risk of Crohn's disease and ulcerative colitis.

PubMed

Xu, L; Lochhead, P; Ko, Y; Claggett, B; Leong, R W; Ananthakrishnan, A N

2017-11-01

Breastfeeding is a modifiable factor that may influence development of inflammatory bowel diseases. However, literature on this has been inconsistent and not accounted for heterogeneity in populations and exposure. To conduct a meta-analysis to examine the association between breastfeeding in infancy and risk of Crohn's disease (CD) and ulcerative colitis (UC). A systematic search of Medline/PubMed and Embase was performed for full text, English-language literature through November 2016. Studies were included if they described breastfeeding in infancy in patients with CD or UC, and healthy controls. Data were pooled using a random effects model for analysis. A total of 35 studies were included in the final analysis, comprising 7536 individuals with CD, 7353 with UC and 330 222 controls. Ever being breastfed was associated with a lower risk of CD (OR 0.71, 95% CI 0.59-0.85) and UC (OR 0.78, 95% CI 0.67-0.91). While this inverse association was observed in all ethnicity groups, the magnitude of protection was significantly greater among Asians (OR 0.31, 95% CI 0.20-0.48) compared to Caucasians (OR 0.78, 95% CI 0.66-0.93; P = .0001) in CD. Breastfeeding duration showed a dose-dependent association, with strongest decrease in risk when breastfed for at least 12 months for CD (OR 0.20, 95% CI 0.08-0.50) and UC (OR 0.21, 95% CI 0.10-0.43) as compared to 3 or 6 months. Breastfeeding in infancy protects against the development of CD and ulcerative colitis. © 2017 John Wiley & Sons Ltd.

Epstein Barr virus-positive mucocutaneous ulcer of the colon associated Hodgkin lymphoma in Crohn's disease.

PubMed

Moran, Neil R; Webster, Bradley; Lee, Kenneth M; Trotman, Judith; Kwan, Yiu-Lam; Napoli, John; Leong, Rupert W

2015-05-21

Epstein Barr virus (EBV) positive mucocutaneous ulcers (EBVMCU) form part of a spectrum of EBV-associated lymphoproliferative disease. They have been reported in the setting of immunosenescence and iatrogenic immunosuppression, affecting the oropharyngeal mucosa, skin and gastrointestinal tract (GIT). Case reports and series to date suggest a benign natural history responding to conservative management, particularly in the GIT. We report an unusual case of EBVMCU in the colon, arising in the setting of immunosuppression in the treatment of Crohn's disease, with progression to Hodgkin lymphoma 18 mo after cessation of infliximab. The patient presented with multiple areas of segmental colonic ulceration, histologically showing a polymorphous infiltrate with EBV positive Reed-Sternberg-like cells. A diagnosis of EBVMCU was made. The ulcers failed to regress upon cessation of infliximab and methotrexate for 18 mo. Following commencement of prednisolone for her Crohn's disease, the patient developed widespread Hodgkin lymphoma which ultimately presented as a life-threatening lower GIT bleed requiring emergency colectomy. This is the first report of progression of EBVMCU to Hodgkin lymphoma, in the setting of ongoing iatrogenic immunosuppression and inflammatory bowel disease.

Review of the use of intralesional steroid injections in the management of ileocolonic Crohn's strictures

PubMed Central

Bevan, Roisin; Rees, Colin J; Rutter, Matthew D; Macafee, David A L

2013-01-01

Most patients with Crohn's disease present with either terminal ileal or colonic disease, with 70% requiring surgery by 10 years after diagnosis. Recurrent stricturing at the anastomotic site is common, often symptomatic and can require re-operation with its inherent risks. Balloon dilation has been shown to provide good symptom relief from such strictures. However, repeat dilations may be required, and further surgical intervention to an anastomotic stricture is needed in up to 30% of cases. Injection of corticosteroids has been suggested as an adjunct to dilation in order to improve outcomes. This paper reviews the current literature on the use of intralesional steroid injections following endoscopic balloon dilation of anastomotic and de novo Crohn's strictures. There have been only two randomised placebo controlled trials and five small non-controlled or retrospective studies. Study numbers vary from 10 to 29 patients. The two randomised trials conflict in their conclusions and numbers are small in these studies. Currently therefore, no firm support can be given to the routine use of intralesional steroid injections. PMID:28839732

Effect of infliximab top-down therapy on weight gain in pediatric Crohns disease.

PubMed

Kim, Mi Jin; Lee, Woo Yong; Choi, Kyong Eun; Choe, Yon Ho

2012-12-01

This retrospective-medical-record review was conducted to evaluate effect of infliximab therapy, particularly with a top-down strategy, on the nutritional parameters of children with Crohns disease (CD). 42 patients who were diagnosed with Crohns disease at the Pediatric Gastroenterology center of a tertiary care teaching hospital and achieved remission at two months and one year after beginning of treatment were divided into four subgroups according to the treatment regimen; azathioprine group (n = 11), steroid group (n = 11), infliximab top-down group (n = 11) and step-up group (n = 9). Weight, height, and serum albumin were measured at diagnosis, and then at two months and one year after the initiation of treatment. At 2 months, the Z score increment for weight was highest in the steroid group, followed by the top-down, step-up, and azathioprine groups. At one year, the Z score increment was highest in top-down group, followed by steroid, azathioprine, and step-up group. There were no significant differences between the four groups in Z score increment for height and serum albumin during the study period. The top-down infliximab treatment resulted in superior outcome for weight gain, compared to the step-up therapy and other treatment regimens.

Intestinal Behçet and Crohn's disease: two sides of the same coin.

PubMed

Valenti, Simona; Gallizzi, Romina; De Vivo, Dominique; Romano, Claudio

2017-04-20

Behçet's disease (BD) and Crohn's disease (CD) are chronic immune-mediated, inflammatory disorders affecting many different systems (joints, skin, eyes, gastrointestinal and biliary tracts). Both disorders have fluctuating courses and when gastrointestinal symptoms are prevalent, differential diagnosis can be difficult. BD involves the gastrointestinal tract in 10-15% of cases with localized lesions in the ileocecal region. The clinical picture is heterogeneous with various clusters of disease expression. CD is a chronic inflammatory disorder, which can affect any part of the intestinal tract, as well as extra-intestinal tissue. Factors that contribute towards the pathogenesis of both disease include the host's genetic profile, and immune system, and environmental factors such as the gut microbiota. The aim of this manuscript is to provide a narrative review of clinical features of BD and CD, highlighting the importance of differential diagnosis and therapeutic approach, especially in the presence of gastrointestinal involvement. A comprehensive search of published literature using the Pubmed ( http://www.ncbi.nlm.nih.gov/pubmed/ ) database was carried out to identify all articles published in English from 1999 to October 2016, using 4 key terms: "Behçet Disease", "Intestinal Behçet's Disease", "Crohn's Disease" and" Inflammatory Bowel Disease".

Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.

PubMed

Marigorta, Urko M; Denson, Lee A; Hyams, Jeffrey S; Mondal, Kajari; Prince, Jarod; Walters, Thomas D; Griffiths, Anne; Noe, Joshua D; Crandall, Wallace V; Rosh, Joel R; Mack, David R; Kellermayer, Richard; Heyman, Melvin B; Baker, Susan S; Stephens, Michael C; Baldassano, Robert N; Markowitz, James F; Kim, Mi-Ok; Dubinsky, Marla C; Cho, Judy; Aronow, Bruce J; Kugathasan, Subra; Gibson, Greg

2017-10-01

Gene expression profiling can be used to uncover the mechanisms by which loci identified through genome-wide association studies (GWAS) contribute to pathology. Given that most GWAS hits are in putative regulatory regions and transcript abundance is physiologically closer to the phenotype of interest, we hypothesized that summation of risk-allele-associated gene expression, namely a transcriptional risk score (TRS), should provide accurate estimates of disease risk. We integrate summary-level GWAS and expression quantitative trait locus (eQTL) data with RNA-seq data from the RISK study, an inception cohort of pediatric Crohn's disease. We show that TRSs based on genes regulated by variants linked to inflammatory bowel disease (IBD) not only outperform genetic risk scores (GRSs) in distinguishing Crohn's disease from healthy samples, but also serve to identify patients who in time will progress to complicated disease. Our dissection of eQTL effects may be used to distinguish genes whose association with disease is through promotion versus protection, thereby linking statistical association to biological mechanism. The TRS approach constitutes a potential strategy for personalized medicine that enhances inference from static genotypic risk assessment.

[Comparison of the results of laparotomy and laparoscopic surgery in patients with Crohn's disease].

PubMed

Horváth, Gyula; Simonka, Zsolt; Lázár, György

2014-01-05

Crohn's disease is an inflammatory bowel disease which may affect different parts of the gastrointestinal tract. To compare retrospectively the results of laparotomy and laparoscopic surgery performed in patients with Crohn's disease between January 1, 2005 and October 31, 2012 in the Department of Surgery, University of Szeged, Hungary. Patients were divided into two groups based on the types of surgery; 103 patients underwent laparotomy and 30 patients had laparoscopic surgery programmed. 22 patients had 24 primary acute interventions. The mean age was significantly lower in the laparoscopic surgery group (p = 0.042). The laparoscopic ileocecal resections have been found significantly shorter than laparotomies (p = 0.033). When ileocecal resection was performed the operation time was significantly longer (p = 0.033) while hospitalization time (p = 0.025) and intensive care unit treatment time (p<0.001) were shorter and the bowel passage also started earlier in the laparoscopic group as compared to the laparotomy group. Laparoscopic surgery results in smaller surgical trauma, better cosmetic outcome, shorter hospitalization time and not higher complication- and morbidity-rate as well as shorter operation time in certain cases. However, it requires more qualified surgical team and the operation expenses are higher.

Management of intra-abdominal abscesses in children with Crohn's disease: a 12-year, retrospective single-center review.

PubMed

Dotson, Jennifer L; Bashaw, Hillary; Nwomeh, Benedict; Crandall, Wallace V

2015-05-01

Intra-abdominal abscesses (IAA) are complications of Crohn's disease, which often result in hospitalization, surgery, and increased cost. Initial management may include medical therapy, percutaneous drainage (PD), or surgery, although the optimal management of IAA in children is unclear. Retrospective review of all pediatric patients with Crohn's disease who developed an IAA from January 1, 2000 to April 30, 2012. Three groups, based on initial IAA treatment modality (medical, PD, and surgery), were compared. Thirty cases of IAA were identified (mean age at IAA diagnosis, 15.4 ± 2.6 yr, 67% female, median Crohn's disease duration, 2.6 mo). Computed tomography was the most common initial (93%) and follow-up (47%) imaging. The average time to follow-up imaging was 8.5 days. For initial management, 18 received medical therapy, 10 PD, and 2 had surgery. The medical therapy group received more computed tomography scans for follow-up imaging than the PD group (12 [67%] versus 2 [20%], P = 0.046). There were no significant differences in abscess characteristics or management of posttreatment course between these 2 groups. Surgical resection occurred in 3 patients (17%) in the medical group and 2 (20%) in the PD group during index hospitalization. No significant differences were identified among treatment groups for readmissions, complications, or abscess recurrence. By 1 year, 12 of the 18 medically managed patients (67%) had surgery, and 6 of the 10 patients (60%) treated with initial PD ultimately had surgery. The majority of patients with IAA require definitive surgical treatment, and there were no clear predictors of those who did not.

Bone mineral density in relation to efficacy and side effects of budesonide and prednisolone in Crohn's disease.

PubMed

Schoon, Erik J; Bollani, Simona; Mills, Peter R; Israeli, Eran; Felsenberg, Dieter; Ljunghall, Sverker; Persson, Tore; Haptén-White, Louise; Graffner, Hans; Bianchi Porro, Gabriele; Vatn, Morten; Stockbrügger, Reinhold W

2005-02-01

Osteoporosis frequently occurs in Crohn's disease, often because of corticosteroids. Budesonide as controlled release capsules is a locally acting corticosteroid with low systemic bioavailability. We investigated its effects on bone compared with prednisolone. In 34 international centers, 272 patients with Crohn's disease involving ileum and/or colon ascendens were randomized to once daily treatment with budesonide or prednisolone for 2 years at doses adapted to disease activity. One hundred eighty-one corticosteroid-free patients had active disease (98 had never received corticosteroids, corticosteroid naive; 83 had received corticosteroids previously, corticosteroid exposed), and 90 had quiescent disease, receiving long-term low doses of corticosteroids, corticosteroid-dependent; in 1 patient, no efficacy data were obtained. Bone mineral density and fractures were assessed in a double-blinded fashion; disease activity, side effects, and quality of life were monitored. Neither the corticosteroid-free nor the corticosteroid-dependent patients treated with budesonide differed significantly in bone mineral density from those receiving prednisolone. However, corticosteroid-naive patients receiving budesonide had smaller reductions in bone mineral density than those on prednisolone (mean, -1.04% vs -3.84%; P = .0084). Treatment-emergent corticosteroid side effects were less frequent with budesonide. Efficacy was similar in both groups. Treatment with budesonide is associated with better preserved bone mass compared with prednisolone in only the corticosteroid-naive patients with active ileocecal Crohn's disease. In both the corticosteroid-free and corticosteroid-dependent groups, budesonide and prednisolone were equally effective for up to 2 years, but budesonide caused fewer corticosteroid side effects.

Antibodies to Coprococcus comes in sera of patients with Crohn's disease. Isolation and purification of the agglutinating antigen tested with an ELISA technique.

PubMed

Hazenberg, M P; van de Merwe, J P; Peña, A S; Pennock-Schröder, A M; van Lieshout, L M

1987-07-01

Previous studies showed that agglutinating antibodies to Coprococcus comes, an anaerobic Gram-positive coccoid rod isolated from the faecal flora of patients with Crohn's disease, are more frequently found in sera of Crohn patients than in ulcerative colitis patients and healthy subjects. Isolation of the antigen may be useful in developing a more sensitive and specific diagnostic test. The present study describes first a method to improve the presentation of the relevant agglutinating antigen by the bacterium and second, the purification by column chromatography of a relatively crude antigen extract of C. comes described previously by Hazenberg et al. (1). Comparative results with the agglutination reactions and ELISA technique of extensive series of patients with Crohn's disease and healthy subjects have shown that the agglutinating antigen of C. comes has been isolated. Although the present ELISA technique cannot replace the simple and reliable agglutination reaction for screening purposes, the purified antigen will allow further immunological studies and it is to be hoped that a deeper insight into pathogenesis of the disease will be gained.

Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease.

PubMed

Crowson, A Neil; Nuovo, Gerard J; Mihm, Martin C; Magro, Cynthia

2003-11-01

The classic pathology of skin disease discontinuous from the inflamed gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic Crohn's disease. The purpose of this study was two-fold: First, we explored the full spectrum of cutaneous lesions associated with Crohn's disease, and second, we sought to explore a potential molecular basis of the skin lesions in patients with CD. In this regard, we analyzed skin and GI tract biopsies from affected patients for the consensus bacterial SrRNA to determine whether direct bacterial infection was associated with either condition. Formalin-fixed, paraffin-embedded sections were studied and correlated to clinical presentation and histories from 33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract material included biopsies from 3 patients who had skin lesions and from 7 patients in whom there were no known skin manifestations. There were 8 cases of neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile neutrophilic folliculitis, 5 cases of panniculitis, 4 cases of vasculitis, 2 cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and 1 case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8 of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were from patients who also developed skin lesions at some point in their clinical course; in contrast, none of the skin biopsies had detectable bacterial RNA. The dermatopathological manifestations of CD discontiguous from the involved GI tract mucosa have in common a vascular injury syndrome, typically with a prominent extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition, this study, the first to

Placental involvement by non-Hodgkin lymphoma in a Crohn disease patient on long-term thiopurine therapy.

PubMed

Chen, G; Crispin, P; Cherian, M; Dahlstrom, J E; Sethna, F F; Kaye, G; Pavli, P; Subramaniam, K

2016-01-01

We report the first published case of aggressive diffuse large B-cell (non-Hodgkin) lymphoma in a 35-year-old pregnant woman who had Crohn disease and was taking long-term thiopurine therapy: the patient developed placental insufficiency, and there was intrauterine fetal death. © 2015 Royal Australasian College of Physicians.

High Spatiotemporal Resolution Dynamic Contrast-Enhanced MR Enterography in Crohn Disease Terminal Ileitis Using Continuous Golden-Angle Radial Sampling, Compressed Sensing, and Parallel Imaging.

PubMed

Ream, Justin M; Doshi, Ankur; Lala, Shailee V; Kim, Sooah; Rusinek, Henry; Chandarana, Hersh

2015-06-01

The purpose of this article was to assess the feasibility of golden-angle radial acquisition with compress sensing reconstruction (Golden-angle RAdial Sparse Parallel [GRASP]) for acquiring high temporal resolution data for pharmacokinetic modeling while maintaining high image quality in patients with Crohn disease terminal ileitis. Fourteen patients with biopsy-proven Crohn terminal ileitis were scanned using both contrast-enhanced GRASP and Cartesian breath-hold (volume-interpolated breath-hold examination [VIBE]) acquisitions. GRASP data were reconstructed with 2.4-second temporal resolution and fitted to the generalized kinetic model using an individualized arterial input function to derive the volume transfer coefficient (K(trans)) and interstitial volume (v(e)). Reconstructions, including data from the entire GRASP acquisition and Cartesian VIBE acquisitions, were rated for image quality, artifact, and detection of typical Crohn ileitis features. Inflamed loops of ileum had significantly higher K(trans) (3.36 ± 2.49 vs 0.86 ± 0.49 min(-1), p < 0.005) and v(e) (0.53 ± 0.15 vs 0.20 ± 0.11, p < 0.005) compared with normal bowel loops. There were no significant differences between GRASP and Cartesian VIBE for overall image quality (p = 0.180) or detection of Crohn ileitis features, although streak artifact was worse with the GRASP acquisition (p = 0.001). High temporal resolution data for pharmacokinetic modeling and high spatial resolution data for morphologic image analysis can be achieved in the same acquisition using GRASP.

A case of gas gangrene in an immunosuppressed Crohn's patient.

PubMed

Kiel, Natalie; Ho, Vincent; Pascoe, Andrew

2011-09-07

Clostridium septicum (C. septicum) gas gangrene is well documented in the literature, typically in the setting of trauma or immunosuppression. In this paper, we report a unique case of spontaneous clostridial myonecrosis in a patient with Crohn's disease and sulfasalazine-induced neutropenia. The patient presented with left thigh pain, vomiting and diarrhea. Blood tests demonstrated a profound neutropenia, and magnetic resonance imaging of the thigh confirmed extensive myonecrosis. The patient underwent emergency hip disarticulation, followed by hemicolectomy. C. septicum was cultured from the blood. Following completion of antibiotic therapy, the patient developed myonecrosis of the right pectoral muscle necessitating further debridement, and remains on lifelong prophylactic antibiotic therapy.

Infliximab "Top-Down" Strategy is Superior to "Step-Up" in Maintaining Long-Term Remission in the Treatment of Pediatric Crohn Disease.

PubMed

Lee, Yoo Min; Kang, Ben; Lee, Yoon; Kim, Mi Jin; Choe, Yon Ho

2015-06-01

We aimed to compare the efficacy of remission maintenance between infliximab "top-down" and "step-up" strategies in moderate to severe pediatric Crohn disease during 3 years. We also aimed to determine prognostic factors that may influence the relapse-free rate in these patients. The present study was a retrospective review of a prospective cohort, based on an infliximab treatment protocol for pediatric Crohn disease used at Samsung Medical Center. A total of 31 patients (group A) were treated with early infliximab induction ("top-down" strategy) and 20 patients (group B) refractory to conventional therapy underwent infliximab treatment ("step-up" strategy). The efficacy of infliximab treatment was assessed by relapse-free rate and remission period rate for 3 years. A total of 11 prognostic factors that may influence the relapse-free rate were further analyzed. The relapse-free rates at 3 years were 35.5% (95% confidence interval [CI] 0.194-0.519) in group A and 15.0% (95% CI 0.037-0.335) in group B (P = 0.0094). Overall remission period rate for 3 years also showed a significant difference between the 2 groups (92.1%  ± 7.2% vs 78.3%  ± 16.6%; P = 0.005). Multivariable analysis revealed that the duration from the initial diagnosis to infliximab infusion was the only factor associated with relapse-free remission for 3 years (hazard ratio = 1.077; 95% CI 1.025-1.131). "Top-down" strategy had a longer remission period compared with the "step-up" strategy in pediatric Crohn disease during a study period of 3 years, based on relapse-free rate and remission period rate. Earlier introduction of infliximab is recommended in pediatric patients with moderate to severe Crohn disease.

Metabolomics reveals metabolic biomarkers of Crohn's disease

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

Jansson, J.K.; Willing, B.; Lucio, M.

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonicmore » acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.« less

Safety of infliximab in Crohn's disease: a large single-center experience.

PubMed

Hamzaoglu, H; Cooper, J; Alsahli, M; Falchuk, K R; Peppercorn, M A; Farrell, R J

2010-12-01

The aim of this study was to evaluate the short- and long-term safety experience of infliximab treatment in patients with Crohn's disease (CD) in clinical practice. The medical records of 297 consecutive patients with CD treated with infliximab at the Beth Israel Deaconess Medical Center were reviewed for demographic features and adverse events. The 297 patients received a total of 1794 infusions. Patients received a median of four infusions and had a median follow-up of 14.3 months. Forty-four patients (15%) experienced a serious adverse event, requiring the infusion to be stopped in 33 patients (11%). Acute infusion reactions occurred in 18 patients (6%) including respiratory problems in 10 patients (3%) and an anaphylactoid reaction in 1 patient (0.3%). Serum sickness-like disease occurred in one patient (0.3%) and three patients (1%) developed drug-induced lupus. One patient developed a probable new demyelination disorder. Eight patients (2.7%), all of whom were on concurrent immunosuppressants, developed a serious infection, one resulting in fatal sepsis. Six patients (2%) developed malignancies including two lymphomas and two skin cancers. A total of four (1.3%) deaths were observed (median age 72.5 years); two due to gastrointestinal bleeding, one due to sepsis, and one due to malignancy. While short- and long-term infliximab therapy was generally well tolerated, serious adverse events occurred in 15% of patients including drug-induced lupus, fatal sepsis, and malignancy. Concomitant immunosuppressants were significantly associated with infections and deaths, particularly among elderly patients. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

MedEdPORTAL: Educational Scholarship for Teaching

ERIC Educational Resources Information Center

Reynolds, Robby J.; Candler, Christopher S.

2008-01-01

MedEdPORTAL is an online publication service provided at no charge by the Association of American Medical Colleges (AAMC). The intent is to promote collaboration and educational scholarship by helping educators publish and share educational resources. With MedEdPORTAL, users can quickly locate high-quality, peer-reviewed teaching materials in both…

Update on the Medical Management of Crohn's Disease.

PubMed

Deepak, Parakkal; Bruining, David H

2015-11-01

The medical management of Crohn's disease is a rapidly evolving field with expanding therapeutic drug options and treatment strategies. In addition to corticosteroids, immunomodulators, and anti-tumor necrosis (anti-TNF) agents, a new anti-adhesion medication (vedolizumab) has been approved. Individualized patient-based dosing of immunomodulators and biologic agents is now possible with therapeutic drug monitoring (TDM). There is a changing paradigm in treatment goals to achieve deeper remission identified by composite clinical and endoscopic endpoints. More aggressive treatment strategies in the postoperative setting have been proposed due to emerging data on medication efficacy in this setting. Management algorithms that stratify CD patients into risk groups to balance treatment benefit against adverse events and costs are being developed to translate research into clinical practice. This review provides an update on these new developments for practicing gastroenterologists.

Value of diffusion-weighted imaging when added to magnetic resonance enterographic evaluation of Crohn disease in children.

PubMed

Shenoy-Bhangle, Anuradha S; Nimkin, Katherine; Aranson, Thomas; Gee, Michael S

2016-01-01

MR enterography is increasingly utilized for noninvasive evaluation of disease activity in young patients with Crohn disease and has great impact on clinical management. Diffusion-weighted imaging (DWI) is a rapid MR imaging technique that measures molecular diffusion of water and is sensitive to the inflammatory process; however, its value to MR enterography has not been rigorously evaluated. To determine whether the addition of DWI to MR enterography is helpful in evaluating Crohn disease activity in young patients when compared to a histological reference. In this single-institution retrospective study, we searched an imaging database for the period January 2010 to December 2012 to identify patients age 19 years and younger who had MR enterography with diffusion-weighted imaging (DWI). We used an electronic medical record search to identify those who had MR enterography and colonoscopy performed within 28 days of each other. All MR enterography scans were performed on a 1.5-T or 3-T clinical MR scanner with phased-array torso coil configuration using standard pulse sequences as well as axial DWI with b values of 50, 400 and 800. Bowel segments were evaluated for disease activity based on standard MR enterography sequences; in addition, segmental apparent diffusion coefficient (ADC) values were calculated based on DWI. Histological reference for disease activity was based on assessment for mucosal inflammatory changes on endoscopic biopsy. MR enterography and DWI evaluation were performed in a blinded fashion with respect to histological results. We included imaging of 78 bowel segments from 27 patients (mean age 14.5 ± 3.02 years) with known Crohn disease in the study. The mean ADC for bowel segments with active disease was 1.56 ± 0.7 × 10(3) mm(2)/s compared with 2.58 ± 1.4 × 10(3) mm(2)/s for segments without active disease, a difference that was statistically significant (P < 0.01, Student's t-test). Using a threshold value of 2

Developing in vitro expanded CD45RA+ regulatory T cells as an adoptive cell therapy for Crohn's disease.

PubMed

Canavan, James B; Scottà, Cristiano; Vossenkämper, Anna; Goldberg, Rimma; Elder, Matthew J; Shoval, Irit; Marks, Ellen; Stolarczyk, Emilie; Lo, Jonathan W; Powell, Nick; Fazekasova, Henrieta; Irving, Peter M; Sanderson, Jeremy D; Howard, Jane K; Yagel, Simcha; Afzali, Behdad; MacDonald, Thomas T; Hernandez-Fuentes, Maria P; Shpigel, Nahum Y; Lombardi, Giovanna; Lord, Graham M

2016-04-01

Thymus-derived regulatory T cells (Tregs) mediate dominant peripheral tolerance and treat experimental colitis. Tregs can be expanded from patient blood and were safely used in recent phase 1 studies in graft versus host disease and type 1 diabetes. Treg cell therapy is also conceptually attractive for Crohn's disease (CD). However, barriers exist to this approach. The stability of Tregs expanded from Crohn's blood is unknown. The potential for adoptively transferred Tregs to express interleukin-17 and exacerbate Crohn's lesions is of concern. Mucosal T cells are resistant to Treg-mediated suppression in active CD. The capacity for expanded Tregs to home to gut and lymphoid tissue is unknown. To define the optimum population for Treg cell therapy in CD, CD4(+)CD25(+)CD127(lo)CD45RA(+) and CD4(+)CD25(+)CD127(lo)CD45RA(-) Treg subsets were isolated from patients' blood and expanded in vitro using a workflow that can be readily transferred to a good manufacturing practice background. Tregs can be expanded from the blood of patients with CD to potential target dose within 22-24 days. Expanded CD45RA(+) Tregs have an epigenetically stable FOXP3 locus and do not convert to a Th17 phenotype in vitro, in contrast to CD45RA(-) Tregs. CD45RA(+) Tregs highly express α4β7 integrin, CD62L and CC motif receptor 7 (CCR7). CD45RA(+) Tregs also home to human small bowel in a C.B-17 severe combined immune deficiency (SCID) xenotransplant model. Importantly, in vitro expansion enhances the suppressive ability of CD45RA(+) Tregs. These cells also suppress activation of lamina propria and mesenteric lymph node lymphocytes isolated from inflamed Crohn's mucosa. CD4(+)CD25(+)CD127(lo)CD45RA(+) Tregs may be the most appropriate population from which to expand Tregs for autologous Treg therapy for CD, paving the way for future clinical trials. 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/

Challenging Ulcerative Vulvar Conditions: Hidradenitis Suppurativa, Crohn Disease, and Aphthous Ulcers.

PubMed

Stewart, Kristen M A

2017-09-01

This article discusses the clinical evaluation and approach to patients with 3 complex ulcerative vulvar conditions: hidradenitis suppurativa, metastatic Crohn disease of the vulva, and aphthous ulcers. These conditions are particularly challenging to medical providers because, although each is known to present with nonspecific examination findings that vary in morphology, the predominance of the diagnosis is based on clinical examination and exclusion of a wide variety of other conditions. Care of patients with these conditions is further complicated by the lack of therapeutic data and the significant impact these conditions have on quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

Budesonide for induction of remission in Crohn's disease.

PubMed

Rezaie, Ali; Kuenzig, M Ellen; Benchimol, Eric I; Griffiths, Anne Marie; Otley, Anthony R; Steinhart, A Hillary; Kaplan, Gilaad G; Seow, Cynthia H

2015-06-03

Corticosteroids are commonly used for the induction of remission in Crohn's disease. However, traditional corticosteroids can cause significant adverse events. Budesonide is an alternative glucocorticoid with limited systemic bioavailability. The primary objective was to evaluate the efficacy and safety of oral budesonide for the induction of remission in Crohn's disease. The following electronic databases were searched up to June 2014: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched. Randomised controlled trials comparing budesonide to a placebo or active comparator were considered for inclusion. Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality. Methodological quality was assessed using the Cochrane risk of bias tool The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Meta-analysis was performed using RevMan 5.3.5 software. The primary outcome was induction of remission (defined by a Crohn's disease activity index (CDAI) < 150) by week 8 to 16 of treatment. Secondary outcomes included: time to remission, mean change in CDAI, clinical, histological or endoscopic improvement, improvement in quality of life, adverse events and early withdrawal. We calculated the relative risk (RR) and corresponding 95% confidence intervals (CIs) for each dichotomous outcome and the mean difference and corresponding 95% CI for each continuous outcome. Data were analyzed on an intention-to-treat basis. A random-effects model was used for the pooled analyses. The overall quality of the evidence supporting the primary outcomes and selected secondary outcomes was evaluated using the GRADE criteria. Fourteen studies (1805 patients) were included: Nine (779 patients) compared budesonide to

An evaluation of health care expenditures in Crohn's disease using the United States Medical Expenditure Panel Survey from 2003 to 2013.

PubMed

Bounthavong, Mark; Li, Meng; Watanabe, Jonathan H

Previous estimates of the economic burden of Crohn's disease (CD) varied widely from $2.0 to $18.2 billion per year (adjusted to 2015 $US). However, these estimates do not reflect recent changes in pharmaceutical treatment options and guidelines. The goal of this study was to update cost estimates of Crohn's disease based on a representative sample of the US population from the most recent 11 years (2003-2013) of the Medical Expenditure Panel Survey (MEPS). A secondary aim described expenditure trends in respondents with and without Crohn's disease pre-post FDA approvals of new biologics and the American College of Gastroenterology Crohn's disease treatment guidelines. Average annual expenditures (total, prescription, inpatient, and outpatient) were evaluated using a pooled cross-sectional design. Respondent data from the most recent 11 years (2003-2013) of MEPS were analyzed. Two-part generalized linear models with power-link were used to estimate the average annual expenditures per patient adjusted to multiple covariates. Confidence intervals (CI) were estimated using bootstrap methods. Difference-in-differences estimations were performed to compare the changes in health care expenditures pre-post FDA approvals of new biologics and the American College of Gastroenterology Crohn's disease treatment guidelines. The annual aggregate economic burden of CD was $6.3 billion in the US. Respondents with CD had higher total (+$6442; 95% CI: $4864 to $8297), prescription (+$3283; 95% CI: $2289 to $4445), inpatient (+$1764; 95% CI: $748 to $3551), and outpatient (+$1191; 95% CI: $592 to $2160) expenditures compared to respondents without CD. In the difference-in-differences estimation, respondents with CD had significantly higher total (P = 0.001) and prescription (P < 0.001) expenditures compared with respondents without CD. Although inpatient and outpatient expenditures were higher in respondents with CD, they were not statistically significant. Respondents with CD

Application of the Vienna Classification for Crohn's disease to a single clinician database of 877 patients.

PubMed

Freeman, H J

2001-02-01

An international working party at the World Congress of Gastroenterology held in Vienna, Austria from September 6 to 11, 1998 defined a classification for Crohn's disease based on patient age at diagnosis (eg, less than 40 years of age, 40 years of age or older), disease location (eg, terminal ileum, colon, ileocolon or upper gastrointestinal tract) and behaviour (eg, stricturing, penetrating). Disease location in the upper gastrointestinal tract was defined by disease being present proximal to the terminal ileum, regardless of terminal ileal or colon involvement. A 20-year, single clinician database of 877 patients from a university campus hospital was used, and comprised 492 women (56.1%) and 385 men (43.9%). Of these patients, 740 (84.4%) were diagnosed before age 40 years and 137 (15.6%) were diagnosed by 40 years of age or older. Disease was located in the terminal ileum alone in 222 patients (25.3%), colon alone in 238 patients (27.2%) and ileocolon in 304 patients (34.6%). Another 113 patients (13.1%) had disease in the upper gastrointestinal tract, usually with disease also in the terminal ileum (23 patients), colon (12 patients) or ileocolon (71 patients). Only seven of 877 patients had disease located in the upper gastrointestinal tract alone with no distal disease. Disease behaviour could be classified as nonstricturing and nonpenetrating in 256 patients (29.2%), stricturing in 294 patients (33.6%) and penetrating in 327 patients (37.2%). Of the 877 patients with Crohn's disease, 837 were white, 38 were Asian and two were black. In this tertiary care setting of a single clinician practice in a Canadian teaching hospital at the University of British Columbia, Crohn's disease predominantly affects women, and young adults with a high rate of stricturing and penetrating complications.

Patterns and operative treatment of recurrent Crohn's disease: a prospective longitudinal study.

PubMed

Fichera, Alessandro; Lovadina, Stefano; Rubin, Michele; Cimino, Fabrizio; Hurst, Roger D; Michelassi, Fabrizio

2006-10-01

It is believed commonly that Crohn's recurrences always occur at the site of a previous intestinal anastomosis; yet this concept is probably inaccurate and not mindful of the panintestinal nature of the disease. Between October, 1984 and March, 2003, we carried out 1,132 procedures (464 for primary and 668 for recurrent disease) on 981 consecutive patients. Patients in whom we carried out both the original procedure as well as the procedure for recurrent disease constitute this study population. Operative procedures for perineal complications were excluded from this analysis. Data were accrued prospectively. Seventy-eight patients met the study inclusion criteria. They had a total of 149 sites of disease (duodenum, n = 3; jejunum/ileum, n = 53; terminal ileum/neo terminal ileum, n = 67; colon and rectum, n = 26). One hundred thirty-four sites required operative intervention (85 resections and 49 strictureplasties) and 15 did not. Crohn's disease recurred in 79 sites after a mean of 48.4 months (range, 1-161 months, median, 41 months). Site of operative intervention and operative technique influenced patterns of recurrence: when an anastomosis or strictureplasty was constructed with small bowel, the majority of recurrences were limited to the anastomotic line (17/29, 59%); when it was constructed with small bowel and colon, the majority of recurrences extended to the proximal limb (29/35, 83%). The difference in recurrence pattern is significant (P < .01). In addition, fewer recurrences occurred at strictureplasty than resection sites (22/49, 45%, vs 57/85, 70%, respectively, P < .05). At the time of the second procedure, 40 additional recurrences were identified distant from the original operative site. Four of these represented progression of disease at the 15 sites that did not originally need operative intervention. Of 119 total recurrences, 115 required 73 resections, 40 strictureplasties, and 2 other procedures. The site of the original operative intervention

Effectiveness and safety of vedolizumab for treatment of Crohn's disease: a systematic review and meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Smela-Lipińska, Beata; Pilc, Andrzej

2016-10-01

The aim of this systematic review (SR) and meta-analysis was to assess the efficacy and safety of vedolizumab in the treatment of Crohn's disease (CD). A systematic literature search was conducted in Medline/PubMed, Embase and Cochrane Library until 25 January, 2015. Included studies were critically appraised according to the PRISMA protocol. Assessment in specified subgroups of CD patients and meta-analysis with Revman software were performed. Two randomized controlled trial (RCTs) were included in a meta-analysis for the induction phase of therapy: GEMINI II and GEMINI III. The clinical response was significantly higher for patients who received vedolizumab compared to placebo in the general population (risk benefit (RB) = 1.48; p = 0.0006) and in both analyzed subgroups: patients with previous failure of anti-TNFs treatment (RB = 1.51; p = 0.006) and patients naive to earlier anti-TNFs (RB = 1.41; p = 0.001). The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for patients who received vedolizumab compared to placebo (RB = 1.77; p = 0.003; RB = 2.29; p = 0.0004; respectively). Meta-analysis for adverse events, serious adverse events (SAEs) and serious infections, revealed that vedolizumab was as safe as placebo in the induction phase of therapy. The clinical response was significantly higher for patients who received vedolizumab in the general population and in both analyzed subgroups of patients. The clinical remission in the general population and subpopulation of TNF-antagonist naive patients was significantly higher for vedolizumab, but no significant differences were revealed in the subgroup of patients with previous TNF antagonist failure.

A case of anorexia nervosa with comorbid Crohn's disease: beneficial effects of anti-TNF-α therapy?

PubMed

Solmi, Marco; Santonastaso, Paolo; Caccaro, Roberta; Favaro, Angela

2013-09-01

This case report describes a 26-year-old woman affected by long-lasting anorexia nervosa (AN) and Crohn's disease. Worsening of the bowel illness led to the prescription of immunosuppressive therapy (biologic infliximab for 4 months, followed by adalimumab for 6 months) and referral to our Eating Disorders Unit. Although she initially demonstrated denial of her eating disorder, in a few months she gradually improved her weight and psychopathology. Crohn's disease can worsen AN by modifying hunger and energy expenditure through the effects of TNF-α and IL-6, pro-inflammatory cytokines which moderate leptin and melanocortin signaling. Previous studies have observed the antidepressant effects of TNF antagonist in patients with treatment-resistant depression with high baseline inflammatory biomarkers. Our case report suggests that future studies are needed to clarify the existence, patterns, and extent of increased inflammatory markers in patients with AN, and whether they determine clinical features or identify subgroups of patients. Potential therapeutic significance of above issues remains to be determined. Copyright © 2013 Wiley Periodicals, Inc.

Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn's disease patients.

PubMed

Landsman, Marc J; Sultan, Mohamed; Stevens, Michael; Charabaty, Aline; Mattar, Mark C

2014-12-01

Management of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, stretches beyond control of flares. Some infections of the gastrointestinal tract are more commonly seen in patients with IBD. Work from the Human Microbiome Project has been instrumental in our understanding of the interplay between the vast gut microbiota and host immune responses. Patients with IBD may be more prone to infectious complications based on their underlying inflammatory disease and variations in their microbiome. Immunosuppressant medications commonly used to treat patients with Crohn's and colitis also play a role in predisposing these patients to acquire these infections. Here, we present a detailed review of the data focusing on the most common infections of the gastrointestinal tract in patients with IBD: Clostridium difficile infections (CDI) and cytomegalovirus (CMV). We will discuss appropriate diagnostic tools and treatment options for these infections. Other less common infections will also be reviewed briefly. Studying the various infections of the gastrointestinal tract in these patients could enhance our understanding of the pathophysiology of IBD.

Oridonin's therapeutic effect: suppressing Th1/Th17 simultaneously in a mouse model of Crohn's disease.

PubMed

Wang, Shubei; Zhang, Yong; Saas, Philippe; Wang, Haili; Xu, Ying; Chen, Ke; Zhong, Jie; Yuan, Yaozong; Wang, Ying; Sun, Yunwei

2015-03-01

Crohn's disease is a chronic inflammatory bowel disease. Oridonin is an effective component isolated from Rabdosia rubescens. It can inhibit the activation of transcription factor nuclear factor-kappa B and suppress the over expression of cytokines. We postulated that oridonin may be a potential therapeutic candidate for Crohn's disease. To confirm the postulation, we investigated clinical and immunologic modulations of oridonin in a mouse model of trinitrobenzene sulfonic acid-induced colitis. It was found that oridonin attenuated trinitrobenzene sulfonic acid-induced colitis as represented by a reduction in colonic interferon-γ/inteleukin-17 secretion and a decrement in splenic Th1/Th17 cells and effector memory CD4(+) T cells. Oridonin treatment inhibited the proliferation of CD4(+) T cells and upregulated the apoptosis of lymphocytes by inhibiting nuclear translocation of transcription factor nuclear factor-kappa B. Oridonin is a potential modulator for trinitrobenzene sulfonic acid-induced colitis and other Th1/Th17 mediated inflammatory diseases. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn's disease: study protocol for a randomised controlled trial.

PubMed

Tew, Garry A; Carpenter, Roger; Seed, Michael; Anderson, Simon; Langmead, Louise; Fairhurst, Caroline; Bottoms, Lindsay

2017-01-01

Structured exercise training has been proposed as a useful adjunctive therapy for Crohn's disease by improving immune function and psychological health, reducing fatigue and promoting gains in muscle and bone strength. However, the evidence for exercise in Crohn's disease is sparse, with only a handful of small prospective trials [1, 2], with methodological limitations, including the use of non-randomised and non-controlled study designs and small sample sizes. Here, we describe the protocol for a study that aims to assess the feasibility and acceptability of two common types of exercise training-high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT)-in adults with inactive or mildly active Crohn's disease (CD). This is a randomised, controlled, assessor-blinded, feasibility trial with three parallel groups. Forty-five adults with inactive or mildly active Crohn's disease will be randomly assigned 1:1:1 to HIIT, MICT or usual care control. Participants in the HIIT and MICT groups will be invited to undertake three sessions of supervised exercise each week for 12 consecutive weeks. HIIT sessions will consist of ten 1-min intervals of cycling exercise at 90% of peak power output separated by 1 min of active recovery. MICT sessions will involve 30 min of continuous cycling at 35% of peak power output. Participants will be assessed before randomisation and 13 and 26 weeks after randomisation. Feasibility outcomes include rates of recruitment, retention and adherence. Interviews with participants will explore the acceptability of the exercise programmes and study procedures. Clinical/health outcomes include cardiorespiratory fitness, body mass index, resting blood pressure, markers of disease activity (faecal calprotectin and Crohn's Disease Activity Index) and activated T cell cytokine profiles. Study questionnaires include the Inflammatory Bowel Disease Quality of Life Questionnaire, EQ-5D-5L, IBD Fatigue Scale, Hospital and

Comparison of CT enterography and MR enterography imaging features of active Crohn disease in children and adolescents.

PubMed

Gale, Heather I; Sharatz, Steven M; Taphey, Mayureewan; Bradley, William F; Nimkin, Katherine; Gee, Michael S

2017-09-01

Assessment for active Crohn disease by CT enterography and MR enterography relies on identifying mural and perienteric imaging features. To evaluate the performance of established imaging features of active Crohn disease in children and adolescents on CT and MR enterography compared with histological reference. We included patients ages 18 years and younger who underwent either CT or MR enterography from 2007 to 2014 and had endoscopic biopsy within 28 days of imaging. Two pediatric radiologists blinded to the histological results reviewed imaging studies and scored the bowel for the presence or absence of mural features (wall thickening >3 mm, mural hyperenhancement) and perienteric features (mesenteric hypervascularity, edema, fibrofatty proliferation and lymphadenopathy) of active disease. We performed univariate analysis and multivariate logistic regression to compare imaging features with histological reference. We evaluated 452 bowel segments (135 from CT enterography, 317 from MR enterography) from 84 patients. Mural imaging features had the highest association with active inflammation both for MR enterography (wall thickening had 80% accuracy, 69% sensitivity and 91% specificity; mural hyperenhancement had 78%, 53% and 96%, respectively) and CT enterography (wall thickening had 84% accuracy, 72% sensitivity and 91% specificity; mural hyperenhancement had 76%, 51% and 91%, respectively), with perienteric imaging features performing significantly worse on MR enterography relative to CT enterography (P < 0.001). Mural features are predictors of active inflammation for both CT and MR enterography, while perienteric features can be distinguished better on CT enterography compared with MR enterography. This likely reflects the increased conspicuity of the mesentery on CT enterography and suggests that mural features are the most reliable imaging features of active Crohn disease in children and adolescents.

Health-related quality of life in youth with Crohn disease: role of disease activity and parenting stress.

PubMed

Gray, Wendy N; Boyle, Shana L; Graef, Danielle M; Janicke, David M; Jolley, Christopher D; Denson, Lee A; Baldassano, Robert N; Hommel, Kevin A

2015-06-01

Health-related quality of life (HRQOL) is an important, but understudied construct in pediatric inflammatory bowel disease. Family level predictors of HRQOL have been understudied as are the mechanisms through which disease activity affects HRQOL. The present study examines the relation between a family level factor (parenting stress) and HRQOL in youth with Crohn disease. Parenting stress is examined as a mechanism through which disease activity affects HRQOL. A total of 99 adolescents with Crohn disease and their parents were recruited across 3 sites. Adolescents completed the IMPACT-III (inflammatory bowel disease-specific HRQOL). Parents completed the Pediatric Inventory for Parents, a measure of medically related parenting stress that assesses stress because of the occurrence of medical stressors and stress because of the perceived difficulty of stressors. Disease activity was obtained from medical records. Parenting stress because of the occurrence of medical stressors partially mediated the disease severity-HRQOL relation, reducing the relation between these variables from 49.67% to 31.58% (B= -0.56, P < 0.0001). Bootstrapping analysis confirmed that the indirect effect of disease severity on HRQOL via parenting stress significantly differed from zero. Parenting stress because of the perceived difficulty of medical stressors partially mediated the disease severity-HRQOL relation, reducing the relation from 49.67% to 30.29% (B= -0.55, P < 0.0001). The indirect effect was confirmed via bootstrapping procedures. As disease severity increased, parenting stress also increased, and adolescent HRQOL decreased. Parenting stress should be considered and assessed for along with medical factors as part of a comprehensive approach to improve HRQOL in adolescents with Crohn disease.

Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn's disease.

PubMed

Bauditz, J; Wedel, S; Lochs, H

2002-02-01

Thalidomide improves clinical symptoms in patients with therapy refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor alpha (TNF-alpha) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). Ten patients with therapy refractory IBD (nine Crohn's disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-alpha, interleukin (IL)-1 beta, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-alpha and IL-12 decreased during treatment with thalidomide: LPMC (TNF-alpha: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-alpha: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1 beta and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-alpha and IL-12 production. The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-alpha and IL-12.

Psychological well-being and quality of life in Crohn's disease patients with an ostomy: a preliminary investigation.

PubMed

Knowles, Simon R; Wilson, Jarrad; Wilkinson, Annette; Connell, William; Salzberg, Michael; Castle, David; Desmond, Paul; Kamm, Michael A

2013-01-01

The aims of this research were to explore associations among elective versus emergency surgery, type of ostomy (permanent vs temporary), illness perceptions and coping style, anxiety, depression, and health-related quality of life in persons with Crohn's disease. A further aim was to determine the extent of current and past use of psychological care and use of psychotropic medications. The sample comprised 31 persons (17 men and 14 women; mean age 45 years) with Crohn's disease and an ostomy from 2 large teaching hospitals in Melbourne, Australia. Data were collected using a descriptive, cross-sectional design. The questionnaire incorporated 3 validated instruments: the Brief Illness Perceptions Questionnaire, the Hospital Anxiety and Depression Scale, and the Stoma Quality of Life Scale. Poor illness perception correlated significantly with increased anxiety, depression, and reduced health-related quality of life (specifically, sexuality and body image, work and social functioning, stoma function, and financial concerns). Forty-eight percent of patients scored more than the cutoff for anxiety, and 42% scored more than the cutoff for depression on the Hospital Anxiety and Depression Scale. Of these, only 20% and 31%, respectively, reported currently receiving psychological care. The timing of ostomy surgery (planned vs emergency) or ostomy type (permanent vs temporary) was not significantly associated with anxiety, depression, or health-related impaired quality of life. In this exploratory, cross-sectional study, patients with Crohn's disease and a stoma had high rates of psychological comorbidity and low scores on quality of life. Adverse illness perception appeared to explain some of these findings, but most were not receiving psychological help. Psychological care is indicated for many of these patients and further research is indicated.

Once versus three times daily dosing of oral budesonide for active Crohn's disease: a double-blind, double-dummy, randomised trial.

PubMed

Dignass, Axel; Stoynov, Simeon; Dorofeyev, Andrey E; Grigorieva, Galina A; Tomsová, Eva; Altorjay, István; Tuculanu, Daniel; Bunganič, Ivan; Pokrotnieks, Juris; Kupčinskas, Limas; Dilger, Karin; Greinwald, Roland; Mueller, Ralph

2014-09-01

Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

IL-23 Blockade for Crohn s disease: next generation of anti-cytokine therapy.

PubMed

Furfaro, Federica; Gilardi, Daniela; Allocca, Mariangela; Cicerone, Clelia; Correale, Carmen; Fiorino, Gionata; Danese, Silvio

2017-05-01

Adaptive immunity in intestinal inflammation may play a key role in the pathogenesis of Crohn's disease. In particular, interleukin (IL)-23 may be a key mediator in chronic intestinal inflammation by inducing the differentiation of naïve CD4 + T cells into Th17, with the production of several pro-inflammatory cytokines. Furthermore, IL-23 induces interferon-γ (IFN- γ) production from activated T cells, a critical cytokine in innate and adaptive immunity against infections. Areas covered: We aim to review the available data from literature regarding the role of IL-23, with a more specific focus on the recent progresses in the therapeutic modulation of this cytokine. Expert commentary: Increased knowledge regarding the role of IL-23 has allowed for the development of effective therapeutic progresses by blocking the IL-23 mediated pathways. Primary or secondary loss of response to anti-TNF therapies in Crohn's disease patients during the first year is widely described in literature: the development of new drugs, with alternative mechanisms of action, is thus a key point to consider for the optimal management of these subjects. Drugs blocking the IL-12/23 pathway showed a good efficacy and safety profile in immune-mediated diseases Further studies are necessary regarding the role of the single blockade of IL-23.

Crohn's disease mistaken for long-standing idiopathic mesenteric panniculitis: A case report and management algorithm.

PubMed

Nuzzo, Alexandre; Zappa, Magaly; Cazals-Hatem, Dominique; Bouhnik, Yoram

2016-09-01

Mesenteric panniculitis (MP) is mostly an associated sign of an intra-abdominal or systemic inflammatory primary disease. Nevertheless, etiological and differential diagnosis of idiopathic MP can be challenging when an associate primary cause is not in the foreground. We report here the case of an isolated small bowel Crohn's disease, long time considered as idiopathic MP. This patient presented to our department with a 10-year history of acute abdominal symptoms evolving with flare-up and remission. A diagnosis of idiopathic MP was made based on compatible CT-scan features along with normal laboratory tests and upper and lower bowel endoscopies. As symptoms recurred, a steroid course was proposed which dramatically improved his condition for years. Finally, an explorative laparoscopy was performed because of concern of malignancy when he returned to our unit with a steroid refractory flare-up and weight loss, along with MP nodes growing up to 10 mm. Crohn's disease was eventually diagnosed, based on histopathological middle-gut bowel resection and numerous granulomas in mesenteric nodes without necrosis. This case emphasizes the importance of excluding inflammatory intestinal lesions before making the diagnosis of idiopathic MP (fecal calprotectin, magnetic resonance enterography, wireless capsule endoscopy).

[Acute small bowel diverticulitis in a patient with crohn’s disease].

PubMed

Hevia, Macarena; Quera, Rodrigo; Soto, Leonardo; Regueira, Tomás; O'Brien, Andrés; Larach, Andrés; Kronberg, Udo

2017-03-01

Diverticular disease of the small intestine is rare, especially when it is located in the jejunum. It is generally asymptomatic, but in some patients it may have complications such as acute diverticulitis with peritonitis, gastrointestinal bleeding or obstruction. In such cases, the recommended treatment is surgery. We report a 77-year-old patient with ileal Crohn’s disease with a long-standing inflammatory phenotype, who developed acute diverticulitis of the jejunum presenting a severe septic shock and secondary multiple-organ failure. It resolved with medical treatment and prolonged antibiotic therapy.

Stricturoplasty-a bowel-sparing option for long segment small bowel Crohn's disease.

PubMed

Limmer, Alexandra M; Koh, Hoey C; Gilmore, Andrew

2017-08-01

Stricturoplasty is a surgical option for management of severe stricturing Crohn's disease of the small bowel. It avoids the need for small bowel resection and the associated metabolic complications. This report contrasts the indications and technical aspects of two different stricturoplasty techniques. Case 1 describes an extensive Michelassi (side-to-side isoperistaltic) stricturoplasty performed for a 100 cm segment of diseased small bowel in a 45-year-old patient. Case 2 describes the performance of 12 Heineke-Mikulicz stricturoplasties in a 23-year-old patient with multiple short fibrotic strictures.

Stricturoplasty—a bowel-sparing option for long segment small bowel Crohn's disease

PubMed Central

Koh, Hoey C.; Gilmore, Andrew

2017-01-01

Abstract Stricturoplasty is a surgical option for management of severe stricturing Crohn's disease of the small bowel. It avoids the need for small bowel resection and the associated metabolic complications. This report contrasts the indications and technical aspects of two different stricturoplasty techniques. Case 1 describes an extensive Michelassi (side-to-side isoperistaltic) stricturoplasty performed for a 100 cm segment of diseased small bowel in a 45-year-old patient. Case 2 describes the performance of 12 Heineke-Mikulicz stricturoplasties in a 23-year-old patient with multiple short fibrotic strictures. PMID:29423160

Accuracy of computed tomographic features in differentiating intestinal tuberculosis from Crohn's disease: a systematic review with meta-analysis.

PubMed

Kedia, Saurabh; Sharma, Raju; Sreenivas, Vishnubhatla; Madhusudhan, Kumble Seetharama; Sharma, Vishal; Bopanna, Sawan; Pratap Mouli, Venigalla; Dhingra, Rajan; Yadav, Dawesh Prakash; Makharia, Govind; Ahuja, Vineet

2017-04-01

Abdominal computed tomography (CT) can noninvasively image the entire gastrointestinal tract and assess extraintestinal features that are important in differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB). The present meta-analysis pooled the results of all studies on the role of CT abdomen in differentiating between CD and ITB. We searched PubMed and Embase for all publications in English that analyzed the features differentiating between CD and ITB on abdominal CT. The features included comb sign, necrotic lymph nodes, asymmetric bowel wall thickening, skip lesions, fibrofatty proliferation, mural stratification, ileocaecal area, long segment, and left colonic involvements. Sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio (DOR) were calculated for all the features. Symmetric receiver operating characteristic curve was plotted for features present in >3 studies. Heterogeneity and publication bias was assessed and sensitivity analysis was performed by excluding studies that compared features on conventional abdominal CT instead of CT enterography (CTE). We included 6 studies (4 CTE, 1 conventional abdominal CT, and 1 CTE+conventional abdominal CT) involving 417 and 195 patients with CD and ITB, respectively. Necrotic lymph nodes had the highest diagnostic accuracy (sensitivity, 23%; specificity, 100%; DOR, 30.2) for ITB diagnosis, and comb sign (sensitivity, 82%; specificity, 81%; DOR, 21.5) followed by skip lesions (sensitivity, 86%; specificity, 74%; DOR, 16.5) had the highest diagnostic accuracy for CD diagnosis. On sensitivity analysis, the diagnostic accuracy of other features excluding asymmetric bowel wall thickening remained similar. Necrotic lymph nodes and comb sign on abdominal CT had the best diagnostic accuracy in differentiating CD and ITB.

High Prevalence of Anal Canal High-Risk Human Papillomavirus Infection in Patients With Crohn's Disease.

PubMed

Vuitton, Lucine; Jacquin, Elise; Parmentier, Anne-Laure; Crochet, Elise; Fein, Francine; Dupont-Gossart, Anne-Claire; Plastaras, Laurianne; Bretagne, Charles-Henri; Mauny, Frédéric; Koch, Stéphane; Prétet, Jean-Luc; Mougin, Christiane; Valmary-Degano, Séverine

2018-03-15

The increasing incidence of anal canal carcinomas requires better knowledge on anal human papillomavirus (HPV) infection. We aimed to assess anal canal HPV infection prevalence and risk factors among patients seen at a gastroenterology department in France. We analyzed anal tissue samples collected from 469 consecutive patients (median age 54 years, 52% women), including 112 who received immunosuppressant therapies and 101 with inflammatory bowel disease (70 with Crohn's disease), who underwent colonoscopy examinations from April 1, 2012 to April 30, 2015. HPV was detected and genotyped using the INNO-LiPA assay, and we collected medical and demographic data from all subjects. Risk factors for any HPV, high-risk HPV (HR-HPV) and HPV16 infection were assessed by bivariate and multivariate analysis. The primary outcomes association of HR-HPV or HPV16 with medical and demographic features. We detected HPV DNA in anal tissues from 34% of the subjects and HR-HPV in 18%. HPV16 was the most prevalent genotype (detected in 7%), followed by HPV51, HPV52, and HPV39. HR-HPV was detected in a significantly higher proportion of samples from women (23.1%) than men (12.8%) (P = .0035); HR-HPV and HPV16 were detected in a significantly higher proportion of patients with Crohn's disease (30.0%) than without (18.1%) (P = .005). Female sex, history of sexually transmitted disease, lifetime and past year-number of sexual partners, active smoking, and immunosuppressive therapies were independent risk factors for anal HR-HPV infection in multivariate analysis. One third of patients who underwent colonoscopy at a gastroenterology department were found to have anal canal HPV infection. We detected HR-HPV infection in almost 20% of patients and in a significantly higher proportion of patients with Crohn's disease than without. Increasing our knowledge of HPV infection of anal tissues could help physicians identify populations at risk and promote prophylaxis with vaccination and adequate

[Postoperative recurrence of Crohn's disease, and its prevention].

PubMed

Lakatos, László; Lakatos, Péter László

2010-05-23

Crohn's disease is a chronic, progressive disabling condition ultimately leading to stricturing and/or penetrating complications. The need for surgery may be as high as 70% in patients with severe active disease or complications. However, relapse may develop in a significant proportion of the patients after surgery leading to frequent re-operations. Despite emerging data, postoperative prevention is still controversial. After careful evaluation of the individual risk a tailored therapy should be considered. In patients with small risk for relapse mesalazine or in selected cases no-treatment may be an option. In patients with a moderate-to-high risk azathioprine should be considered together with metronidazole in the three months. Follow-up ileocolonoscopy 6-12 months after the surgery is helpful in the determination of endoscopic severity and may assist in the optimization of the therapy. In most severe cases anti-TNF agents may be appropriate for postoperative prevention and therapy.

The assessment of online heath videos for surgery in Crohn's Disease.

PubMed

Marshall, J H; Baker, D M; Lee, M J; Jones, G L; Lobo, A J; Brown, S R

2018-02-10

YouTube ™ is an open-access, non-peer reviewed video-hosting site and is used as a source of publicly available healthcare information. This study aimed to assess the thematic content of the most viewed videos relating to surgery and Crohn's Disease and to explore the viewer interactions to these videos. A search of YouTube ™ was carried out using one search string. The 50 most viewed videos were identified and categorised by source, content themes and assessed for viewer interactions. Video comments were used to describe the usefulness of the video content to viewers. The majority of videos were uploaded by patients (n=21).The remainder were uploaded by individual health care professionals (n=9), hospital/speciality associations (n=18) and industry (n=2). The median number of likes for patient videos was significantly higher than hospital/speciality association videos (p=<0.001). Patient videos received more comments praising the video content(n=27), and more comments asking for further information (n=14). The median number of likes for 'experience of surgery' (p=<0.001) and 'experience ofdisease' (p=0.0015) themed videos, were significantly higher than 'disease management' themed videos. Crohn's disease patients use YouTube ™ as a surgical information source. The content of patient sourced videos focused on surgical and disease experience, suggesting these themes are important to patients.Current patient developed videos provide limited information, as reflected by viewers requesting further information. Storytelling patient-centred videos combined with clinical evidence may be a good model for future videos. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming

PubMed Central

Spitler, Kathryn M.; Ponce, Jessica M.; Oudit, Gavin Y.; Hall, Duane D.

2017-01-01

The mediator complex, a multisubunit nuclear complex, plays an integral role in regulating gene expression by acting as a bridge between transcription factors and RNA polymerase II. Genetic deletion of mediator subunit 1 (Med1) results in embryonic lethality, due in large part to impaired cardiac development. We first established that Med1 is dynamically expressed in cardiac development and disease, with marked upregulation of Med1 in both human and murine failing hearts. To determine if Med1 deficiency protects against cardiac stress, we generated two cardiac-specific Med1 knockout mouse models in which Med1 is conditionally deleted (Med1cKO mice) or inducibly deleted in adult mice (Med1cKO-MCM mice). In both models, cardiac deletion of Med1 resulted in early lethality accompanied by pronounced changes in cardiac function, including left ventricular dilation, decreased ejection fraction, and pathological structural remodeling. We next defined how Med1 deficiency alters the cardiac transcriptional profile using RNA-sequencing analysis. Med1cKO mice demonstrated significant dysregulation of genes related to cardiac metabolism, in particular genes that are coordinated by the transcription factors Pgc1α, Pparα, and Errα. Consistent with the roles of these transcription factors in regulation of mitochondrial genes, we observed significant alterations in mitochondrial size, mitochondrial gene expression, complex activity, and electron transport chain expression under Med1 deficiency. Taken together, these data identify Med1 as an important regulator of vital cardiac gene expression and maintenance of normal heart function. NEW & NOTEWORTHY Disruption of transcriptional gene expression is a hallmark of dilated cardiomyopathy; however, its etiology is not well understood. Cardiac-specific deletion of the transcriptional coactivator mediator subunit 1 (Med1) results in dilated cardiomyopathy, decreased cardiac function, and lethality. Med1 deletion disrupted cardiac

Treatment Perspectives in Crohn's Disease.

PubMed

Vetter, Marcel; Neurath, Markus F

2018-06-05

Crohn's disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy. © 2018 S. Karger AG, Basel.

Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn's disease: changes following treatment with immunomodulators and/or anti-TNF antibodies.

PubMed

Moreno, Nadia; Ripollés, Tomás; Paredes, José María; Ortiz, Inmaculada; Martínez, María Jesús; López, Antonio; Delgado, Fructuoso; Moreno-Osset, Eduardo

2014-09-01

The objective of this study was to analyze the accuracy of abdominal ultrasonography (AUS) in the assessment of mucosal healing in patients with Crohn's disease (CD) receiving immunomodulators and/or biological treatment, with ileocolonoscopy as the reference standard. Thirty patients were included in a prospective longitudinal study. All patients underwent ileocolonoscopy and AUS before and after a minimum of one year of treatment. The Crohn's Disease Endoscopic Inflammatory Index of Severity (CDEIS) was used for endoscopic assessment whereas AUS was analyzed by means of bowel wall thickness, color Doppler grade and percentage of increase of parietal enhancement after contrast injection. In the segmental analysis, endoscopic healing was found in 71.2% of the segments and AUS findings were normalized in 62.8%, with a significant correlation between the two techniques (κ=0.76, p<0.001). In the overall assessment performed after treatment, 18 (60%) patients exhibited endoscopic remission (CDEIS <6 points); of these patients, 15 (83.3%) had normalized sonographic findings, with a good correlation between endoscopic remission and sonographic normalization (κ=0.73, p<0.001). Of the three variables assessed by AUS, parietal thickness was the best variable to predict mucosal healing in both analyses, segmental and global. Abdominal ultrasonography is a useful and reliable technique for the assessment of the endoscopic response to treatment with immunomodulators and/or biological drugs in Crohn's disease. AUS is a highly accurate technique for evaluating the healing of the intestinal mucosa. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Thalidomide reduces tumour necrosis factor α and interleukin 12 production in patients with chronic active Crohn's disease

PubMed Central

Bauditz, J; Wedel, S; Lochs, H

2002-01-01

Background: Thalidomide improves clinical symptoms in patients with therapy refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor α (TNF-α) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. Aim: The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). Methods: Ten patients with therapy refractory IBD (nine Crohn's disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-α, interleukin (IL)-1β, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. Results: Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-α and IL-12 decreased during treatment with thalidomide: LPMC (TNF-α: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-α: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1β and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-α and IL-12 production. Conclusion: The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-α and IL-12. PMID:11788559

The Value of Vedolizumab as Rescue Therapy in Moderate-Severe Crohn's Disease Patients with Adalimumab Non-response in the USA.

PubMed

Erim, Daniel O; Mahendraratnam, Nirosha; Okafor, Phillip N; Wheeler, Stephanie B

2015-08-01

In May 2014, vedolizumab was approved by the Food and Drug Administration for the treatment of moderate-to-severe Crohn's disease. In clinical practice it is typically used in patients who are primary or secondary non-responders to adalimumab [Humira]. We aim to estimate the incremental benefits and costs of using vedolizumab as rescue therapy for adalimumab non-responders. A Markov model was used to simulate the clinical course of Crohn's disease in a hypothetical cohort of 10,000 patients over a 12-month period. The treatment strategies evaluated were adalimumab only [with and without dose intensification] and adalimumab and vedolizumab [with and without adalimumab dose intensification]. The base case strategy was adalimumab only with 25% of non-responders undergoing dose intensification. Our primary outcomes were changes in costs and quality of life measures over the analytical horizon. In a 1-year period, initiating vedolizumab as rescue therapy in adalimumab non-responders reduces the average total cost per patient by 10%, and increases the average amount of time spent in remission or mild disease by up to 2 months. Treating on-label adalimumab non-responders with vedolizumab can, in the short term, significantly improves the quality of life of Crohn's disease patients that do not respond to adalimumab. 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 prospective evaluation of the ligation of the intersphincteric tract procedure for complex anal fistula in patients with Crohn's disease.

PubMed

Gingold, Daniel S; Murrell, Zuri A; Fleshner, Phillip R

2014-12-01

To evaluate 2- and 12-month outcomes after ligation of the intersphincteric fistula tract (LIFT) in Crohn's disease (CD). Surgical approaches to perianal fistulas in CD are frequently ineffective and hampered by concerns over adequate wound healing and sphincter injury. The efficacy of LIFT in CD patients is unknown. Consecutive cases of CD patients with transsphincteric fistulas were prospectively analyzed. Fistula healing and 2 validated quality-of-life indices were assessed. Fifteen CD patients (9 women; mean age = 34.8 years) were identified. Location of the fistula was lateral (n = 10; 67%) or midline (n = 5; 33%). LIFT site healing was seen in 9 patients (60%) at 2-month follow-up. No patient developed fecal incontinence. LIFT site healing was seen in 8 of the 12 patients (67%) with complete 12-month follow-up. Significant factors for long-term LIFT site healing were lateral versus midline location (P = 0.02) and longer mean fistula length (P = 0.02). Patients who had successful operations significantly improved both their mean Wexner Perianal Crohn's Disease Activity Index and McMaster Perianal Crohn's Disease Activity Index quality-of-life scores at 2-month follow-up (14.0-3.8, P = 0.001, and 10.4-1.8, P = 0.0001, respectively). CD-associated anal fistulas may be treated with LIFT. This surgical procedure is a safe, outpatient procedure that minimizes both perianal wound creation and sphincter injury.

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy

PubMed Central

Li, Chao; Vu, Kent; Hazelgrove, Krystina

2015-01-01

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. PMID:26428636

Increased IGF-IEc expression and mechano-growth factor production in intestinal muscle of fibrostenotic Crohn's disease and smooth muscle hypertrophy.

PubMed

Li, Chao; Vu, Kent; Hazelgrove, Krystina; Kuemmerle, John F

2015-12-01

The igf1 gene is alternatively spliced as IGF-IEa and IGF-IEc variants in humans. In fibrostenotic Crohn's disease, the fibrogenic cytokine TGF-β1 induces IGF-IEa expression and IGF-I production in intestinal smooth muscle and results in muscle hyperplasia and collagen I production that contribute to stricture formation. Mechano-growth factor (MGF) derived from IGF-IEc induces skeletal and cardiac muscle hypertrophy following stress. We hypothesized that increased IGF-IEc expression and MGF production mediated smooth muscle hypertrophy also characteristic of fibrostenotic Crohn's disease. IGF-IEc transcripts and MGF protein were increased in muscle cells isolated from fibrostenotic intestine under regulation by endogenous TGF-β1. Erk5 and MEF2C were phosphorylated in vivo in fibrostenotic muscle; both were phosphorylated and colocalized to nucleus in response to synthetic MGF in vitro. Smooth muscle-specific protein expression of α-smooth muscle actin, γ-smooth muscle actin, and smoothelin was increased in affected intestine. Erk5 inhibition or MEF2C siRNA blocked smooth muscle-specific gene expression and hypertrophy induced by synthetic MGF. Conditioned media of cultured fibrostenotic muscle induced muscle hypertrophy that was inhibited by immunoneutralization of endogenous MGF or pro-IGF-IEc. The results indicate that TGF-β1-dependent IGF-IEc expression and MGF production in patients with fibrostenotic Crohn's disease regulates smooth muscle cell hypertrophy a critical factor that contributes to intestinal stricture formation. Copyright © 2015 the American Physiological Society.

The alternate effects of anti-TNFα therapeutics and their role in mycobacterial granulomatous infection in Crohn's disease.

PubMed

Qasem, Ahmad; Naser, Abed Elrahman; Naser, Saleh A

2017-07-01

Crohn's disease is an inflammatory bowel disease that has been debated to be associated with bacterial triggers such as Mycobacterium avium subspecies paratuberculosis (MAP). Standard treatment of Crohn's disease (CD) patients includes a family of immunomodulators and biologics such as Anti-Tumor Necrosis Factor alpha (Anti-TNFα). This cytokine in particular has been known to play vital roles in fighting microbial infections through formation and maintenance of granulomas. Areas covered: This perspective is focused on elucidating the negative effects of using Anti-TNFα therapeutic agents as a treatment option in CD patients who are more likely suspected to have MAP infection, and the role of other immunomodulators in MAP infection. Expert commentary: While treatment with Anti-TNFα is beneficial to reduce inflammation and to provide short term relief to the patients, it also compromises the immune system causing susceptibility to microbial infection. More than 50% of CD patients have shown no response to Anti-TNFα treatment which indicates a demand for introducing novel CD treatment in combination with antibiotics as a future CD treatment plan.

Semiautomatic Assessment of the Terminal Ileum and Colon in Patients with Crohn Disease Using MRI (the VIGOR++ Project).

PubMed

Puylaert, Carl A J; Schüffler, Peter J; Naziroglu, Robiel E; Tielbeek, Jeroen A W; Li, Zhang; Makanyanga, Jesica C; Tutein Nolthenius, Charlotte J; Nio, C Yung; Pendsé, Douglas A; Menys, Alex; Ponsioen, Cyriel Y; Atkinson, David; Forbes, Alastair; Buhmann, Joachim M; Fuchs, Thomas J; Hatzakis, Haralambos; van Vliet, Lucas J; Stoker, Jaap; Taylor, Stuart A; Vos, Frans M

2018-02-07

The objective of this study was to develop and validate a predictive magnetic resonance imaging (MRI) activity score for ileocolonic Crohn disease activity based on both subjective and semiautomatic MRI features. An MRI activity score (the "virtual gastrointestinal tract [VIGOR]" score) was developed from 27 validated magnetic resonance enterography datasets, including subjective radiologist observation of mural T2 signal and semiautomatic measurements of bowel wall thickness, excess volume, and dynamic contrast enhancement (initial slope of increase). A second subjective score was developed based on only radiologist observations. For validation, two observers applied both scores and three existing scores to a prospective dataset of 106 patients (59 women, median age 33) with known Crohn disease, using the endoscopic Crohn's Disease Endoscopic Index of Severity (CDEIS) as a reference standard. The VIGOR score (17.1 × initial slope of increase + 0.2 × excess volume + 2.3 × mural T2) and other activity scores all had comparable correlation to the CDEIS scores (observer 1: r = 0.58 and 0.59, and observer 2: r = 0.34-0.40 and 0.43-0.51, respectively). The VIGOR score, however, improved interobserver agreement compared to the other activity scores (intraclass correlation coefficient = 0.81 vs 0.44-0.59). A diagnostic accuracy of 80%-81% was seen for the VIGOR score, similar to the other scores. The VIGOR score achieves comparable accuracy to conventional MRI activity scores, but with significantly improved reproducibility, favoring its use for disease monitoring and therapy evaluation. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Smoking does influence disease behaviour and impacts the need for therapy in Crohn's disease in the biologic era.

PubMed

Nunes, T; Etchevers, M J; Domènech, E; García-Sánchez, V; Ber, Y; Peñalva, M; Merino, O; Nos, P; Garcia-Planella, E; Casbas, A G; Esteve, M; Taxonera Samsó, C; Montoro Huguet, M; Gisbert, J P; Martín Arranz, M D; García-Sepulcre, M F; Barreiro-de Acosta, M; Beltrán, B; Alcaide Suárez, N; Saro Gismera, C; Cabriada, J L; Cañas-Ventura, A; Gomollón, F; Panés, J

2013-10-01

Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers. © 2013 John Wiley & Sons Ltd.

Patients with Crohn's Disease Are More Likely to Remain on Biologics than Immunomodulators: A Meta-Analysis of Treatment Durability.

PubMed

Shah, Eric D; Siegel, Corey A; Chong, Kelly; Melmed, Gil Y

2015-08-01

The comparative effectiveness of treatments for moderate-to-severe Crohn's disease can be influenced by the likelihood of remaining on medication. We aimed to clarify this treatment durability by assessing subject discontinuations from clinical trials in the context of treatment efficacy. We conducted a literature search for double-blind RCT of Crohn's disease therapies recommended in international guidelines or with recent positive phase III trial results. Durability was defined through study discontinuation due to adverse events or disease exacerbation represented by number needed to discontinue (NND). Efficacy was defined as clinical remission represented by number needed to treat (NNT). The primary endpoint was NND/NNT, with a higher value representing more durable and effective treatment. Treatment with azathioprine/6-mercaptopurine (AZA/6MP) was associated with more discontinuations than with clinical remission (NND/NNT = 0.92) in maintenance trials. For induction, methotrexate was associated with similar rates of discontinuations and remission (NND/NNT = 1.4). In one maintenance trial, the remission rate for methotrexate was greater than the study discontinuation rate (NND/NNT = 23.3). In contrast, anti-TNF trials revealed greater durability among induction (no excess discontinuation) and maintenance (NND/NNT = 37.9) trials. Trials of anti-trafficking agents had fewer discontinuations in the drug treatment arms than placebo resulting in most favorable NND/NNT ratios. For patients with Crohn's disease, biologic therapies had higher durability than immunomodulators for induction and maintenance therapy. We also report the results of a novel NND/NNT ratio that should be validated in a prospective head-to-head placebo-controlled trial.

OvidSP Medline-to-PubMed search filter translation: a methodology for extending search filter range to include PubMed's unique content

PubMed Central

2013-01-01

Background PubMed translations of OvidSP Medline search filters offer searchers improved ease of access. They may also facilitate access to PubMed’s unique content, including citations for the most recently published biomedical evidence. Retrieving this content requires a search strategy comprising natural language terms (‘textwords’), rather than Medical Subject Headings (MeSH). We describe a reproducible methodology that uses a validated PubMed search filter translation to create a textword-only strategy to extend retrieval to PubMed’s unique heart failure literature. Methods We translated an OvidSP Medline heart failure search filter for PubMed and established version equivalence in terms of indexed literature retrieval. The PubMed version was then run within PubMed to identify citations retrieved by the filter’s MeSH terms (Heart failure, Left ventricular dysfunction, and Cardiomyopathy). It was then rerun with the same MeSH terms restricted to searching on title and abstract fields (i.e. as ‘textwords’). Citations retrieved by the MeSH search but not the textword search were isolated. Frequency analysis of their titles/abstracts identified natural language alternatives for those MeSH terms that performed less effectively as textwords. These terms were tested in combination to determine the best performing search string for reclaiming this ‘lost set’. This string, restricted to searching on PubMed’s unique content, was then combined with the validated PubMed translation to extend the filter’s performance in this database. Results The PubMed heart failure filter retrieved 6829 citations. Of these, 834 (12%) failed to be retrieved when MeSH terms were converted to textwords. Frequency analysis of the 834 citations identified five high frequency natural language alternatives that could improve retrieval of this set (cardiac failure, cardiac resynchronization, left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and

DynaMed Plus®: An Evidence-Based Clinical Reference Resource.

PubMed

Charbonneau, Deborah H; James, LaTeesa N

2018-01-01

DynaMed Plus ® from EBSCO Health is an evidence-based tool that health professionals can use to inform clinical care. DynaMed Plus content undergoes a review process, and the evidence is synthesized in detailed topic overviews. A unique three-level rating scale is used to assess the quality of available evidence. Topic overviews summarize current evidence and provide recommendations to support health providers at the point-of-care. Additionally, DynaMed Plus content can be accessed via a desktop computer or mobile platforms. Given this, DynaMed Plus can be a time-saving resource for health providers. Overall, DynaMed Plus provides evidence summaries using an easy-to-read bullet format, and the resource incorporates images, clinical calculators, patient handouts, and practice guidelines in one place.

PubMed Interact: an Interactive Search Application for MEDLINE/PubMed

PubMed Central

Muin, Michael; Fontelo, Paul; Ackerman, Michael

2006-01-01

Online search and retrieval systems are important resources for medical literature research. Progressive Web 2.0 technologies provide opportunities to improve search strategies and user experience. Using PHP, Document Object Model (DOM) manipulation and Asynchronous JavaScript and XML (Ajax), PubMed Interact allows greater functionality so users can refine search parameters with ease and interact with the search results to retrieve and display relevant information and related articles. PMID:17238658

Comparison of PubMed and Google Scholar literature searches.

PubMed

Anders, Michael E; Evans, Dennis P

2010-05-01

Literature searches are essential to evidence-based respiratory care. To conduct literature searches, respiratory therapists rely on search engines to retrieve information, but there is a dearth of literature on the comparative efficiencies of search engines for researching clinical questions in respiratory care. To compare PubMed and Google Scholar search results for clinical topics in respiratory care to that of a benchmark. We performed literature searches with PubMed and Google Scholar, on 3 clinical topics. In PubMed we used the Clinical Queries search filter. In Google Scholar we used the search filters in the Advanced Scholar Search option. We used the reference list of a related Cochrane Collaboration evidence-based systematic review as the benchmark for each of the search results. We calculated recall (sensitivity) and precision (positive predictive value) with 2 x 2 contingency tables. We compared the results with the chi-square test of independence and Fisher's exact test. PubMed and Google Scholar had similar recall for both overall search results (71% vs 69%) and full-text results (43% vs 51%). PubMed had better precision than Google Scholar for both overall search results (13% vs 0.07%, P < .001) and full-text results (8% vs 0.05%, P < .001). Our results suggest that PubMed searches with the Clinical Queries filter are more precise than with the Advanced Scholar Search in Google Scholar for respiratory care topics. PubMed appears to be more practical to conduct efficient, valid searches for informing evidence-based patient-care protocols, for guiding the care of individual patients, and for educational purposes.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

PubMed

Juillerat, Pascal; Pittet, Valérie; Mottet, Christian; Felley, Christian; Gonvers, Jean-Jacques; Vader, John-Paul; Burnand, Bernard; Froehlich, Florian; Wolters, Frank L; Stockbrügger, Reinhold W; Michetti, Pierre

2010-12-01

The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

Associations between PTPN2 polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis.

PubMed

Zhang, Ji-Xiang; He, Jian-Hua; Wang, Jun; Song, Jia; Lei, Hong-Bo; Wang, Jing; Dong, Wei-Guo

2014-01-01

Ulcerative colitis (UC) and Crohn's disease (CD) result from an interaction between genetic and environmental factors. Though several polymorphisms have been identified in PTPN2, their roles in the incidence of UC and CD are conflicting. This meta-analysis was aimed to clarify the impact of these polymorphisms on UC and CD risk. PubMed, EMBASE, Cochrane Library and CBM were searched until 23 July 2013 for eligible studies on three PTPN2 polymorphisms: rs2542151, rs1893217 and rs7234029. Data were extracted, and pooled odd ratios (ORs) as well as 95 % confidence intervals (95 % CIs) were calculated. The meta-analysis indicated that rs2542151, rs1893217 and rs1893217 were associated with increased CD risk, while the former was associated with increased UC risk. The differences in age of onset and ethnic groups may influence the associations. Gene-gene and gene-environment interactions should be investigated in the future. Seventeen studies with 18,308 cases and 20,406 controls were included. Significant associations were found between rs2542151 polymorphism and CD susceptibility (OR = 1.22, 95 % CI, 1.15-1.30, I (2) = 32 %), as well as between rs2542151 and UC susceptibility (OR = 1.16, 95 % CI, 1.07-1.25, I (2) = 39 %). A similar result was found in Caucasians, but not in Asians. Moreover, a significant increase in CD risk for all carriers of the minor allele of rs1893217 (OR = 1.45, 95 % CI, 1.23-1.70, I (2) = 0 %) and rs7234029 (OR = 1.36, 95 % CI, 1.16-1.59, I (2) = 0 %) were found. For children, the rs1893217 polymorphism appeared to confer susceptibility to CD (OR = 1.56, 95 % CI, 1.28-1.89, I (2) = 0 %).

An unusual cutaneous manifestation of Crohn's disease.

PubMed

Weiser, Jessica A; Markowitz, David M; Husain, Sameera; Grossman, Marc E

2011-01-01

A 61-year-old man with a 12-year history of quiescent Crohn's disease on mesalamine presented to his gastroenterologist in April 2009, complaining of abdominal cramping, diarrhea, and a 25-lb weight loss over 6 weeks. He did not respond to prednisone 50 mg and 6-mercaptopurine 100 mg daily. Abdominal computed tomography findings revealed diffuse submucosal edema consistent with extensive colitis. Colonoscopy demonstrated diffuse inflammation with erythema, friability, and shallow ulcerations in the rectum and colon. Biopsies were consistent with Crohn's colitis. He was admitted for infliximab infusion for his unremitting diarrhea. Five days before admission, the patient noted mild swelling and redness of the left lower eyelid, which progressed to involve the right lower eyelid with frank pus draining from both eyes. He had no visual impairment or eye pain. Two days before admission, an ophthalmologist prescribed a steroid eyedrop with no relief. He also complained of seropurulent painful skin lesions on his face and scalp, which spread to involve his upper trunk and proximal arms. On admission to the hospital, dermatology, ophthalmology, and infectious disease consultations were obtained to rule out disseminated infection before initiation of infliximab therapy. The patient was afebrile and hemodynamically stable. His oral mucosa was normal. He had prominent bilateral lower eyelid edema, erythema, and superficial erosions with hemorrhagic crusting and frank green purulent drainage from both eyes, with crusting along the lower lash line and bilateral sclera injection (Figure 1). On his scalp, face, trunk, and proximal extremities, he had 25 to 30 erythematous, 4- to 8-mm papulopustules with narrow red halos, some with central necrosis and crusting (Figure 2). Cultures from the purulent ocular drainage and pustules on the trunk and arms were all negative for bacteria, virus, and fungi. Gram stain from the eye drainage showed polymorphonuclear leukocytes without

LactMed: New NLM Database on Drugs and Lactation

MedlinePlus

... Issues Research News From NIH LactMed: New NLM Database on Drugs and Lactation Past Issues / Summer 2006 ... Javascript on. Photo: Comstock LactMed, a free online database with information on drugs and lactation, is one ...

Telocytes in Crohn's disease.

PubMed

Milia, Anna Franca; Ruffo, Martina; Manetti, Mirko; Rosa, Irene; Conte, Dalila; Fazi, Marilena; Messerini, Luca; Ibba-Manneschi, Lidia

2013-12-01

Crohn's disease (CD) is a relapsing chronic inflammatory disorder that may involve all the gastrointestinal tract with a prevalence of terminal ileum. Intestinal lesions have a characteristic discontinuous and segmental distribution and may affect all layers of the gut wall. Telocytes (TC), a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including gastrointestinal tract of humans and mammals. Several roles have been proposed for TC, including mechanical support, spatial relationships with different cell types, intercellular signalling and modulation of intestinal motility. The aim of our study was to investigate the presence and distribution of TC in disease-affected and -unaffected ileal specimens from CD patients compared with controls. TC were identified by CD34/PDGFRα immunohistochemistry. In affected CD specimens TC disappeared, particularly where fibrosis and architectural derangement of the intestinal wall were observed. In the thickened muscularis mucosae and submucosa, few TC entrapped in the fibrotic extracellular matrix were found. A discontinuous network of TC was present around smooth muscle bundles, ganglia and enteric strands in the altered muscularis propria. At the myenteric plexus, the loss of TC network was paralleled by the loss of interstitial cells of Cajal network. In the unaffected CD specimens, TC were preserved in their distribution. Our results suggest that in CD the loss of TC might have important pathophysiological implications contributing to the architectural derangement of the intestinal wall and gut dysmotility. Further functional studies are necessary to better clarify the role of TC loss in CD pathophysiology. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

MedlinePlus FAQ: MedlinePlus and MEDLINE/PubMed

MedlinePlus

... What is the difference between MedlinePlus and MEDLINE/PubMed? To use the sharing features on this page, ... latest health professional articles on your topic. MEDLINE/PubMed: Is a database of professional biomedical literature Is ...

Prospective cohort study of ultrasound-ultrasound and ultrasound-MR enterography agreement in the evaluation of pediatric small bowel Crohn disease.

PubMed

Dillman, Jonathan R; Smith, Ethan A; Sanchez, Ramon; DiPietro, Michael A; Dehkordy, Soudabeh Fazeli; Adler, Jeremy; DeMatos-Maillard, Vera; Khalatbari, Shokoufeh; Davenport, Matthew S

2016-04-01

There is a paucity of published literature describing ultrasound (US)-US and US-MR enterography (MRE) inter-radiologist agreement in pediatric small bowel Crohn disease. To prospectively assess US-US and US-MRE inter-radiologist agreement in pediatric small bowel Crohn disease. Institutional Review Board approval and informed consent/assent were obtained for this HIPAA-compliant prospective cohort study of children with newly diagnosed distal small bowel Crohn disease (July 2012 to December 2014). Enrolled subjects (n = 29) underwent two small bowel US examinations performed by blinded independent radiologists both before and at multiple time points after initiation of medical therapy (231 unique US examinations, in total); 134 US examinations were associated with concurrent MRE. The MRE examination was interpreted by a third blinded radiologist. The following was documented on each examination: involved length of ileum (cm); maximum bowel wall thickness (mm); amount of bowel wall and mesenteric Doppler signal, and presence of stricture, penetrating disease and/or abscess. Inter-radiologist agreement was assessed with single-measure, three-way, mixed-model intra-class correlation coefficients (ICC) and prevalence-adjusted, bias-adjusted kappa statistics (κ). Numbers in brackets are 95% confidence intervals. Ultrasound-US agreement was moderate for involved length (ICC: 0.41 [0.35-0.49]); substantial for maximum bowel wall thickness (ICC: 0.67 [0.64-0.70]); moderate for bowel wall Doppler signal (ICC: 0.53 [0.48-0.59]); slight for mesenteric Doppler signal (ICC: 0.25 [0.18-0.42]), and moderate to almost perfect for stricture (κ: 0.54), penetrating disease (κ: 0.80), and abscess (κ: 0.96). US-MRE agreement was moderate for involved length (ICC: 0.42 [0.37-0.49]); substantial for maximum bowel wall thickness (ICC: 0.66 [0.65-0.69]), and substantial to almost perfect for stricture (κ: 0.61), penetrating disease (κ: 0.72) and abscess (κ: 0.88). Ultrasound

GOClonto: an ontological clustering approach for conceptualizing PubMed abstracts.

PubMed

Zheng, Hai-Tao; Borchert, Charles; Kim, Hong-Gee

2010-02-01

Concurrent with progress in biomedical sciences, an overwhelming of textual knowledge is accumulating in the biomedical literature. PubMed is the most comprehensive database collecting and managing biomedical literature. To help researchers easily understand collections of PubMed abstracts, numerous clustering methods have been proposed to group similar abstracts based on their shared features. However, most of these methods do not explore the semantic relationships among groupings of documents, which could help better illuminate the groupings of PubMed abstracts. To address this issue, we proposed an ontological clustering method called GOClonto for conceptualizing PubMed abstracts. GOClonto uses latent semantic analysis (LSA) and gene ontology (GO) to identify key gene-related concepts and their relationships as well as allocate PubMed abstracts based on these key gene-related concepts. Based on two PubMed abstract collections, the experimental results show that GOClonto is able to identify key gene-related concepts and outperforms the STC (suffix tree clustering) algorithm, the Lingo algorithm, the Fuzzy Ants algorithm, and the clustering based TRS (tolerance rough set) algorithm. Moreover, the two ontologies generated by GOClonto show significant informative conceptual structures.

Gingival enlargement unveiling Crohn's disease - A report of a rarefied case.

PubMed

Malathi, Krishnamurthi; Muthukumaraswamy, Arunachalam; Rajula, MariaAntony PremBlaisie; Arjun, Singh

2017-01-01

This article highlights a peculiar case of Crohn's disease (CD) with the primary presenting symptom as localized gingival overgrowth in the anterior region of maxilla. The patient underwent surgical treatment with external bevel gingivectomy procedure. Follow-up after 6 months revealed no recurrence. A final diagnosis of CD was made, after following histopathological evaluation of the gingival biopsy and other special investigations. It is thus crucial to associate the localized granulomatous gingival overgrowth to systemic signs of CD. Intraoral occurrence preceding intestinal involvement is very rare in CD with an incidence of about 8%-9% of patients. Therefore, precise diagnosis, treatment planning, and timely management are vital to the overall health and welfare of patients.

Adult attachment and early parental experiences in patients with Crohn's disease.

PubMed

Agostini, Alessandro; Rizzello, Fernando; Ravegnani, Gianni; Gionchetti, Paolo; Tambasco, Rosy; Straforini, Giulia; Ercolani, Mauro; Campieri, Massimo

2010-01-01

Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease. The relationship of attachment to the illness is considered to be bidirectional. The authors investigated aspects of this bidirectional relationship. A group of 102 patients with CD and 306 healthy subjects filled out the Attachment Style Questionnaire and the Parental Bonding Instrument. Patients with CD exhibit a predominantly insecure attachment and perceived their parents' behaviors as characterized by low maternal care and high paternal overprotection. The evaluation of attachment style and early parental experiences in patients with CD may shed light on the bidirectional relationship between attachment and illness. These findings may confirm the bidirectional relationship between insecure attachment and chronic illness.

Chronic granulomatous disease mimicking early-onset Crohn's disease with cutaneous manifestations.

PubMed

Barbato, Maria; Ragusa, Giovanni; Civitelli, Fortunata; Marcheggiano, Adriana; Di Nardo, Giovanni; Iacobini, Metello; Melengu, Taulant; Cucchiara, Salvatore; Duse, Marzia

2014-06-20

Chronic granulomatous disease is a rare inherited disorder of the innate immune system. In patients with a clinical history of recurrent or persistent infections, especially infections caused by uncommon species, chronic granulomatous disease should be considered. We report the case of a 5-year-old boy with a presumptive diagnosis of Crohn's disease with extraintestinal manifestations. Chronic granulomatous disease was suspected in this case after Serratia marcescens was isolated from a skin ulcer culture. Granulomas were confirmed on histology and chronic granulomatous disease was diagnosed. This case emphasizes the importance of high clinical suspicion of an alternative diagnosis of immune deficiency in patients with presumed inflammatory bowel disease and opportunistic infections, especially when disease occurs in early life.

Systematic review with network meta-analysis: comparative efficacy and safety of budesonide and mesalazine (mesalamine) for Crohn's disease.

PubMed

Moja, L; Danese, S; Fiorino, G; Del Giovane, C; Bonovas, S

2015-06-01

Budesonide and mesalazine (mesalamine) are commonly used in the medical management of patients with mild to moderate Crohn's disease. To assess their comparative efficacy and harm using the methodology of network meta-analysis. A comprehensive search of Medline, Embase, the Cochrane Library and ClinicalTrials.gov, through October 2014, was performed to identify randomised controlled trials (RCTs) that recruited adult patients with active or quiescent Crohn's disease, and compared budesonide or mesalazine with placebo, or against each other, or different dosing strategies of one drug. Twenty-five RCTs were combined using Bayesian network meta-analysis. Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval (CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top of the hierarchy of the competing treatments. For maintenance of remission, budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI, 1.05-2.75), being also at the best ranking position among all compared treatment strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo or budesonide, for induction or maintenance of remission) reached significance. The occurrence of withdrawals due to adverse events was not shown different between budesonide, mesalazine and placebo, in both the induction and maintenance phases. Budesonide, at the doses of 9 mg/day, or higher, for induction of remission in active mild or moderate Crohn's disease, and at 6 mg/day for maintenance of remission, appears to be the best treatment choice. © 2015 John Wiley & Sons Ltd.

Increase in bone mineral density in strictly treated Crohn's disease patients with concomitant calcium and vitamin D supplementation.

PubMed

Bakker, Sjoerd F; Dik, Vincent K; Witte, Birgit I; Lips, Paul; Roos, Jan C; Van Bodegraven, Adriaan A

2013-06-01

Decreased bone mineral density (BMD) is common in Crohn's disease (CD) patients. This paper reports on the prevalence of decreased BMD in a referral cohort study of CD-patients next to the change of BMD over time in relation with CD-associated clinical characteristics. 205 CD patients of a referral hospital were enrolled between January1998-January 2010 when measurement of BMD by dual X-ray absorptiometry (DXA) was available. Follow-up DXA scan was performed in subjects with known risk factors besides Crohn indicative for low BMD. Treatment of CD patients was according to a protocol which is comparable to the current (inter)national guidelines. In osteopenic patients, supplemental vitamin D (800 IU) and Calcium (500-1000 mg) were prescribed. Mean BMD at baseline was 0.97 ± 0.16 gram/cm(2) in lumbar spine and 0.87 ± 0.12 gram/cm(2) in the total hip. At baseline, higher age and low Body Mass Index (BMI), were negatively correlated with BMD. Eighty-four patients underwent a second BMD assessment with a median interval period of 4 years (IQR 3-6). A mean annual increase of +0.76% (95%CI: -2.63%; +3.87%) in lumbar spine and +0.43% (95%CI: -2.65% ; +1.11%) in total hip was observed. Higher age, male sex, low BMI, and a higher age at diagnosis of CD were associated with low BMD. Follow-up of BMD in CD patients showed a contraintuitive small increase of BMD at lumbar spine and total hip in CD patients only using supplemental vitamin D and calcium next to strict treatment of CD. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-12-01

Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS ® software. The PROSPERO registration number was CRD42016032606. Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Serum Adipocytokine Levels as Surrogate Markers for Disease Activity of Crohn's Disease.

PubMed

Kim, Su Hwan; Jang, Seung Hyeon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Kim, You Sun; Han, Dong Soo; Kim, Joo Sung

2017-05-01

Determining inflammatory activity is crucial for assessing disease activity and for tailoring therapy in patients with Crohn׳s disease (CD). This study aimed to evaluate adipocytokine levels in patients with CD and to determine whether they can serve as surrogate markers for disease activity. Serum samples and information regarding the clinical features of patients in the CD Network Project registry were collected from March 2009 to February 2012. Patients with CD and disease duration of at least 2 years were enrolled in this study. Fasting serum leptin, adiponectin, obestatin and ghrelin levels were measured, and their correlation with clinical features of the patients was analyzed. Serum adipocytokine levels were evaluated according to disease activity as determined by CD activity index score. A total of 153 patients with CD were included. Serum ghrelin levels negatively correlated with patient age (P = 0.041) and age at diagnosis (P = 0.017), and positively correlated with C-reactive protein (CRP) levels (P = 0.017). Multiple regression analysis showed that serum ghrelin levels were related only to CRP levels (P = 0.032). Like ghrelin, serum leptin levels were also related to CRP levels (P < 0.001). Obestatin and adiponectin levels were not related to CRP levels. Serum adipocytokine levels did not significantly differ across different disease locations or behaviors. Serum ghrelin levels were significantly lower in patients with CD with a history of surgery than in those without (P = 0.007). Serum ghrelin and leptin levels may be useful as surrogate markers for disease activity in patients with CD. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Readmission After Abdominal Surgery for Crohn's Disease: Identification of High-Risk Patients.

PubMed

Mege, Diane; Michelassi, Fabrizio

2018-05-16

Although many predictive factors for postoperative morbidity are known, few data are available about readmission after abdominal surgery for Crohn's disease (CD). The objective of this study is to identify predictive factors and high-risk patients for readmission after abdominal CD surgery. All patients who underwent abdominal surgery for CD in one tertiary referral center between January 2004 and December 2016 were included. Patients who required readmission and those without were compared. Perineal procedures, elective readmissions, and abdominal procedures for non-Crohn's indications were not included. Nine hundred eight abdominal procedures were performed in 712 patients. Readmission rates were 8, 8.5, 8.6, 8.8, and 8.9% at 30, 60, and 90 days and 12 and 60 months, respectively. The main reasons were wound infection (14%), deep abscess (13%), small-bowel obstruction (13%), and dehydration (11%). Eight (11%) patients required percutaneous drainage and 19 (27%) underwent an unplanned surgery. After multivariate analysis, three independent predictive factors for readmission were identified: older age (OR 1.02, 95%CI 1.005-1.04; p < 0.006), a history of previous proctectomy (OR 3, 95%CI 1.2-9, p < 0.02), and higher blood loss volume during surgery (OR 1.0001, 95%CI 1-1.002, p < 0.05). Readmission occurred in 8-9% of abdominal procedures for CD within 1-3 months after surgery and it required unplanned reoperation in a quarter of them. Identification of high-risk groups and knowledge of the more common postoperative complications requiring readmission help in increasing postoperative vigilance to select patients who may benefit from early interventions.

Inflammation-driven malnutrition: a new screening tool predicts outcome in Crohn's disease.

PubMed

Jansen, Irene; Prager, Matthias; Valentini, Luzia; Büning, Carsten

2016-09-01

Malnutrition is a frequent feature in Crohn's disease (CD), affects patient outcome and must be recognised. For chronic inflammatory diseases, recent guidelines recommend the development of combined malnutrition and inflammation risk scores. We aimed to design and evaluate a new screening tool that combines both malnutrition and inflammation parameters that might help predict clinical outcome. In a prospective cohort study, we examined fifty-five patients with CD in remission (Crohn's disease activity index (CDAI) <200) at 0 and 6 months. We assessed disease activity (CDAI, Harvey-Bradshaw index), inflammation (C-reactive protein (CRP), faecal calprotectin (FC)), malnutrition (BMI, subjective global assessment (SGA), serum albumin, handgrip strength), body composition (bioelectrical impedance analysis) and administered the newly developed 'Malnutrition Inflammation Risk Tool' (MIRT; containing BMI, unintentional weight loss over 3 months and CRP). All parameters were evaluated regarding their ability to predict disease outcome prospectively at 6 months. At baseline, more than one-third of patients showed elevated inflammatory markers despite clinical remission (36·4 % CRP ≥5 mg/l, 41·5 % FC ≥100 µg/g). Prevalence of malnutrition at baseline according to BMI, SGA and serum albumin was 2-16 %. At 6 months, MIRT significantly predicted outcome in numerous nutritional and clinical parameters (SGA, CD-related flares, hospitalisations and surgeries). In contrast, SGA, handgrip strength, BMI, albumin and body composition had no influence on the clinical course. The newly developed MIRT was found to reliably predict clinical outcome in CD patients. This screening tool might be used to facilitate clinical decision making, including treatment of both inflammation and malnutrition in order to prevent complications.

A comprehensive review and update on Crohn's disease.

PubMed

Gajendran, Mahesh; Loganathan, Priyadarshini; Catinella, Anthony P; Hashash, Jana G

2018-02-01

The term inflammatory bowel disease (IBD) refers principally to two major categories of chronic relapsing inflammatory intestinal disorders: Crohn's disease (CD) and ulcerative colitis (UC). In the United States, it is currently estimated that about 1.5 million people suffer from IBD, causing considerable suffering, mortality and economic loss every year. Yet the cause of IBD is unknown, and until we understand more, prevention or cure will not be possible. There is a lot of variation in the incidence and prevalence of CD based on geographic region, environment, immigrant population, and ethnic groups. The annual incidence of CD in North America is reported to be 3.1-20.2 per 100,000 with a prevalence of 201 per 100,000 population. Based on the epidemiological, genetic and immunological data, CD is considered to be a heterogeneous disorder with multifactorial etiology in which genetics and environment interact to manifest the disease. Several genes have been studied so for with respect to CD, but thus far the strong and replicated associations have been identified with NOD2, IL23R and ATG16L1 genes. The risk factors implicated with CD include smoking, low fiber- high carbohydrate diet, altered microbiome and medications such as non-steroidal anti-inflammatory drugs. CD is typically characterized by transmural inflammation of the intestine and could affect any part of the gastrointestinal tract from mouth to perianal area. In terms of distribution of the disease 25% of the patients have colitis only, 25% is ileitis only and 50% have ileocolitis. The Montreal classification is based on the age at diagnosis (<16, 17-40, > 40), disease location (Ileal, colonic, Ileocolonic) and the disease behavior (nonstricturing/nonpenetrating, stricturing, penetrating). The key features for diagnosing CD comprises a combination of radiographic, endoscopic and pathological findings demonstrating focal, asymmetric, transmural or granulomatous features. Abdominal Computed tomography

Concomitant Use of Immunomodulators Affects the Durability of Infliximab Therapy in Children With Crohn's Disease.

PubMed

Grossi, Victoria; Lerer, Trudy; Griffiths, Anne; LeLeiko, Neal; Cabrera, Jose; Otley, Anthony; Rick, James; Mack, David; Bousvaros, Athos; Rosh, Joel; Grossman, Andrew; Saeed, Shehzaad; Kay, Marsha; Boyle, Brendan; Oliva-Hemker, Maria; Keljo, David; Pfefferkorn, Marian; Faubion, William; Kappelman, Michael D; Sudel, Boris; Markowitz, James; Hyams, Jeffrey S

2015-10-01

It is important to determine the effects of immunomodulators on the ability of children to remain on infliximab therapy for Crohn's disease (durability of therapy), given the potential benefits and risks of concomitant therapy-especially with thiopurines in male patients. We investigated how immunomodulatory treatment affects the durability of infliximab therapy. We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group Registry, from January 2002 through August 2014, on 502 children with Crohn's disease who participated in a prospective multicenter study. Data were collected from patients who received at least a 3-dose induction regimen of infliximab, and their concomitant use of immunomodulators: no thiopurine or methotrexate treatment, treatment for 6 months or less during infliximab therapy, or treatment for more than 6 months during infliximab therapy. The probabilities (± standard error) that children remained on infliximab therapy for 1 year, 3 years, and 5 years after the treatment began were 0.84 ± 0.02, 0.69 ± 0.03, and 0.60 ± 0.03, respectively. Age, sex, and disease extent or location did not affect the durability of infliximab therapy. Greater length of concomitant use of immunomodulators was associated with increased time of infliximab therapy. The probability that patients with more than 6 months of immunomodulator use remained on infliximab therapy for 5 years was 0.70 ± 0.04, compared with 0.48 ± 0.08 for patients who did not receive immunomodulators and 0.55 ± 0.06 for patients who received immunomodulators for 6 months or less (P < .001). In boys who received immunomodulators for 6 months or more after starting infliximab, the overall durability of infliximab therapy was greater among patients receiving methotrexate than thiopurine (P < .01); the probabilities that they remained on infliximab therapy for 5 years were 0.97 ± 0.03 vs 0.58 ± 0.08, respectively. In children with Crohn's disease, concomitant

Crohn disease: a current perspective on genetics, autophagy and immunity.

PubMed

Stappenbeck, Thaddeus S; Rioux, John D; Mizoguchi, Atsushi; Saitoh, Tatsuya; Huett, Alan; Darfeuille-Michaud, Arlette; Wileman, Tom; Mizushima, Noboru; Carding, Simon; Akira, Shizuo; Parkes, Miles; Xavier, Ramnik J

2011-04-01

Crohn disease (CD) is a chronic and debilitating inflammatory condition of the gastrointestinal tract. Prevalence in Western populations is 100-150/100,000 and somewhat higher in Ashkenazi Jews. Peak incidence is in early adult life, although any age can be affected and a majority of affected individuals progress to relapsing and chronic disease. Medical treatments rely significantly on empirical corticosteroid therapy and immunosuppression, and intestinal resectional surgery is frequently required. Thus, 80% of patients with CD come to surgery for refractory disease or complications. It is hoped that an improved understanding of pathogenic mechanisms, for example by studying the genetic basis of CD and other forms of inflammatory bowel diseases (IBD), will lead to improved therapies and possibly preventative strategies in individuals identified as being at risk.

Understanding PubMed user search behavior through log analysis.

PubMed

Islamaj Dogan, Rezarta; Murray, G Craig; Névéol, Aurélie; Lu, Zhiyong

2009-01-01

This article reports on a detailed investigation of PubMed users' needs and behavior as a step toward improving biomedical information retrieval. PubMed is providing free service to researchers with access to more than 19 million citations for biomedical articles from MEDLINE and life science journals. It is accessed by millions of users each day. Efficient search tools are crucial for biomedical researchers to keep abreast of the biomedical literature relating to their own research. This study provides insight into PubMed users' needs and their behavior. This investigation was conducted through the analysis of one month of log data, consisting of more than 23 million user sessions and more than 58 million user queries. Multiple aspects of users' interactions with PubMed are characterized in detail with evidence from these logs. Despite having many features in common with general Web searches, biomedical information searches have unique characteristics that are made evident in this study. PubMed users are more persistent in seeking information and they reformulate queries often. The three most frequent types of search are search by author name, search by gene/protein, and search by disease. Use of abbreviation in queries is very frequent. Factors such as result set size influence users' decisions. Analysis of characteristics such as these plays a critical role in identifying users' information needs and their search habits. In turn, such an analysis also provides useful insight for improving biomedical information retrieval.Database URL:http://www.ncbi.nlm.nih.gov/PubMed.

Death, dying and informatics: misrepresenting religion on MedLine.

PubMed

Rodríguez Del Pozo, Pablo; Fins, Joseph J

2005-07-01

The globalization of medical science carries for doctors worldwide a correlative duty to deepen their understanding of patients' cultural contexts and religious backgrounds, in order to satisfy each as a unique individual. To become better informed, practitioners may turn to MedLine, but it is unclear whether the information found there is an accurate representation of culture and religion. To test MedLine's representation of this field, we chose the topic of death and dying in the three major monotheistic religions. We searched MedLine using PubMed in order to retrieve and thematically analyze full-length scholarly journal papers or case reports dealing with religious traditions and end-of-life care. Our search consisted of a string of words that included the most common denominations of the three religions, the standard heading terms used by the National Reference Center for Bioethics Literature (NRCBL), and the Medical Subject Headings (MeSH) used by the National Library of Medicine. Eligible articles were limited to English-language papers with an abstract. We found that while a bibliographic search in MedLine on this topic produced instant results and some valuable literature, the aggregate reflected a selection bias. American writers were over-represented given the global prevalence of these religious traditions. Denominationally affiliated authors predominated in representing the Christian traditions. The Islamic tradition was under-represented. MedLine's capability to identify the most current, reliable and accurate information about purely scientific topics should not be assumed to be the same case when considering the interface of religion, culture and end-of-life care.

Crohn's disease complicated by Epstein-Barr virus-driven haemophagocytic lymphohistiocytosis successfully treated with rituximab.

PubMed

Thompson, Grace; Pepperell, Dominic; Lawrence, Ian; McGettigan, Benjamin David

2017-02-22

We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication. 2017 BMJ Publishing Group Ltd.

The diagnostic value of polymerase chain reaction for Mycobacterium tuberculosis to distinguish intestinal tuberculosis from crohn's disease: A meta-analysis.

PubMed

Jin, Ting; Fei, Baoying; Zhang, Yu; He, Xujun

2017-01-01

Intestinal tuberculosis (ITB) and Crohn's disease (CD) are important differential diagnoses that can be difficult to distinguish. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis (MTB) is an efficient and promising tool. This meta-analysis was performed to systematically and objectively assess the potential diagnostic accuracy and clinical value of PCR for MTB in distinguishing ITB from CD. We searched PubMed, Embase, Web of Science, Science Direct, and the Cochrane Library for eligible studies, and nine articles with 12 groups of data were identified. The included studies were subjected to quality assessment using the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The summary estimates were as follows: sensitivity 0.47 (95% CI: 0.42-0.51); specificity 0.95 (95% CI: 0.93-0.97); the positive likelihood ratio (PLR) 10.68 (95% CI: 6.98-16.35); the negative likelihood ratio (NLR) 0.49 (95% CI: 0.33-0.71); and diagnostic odds ratio (DOR) 21.92 (95% CI: 13.17-36.48). The area under the curve (AUC) was 0.9311, with a Q* value of 0.8664. Heterogeneity was found in the NLR. The heterogeneity of the studies was evaluated by meta-regression analysis and subgroup analysis. The current evidence suggests that PCR for MTB is a promising and highly specific diagnostic method to distinguish ITB from CD. However, physicians should also keep in mind that negative results cannot exclude ITB for its low sensitivity. Additional prospective studies are needed to further evaluate the diagnostic accuracy of PCR.

75 FR 39201 - MedBow-Routt Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

... DEPARTMENT OF AGRICULTURE Forest Service MedBow-Routt Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The MedBow-Routt Resource Advisory Committee will meet... and Community Self-Determination Act (Pub. L. 110-343) and in compliance with the Federal Advisory...

75 FR 52304 - MedBow-Routt Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... DEPARTMENT OF AGRICULTURE Forest Service MedBow-Routt Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The MedBow-Routt Resource Advisory Committee will meet... Community Self-Determination Act (Pub. L. 110- 343) and in compliance with the Federal Advisory Committee...

76 FR 12016 - MedBow-Routt Resource Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... DEPARTMENT OF AGRICULTURE Forest Service MedBow-Routt Resource Advisory Committee AGENCY: Forest Service, USDA. ACTION: Notice of meeting. SUMMARY: The MedBow-Routt Resource Advisory Committee will meet... Community Self-Determination Act (Pub. L. 110- 343) and in compliance with the Federal Advisory Committee...

Retrieval of diagnostic and treatment studies for clinical use through PubMed and PubMed's Clinical Queries filters.

PubMed

Lokker, Cynthia; Haynes, R Brian; Wilczynski, Nancy L; McKibbon, K Ann; Walter, Stephen D

2011-01-01

Clinical Queries filters were developed to improve the retrieval of high-quality studies in searches on clinical matters. The study objective was to determine the yield of relevant citations and physician satisfaction while searching for diagnostic and treatment studies using the Clinical Queries page of PubMed compared with searching PubMed without these filters. Forty practicing physicians, presented with standardized treatment and diagnosis questions and one question of their choosing, entered search terms which were processed in a random, blinded fashion through PubMed alone and PubMed Clinical Queries. Participants rated search retrievals for applicability to the question at hand and satisfaction. For treatment, the primary outcome of retrieval of relevant articles was not significantly different between the groups, but a higher proportion of articles from the Clinical Queries searches met methodologic criteria (p=0.049), and more articles were published in core internal medicine journals (p=0.056). For diagnosis, the filtered results returned more relevant articles (p=0.031) and fewer irrelevant articles (overall retrieval less, p=0.023); participants needed to screen fewer articles before arriving at the first relevant citation (p<0.05). Relevance was also influenced by content terms used by participants in searching. Participants varied greatly in their search performance. Clinical Queries filtered searches returned more high-quality studies, though the retrieval of relevant articles was only statistically different between the groups for diagnosis questions. Retrieving clinically important research studies from Medline is a challenging task for physicians. Methodological search filters can improve search retrieval.

Vedolizumab in the treatment of Crohn's disease.

PubMed

Tarabar, Dino; Hirsch, Ayal; Rubin, David T

2016-01-01

Vedolizumab, a recent addition to the therapeutic armamentarium in Crohn's disease, is promising in efficacy, durability of remission and safety. It is the first gut selective biologic treatment, acting by targeting α4β7-integrin, a receptor expressed on activated lymphocytes and binding to MAdCAM1, a cell adhesion molecule selectively expressed in the circulatory system of the digestive tract, preventing trafficking of lymphocytes to the gut. The pivotal GEMINI studies have demonstrated the efficacy and safety of vedolizumab in achieving clinical response and clinical remission in patients with moderately to severely active CD who are naïve or have previously failed therapy with TNF-antagonists, immunomodulators or dependent on steroids. Vedolizumab had a favorable safety profile and specifically showed no evidence of PML, reactivation of latent TB or hepatitis B. Overall, the number of malignancies in the clinical trials was small; however, long-term exposure was limited. Vedolizumab can be given as a first-line therapy or following treatment failure, and was tolerated as part of combination therapy. More medications with similar and novel therapeutic mechanisms are anticipated in the coming years.

Pharmacogenetic biomarkers of response in Crohn's disease.

PubMed

Linares-Pineda, T M; Cañadas-Garre, M; Sánchez-Pozo, A; Calleja-Hernández, M Á

2018-01-01

Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment. Several studies have considered the possibility that these differences in response are caused by the genetic variability of patients. Many genes have been investigated as potential predictors of response to biological drugs, such as ADAM17, ATG16L1, EMSY, CASP9, CCNY, CNTN5, FASLG, FCGR, NOD2, PTGER4, IL13, IL1B, IL27, IL11, IL17F, TNF and TNFR genes. In this review, we will gather the information on influence of gene polymorphisms investigated to date on response to biological drugs in CD patients.