Clinical Outcomes in International Federation of Gynecology and Obstetrics Stage IA Endometrial Cancer With Myometrial Invasion Treated With or Without Postoperative Vaginal Brachytherapy

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

Diavolitsis, V.; Rademaker, A.; Lurain, J.

2012-10-01

Purpose: To assess the clinical outcomes of patients with Stage IA endometrial cancer with myometrial invasion treated with postoperative vaginal brachytherapy (VBT) with those who received no adjuvant therapy (NAT). Methods and Materials: All patients treated with hysterectomy for endometrial cancer at Northwestern Memorial Hospital between 1978 and 2005 were identified. Those patients with Stage IA disease with myometrial invasion who were treated with VBT alone or NAT were identified and included in the present analysis. Results: Of 252 patients with Stage IA endometrial cancer with superficial (<50%) myometrial invasion who met the inclusion criteria, 169 underwent VBT and 83more » received NAT. The median follow-up in the VBT and NAT groups was 103 and 61 months, respectively. In the VBT group, 56.8% had Grade 1, 37.9% had Grade 2, and 5.3% had Grade 3 tumors. In the NAT group, 75.9%, 20.5%, and 3.6% had Grade 1, 2, and 3 tumors, respectively. Lymphatic or vascular space invasion was noted in 12.4% of the VBT patients and 5.6% of the NAT patients. The 5-year overall survival rate was 95.5%. The 5-year recurrence-free survival rate was 92.4% for all patients, 94.4% for the VBT group, and 87.4% for the NAT group (p = NS). Of the 169 VBT patients and 83 NAT patients, 8 (4.7%) and 6 (7.2%) developed recurrent disease. One vaginal recurrence occurred in the VBT group (0.6%) and three in the NAT group (3.8%). Recurrences developed 2-102 months after surgical treatment. Two of the four vaginal recurrences were salvaged. No Grade 3 or higher acute or late radiation toxicity was noted. Conclusions: The use of postoperative VBT in patients with Stage I endometrial cancer with <50% myometrial invasion yielded excellent vaginal disease control and disease-free survival, with minimal toxicity.« less

Hormonal therapy for women with stage IA endometrial cancer of all grades.

PubMed

Park, Jeong-Yeol; Kim, Dae-Yeon; Kim, Tae-Jin; Kim, Jae Weon; Kim, Jong-Hyeok; Kim, Yong-Man; Kim, Young-Tak; Bae, Duk-Soo; Nam, Joo-Hyun

2013-07-01

To estimate the oncologic and pregnancy outcomes after oral progestin treatment of women of reproductive age with stage IA endometrial adenocarcinoma with stage IA, grade 1 differentiation with superficial myometrial invasion or stage IA, grade 2-3 differentiation with or without superficial myometrial invasion. Medical records of 48 women (age 40 years or younger) with endometrioid adenocarcinoma of the uterus who met inclusion criteria and were treated conservatively with oral progestin were reviewed. Follow-up was performed primarily with imaging techniques followed by endometrial biopsy when indicated. The median age was 30 years (range, 23-40 years). Fourteen patients (29.2%) received daily oral megestrol acetate (median dose 160 mg per day, range 40-240 mg per day) and 34 (70.8%) received daily oral medroxyprogesterone acetate (median dose 500 mg per day, range 80-1,000 mg per day). Complete responses were observed for 37 patients (77.1%) after the median treatment duration of 10 months (range 3-20 months). Complete response rates were 76.5%, 73.9%, and 87.5% for patients with stage IA, grade 2-3 without myometrial invasion (n=17), for patients with stage IA, grade 1 with superficial myometrial invasion (n=23), and for patients with stage IA, grade 2-3 with superficial myometrial invasion (n=8), respectively (P=.731). Recurrence rates for 37 patients who achieved complete response after a median follow-up time of 48 months (range 7-136 months) were 23.1%, 47.1%, and 71.4%, respectively (P=.104). None experienced disease progression or died of the disease. Nine patients gave birth to 10 healthy newborns. Progestin treatment appears to be reasonably effective for patients with stage IA, grade 2-3 differentiation without myometrial invasion and patients with stage IA grade 1 differentiation with superficial myometrial invasion. III.

Molecular profiling identifies prognostic markers of stage IA lung adenocarcinoma.

PubMed

Zhang, Jie; Shao, Jinchen; Zhu, Lei; Zhao, Ruiying; Xing, Jie; Wang, Jun; Guo, Xiaohui; Tu, Shichun; Han, Baohui; Yu, Keke

2017-09-26

We previously showed that different pathologic subtypes were associated with different prognostic values in patients with stage IA lung adenocarcinoma (AC). We hypothesize that differential gene expression profiles of different subtypes may be valuable factors for prognosis in stage IA lung adenocarcinoma. We performed microarray gene expression profiling on tumor tissues micro-dissected from patients with acinar and solid predominant subtypes of stage IA lung adenocarcinoma. These patients had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China in 2012. No patient had preoperative treatment. We performed the Gene Set Enrichment Analysis (GSEA) analysis to look for gene expression signatures associated with tumor subtypes. The histologic subtypes of all patients were classified according to the 2015 WHO lung Adenocarcinoma classification. We found that patients with the solid predominant subtype are enriched for genes involved in RNA polymerase activity as well as inactivation of the p53 pathway. Further, we identified a list of genes that may serve as prognostic markers for stage IA lung adenocarcinoma. Validation in the TCGA database shows that these genes are correlated with survival, suggesting that they are novel prognostic factors for stage IA lung adenocarcinoma. In conclusion, we have uncovered novel prognostic factors for stage IA lung adenocarcinoma using gene expression profiling in combination with histopathology subtyping.

Intravital Microscopy for Identifying Tumor Vessels in Patients With Stage IA-IV Melanoma That is Being Removed by Surgery

ClinicalTrials.gov

2017-06-05

Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

Sublobectomy versus lobectomy for stage IA (T1a) non-small-cell lung cancer: a meta-analysis study.

PubMed

Liu, Yaxin; Huang, Cheng; Liu, Hongsheng; Chen, Yeye; Li, Shanqing

2014-05-01

Although lobectomy is considered the standard surgical treatment for the majority of patients with non-small-cell lung cancer (NSCLC), the operation project for patients with stage IA NSCLC (T1a, tumor diameter≤2 cm) remains controversial. Sublobectomy is appropriate only in certain patients as many doctors consider it to be overtreatment. We evaluated the five-year overall survival rate of sublobectomy and lobectomy for stage IA NSCLC (T1a, tumor diameter≤2 cm) through a meta-analysis. The five-year overall survival rate (OS) of stage IA (T1a) NSCLC after sublobectomy (including wedge resection and segmentectomy) and lobectomy were compared. We also compared the OS of stage IA (T1a) NSCLC after segmentectomy and lobectomy. The log (hazard ratio, ln (HR)) and its standard error (SE) were used as the outcome measure for data combining. There were 12 eligible studies published between 1994 and 2013 in which the total number of participants was 18,720. When compared to lobectomy, there was a statistically significant difference of sublobectomy on OS of stage IA (T1a) NSCLC patients (HR 1.38; 95% confidence interval (95% CI), 1.19 to 1.61; P<0.0001). For the comparison between segmentectomy and lobectomy, there was also a statistically significant difference of segmentectomy alone on OS of stage IA (T1a) NSCLC patients (HR 1.48; 95% CI: 1.27 to 1.73; P<0.00001) CONCLUSIONS: We have concluded that in stage IA (T1a) patients sublobectomy, including segmentectomy and wedge resection, causes a lower survival rate than lobectomy.

Intravital Microscopy in Evaluating Patients With Primary Peritoneal, Fallopian Tube, or Stage IA-IV Ovarian Cancer

ClinicalTrials.gov

2018-06-20

Fallopian Tube Carcinoma; Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Ovarian Cancer; Stage IB Ovarian Cancer; Stage IC Ovarian Cancer; Stage II Ovarian Cancer; Stage IIA Ovarian Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Ovarian Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Ovarian Cancer

Sublobar resection versus lobectomy in patients aged ≤35 years with stage IA non-small cell lung cancer: a SEER database analysis.

PubMed

Gu, Chang; Wang, Rui; Pan, Xufeng; Huang, Qingyuan; Zhang, Yangyang; Yang, Jun; Shi, Jianxin

2017-11-01

Sublobar resection has been increasingly adopted in elderly patients with stage IA non-small cell lung cancer (NSCLC), but the equivalency of sublobar resection versus lobectomy among young patients with stage IA NSCLC is unknown. Using the Surveillance, Epidemiology, and End Results (SEER) registry, we identified patients aged ≤35 years who were diagnosed between 2004 and 2013 with pathological stage IA NSCLC and treated with sublobar resection or lobectomy. We used propensity-score matching to minimize the effect of potential confounders that existed in the baseline characteristics of patients in different treatment groups. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of patients who underwent sublobar resection or lobectomy were compared in stratification analysis. Overall, we identified 188 patients who had stage IA disease, 32 (17%) of whom underwent sublobar resection. We did not identify any difference in OS/LCSS between patients who received sublobar resection versus lobectomy before (log-rank p = 0.6354) or after (log-rank p = 0.5305) adjusting for propensity scores. Similarly, we still could not recognize different OS/LCSS rates among stratified T stage groups or stratified lymph node-removed groups before or after adjusting for propensity scores. Sublobar resection is not inferior to lobectomy for young patients with stage IA NSCLC. Considering sublobar resection better preserves lung function and has reduced overall morbidity, sublobar resection may be preferable for the treatment of young patients with stage IA NSCLC.

Health and Recovery Program in Increasing Physical Activity Level in Stage IA-IIIA Endometrial Cancer Survivors

ClinicalTrials.gov

2018-03-05

Cancer Survivor; Endometrial Carcinoma; Stage I Uterine Corpus Cancer AJCC v7; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7

Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2015-12-03

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

Propensity score-matching analysis of hybrid video-assisted thoracoscopic surgery and thoracoscopic lobectomy for clinical stage I lung cancer†.

PubMed

Iwata, Hisashi; Shirahashi, Koyo; Yamamoto, Hirotaka; Marui, Tsutomu; Matsumoto, Shinsuke; Mizuno, Yoshimasa; Matsumoto, Mitsuyoshi; Mitta, Shohei; Miyamoto, Yusaku; Komuro, Hiroyasu

2016-04-01

Video-assisted thoracoscopic surgery (VATS) lobectomy is classified into hybrid VATS (direct and video vision) and thoracoscopic VATS (video vision only). In this study, the outcomes of hybrid VATS and thoracoscopic VATS for clinical stage I lung cancer were compared using a propensity score-matching analysis. Hybrid and thoracoscopic VATS were performed in 178 and 76 patients, respectively. Propensity scores were calculated using logistic regression analysis and matched within a score of ±0.03 for age, sex, size of tumour, Charlson comorbidity index, preoperative therapy, percent vital capacity, forced expiratory volume in 1 s, clinical stage, pathological stage and histology. In the non-matched analysis, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean age, 69 ± 9 and 66 ± 10 years (P = 0.04); tumour size, 24 ± 10 and 20 ± 7 mm (P < 0.01); 2-deoxy-2 [F-18]fluorodeoxyglucose positron emission tomography SUV, 5.6 ± 4.4 and 3.6 ± 3.2 (P < 0.01); clinical stage (IA/IB), 130/48 and 69/7 (P < 0.01); pathological stage (IA/IB/IIA and IIB/IIIA and IIIB), 89/56/15/18 and 57/14/2/3 (P < 0.01); postoperative complications, 66 (37.1%) and 16 (21.1%; P = 0.01); respiratory complications, 32 (18.0%) and 6 (7.9%; P = 0.04); 5-year overall survival (OS), 77.0 and 88.8% (log-rank P = 0.045); and 5-year disease-free survival (DFS), 67.2 and 81.1% (log-rank P = 0.02). In 66 matched cases, the results for hybrid and thoracoscopic VATS, respectively, were as follows: mean operative time, 245 ± 96 and 285 ± 85 min (P = 0.01); blood loss, 95 ± 100 and 86 ± 123 ml (P = 0.67); mean duration of drainage, 3.6 ± 2.7 and 3.2 ± 2.2 days (P = 0.37); postoperative complications, 21 (31.8%) and 14 (21.2%; P = 0.17); respiratory complications, 11 (16.7%) and 5 (7.6%; P = 0.11); 5-year OS, 72.5 and 86.0% (log-rank P = 0.25); and 5-year DFS, 68.4 and 77.2% (log-rank P = 0.17). In this single-institution, propensity score-matched study, hybrid VATS showed a shorter operative time and similar outcomes compared with thoracoscopic lobectomy for clinical stage IA lung cancer. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

PubMed

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise <10% of PDAC. Using the NCDB 2006-2012, resected PDAC patients with stage I disease who received adjuvant therapy (chemotherapy or chemoradiation) were analyzed. Factors associated with overall survival (OS) were identified. 3909 patients with resected stage IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and <0.001). For patients with Stage IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Comparing cognition, mealtime performance, and nutritional status in people with dementia with or without ideational apraxia.

PubMed

Wu, Hua-Shan; Lin, Li-Chan

2015-03-01

To describe the prevalence rate of ideational apraxia (IA) affecting self-feeding in people with dementia, confirm the stage of dementia at which IA most commonly occurs, and compare mealtime performance and nutritional status between people with dementia (PWD) with and without IA. A cross-sectional design with between-subject comparison was used. Among the 395 potential participants recruited from dementia special care units at nine long-term care facilities in central and northern Taiwan, 98 met the operational definition of IA and were included in the PWD with IA group. From the remaining pool, 98 participants, matched for age and sex with the PWD with IA group, were randomly allocated to the PWD without IA group. Eating Behavior Scale (EBS) scores, food intake, total eating time, meal assistance, body mass index, Mini-Nutritional Assessment (MNA), and Mini-Mental State Examination scores were collected. The prevalence rate of IA affecting self-feeding in our study population of PWD was 24.8%. PWD with IA had significantly lower EBS scores, had more food intake (p < .001), spent more time being fed by caregivers, needed more verbal and feeding assistance, and had lower MNA scores than PWD without IA. Decline in the self-feeding ability of PWD affected by IA most commonly occurred in the severe stage of dementia. When dementia progresses to the late stage, staff should pay special attention to residents' mealtime performance and nutritional status. For PWD with IA, reassigning staff at mealtimes based on eating ability and providing memory training are recommended. © The Author(s) 2014.

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

ClinicalTrials.gov

2013-12-17

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

ClinicalTrials.gov

2018-02-23

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer

HER3 expression is enhanced during progression of lung adenocarcinoma without EGFR mutation from stage 0 to IA1.

PubMed

Kumagai, Toru; Tomita, Yasuhiko; Nakatsuka, Shin-Ichi; Kimura, Madoka; Kunimasa, Kei; Inoue, Takako; Tamiya, Motohiro; Nishino, Kazumi; Susaki, Yoshiyuki; Kusu, Takashi; Tokunaga, Toshiteru; Okami, Jiro; Higashiyama, Masahiko; Imamura, Fumio

2018-04-01

Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively. HER2 and HER3 expression was detected in 22.2% and 86.1% of samples, respectively. The frequency of EGFR mutation was 45.7% and was not significantly different between stage 0 and IA1 (40.0% and 48.0%, respectively), suggesting that EGFR mutation does not correlate with cancer progression from stage 0 to IA1. HER2 expression also did not correlate to progression. However, not only the frequency, but also the intensity of HER3 expression was increased in stage IA1 lung adenocarcinoma, particularly in lung adenocarcinoma without EGFR mutation. HER3 tends to be intensively expressed during the progression of lung adenocarcinoma without EGFR mutation from carcinoma in situ to invasive carcinoma. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

PubMed

Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

2017-07-01

Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

Studying the Physical Function and Quality of Life Before and After Surgery in Patients With Stage I Cervical Cancer

ClinicalTrials.gov

2018-05-04

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Lymphedema; Sexual Dysfunction and Infertility; Stage IA1 Cervical Cancer AJCC v6 and v7; Stage IA2 Cervical Cancer AJCC v6 and v7; Stage IB1 Cervical Cancer AJCC v6 and v7

The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer.

PubMed

Takenaka, Tomoyoshi; Furuya, Kiyomi; Yamazaki, Koji; Miura, Naoko; Tsutsui, Kana; Takeo, Sadanori

2018-02-01

We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy. We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival. The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS. CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

Spontaneous pregnancy loss in humans and exposure to arsenic in drinking water.

PubMed

Bloom, Michael S; Fitzgerald, Edward F; Kim, Keewan; Neamtiu, Iulia; Gurzau, Eugen S

2010-11-01

Maternal exposure to high concentrations of inorganic arsenic (iAs) in naturally contaminated drinking groundwater sources has been associated with an increased risk for the spontaneous loss of clinically recognized pregnancies in several epidemiologic studies. Whereas a large worldwide population depends on drinking groundwater sources with high levels of iAs contamination, in quantities exceeding 10 parts per billion (ppb), an even larger population is likely to be exposed to mild-moderate drinking groundwater iAs contamination, in quantities <10ppb. Only a single epidemiologic study to date has considered spontaneous pregnancy loss in association with consumption of drinking water with mild-moderate iAs contamination; the vast majority of published studies of spontaneous loss addressed populations with substantial exposure. The aim of this review is to evaluate the published literature to assess the plausibility for a causal association between exposure to iAs-contaminated drinking water and the spontaneous loss of clinically recognized pregnancy. In spite of numerous methodologic limitations resulting from circumstance or design, a consistent pattern of increased risk for loss is suggested by the epidemiologic literature. Moreover, these study results are corroborated by a large number of experimental studies, albeit usually conducted at concentrations exceeding that to which humans are exposed via contaminated drinking water. In this review, we discuss sources of human iAs exposure, highlight several experimental studies pertinent to a possible causal link between iAs and spontaneous pregnancy loss in humans, and provide a critical review of published epidemiologic studies of pregnancy loss and drinking water iAs exposures, and their limitations. Based on a review of the published literature, we recommend the future conduct of a two-stage comprehensive prospective study of low-moderate iAs drinking water exposure and spontaneous pregnancy loss. Copyright © 2010 Elsevier GmbH. All rights reserved.

Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2017-12-08

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall survival rates exceeding 90% after involved-field radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than stage IA). In contrast, patients with advanced disease at diagnosis tend to relapse either with NLPHL histology or with histological transformation into aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL patients with multiple relapses successfully respond to salvage therapy in many cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to high-dose chemotherapy followed by autologous stem cell transplantation. Treatment at disease recurrence should be chosen on the basis of various factors, including histology at relapse, time to relapse, extent of disease at relapse, and prior treatment. Because death among NLPHL patients is more often caused by therapy-related late effects than lymphoma-related complications, optimizing the risk-benefit ratio of treatment by decreasing toxicity whenever possible is the major goal of clinical research in this disease. © 2016 by The American Society of Hematology. All rights reserved.

Cervical Cancer Stage IA

MedlinePlus

... of the cervix and vagina. An inset shows cancer in the cervix that is up to 5 mm deep, but ... microscope is found in the tissues of the cervix. In stage IA1, the cancer is not more than 3 millimeters deep and ...

Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective study on long-term outcome with propensity score analysis

PubMed Central

De Angelis, Carmine; Di Maio, Massimo; Crispo, Anna; Giuliano, Mario; Schettini, Francesco; Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Cinausero, Marika; Riccardi, Ferdinando; Ciancia, Giuseppe; De Laurentiis, Michelino; Puglisi, Fabio; De Placido, Sabino; Arpino, Grazia

2017-01-01

The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively evaluated predictive factors and clinical outcome of 1,222 patients from 4 oncologic centers. Three hundred and eighty patients received CT and HT (CT-cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and overall survival (OS) were evaluated with univariate and multivariate analyses. We also applied the propensity score methodology. Compared with the HT-cohort, patients in the CT-cohort were more likely to be younger, have larger tumors of a higher histological grade that were Ki67-positive, and lower estrogen and progesterone receptor expression. At univariate analysis, a higher histological grade and Ki67 were significantly associated to a lower DFS. At multivariable analysis, only histological grade was predictive of DFS. The CT-cohort had a worse outcome than the HT-cohort in terms of DFS and OS, but differences disappeared when matched according to propensity score. In summary, patients with stage IA luminal-like BC had an excellent prognosis, however relapse and mortality were higher in the CT-cohort than in the HT-cohort. Longer use of adjuvant HT or other therapeutic strategies may be needed to improve outcome. PMID:29348868

The versican gene and the risk of intracranial aneurysms.

PubMed

Ruigrok, Ynte M; Rinkel, Gabriël J E; Wijmenga, Cisca

2006-09-01

The proteoglycan versican is an excellent candidate gene for intracranial aneurysms (IAs) because it plays an important role in extracellular matrix assembly and is localized in a previously implicated locus for IAs on chromosome 5q. We analyzed all the common variations using 16-tag single nucleotide polymorphisms (SNPs) and haplotypes in the versican gene using a 2-stage genotyping approach. For stage 1, 16 SNPs were genotyped in 307 cases and 639 controls. For stage 2, the two SNPs yielding the most significant associations (P<0.01) were genotyped in a second independent cohort of 310 cases for confirmation of the associations. In stage 1, we found several SNPs in strong linkage disequilibrium and haplotypes constituting these SNPs associated with IAs in the Dutch population (strongest SNP association for rs173686 with odds ratio=1.34, 95% CI=1.09 to 1.65, P=0.004). In stage 2, we confirmed association for the 2 SNPs with the most significant associations (strongest SNP association for rs173686 with odds ratio=1.36, 95% CI=1.11 to 1.67, P=0.003). SNPs in strong linkage disequilibrium and haplotypes constituting these SNPs in the versican gene are associated with IAs suggesting that variation in or near the versican gene plays a role in susceptibility to IAs.

Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-01-09

Mixed Mesodermal (Mullerian) Tumor; Ovarian Carcinosarcoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Sarcoma AJCC v7; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Sarcoma AJCC v7; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Uterine Sarcoma AJCC v7; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Uterine Sarcoma AJCC v7; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Uterine Sarcoma AJCC v7; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Sarcoma AJCC v7; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Sarcoma AJCC v7; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Sarcoma AJCC v7; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Sarcoma AJCC v7; Stage IVB Uterine Sarcoma AJCC v7; Uterine Carcinosarcoma

Evaluation of the new IASLC/ATS/ERS proposed classification of adenocarcinoma based on lepidic pattern in patients with pathological stage IA pulmonary adenocarcinoma.

PubMed

Nakagiri, Tomoyuki; Sawabata, Noriyoshi; Morii, Eiichi; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Okumura, Meinoshin

2014-11-01

The International association for the study of cancer (IASLC)/American thoracic society (ATS)/European respiratory society (ERS) has established a new subclassification of lung adenocarcinoma, especially for the lepidic pattern component, formerly called bronchioloalveolar adenocarcinoma (BAC). According to the new classification, BAC has been classified into the following 4 main subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and variants of invasive adenocarcinoma (VIA). An observational study was conducted to validate this classification in patients with pathological stage IA pulmonary adenocarcinoma. 147 patients treated for pathological stage IA lung adenocarcinoma by complete resection at Osaka University Medical Hospital from January 1993 to December 2002 were assessed. The tumor specimens of the cohort were classified into the 4 subgroups. In addition, these groups were compared for various prognostic factors. Adenocarcinoma in situ was observed in 30 patients, MIA in 8, IA in 104, and VIA in 5 patients, with 5-year survival rates of 100, 100, 85.5, and 60.0 %, respectively. The relationship between the histological classification and K-ras mutation was significant (p < 0.001), especially when comparing the VIA group with the others (p ≪ 0.001). Ki67-labeling indices were significantly different between the AIS and IA groups (p = 0.040). This study validated the proposed IASLC/ATS/ERS classification for pulmonary adenocarcinoma in patients with pathological stage IA pulmonary adenocarcinoma. The difference between AIS and IA may depend on the proliferation of the carcinoma. In addition, the difference between VIA and the other adenocarcinoma types may depend on genetic factors, especially K-ras mutations.

The Melbourne Pre-Diabetes Study: prediction of type 1 diabetes mellitus using antibody and metabolic testing.

PubMed

Colman, P G; McNair, P; Margetts, H; Schmidli, R S; Werther, G A; Alford, F P; Ward, G M; Tait, B D; Honeyman, M C; Harrison, L C

1998-07-20

To determine the utility of various autoantibodies in predicting progression to clinical diabetes in first-degree relatives of patients with type 1 diabetes mellitus. 3315 first-degree relatives of patients with type 1 diabetes (1161 parents, 1206 siblings and 948 offspring) recruited through diabetes clinics, private endocrinologists, Diabetes Australia and the Juvenile Diabetes Foundation. Prevalence of islet cell antibodies (ICA) levels > or = 20 JDFu, insulin autoantibodies (IAA) levels > 100 nU/mL, and antibodies to glutamic acid decarboxylase (GADAb) and tyrosine phosphatase IA2 (IA2Ab); change in beta cell function over time; and development of clinical diabetes. 2.6% of relatives had elevated ICA levels, 1.3% had elevated IAA levels and 0.3% had both. High ICA levels were significantly more frequent in siblings than in offspring or parents, and were more frequent in relatives younger than 20 years. GADAb were detected in 68% and IA2Ab in 57% of relatives with elevated ICA and/or IAA levels. Diabetes developed in 33 relatives (25 siblings, 2 offspring and 6 parents). Before diagnosis of clinical diabetes, high ICA levels were detected in 18 (58%), high IAA levels in 7 (23%), both in 5 (15%), and either in 19 (61%); GADAb were detected in 26 (84%), IA2Ab in 13 (42%), both in 11 (35%), and either in 28 (90%). First phase insulin release (FPIR) less than 50 mU/L was very strongly associated with progression to diabetes. In relatives with FPIR initially greater than 50 mU/L who eventually developed diabetes, there was a gradual and continuous reduction in FPIR over time before diagnosis. Type 1 diabetes can be diagnosed in the preclinical stage. The recently described antibodies to glutamic acid decarboxylase and tyrosine phosphatase IA2 appear superior to ICA as screening tools for the preclinical diagnosis of type 1 diabetes.

Nerve-sparing radical hysterectomy for stage IA2-IIB cervical cancer: 5-year survival of 501 consecutive cases.

PubMed

Papp, Z; Csapó, Zs; Hupuczi, P; Mayer, A

2006-01-01

The purpose of this study was to assess the 5-year survival and morbidity in cases with radical hysterectomy and pelvic lymphadenectomy with pre- and postoperative irradiation performed to treat Stage IA2-IIB cervical cancer. During a 10(1/2)-year period between July 1990 and December 2000, 501 consecutive radical hysterectomies with bilateral pelvic lymphadenectomy were performed by the same gynecological surgeon in Stage IA2, IB, IIA and IIB cervical cancer. The patients were treated by pre- and postoperative irradiation as well. Apart from recurrence, perioperative complications were minimal with no long-term morbidity. The absolute 5-year survival rates for the patients in Stage IA2, IB1, IB2, IIA and IIB were 94.4%, 90.7%, 84.1%, 71.1%, and 55.4%, respectively. The respective 5-year survival rates for patients without or with lymph node metastasis were 94.5% and 33.3% in Stage IB2, 81.7% and 48.7% in Stage IIA and 70.2% and 36.5% in Stage IIB, respectively. Nerve-sparing radical hysterectomy with pelvic lymph node dissection and pre- and postoperative irradiation remains the treatment of choice for most patients with early-stage and even Stage IIB cervical cancer. The radicalism and extent of lymph node dissection and parametrial resection should be individualized and tailored to tumor- and patient-related risk factors.

A novel acute HIV infection staging system based on 4th generation immunoassay.

PubMed

Ananworanich, Jintanat; Fletcher, James L K; Pinyakorn, Suteeraporn; van Griensven, Frits; Vandergeeten, Claire; Schuetz, Alexandra; Pankam, Tippawan; Trichavaroj, Rapee; Akapirat, Siriwat; Chomchey, Nitiya; Phanuphak, Praphan; Chomont, Nicolas; Michael, Nelson L; Kim, Jerome H; de Souza, Mark

2013-05-29

Fourth generation (4thG) immunoassay (IA) is becoming the standard HIV screening method but was not available when the Fiebig acute HIV infection (AHI) staging system was proposed. Here we evaluated AHI staging based on a 4thG IA (4thG staging). Screening for AHI was performed in real-time by pooled nucleic acid testing (NAT, n=48,828 samples) and sequential enzyme immunoassay (EIA, n=3,939 samples) identifying 63 subjects with non-reactive 2nd generation EIA (Fiebig stages I (n=25), II (n=7), III (n=29), IV (n=2)). The majority of samples tested (n=53) were subtype CRF_01AE (77%). NAT+ subjects were re-staged into three 4thG stages: stage 1 (n=20; 4th gen EIA-, 3rd gen EIA-), stage 2 (n=12; 4th gen EIA+, 3rd gen EIA-), stage 3 (n=31; 4th gen EIA+, 3rd gen EIA+, Western blot-/indeterminate). 4thG staging distinguishes groups of AHI subjects by time since presumed HIV exposure, pattern of CD8+ T, B and natural killer cell absolute numbers, and HIV RNA and DNA levels. This staging system further stratified Fiebig I subjects: 18 subjects in 4thG stage 1 had lower HIV RNA and DNA levels than 7 subjects in 4thG stage 2. Using 4th generation IA as part of AHI staging distinguishes groups of patients by time since exposure to HIV, lymphocyte numbers and HIV viral burden. It identifies two groups of Fiebig stage I subjects who display different levels of HIV RNA and DNA, which may have implication for HIV cure. 4th generation IA should be incorporated into AHI staging systems.

OPT-821 With or Without Vaccine Therapy in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in Second or Third Complete Remission

ClinicalTrials.gov

2017-09-12

Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Primary Fallopian Tube Carcinoma: A Case Report and Literature Review.

PubMed

Rexhepi, Meral; Trajkovska, Elizabeta; Ismaili, Hysni; Besimi, Florin; Rufati, Nagip

2017-06-15

Primary fallopian tube carcinoma (PFTC) is a rare tumour of the female genital tract with an incidence of 0.1-1.8% of all genital malignancies, and it is very difficult to diagnose preoperatively, because of its non-specific symptomatology. In most cases, it is an intraoperative finding or a histopathological diagnosis. It is a tumour that histologically and clinically resembles epithelial ovarian cancer. We are reporting a case of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of the right fallopian tube in stage IA. The patient has lower abdominal pain, watery vaginal discharge and repeated episodes of bleeding from the vagina. The clinical and radiological findings suggested a right adnexal tumour with elevated CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and peritoneal washing were performed. Pathologic confirmation of primary serous cystadenocarcinoma of the right fallopian tube was made. Peritoneal washings were negative for malignancy. FIGO stage was considered as IA, and the patient received no courses of chemotherapy and postoperative radiation because she refused it. Ten months after initial surgery, the patient is alive and in good condition. Cytoreduction surgery followed by adequate cycles of chemotherapy is an important strategy to improve patients' prognosis.

Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-21

Borderline Ovarian Mucinous Tumor; Ovarian Mucinous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer

The Quality of Staging Non-Small Cell Lung Cancer in the Netherlands: Data From the Dutch Lung Surgery Audit.

PubMed

Heineman, David Jonathan; Ten Berge, Martijn Geert; Daniels, Johannes Marlene; Versteegh, Michaël Ignatius; Marang-van de Mheen, Perla Jacqueline; Wouters, Michael Wilhelmus; Schreurs, Wilhelmina Hendrika

2016-11-01

Clinical staging of non-small cell lung cancer (NSCLC) determines the initial treatment offered to a patient. The similarity between clinical and pathologic staging in some studies is as low as 50%, and others publish results as high as 91%. The Dutch Lung Surgery Audit is a clinical database that registers the clinical and pathologic TNM of almost all NSCLC patients who undergo operations in the Netherlands. The objective of this study was to determine the accuracy of clinical staging of NSCLC. Prospective data were derived from the Dutch Lung Surgery Audit in 2013 and 2014. Patients were included if they had undergone a surgical resection for stage IA to IIIB NSCLC without neoadjuvant treatment and had a positron emission tomography-computed tomography scan as part of the clinical workup. Clinical (c)TNM and pathologic (p)TNM were compared, and whether discrepancy was based on tumor or nodal staging was determined. From 2,834 patients identified, 2,336 (82.4%) fulfilled the inclusion criteria and had complete data. Of these 2,336, 1,276 (54.6%) were staged accurately, 707 (30.3%) were clinically understaged, and 353 (15.1%) were clinically overstaged. In the understaged group, 346 patients had a higher pN stage (14.8%), of which 148 patients had unforeseen N2 disease (6.3%). In the overstaged group, 133 patients had a cN that was higher than the pN (5.7%). Accuracy of NSCLC staging in the Netherlands is low (54.6%), even in the era of positron emission tomography-computed tomography. Especially accurate nodal staging remains challenging. Future efforts should include the identification of specific pitfalls in NSCLC staging. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Electronic Monitoring Device of Patient-Reported Outcomes and Function in Improving Patient-Centered Care in Patients With Gastrointestinal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-06-06

Stage I Adult Liver Cancer; Stage I Colorectal Cancer; Stage IA Gastric Cancer; Stage IA Pancreatic Cancer; Stage IB Gastric Cancer; Stage IB Pancreatic Cancer; Stage II Adult Liver Cancer; Stage IIA Colorectal Cancer; Stage IIA Gastric Cancer; Stage IIA Pancreatic Cancer; Stage IIB Colorectal Cancer; Stage IIB Gastric Cancer; Stage IIB Pancreatic Cancer; Stage IIC Colorectal Cancer; Stage III Pancreatic Cancer; Stage IIIA Adult Liver Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Adult Liver Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Adult Liver Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer; Stage IVA Colorectal Cancer; Stage IVA Liver Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Liver Cancer; Stage IVB Pancreatic Cancer

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

Chernyshova, A. L.; Lyapunov, A. Yu., E-mail: Lyapunov1720.90@mail.ru; Kolomiets, L. A.

The study included 26 patients with FIGO stage Ia1–Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors

ClinicalTrials.gov

2016-10-03

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Estrogen Receptor Negative; Estrogen Receptor Positive; Glioblastoma; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Metastatic Renal Cell Cancer; Recurrent Adult Brain Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Lung Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Uterine Corpus Carcinoma; Resectable Hepatocellular Carcinoma; Sarcoma; Stage IA Breast Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Corpus Cancer; Stage IB Breast Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Corpus Cancer; Stage IC Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage IIA Breast Cancer; Stage IIA Lung Carcinoma; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Esophageal Cancer; Stage IIB Lung Carcinoma; Stage IIB Ovarian Cancer; Stage IIB Skin Melanoma; Stage IIC Ovarian Cancer; Stage IIC Skin Melanoma; Stage IIIA Breast Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Ovarian Cancer; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Esophageal Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER)

ClinicalTrials.gov

2018-03-20

Febrile Neutropenia; Stage 0 Breast Cancer; Stage 0 Colorectal Cancer; Stage 0 Non-Small Cell Lung Cancer; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Breast Cancer; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

ClinicalTrials.gov

2018-04-11

Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

Optimization of the extent of surgical treatment in patients with stage I in cervical cancer

NASA Astrophysics Data System (ADS)

Chernyshova, A. L.; Kolomiets, L. A.; Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.

2016-08-01

The study included 26 patients with FIGO stage Ia1-Ib1 cervical cancer who underwent fertility-sparing surgery (transabdominaltrachelectomy). To visualize sentinel lymph nodes, lymphoscintigraphy with injection of 99mTc-labelled nanocolloid was performed the day before surgery. Intraoperative identification of sentinel lymph nodes using hand-held gamma probe was carried out to determine the radioactive counts over the draining lymph node basin. The sentinel lymph node detection in cervical cancer patients contributes to the accurate clinical assessment of the pelvic lymph node status, precise staging of the disease and tailoring of surgical treatment to individual patient.

The development of ecological impact assessment in China.

PubMed

Liu, Xuehua; Li, Zhouyuan; Liao, Chenghao; Wang, Qing; Zhu, Annah; Li, Dong; Li, Yajun; Tang, Zhuo

2015-12-01

The balance between economic development and ecological conservation in China has become a critical issue in recent decades. Ecological impact assessment (EcoIA) was established beginning in the 1980s as a component of environmental impact assessment (EIA) that focuses specifically on human-related changes in ecosystem structure and function. EcoIA has since been widely applied throughout the country with continuous refinements in theory and practice. As compared to EIA, EcoIA is often performed at a larger scale in the long-term, and thus requires more advanced tools and techniques to quantify and assess. This paper reviews the development of EcoIA over the past 30years in China, with specific consideration given to refinements in legislation and methodology. Three stages in the development of EcoIA in China are identified, along with their achievements and limitations. Supplementing this qualitative analysis, the paper also provides a quantitative bibliometrics review of academic publications concerning EcoIA in China over the three identified stages. Lastly, general trends in the development of EcoIA are summarized with the aim of conveying potential future trajectories. This review is intended to introduce the EcoIA system to scholars interested in the growing field of environmental management in China. Copyright © 2015 Elsevier Ltd. All rights reserved.

Collecting Tumor Samples From Patients With Gynecological Tumors

ClinicalTrials.gov

2016-10-26

Borderline Ovarian Clear Cell Tumor; Borderline Ovarian Serous Tumor; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Childhood Embryonal Rhabdomyosarcoma; Childhood Malignant Ovarian Germ Cell Tumor; Endometrioid Stromal Sarcoma; Gestational Trophoblastic Tumor; Malignant Mesothelioma; Malignant Ovarian Epithelial Tumor; Melanoma; Neoplasm of Uncertain Malignant Potential; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Paget Disease of the Vulva; Recurrent Cervical Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vaginal Carcinoma; Recurrent Vulvar Carcinoma; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Cervical Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage III Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Borderline Ovarian Surface Epithelial-Stromal Tumor; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Stage IVB Vulvar Cancer; Uterine Corpus Cancer; Uterine Corpus Leiomyosarcoma; Vulvar Squamous Cell Carcinoma

Forecasting the impact of stereotactic ablative radiotherapy for early-stage lung cancer on the thoracic surgery workforce.

PubMed

Edwards, Janet P; Datta, Indraneel; Hunt, John Douglas; Stefan, Kevin; Ball, Chad G; Dixon, Elijah; Grondin, Sean C

2016-06-01

To predict variation in thoracic surgery workforce requirements with the introduction of stereotactic ablative radiotherapy (SABR) for the treatment of early-stage non-small-cell lung cancer (NSCLC). Using Canadian census microdata and the Canadian Community Health Survey, a microsimulation model representing the national population was developed. The demand component simulates the incidence of lung cancer, incorporating the impact of computed tomography (CT) screening for high-risk individuals (>30 pack-year smoking history; age 55-74 years). The supply component simulates the number of thoracic surgeons. SABR was introduced into the model to predict changes in the number of operable NSCLC cases per thoracic surgeon, modelling 30, 60 and 90% compliance with SABR for Stage IA and then for both Stage IA and IB NSCLC. In the absence of SABR, the volume of operative NSCLC per surgeon increases by a peak of 49.4% (by 2027) and then gradually declines to the present day volume by 2049. More dramatic decreases are seen with increasing compliance with SABR for Stage IA/IB NSCLCs. If the number of new surgeons entering the workforce per year were reduced by 33%, the operative volume per surgeon would increase by a peak of 57.1% (30% Stage IA SABR compliance) and would decrease by up to 49.1% (90% Stage IA SABR compliance). With the implementation of SABR for treatment of early NSCLC, there would be a decrease in operative volume. The impact would depend on the stage of NSCLC for which SABR is recommended and on compliance. A national strategy for thoracic surgery workforce planning is necessary, given the complex interaction of CT screening and the treatment of medically operable early NSCLC with SABR. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Is Local Viscosupplementation Injection Clinically Superior to Other Therapies in the Treatment of Osteoarthritis of the Knee: A Systematic Review of Overlapping Meta-analyses.

PubMed

Campbell, Kirk A; Erickson, Brandon J; Saltzman, Bryan M; Mascarenhas, Randy; Bach, Bernard R; Cole, Brian J; Verma, Nikhil N

2015-10-01

To conduct a systematic review of overlapping meta-analyses comparing treatment of knee osteoarthritis (OA) with intra-articular viscosupplementation (intra-articular hyaluronic acid [IA-HA]) versus oral nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroids (IA-corticosteroids), intra-articular platelet-rich plasma (IA-PRP), or intra-articular placebo (IA-placebo) to determine which meta-analyses provide the best current evidence and identify potential causes of discordance. Literature searches were performed for meta-analyses examining use of IA-HA versus NSAIDs, IA-corticosteroids, IA-PRP, or IA-placebo. Clinical data were extracted, and meta-analysis quality was assessed. The Jadad algorithm was applied to determine which meta-analyses provided the highest level of evidence. Fourteen meta-analyses met the eligibility criteria and ranged in quality from Level I to IV evidence. In studies reporting patient numbers, there were a total of 20,049 patients: 13,698 receiving IA-HA, 355 receiving NSAIDs, 294 receiving IA-corticosteroids, and 5,702 receiving IA-placebo. Ten studies examined the effects of IA-HA versus IA-placebo; of these, 5 found that IA-HA improved pain and 4 found that IA-HA improved function. No clinically relevant differences in the efficacy of IA-HA versus NSAIDs regarding pain and function were found. Regarding IA-HA versus IA-PRP, IA-HA improved knee function at 2 and 6 months after injection but the effects were less robust than those of IA-PRP. Regarding IA-HA versus IA-corticosteroids, the positive effects of IA-HA were greater at 5 to 13 weeks and persisted for up to 26 weeks. After application of the Jadad algorithm, 2 concordant high-quality meta-analyses were selected and both showed that IA-HA provided clinically relevant improvements in pain and function compared with IA-placebo. This systematic review of overlapping meta-analyses comparing IA-HA with other nonoperative treatment modalities for knee OA shows that the current highest level of evidence suggests that IA-HA is a viable option for knee OA. Its use results in improvements in knee pain and function that can persist for up to 26 weeks. IA-HA has a good safety profile, and its use should be considered in patients with early knee OA. Level IV, systematic review of Level I to IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

PubMed

Hu, Xiaolei; Chen, Fengling

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients

PubMed Central

Hu, Xiaolei

2018-01-01

Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. PMID:29233817

Computerized Cognitive Retraining in Improving Cognitive Function in Breast Cancer Survivors

ClinicalTrials.gov

2017-12-11

Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Primary Fallopian Tube Carcinoma: A Case Report and Literature Review

PubMed Central

Rexhepi, Meral; Trajkovska, Elizabeta; Ismaili, Hysni; Besimi, Florin; Rufati, Nagip

2017-01-01

BACKGROUND: Primary fallopian tube carcinoma (PFTC) is a rare tumour of the female genital tract with an incidence of 0.1-1.8% of all genital malignancies, and it is very difficult to diagnose preoperatively, because of its non-specific symptomatology. In most cases, it is an intraoperative finding or a histopathological diagnosis. It is a tumour that histologically and clinically resembles epithelial ovarian cancer. CASE PRESENTATION: We are reporting a case of a 62-year-old, postmenopausal women with primary fallopian tube carcinoma of the right fallopian tube in stage IA. The patient has lower abdominal pain, watery vaginal discharge and repeated episodes of bleeding from the vagina. The clinical and radiological findings suggested a right adnexal tumour with elevated CA-125 levels. Total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and peritoneal washing were performed. Pathologic confirmation of primary serous cystadenocarcinoma of the right fallopian tube was made. Peritoneal washings were negative for malignancy. FIGO stage was considered as IA, and the patient received no courses of chemotherapy and postoperative radiation because she refused it. Ten months after initial surgery, the patient is alive and in good condition. CONCLUSION: Cytoreduction surgery followed by adequate cycles of chemotherapy is an important strategy to improve patients’ prognosis. PMID:28698755

Clinical, laboratory, and transesophageal echocardiographic correlates of interatrial septal thickness: a population-based transesophageal echocardiographic study.

PubMed

Agmon, Yoram; Meissner, Irene; Tajik, A Jamil; Seward, James B; Petterson, Tanya M; Christianson, Teresa J H; O'Fallon, W Michael; Wiebers, David O; Khandheria, Bijoy K

2005-02-01

The determinants of interatrial septal (IAS) thickening ("lipomatous hypertrophy"), a common echocardiographic finding in the elderly, are poorly defined. The objective of this study was to determine the clinical, laboratory, and transesophageal echocardiographic correlates of IAS thickening in the general population. The thickness of the IAS was measured by transesophageal echocardiography in 384 patients (median age: 66 years; range: 51-101 years; 53% men) participating in a population-based study (Stroke Prevention: Assessment of Risk in a Community). The associations between atherosclerosis risk factors, clinical cardiovascular disease, aortic atherosclerotic plaques, and IAS thickness were examined. Age and body surface area (BSA) were significantly associated with IAS thickness (median: 6 mm; range: 2-17 mm). IAS thickness increased by 12.6% per 10 years of age (95% confidence interval: 9.0-16.4%) adjusting for sex and BSA, and increased by 7.0% per 0.1 m 2 BSA (confidence interval: 5.0-9.2%) adjusting for age and sex. Overall, age, sex, and BSA accounted for 22.5% of the variability in IAS thickness. Current smoking (20.4% increase in IAS thickness in current smokers) and hypertension treatment (8.5% increase in treated patients) were associated with increased IAS thickness, adjusting for age, sex, and BSA ( P < .05), but these two risk factor variables jointly explained only an additional 2.3% of the variability in IAS thickness beyond the variability explained by age, sex, and BSA. Clinical coronary artery and cerebrovascular disease, atrial arrhythmias, and aortic atherosclerotic plaques were not associated with IAS thickness, adjusting for age, sex, and BSA ( P > .3). IAS thickening is an age-associated process. Atherosclerosis risk factors are weakly associated with IAS thickening, whereas atherosclerotic vascular disease is not.

Recombinant Interferon Alfa-2b in Treating Patients With Melanoma

ClinicalTrials.gov

2016-05-17

Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

Neoadjuvant Chemotherapy Followed by Radiation Therapy and Gemcitabine/Sorafenib/Vorinostat in Pancreatic Cancer

ClinicalTrials.gov

2017-11-29

Pancreatic Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Recurrent Pancreatic Carcinoma

Vascular and Cognitive Assessments in Patients With Breast Cancer Undergoing Chemotherapy After Surgery

ClinicalTrials.gov

2017-05-25

Cognitive/Functional Effects; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Cardiac Rehabilitation Program in Improving Cardiorespiratory Fitness in Stage 0-III Breast Cancer Survivors

ClinicalTrials.gov

2018-01-04

Cancer Survivor; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Heavy Metal Exposure in Predicting Peripheral Neuropathy in Patients With Stage I-III Breast Cancer Undergoing Chemotherapy

ClinicalTrials.gov

2017-06-14

Male Breast Cancer; Neurotoxicity; Peripheral Neuropathy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Virtual Weight Loss Program in Maintaining Weight in African American Breast Cancer Survivors

ClinicalTrials.gov

2018-06-13

Cancer Survivor; Invasive Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

ClinicalTrials.gov

2017-08-07

Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Physical Activity Behavioral Intervention in Obese Endometrial Cancer Survivors

ClinicalTrials.gov

2015-10-14

Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

ClinicalTrials.gov

2018-05-11

Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Prognostic impact of the integration of volumetric quantification of the solid part of the tumor on 3DCT and FDG-PET imaging in clinical stage IA adenocarcinoma of the lung.

PubMed

Furumoto, Hideyuki; Shimada, Yoshihisa; Imai, Kentaro; Maehara, Sachio; Maeda, Junichi; Hagiwara, Masaru; Okano, Tetsuya; Masuno, Ryuhei; Kakihana, Masatoshi; Kajiwara, Naohiro; Ohira, Tatsuo; Ikeda, Norihiko

2018-07-01

The aim of this study was to conduct comparative analyses of the biological malignant potential of clinical stage IA adenocarcinoma using positron emission tomography/computed tomography (PET/CT), high-resolution CT (HRCT), and three-dimensional CT (3DCT). The predictive performance of these parameters was evaluated in terms of clinical outcomes and pathological invasiveness (positive lymphatic permeation, blood-vessel invasion, pleural invasion, and lymph-node metastasis). We enrolled 170 patients with c-IA adenocarcinoma who underwent PET/CT, HRCT, and 3D reconstruction of lung structures using the Synapse Vincent system (Fujifilm Corporation, Tokyo, Japan) followed by complete resection. Maximum standardized uptake values (SUV max ) of F 18 -fluorodeoxyglucose and the size and volume of the solid part of the tumor were quantified and analyzed in relation to surgical outcomes. Univariate analysis demonstrated that all the three parameters and whole-tumor volume were associated with unfavorable disease-free survival (DFS), while the volume of the solid part was the independent predictor on multivariate analysis (p < .001). The receiver operating characteristic curves for pathological invasiveness, determined using the variables dichotomized at each cut-off level (SUV max 2.4; solid-part size 1.23 cm; solid-part volume 779 mm 3 ), showed that all were significantly correlated with pathological invasiveness and prognosis, whereas the combination of SUV max and the solid-part volume was the most powerful predictor of survival and pathological invasiveness compared to any other parameters: the 4-year DFS and proportion of pathological invasiveness in patients with SUV max  > 2.4 and solid-part volume > 779 mm 3 versus those with SUV max  ≤ 2.4 or solid-part volume ≤779 mm 3 were 81.2% versus 98.3% (p < .001) and 84.3% versus 15.1% (p < .001), respectively. In c-IA adenocarcinoma, the volume of the solid part of the tumor was the independent predictor for unfavorable DFS, and the integration of the volume of the solid part and SUV max was highly beneficial for the prediction of survival and pathological invasiveness. Copyright © 2018 Elsevier B.V. All rights reserved.

Stress Test in Detecting Heart Damage in Premenopausal Women With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-04-26

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Premenopausal; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With Uterine Cancer

ClinicalTrials.gov

2015-01-16

Stage IA Uterine Sarcoma; Stage IB Uterine Sarcoma; Stage IC Uterine Sarcoma; Stage IIA Uterine Sarcoma; Stage IIB Uterine Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Carcinosarcoma

Recurrence risk of ictal asystole in epilepsy.

PubMed

Hampel, Kevin G; Thijs, Roland D; Elger, Christian E; Surges, Rainer

2017-08-22

To determine the recurrence risk of ictal asystole (IA) and its determining factors in people with epilepsy. We performed a systematic review of published cases with IA in 3 databases and additionally searched our local database for patients with multiple seizures simultaneously recorded with ECG and EEG and at least one IA. IA recurrence risk was estimated by including all seizures without knowledge of the chronological order. Various clinical features were assessed by an individual patient data meta-analysis. A random mixed effect logistic regression model was applied to estimate the average recurrence risk of IA. Plausibility of the calculated IA recurrence risk was checked by analyzing the local dataset with available information in chronological order. Eighty patients with 182 IA in 537 seizures were included. Recurrence risk of IA amounted to 40% (95% confidence interval [CI] 32%-50%). None of the clinical factors (age, sex, type and duration of epilepsy, hemispheric lateralization, duration of IA per patient) appeared to have a significant effect on the short-term recurrence risk of IA. When considering the local dataset only, IA recurrence risk was estimated to 30% (95% CI 14%-53%). Information whether IA coincided with symptoms (i.e., syncope) or not was given in 60 patients: 100 out of 142 IAs were symptomatic. Our data suggest that in case of clinically suspected IA, the recording of 1 or 2 seizures is not sufficient to rule out IA. Furthermore, the high short-term recurrence risk favors aggressive treatment, including pacemaker implantation if seizure freedom cannot be achieved. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Phase I: At-Home Support for Rural Women Using Group Video Calling

ClinicalTrials.gov

2014-10-15

Depression; Post-traumatic Stress Disorder; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

The effect of Interaction Anxiousness Scale and Brief Social Phobia Scale for screening social anxiety disorder in college students: a study on discriminative validity.

PubMed

Cao, Jianqin; Yang, Jinwei; Zhou, Yuqiu; Chu, Fuliu; Zhao, Xiwu; Wang, Weiren; Wang, Yunlong; Peng, Tao

2016-12-01

Social anxiety disorder (SAD) is one of the most prevalent mental health problems, but there is little research concerning the effective screening instruments in practice. This study was designed to examine the discriminative validity of Interaction Anxiousness Scale (IAS) and Brief Social Phobia Scale (BSPS) for the screening of SAD through the compared and combined analysis. Firstly, 421 Chinese undergraduates were screened by the IAS and BSPS. Secondly, in the follow-up stage, 248 students were interviewed by the Structured Clinical Interview for DSM-IV. Receiver operating characteristic (ROC) analysis was used, and the related psychometric characters were checked. The results indicated that the ROC in these two scales demonstrated discrimination is in satisfactory level (range: 0.7-0.8). However, the highest agreement (92.17%) was identified when a cut-off point of 50 measured by the IAS and a cut-off point of 34 by the BSPS were combined, also with higher PPV, SENS, SPEC and OA than that reached when BSPS was used individually, as well as PPV, SPEC and OA in IAS. The findings indicate that the combination of these two scales is valid as the general screening instrument for SAD in maximizing the discriminative validity.

Functional Magnetic Resonance Imaging in Assessing Affect Reactivity and Regulation in Patients With Stage 0-III Breast Cancer

ClinicalTrials.gov

2018-05-30

Healthy Subject; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Use of Image-Guided Stereotactic Body Radiation Therapy in Lieu of Intracavitary Brachytherapy for the Treatment of Inoperable Endometrial Neoplasia

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

Kemmerer, Eric; Hernandez, Enrique; Ferriss, James S.

2013-01-01

Purpose: Retrospective analysis of patients with invasive endometrial neoplasia who were treated with external beam radiation therapy followed by stereotactic body radiation therapy (SBRT) boost because of the inability to undergo surgery or brachytherapy. Methods and Materials: We identified 11 women with stage I-III endometrial cancer with a median age of 78 years that were not candidates for hysterectomy or intracavitary brachytherapy secondary to comorbidities (91%) or refusal (9%). Eight patients were American Joint Committee on Cancer (AJCC) stage I (3 stage IA, 5 stage IB), and 3 patients were AJCC stage III. Patients were treated to a median ofmore » 4500 cGy at 180 cGy per fraction followed by SBRT boost (600 cGy per fraction Multiplication-Sign 5). Results: The most common side effect was acute grade 1 gastrointestinal toxicity in 73% of patients, with no late toxicities observed. With a median follow-up of 10 months since SBRT, 5 patients (45%) experienced locoregional disease progression, with 3 patients (27%) succumbing to their malignancy. At 12 and 18 months from SBRT, the overall freedom from progression was 68% and 41%, respectively. Overall freedom from progression (FFP) was 100% for all patients with AJCC stage IA endometrial carcinoma, whereas it was 33% for stage IB at 18 months. The overall FFP was 100% for International Federation of Obstetrics and Gynecology grade 1 disease. The estimated overall survival was 57% at 18 months from diagnosis. Conclusion: In this study, SBRT boost to the intact uterus was feasible, with encouragingly low rates of acute and late toxicity, and favorable disease control in patients with early-stage disease. Additional studies are needed to provide better insight into the best management of these clinically challenging cases.« less

Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer

ClinicalTrials.gov

2017-12-18

Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Erlotinib Hydrochloride in Treating Patients With Pancreatic Cancer That Can Be Removed by Surgery

ClinicalTrials.gov

2014-10-07

Intraductal Papillary Mucinous Neoplasm of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

Omega-3 Fatty Acid in Treating Patients With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-06-25

Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Male Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

KeraStat Skin Therapy in Treating Radiation Dermatitis in Patients With Newly Diagnosed Stage 0-IIIA Breast Cancer

ClinicalTrials.gov

2017-05-25

Ductal Breast Carcinoma in Situ; Skin Reactions Secondary to Radiation Therapy; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

ClinicalTrials.gov

2017-09-05

Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

ClinicalTrials.gov

2018-02-15

Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

ROS and trehalose regulate sclerotial development in Rhizoctonia solani AG-1 IA.

PubMed

Wang, Chenjiaozi; Pi, Lei; Jiang, Shaofeng; Yang, Mei; Shu, Canwei; Zhou, Erxun

2018-05-01

Rhizoctonia solani AG-1 IA is the causal agent of rice sheath blight (RSB) and causes severe economic losses in rice-growing regions around the world. The sclerotia play an important role in the disease cycle of RSB. In this study, we report the effects of reactive oxygen species (ROS) and trehalose on the sclerotial development of R. solani AG-1 IA. Correlation was found between the level of ROS in R. solani AG-1 IA and sclerotial development. Moreover, we have shown the change of ROS-related enzymatic activities and oxidative burst occurs at the sclerotial initial stage. Six genes related to the ROS scavenging system were quantified in different sclerotial development stages by using quantitative RT-PCR technique, thereby confirming differential gene expression. Fluorescence microscopy analysis of ROS content in mycelia revealed that ROS were predominantly produced at the hyphal branches during the sclerotial initial stage. Furthermore, exogenous trehalose had a significant inhibitory effect on the activities of ROS-related enzymes and oxidative burst and led to a reduction in sclerotial dry weight. Taken together, the findings suggest that ROS has a promoting effect on the development of sclerotia, whereas trehalose serves as an inhibiting factor to sclerotial development in R. solani AG-1 IA. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Endometrial Cancer

ClinicalTrials.gov

2016-01-11

Endometrial Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Doxorubicin Hydrochloride, Vinblastine, Dacarbazine, Brentuximab Vedotin, and Nivolumab in Treating Patients With Stage I-II Hodgkin Lymphoma

ClinicalTrials.gov

2018-04-30

Ann Arbor Stage I Hodgkin Lymphoma; Ann Arbor Stage IA Hodgkin Lymphoma; Ann Arbor Stage IB Hodgkin Lymphoma; Ann Arbor Stage II Hodgkin Lymphoma; Ann Arbor Stage IIA Hodgkin Lymphoma; Ann Arbor Stage IIB Hodgkin Lymphoma

Stereotactic Image-Guided Navigation During Breast Reconstruction in Patients With Breast Cancer

ClinicalTrials.gov

2017-04-12

Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Interactive Gentle Yoga in Improving Quality of Life in Patients With Stage I-III Breast Cancer Undergoing Radiation Therapy

ClinicalTrials.gov

2017-07-28

Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Fatigue; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

A clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer.

PubMed

Zhang, Yang; Sun, Yihua; Xiang, Jiaqing; Zhang, Yawei; Hu, Hong; Chen, Haiquan

2014-10-01

Controversy remains over the appropriate postoperative management for patients with stage Ia non-small cell lung cancer who underwent complete surgical resection as a result of a heterogeneous prognosis. We aimed to identify the predictive factors for recurrence in these patients to aid in the decision making. We reviewed 344 patients with stage Ia non-small cell lung cancer to analyze the associations between recurrence-free survival and the following clinicopathologic variables: age, gender, smoking history, family history, preoperative serum carcinoembryonic antigen level, type of surgical resection, tumor location, tumor histology, lymphovascular invasion, tumor differentiation, and pathologic T status. Cox multivariate survival analysis revealed that central tumor location (P=.019), stage T1b (P=.006), high histologic grade (including large cell carcinoma, solid predominant, micropapillary predominant, and invasive mucinous adenocarcinoma, P=.007), poor differentiation (P=.022), and lymphovascular invasion (P=.035) were independently associated with recurrence-free survival. A nomogram for predicting the probability of 3-year recurrence-free survival was developed using the 5 variables. This model shows good calibration, reasonable discrimination (concordance index=0.733), and small overfitting (2.6%) demonstrated by bootstrapping. We developed a clinicopathologic prediction model for postoperative recurrence in stage Ia non-small cell lung cancer. This model can help with the selection of appropriate postoperative therapeutic strategies for these patients. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Booster Vaccination in Preventing Disease Recurrence in Previously Vaccinated Patients With Melanoma That Has Been Removed By Surgery

ClinicalTrials.gov

2015-01-23

Recurrent Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma; Stage IV Skin Melanoma

Ultrasound in Detecting Taxane-Induced Neuropathy in Patients With Breast Cancer

ClinicalTrials.gov

2018-04-26

Peripheral Neuropathy; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

A Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms (AIMSS)

ClinicalTrials.gov

2015-05-07

Estrogen Receptor-positive Breast Cancer; Musculoskeletal Complications; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Questionnaires in Identifying Upper Extremity Function and Quality of Life After Treatment in Patients With Breast Cancer

ClinicalTrials.gov

2017-04-11

Musculoskeletal Complication; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-Related Toxicity

Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

ClinicalTrials.gov

2014-09-09

Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

Transdermal or Oral Telapristone Acetate in Treating Patients Undergoing Mastectomy

ClinicalTrials.gov

2018-01-22

BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma In Situ; Lobular Breast Carcinoma In Situ; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Shared and Distinct Rupture Discriminants of Small and Large Intracranial Aneurysms.

PubMed

Varble, Nicole; Tutino, Vincent M; Yu, Jihnhee; Sonig, Ashish; Siddiqui, Adnan H; Davies, Jason M; Meng, Hui

2018-04-01

Many ruptured intracranial aneurysms (IAs) are small. Clinical presentations suggest that small and large IAs could have different phenotypes. It is unknown if small and large IAs have different characteristics that discriminate rupture. We analyzed morphological, hemodynamic, and clinical parameters of 413 retrospectively collected IAs (training cohort; 102 ruptured IAs). Hierarchal cluster analysis was performed to determine a size cutoff to dichotomize the IA population into small and large IAs. We applied multivariate logistic regression to build rupture discrimination models for small IAs, large IAs, and an aggregation of all IAs. We validated the ability of these 3 models to predict rupture status in a second, independently collected cohort of 129 IAs (testing cohort; 14 ruptured IAs). Hierarchal cluster analysis in the training cohort confirmed that small and large IAs are best separated at 5 mm based on morphological and hemodynamic features (area under the curve=0.81). For small IAs (<5 mm), the resulting rupture discrimination model included undulation index, oscillatory shear index, previous subarachnoid hemorrhage, and absence of multiple IAs (area under the curve=0.84; 95% confidence interval, 0.78-0.88), whereas for large IAs (≥5 mm), the model included undulation index, low wall shear stress, previous subarachnoid hemorrhage, and IA location (area under the curve=0.87; 95% confidence interval, 0.82-0.93). The model for the aggregated training cohort retained all the parameters in the size-dichotomized models. Results in the testing cohort showed that the size-dichotomized rupture discrimination model had higher sensitivity (64% versus 29%) and accuracy (77% versus 74%), marginally higher area under the curve (0.75; 95% confidence interval, 0.61-0.88 versus 0.67; 95% confidence interval, 0.52-0.82), and similar specificity (78% versus 80%) compared with the aggregate-based model. Small (<5 mm) and large (≥5 mm) IAs have different hemodynamic and clinical, but not morphological, rupture discriminants. Size-dichotomized rupture discrimination models performed better than the aggregate model. © 2018 American Heart Association, Inc.

Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

ClinicalTrials.gov

2018-06-27

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Grade 1 Peripheral Motor Neuropathy, CTCAE; Grade 1 Peripheral Sensory Neuropathy, CTCAE; Grade 2 Peripheral Motor Neuropathy, CTCAE; Grade 2 Peripheral Sensory Neuropathy, CTCAE; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

[Aortic elastic properties and its clinical significance in intracranial aneurysms].

PubMed

Pu, Zhao-xia; You, Xiang-dong; Weng, Wen-chao; Wang, Jian-an; Shi, Jian

2011-09-01

To investigate the aortic elastic properties and its clinical significance in intracranial aneurysms (IAs). One hundred and seven IAs patients (57 with hypertension) and 108 healthy subjects were recruited. The internal aortic diameters in systole and diastole were measured by the M-mode echocardiography, the aortic elasticity indexes were calculated and compared. The aortic distensibility (DIS) was lower and the aortic stiffness index (SI) was higher in IAs patients than those in controls (both P <0.001). DIS was lower and SI was higher in IAs patients with hypertension (IAs-HP) than those in IAs with no hypertension (P <0.001). Similar results were obtained when the aortic elasticity index were adjusted for body surface area and body mass index. Abnormal aortic elasticity is a common finding in IAs patients and hypertension is closely related to the severity of aortic elasticity.

Biomarkers in Tissue Samples From Patients With Newly Diagnosed Breast Cancer Treated With Zoledronic Acid

ClinicalTrials.gov

2018-06-01

Estrogen Receptor-positive Breast Cancer; Invasive Ductal Breast Carcinoma; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Gemcitabine Hydrochloride, Docetaxel, and Radiation Therapy in Treating Patients With Uterine Sarcoma That Has Been Removed By Surgery

ClinicalTrials.gov

2015-01-16

Stage IA Uterine Sarcoma; Stage IB Uterine Sarcoma; Stage IC Uterine Sarcoma; Stage IIA Uterine Sarcoma; Stage IIB Uterine Sarcoma; Stage IIIA Uterine Sarcoma; Stage IIIB Uterine Sarcoma; Stage IIIC Uterine Sarcoma; Stage IVA Uterine Sarcoma; Stage IVB Uterine Sarcoma; Uterine Corpus Leiomyosarcoma

Interactive Tailored Website to Promote Sun Protection and Skin Self-Check Behaviors in Patients With Stage 0-III Melanoma

ClinicalTrials.gov

2017-11-15

Stage 0 Skin Melanoma; Stage I Skin Melanoma; Stage IA Skin Melanoma; Stage IB Skin Melanoma; Stage II Skin Melanoma; Stage IIA Skin Melanoma; Stage IIB Skin Melanoma; Stage IIC Skin Melanoma; Stage III Skin Melanoma; Stage IIIA Skin Melanoma; Stage IIIB Skin Melanoma; Stage IIIC Skin Melanoma

Fulvestrant and Palbociclib in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

ClinicalTrials.gov

2016-09-21

Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Cryotherapy in Preventing Peripheral Neuropathy and Nail Toxicity in Patients With Breast Cancer Who Are Receiving Paclitaxel

ClinicalTrials.gov

2018-01-09

Chemotherapeutic Agent Toxicity; Pain; Peripheral Neuropathy; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Therapy-related Toxicity

EF5 in Measuring Tumor Hypoxia in Patients With Stage I-III Non-Small Cell Lung Cancer

ClinicalTrials.gov

2015-04-10

Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer

Docosahexaenoic Acid in Preventing Recurrence in Breast Cancer Survivors

ClinicalTrials.gov

2016-06-20

Benign Breast Neoplasm; Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Lobular Breast Carcinoma In Situ; Paget Disease of the Breast; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Combination Chemotherapy With or Without Oregovomab Followed by Stereotactic Body Radiation Therapy and Nelfinavir Mesylate in Treating Patients With Locally Advanced Pancreatic Cancer

ClinicalTrials.gov

2018-04-24

Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

Survivorship Care Planning in Improving Quality of Life in Survivors of Ovarian Cancer

ClinicalTrials.gov

2017-09-27

Cancer Survivor; Stage IA Ovarian Epithelial Cancer; Stage IB Ovarian Epithelial Cancer; Stage IC Ovarian Epithelial Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer

Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

ClinicalTrials.gov

2018-04-17

Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma

Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting

ClinicalTrials.gov

2018-01-11

Breast Cancer; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Broccoli Sprout Extract in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-04

Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

PubMed

Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-03-01

Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

PubMed Central

Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-01-01

Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

ClinicalTrials.gov

2018-01-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

Exercise in Targeting Metabolic Dysregulation in Stage I-III Breast or Prostate Cancer Survivors

ClinicalTrials.gov

2017-09-12

Cancer Survivor; No Evidence of Disease; Obesity; Overweight; Prostate Carcinoma; Sedentary Lifestyle; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

ClinicalTrials.gov

2018-04-13

Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Soy Isoflavones Supplementation in Treating Women at High Risk For or With Breast Cancer

ClinicalTrials.gov

2018-03-30

BRCA1 Mutation Carrier; BRCA2 Mutation Carrier; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer

Dasatinib and Gemcitabine Hydrochloride or Gemcitabine Hydrochloride Alone in Treating Patients With Pancreatic Cancer Previously Treated With Surgery

ClinicalTrials.gov

2018-01-05

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer

VX15/2503 and Immunotherapy in Resectable Pancreatic and Colorectal Cancer

ClinicalTrials.gov

2017-12-26

Colon Carcinoma Metastatic in the Liver; Colorectal Adenocarcinoma; Pancreatic Adenocarcinoma; Resectable Pancreatic Carcinoma; Stage I Pancreatic Cancer; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage II Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Colorectal Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

MK2206 in Treating Patients With Stage I, Stage II, or Stage III Breast Cancer

ClinicalTrials.gov

2017-08-01

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Triple-Negative Breast Carcinoma

Exercise Intervention in Targeting Adiposity and Inflammation With Movement to Improve Prognosis in Breast Cancer

ClinicalTrials.gov

2018-05-01

Cancer Survivor; Central Obesity; Estrogen Receptor Positive; Postmenopausal; Progesterone Receptor Positive; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Relapse and disease specific survival in 1143 Danish women diagnosed with borderline ovarian tumours (BOT).

PubMed

Karlsen, Nikoline Marie Schou; Karlsen, Mona Aarenstrup; Høgdall, Estrid; Nedergaard, Lotte; Christensen, Ib Jarle; Høgdall, Claus

2016-07-01

The aim of the study was to evaluate the rate of relapse as well as disease-free, overall, and disease-specific survival in women with borderline ovarian tumour (BOT). Furthermore, the study aims to identify the clinical parameters correlated to relapse. National clinical data of women diagnosed with BOT from January 2005 to January 2013 constituted the basis for our study population. The prognostic influence of clinical variables was evaluated using univariate and multivariate analyses. A total of 1143 women were eligible for analysis, with 87.9% in FIGO stage I and 12.1% in FIGO stages II-IV. Relapse of BOT was detected in 3.7%, hereof 40.5% with malignant transformation. The five-year disease-free survival was 97.6% in FIGO stage I and 87.3% in FIGO stages II-IV. Younger age, laparoscopic surgical approach, fertility sparing surgery, FIGO stages II-IV, bilateral tumour presence, serous histology, implants and microinvasion of the tumour were significantly associated with relapse in univariate analyses. The overall five-year survival rate was 92.2% in FIGO stage I and 89.0% in FIGO stages II-IV. Out of 77 deaths in total, only seven women died from BOT. A general favourable prognosis in women with BOT was confirmed in our study. Our findings indicate that systematic, long-term follow-up does not seem necessary in women treated for FIGO stage IA BOT with no residual disease or microinvasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Educational Counseling in Improving Communication and Quality of Life in Spouses and Breast Cancer Patients

ClinicalTrials.gov

2018-02-06

Anxiety Disorder; Depression; Ductal Breast Carcinoma in Situ; Lobular Breast Carcinoma in Situ; Psychosocial Effects of Cancer and Its Treatment; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

[Current knowledge on perioperative treatments of non-small cell lung carcinomas].

PubMed

Brosseau, S; Naltet, C; Nguenang, M; Gounant, V; Mordant, P; Milleron, B; Castier, Y; Zalcman, G

2017-06-01

Surgery is still the main treatment in early-stage of non-small cell lung cancer with 5-year survival of stage IA patients exceeding 80%, but 5-year survival of stage II patients rapidly decreasing with tumor size, N status, and visceral pleura invasion. The major metastatic risk in such patients has supported clinical research assessing systemic or loco-regional perioperative treatments. Modern phase 3 trials clearly validated adjuvant or neo-adjuvant platinum-based chemotherapy in resected stage I-III patients as a standard treatment of which value has been reassessed several independent meta-analyses, showing a 5% benefit in 5y-survival, and a decrease of the relative risk for death around from 12 to 25%. Conversely perioperative treatments were not validated for stage IA and IB patients. In more advanced stage patients, neo-adjuvant radio-chemotherapy has not been validated either. Adjuvant radiotherapy for N2 patients is currently tested in the large international phase 3 trial Lung-ART/IFCT-0503. The development of video-assisted thoracic surgery (VATS) has helped adjuvant chemotherapies for elderly patients. Perioperative targeted treatments in NSCLC with EGFR or ALK molecular alterations is currently assessed in the U.S. ALCHEMIST prospective trial. Finally, the role of immune check-points inhibitors is currently evaluated in a large international phase 3 trial testing adjuvant anti-PD-L1 monoclonal antibody, the BR31/IFCT-1401 trial, while a proof-of principle neo-adjuvant trial IONESCO/IFCT-1601, has just begun by the end of the 2016 year, with survival results of both trials expected in 5 to 7 years. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Comparative pharmacokinetics and bioavailability of escin Ia and isoescin Ia after administration of escin and of pure escin Ia and isoescin Ia in rat.

PubMed

Wu, Xiu-Jun; Zhang, Meng-Liang; Cui, Xiang-Yong; Gao, Feng; He, Qun; Li, Xiao-Jiao; Zhang, Ji-Wen; Fawcett, J Paul; Gu, Jing-Kai

2012-01-06

Escin Ia and isoescin Ia have been traditionally used clinically as the chief active ingredients of escin, a major triterpene saponin isolated from horse chestnut (Aesculus hippocastanum) seeds for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. To establish a sensitive LC-MS/MS method and investigate the pharmacokinetic properties of escin Ia and isoescin Ia in rats and the pharmacokinetics difference of sodium escinate with pure escin Ia and isoescin Ia. The absolute bioavailability of escin Ia and isoescin Ia and the bidirectional interconversion of them in vivo were also scarcely reported. Wister rats were administrated an intravenous (i.v.) dose (1.7 mg/kg) of sodium escinate (corresponding to 0.5mg/kg of escin Ia and 0.5mg/kg of isoescin Ia, respectively) and an i.v. dose (0.5mg/kg) or oral dose (4mg/kg) of pure escin Ia or isoescin Ia, respectively. At different time points, the concentrations of escin Ia and isoescin Ia in rat plasma were determined by LC-MS/MS method. Main pharmacokinetic parameters including t(1/2), MRT, CL, V(d), AUC and F were estimated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany) and statistical analysis was performed using the Student's t-test with P<0.05 as the level of significance. After administration of sodium escinate, the t(1/2) and MRT values for both escin Ia and isoescin Ia were larger than corresponding values for the compounds given alone. Absorption of escin Ia and isoescin Ia was very low with F values both <0.25%. Escin Ia and isoescin Ia were found to form the other isomer in vivo with the conversion of escin Ia to isoescin Ia being much extensive than from isoescin Ia to escin Ia. Comparison of the pharmacokinetics of escin Ia and isoescin Ia given alone and together in rat suggest that administration of herbal preparations of escin for clinical use may provide longer duration of action than administration of single isomers. The interconversion of escin Ia and isoescin Ia when given alone indicates that administration of one isomer leads to exposure to the other. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer

ClinicalTrials.gov

2016-07-29

Estrogen Receptor Positive Breast Cancer; Progesterone Receptor Positive Tumor; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer

ClinicalTrials.gov

2018-02-01

Estrogen Receptor Status; HER2 Positive Breast Carcinoma; Progesterone Receptor Status; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage III Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Parental insightfulness: retrospect and prospect.

PubMed

Koren-Karie, Nina; Oppenheim, David

2018-06-01

We open this introductory paper to the special issue with the theoretical and clinical roots of the insightfulness concept. Next, the Insightfulness Assessment (IA) is presented, followed by a review of key empirical findings supporting the IA. The central points in the papers in this special issue are reviewed next. These include the use of the IA with parents of children ranging in age from infancy to adolescence, its applicability outside the parent-child relationship (e.g. insightfulness toward a close friend), its use with high-risk mothers, and the usefulness of insightfulness both as a continuous and a categorical measure. The clinical applications of the IA are discussed, and we close with future directions for IA research.

Internet Addiction: A Logotherapeutic Approach

ERIC Educational Resources Information Center

Didelot, Mary J.; Hollingsworth, Lisa; Buckenmeyer, Janet A.

2012-01-01

Internet addiction (IA) is both the most rapidly growing addiction and the least understood addiction (Watson, 2005). For counselors, treatment issues surrounding the disease are also growing. At the forefront is the lack of understanding concerning treatment protocol to manage the challenging recovery and maintenance stages after IA behavior has…

Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development.

PubMed

Acevedo-Calado, Maria; James, Eddie A; Morran, Michael P; Pietropaolo, Susan L; Ouyang, Qin; Arribas-Layton, David; Songini, Marco; Liguori, Marco; Casu, Anna; Auchus, Richard J; Huang, Shuai; Yu, Liping; Michels, Aaron; Gianani, Roberto; Pietropaolo, Massimo

2017-04-01

The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes. Clinically diagnosed patients with type 2 diabetes ( n = 258; diabetes duration: 0.01-31 years) were evaluated using a new biomarker detecting autoantibodies directed to the extracellular domain of the neuroendocrine autoantigen IA-2 (IA-2ec). The proportion of IA-2ec autoantibodies was also evaluated in newly diagnosed patients with type 1 diabetes ( n = 150; diabetes duration: 0.04-0.49 years). In addition, IA-2 (intracellular domain), GAD65, and zinc transporter 8 autoantibodies were assayed. IA-2ec autoantibodies were detected in patients with type 1 diabetes and, surprisingly, in 5% of patients with type 2 diabetes without serologic responses to other IA-2 antigenic epitopes or other islet autoantigens. We also assessed the ability of IA-2ec-derived peptides to elicit CD4 + T-cell responses by stimulating peripheral blood mononuclear cells from patients with type 1 diabetes ( n = 18) and HLA-matched healthy subjects ( n = 13) with peptides and staining with the peptide/DQ8-specific tetramers, observing disease-associated responses to previously unreported epitopes within IA-2ec. We developed a new antibody biomarker identifying novel antigenic determinants within the N terminus of IA-2. IA-2ec autoantibodies can be detected in patients with type 1 diabetes and in a subgroup of adult autoimmune patients with type 2 diabetes phenotype negative for conventional islet autoantibody testing. These observations suggest that islet autoimmunity may be more common in clinically diagnosed type 2 diabetes than previously observed. © 2017 by the American Diabetes Association.

Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

ClinicalTrials.gov

2018-01-29

Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

64Cu DOTA-Trastuzumab PET/CT in Studying Patients With Gastric Cancer

ClinicalTrials.gov

2017-12-11

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IA Gastric Cancer; Stage IB Gastric Cancer; Stage IIA Gastric Cancer; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy

ClinicalTrials.gov

2017-09-25

Ductal Breast Carcinoma in Situ; Invasive Ductal Breast Carcinoma; Invasive Lobular Breast Carcinoma; Lobular Breast Carcinoma in Situ; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer

Challenging a dogma; AJCC 8th staging system is not sufficient to predict outcomes of patients with malignant pleural mesothelioma.

PubMed

Abdel-Rahman, Omar

2017-11-01

The 8th edition of malignant pleural mesothelioma (MPM) American Joint Committee on Cancer (AJCC) staging system has been published. The current analysis aims to evaluate its performance in a population-based setting among patients recorded within the surveillance, epidemiology and end results (SEER) database. SEER database (2004-2013) has been accessed through SEER*Stat program and AJCC 8th edition stage groups were reconstructed. Survival analyses (overall and cancer-specific) were conducted according to 6th and 8th editions through Kaplan-Meier analysis. Cox-regression multivariate model was also utilized for pair wise comparisons between different prognostic groups for overall and cancer-specific survival. A total of 5382 patients with MPM were identified in the period from 2004 to 2013. According to the 6th edition, significant pair wise P values for overall survival included: IA vs. III (P=0.027); IA vs. IV: P<0.0001; IB vs. IV: P<0.0001; II vs. III: P<0.0001; II vs. IV: P<0.0001; III vs. IV: P<0.0001). According to the 8th edition, significant pair wise P values for overall survival included: all stages vs. IV: P<0.0001; IA vs. II: P=0.046; IA vs. IIIA: P=0.022; IA vs. IIIB: P <0.0001; IB vs. II: P<0.0001; IB vs. IIIB: P<0.0001; II vs. IIIA: P<0.0001; IIIA vs. IIIB: P<0.0001). C-index for 6th edition was 0.539 (SE: 0.008; 95% CI: 0.524-0.555); while C-index for 8th edition was 0.540 (SE: 0.008; 95% CI: 0.525-0.556). Based on the above findings, a simplified staging system was proposed and overall and cancer-specific survivals were evaluated according to the simplified system. For overall and cancer-specific survival assessment, P values for all pair wise comparisons among different stages were significant (<0.01). The prognostic performance of both the 6th and 8th AJCC editions is unsatisfactory; there is a need for a more practical and prognostically relevant staging system for MPM. Copyright © 2017 Elsevier B.V. All rights reserved.

Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery

ClinicalTrials.gov

2017-08-30

Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer

ClinicalTrials.gov

2017-10-10

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Negative; Male Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Staging for vulvar cancer.

PubMed

Hacker, Neville F; Barlow, Ellen L

2015-08-01

Vulvar cancer has been staged by the International Federation of Gynaecology and Obstetrics (FIGO) since 1969, and the original staging system was based on clinical findings only. This system provided a very good spread of prognostic groupings. Because vulvar cancer is virtually always treated surgically, the status of the lymph nodes is the most important prognostic factor and this can only be determined with certainty by histological examination of resected lymph nodes, FIGO introduced a surgical staging system in 1988. This was modified in 1994 to include a category of microinvasive vulvar cancer (stage IA), because such patients have virtually no risk of lymph node metastases. This system did not give a reasonably even spread of prognostic groupings. In addition, patients with stage III disease were shown to be a heterogeneous group prognostically, and the number of positive nodes and the morphology of those nodes were not taken into account. A new surgical staging system for vulvar cancer was introduced by FIGO in 2009. Initial retrospective analyses have suggested that this new staging system has overcome the major deficiencies in the 1994 system. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Oppositional defiant disorder/conduct disorder co-occurrence increases the risk of Internet addiction in adolescents with attention-deficit hyperactivity disorder.

PubMed

Gunes, Hatice; Tanidir, Canan; Adaletli, Hilal; Kilicoglu, Ali Guven; Mutlu, Caner; Bahali, Mustafa Kayhan; Topal, Melike; Bolat, Nurullah; Uneri, Ozden Sukran

2018-06-05

Objectives The aims of this cross-sectional study were to assess the prevalence of Internet addiction (IA) in a clinical sample of adolescents with attention-deficit hyperactivity disorder (ADHD) and to detect the moderating effects of co-occurring oppositional defiant disorder/conduct disorder (ODD/CD) on the association between ADHD and IA. Methods The study group comprised 119 adolescent subjects who were consecutively referred to our outpatient clinic with a diagnosis of ADHD. The Turgay DSM-IV-Based Child and Adolescent Disruptive Behavioral Disorders Screening and Rating Scale (T-DSM-IV-S) was completed by parents, and subjects were asked to complete the Internet Addiction Scale (IAS). Results The IAS results indicated that 63.9% of the participants (n = 76) fell into the IA group. Degree of IA was correlated with hyperactivity/impulsivity symptoms but not with inattention symptoms. As compared to the ADHD-only group (without comorbid ODD/CD), ADHD + ODD/CD subjects returned significantly higher scores on the IAS. Conclusions As adolescents with ADHD are at high risk of developing IA, early IA detection and intervention is of great importance for this group. In addition, adolescents with ADHD + ODD/CD may be more vulnerable to IA than those in the ADHD-only group and may need to be more carefully assessed for IA.

Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: A systematic review and meta-analysis of randomized trials.

PubMed

Altman, Roy D; Devji, Tahira; Bhandari, Mohit; Fierlinger, Anke; Niazi, Faizan; Christensen, Robin

2016-10-01

Hyaluronic acid and corticosteroids are common intra-articular (IA) therapies widely used for the management of mild to moderate knee osteoarthritis (OA). Many trials evaluating the efficacy of IA administered therapies commonly use IA saline injections as a placebo comparator arm. Using a systematic review and meta-analysis, our objective was to assess the clinical benefit associated with use of IA saline in trials of IA therapies in the treatment of patients with painful knee OA. MEDLINE and Embase databases were searched for articles published up to and including August 14th, 2014. Two reviewers assessed the eligibility of potential reports and the risk of bias of included trials. We analyzed short (≤3 months) and long-term (6-12 months) pain reduction of the saline arm of included trials using standardized mean differences (SMDs; estimated assuming a null effect in a comparator group) that were combined and weighted using a random effects model. Treatment-related adverse events (AEs) were tabulated and presented using descriptive statistics. From 40 randomized controlled trials (RCTs) eligible for inclusion only 38 provided sufficient data to be included in the meta-analysis. Based on data with moderate inconsistency IA saline was found to significantly improve short-term knee pain in 32 studies involving 1705 patients (SMD = -0.68; 95% CI: -0.78 to -0.57; P < 0.001; I(2) = 50%). Long-term knee pain was significantly decreased following IA injection with saline in 19 studies involving 1445 patients (SMD = -0.61; 95% CI: -0.76 to -0.45; P < 0.001) with a substantial degree of inconsistency (I(2) = 74%). Overall, 29 of the included trials reported on adverse events, none of which found any serious treatment-related AEs following IA injection with saline. Pain relief observed with IA saline should prompt health care providers to consider the additional effectiveness of current IA treatments that use saline comparators in clinical studies, and challenges of identifying IA saline injection as a "placebo." Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

[Conservative treatment of ectopic pregnancy in a 27 years old patient with stage-Ia ovarian cancer after conservative surgical treatment and chemotherapy].

PubMed

Malinowski, Andrzej; Augustyniak, Tomasz; Bartosiak, Ilona; Maciołek-Bleniewska, Grazyna; Ciesielski, Arkadiusz

2004-01-01

We report a case of conservative treatment of ectopic pregnancy in a 27 years old patient, previously treated for ovarian cancer. Two years before she had surgery because of tumour in the left ovary. Ovarian cancer in stage la according to FIGO was confirmed. Considering the patient s young age, future reproductive plans and the early stage of cancer, the patient qualified for conservative treatment. Left adnexectomy with consequent chemotherapy (6 courses) was performed. Two years later on the ground of clinical symptoms, gynaecologic examination, sonography and changes in HCG serum concentration, ectopic pregnancy was recognised in the right tube. We applied conservative management with intramuscularly administrated Methotrexate. The patient, in good condition, was discharged from hospital on day 12 after injection of Methotrexate.

Excessive interatrial adiposity is associated with left atrial remodeling, augmented contractile performance in asymptomatic population.

PubMed

Lai, Yau-Huei; Yun, Chun-Ho; Su, Cheng-Huang; Yang, Fei-Shih; Yeh, Hung-I; Hou, Charles Jia-Yin; Wu, Tung-Hsin; Cury, Ricardo C; Bezerra, Hiram G; Hung, Chung-Lieh

2016-03-01

Pericardial adipose tissue had been shown to exert local effects on adjacent cardiac structures. Data regarding the mechanistic link between such measures and left atrial (LA) structural/functional remodeling, a clinical hallmark of early stage heart failure (HF) and atrial fibrillation (AF) incidence, in asymptomatic population remain largely unexplored. This retrospective analysis includes 356 subjects free from significant valvular disorders, atrial fibrillation, or clinical HF. Regional adipose tissue including pericardial and periaortic fat volumes, interatrial septal (IAS), and left atrioventricular groove (AVG) fat thickness were all measured by multidetector computed tomography (MDCT) (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). We measured LA volumes, booster performance, reservoir capacity as well as conduit function, and analyzed their association with adiposity measures. All four adiposity measures were positively associated with greater LA volumes (all P < 0.05), while IAS and AVG fat were also related to larger LA kinetic energy and worse reservoir capacity (both P < 0.01). In multivariate models, IAS fat thickness remained independently associated with larger LA volumes, increased LA kinetic energy and ejection force (β-coef: 0.17 & 0.15, both P < 0.05), and impaired LA reservoir and conduit function (β-coef: -0.20 & -0.12, both P < 0.05) after adjusting for clinical variables. Accumulated visceral adiposity, especially interatrial fat depots, was associated with certain LA structural/functional remodeling characterized by impaired LA reservoir and conduit function though augmented kinetic energy and ejection performance. Our data suggested that interatrial fat burden may be associated with certain detrimental LA functions with compensatory LA adaptation in an asymptomatic population. © 2016 The authors.

Significance of epitrochlear lymph node involvement in Hodgkin disease.

PubMed

Chang, B K; Backstrand, K H; Ng, A K; Silver, B; Hitchcock, S L; Mauch, P M

2001-04-01

Epitrochlear involvement in Hodgkin disease (HD) is a rare event, with only limited data available describing this unique presentation, its treatment, and long term outcome. Between 1968 and 1997, 1180 patients with clinical stage (CS) IA-IIB HD were treated at the Harvard Longwood Area Hospitals, among whom 11 were identified to have presented with epitrochlear lymphadenopathy (1%). Together with 6 CS III-IV patients also with clinically involved epitrochlear lymph nodes at diagnosis, these 17 patients form the basis of the current study. The clinical characteristics, histopathologic distribution, and treatment details are described. Two radiation therapy techniques were used: the "single field" and "separate-field" techniques. The median dose to the epitrochlear region was 3600 centigrays. Survival outcome was calculated by the Kaplan-Meier method. The median follow-up was 17 years. The actuarial 15-year freedom from recurrence, cause specific survival, and overall survival (OS) rates for the 17 patients were 70%, 88%, and 70%, respectively. Among the CS IA-IIB patients, the 15-year OS rates of the 1169 patients and 11 patients without and with epitrochlear involvement were 80% and 90%, respectively. Two of the 11 CS IA-IIB and 3 of the 6 CS III-IV patients experienced recurrence. None of the recurrences involved the epitrochlear or ipsilateral brachial region regardless of the treatment technique, and no complications from the local radiation therapy were observed. Feasible and effective radiation therapy techniques are available for patients with HD with epitrochlear involvement. If appropriately treated, the prognosis of patients with this unique presentation appears to be similar to that of other HD patients. Copyright 2001 American Cancer Society.

Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

ClinicalTrials.gov

2018-06-26

Biphasic Mesothelioma; Epithelioid Mesothelioma; Stage I Pleural Malignant Mesothelioma AJCC v7; Stage IA Pleural Malignant Mesothelioma AJCC v7; Stage IB Pleural Malignant Mesothelioma AJCC v7; Stage II Pleural Malignant Mesothelioma AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7

Management of testicular seminoma. Our experience.

PubMed

Sperlongano, P; Pisaniello, D; Di Mauro, U; Pone, D; Casoli, E

2000-01-01

The authors report their experience in the management of seminomas. They examine 12 cases of seminoma among a series of 19 patients with testicular germ cell tumours observed at the Second Surgical Department of the Second University of Naples. Their results showed a better prognosis for patients in early stage of the disease who underwent surgery and adjuvant prophylactic radiotherapy; good survival rates for patients in advanced stages of the disease were achieved by the combined use of surgery, adjuvant radiotherapy and chemotherapy. The authors discuss risk factors, clinical and diagnostic features of seminomas, relating their prognosis with the combined use of both surgery and adjuvant therapies. They consider total orchiectomy, followed by prophylactic radiotherapy, the treatment of choice, especially in stages IA and IIA. They don't perform the routine retroperitoneal lymphadenectomy, differently from American authors, who always achieve it to stage the disease. The authors stress the improvement in the prognosis of seminoma, which has actually reached the 98% of five-year survival rate, for stages I and II.

Is the two-tier ovarian serous carcinoma grading system potentially useful in stratifying uterine serous carcinoma? A large multi-institutional analysis.

PubMed

Ahmed, Quratulain; Hussein, Yaser; Hayek, Kinda; Bandyopadhyay, Sudeshna; Semaan, Assaad; Abdul-Karim, Fadi; Al-Wahab, Zaid; Munkarah, Adnan R; Elshaikh, Mohamed A; Alosh, Baraa; Nucci, Marisa R; Van de Vijver, Koen K; Morris, Robert T; Oliva, Esther; Ali-Fehmi, Rouba

2014-02-01

A subset of uterine serous carcinoma (USC) may have better clinical behavior bringing up the possibility that there may be morphologic features, which would help in their categorization. The aim of this study is to evaluate the potential use of the MD Anderson Cancer Center 2-tier grading system for ovarian carcinoma in USC. Tumors assigned a combined score included in this analysis were 1) low-grade: tumors without marked atypia and 12 mitoses/10 high power field (HPF) and 2) high grade: tumors with severe nuclear atypia and >12 mitoses/10 HPF. Clinicopathologic parameters evaluated included patients' age, tumor size, myometrial invasion (MI), lymphovascular invasion (LVI), lymph node (LN), FIGO stage, and patient outcome. 140 patients with USC were included, 30 low grade uterine serous carcinoma (LGUSC) and 110 high grade uterine serous carcinoma (HGUSC). Of all parameters only 2 (MI and stage IA) reached statistical significance. 67% of LGUSC cases showed myometrial invasion versus 93.6% HGUSC cases (p = 0.003). A higher percentage of LGUSC (63.3%) versus HGUSC (32.7%) were in stage IA (p = 0.01). However, by multivariate analysis including age, LVI, stage and tumor grade only stage was an independent prognostic factor. The presence of atypia and mitosis across a uterine serous carcinoma is notoriously variable in magnitude and extent, potentially making evaluation of these features difficult and subsequent grading subjective. Our findings thus show that actual prognostic utility of application of MDACC two-tier grading system to uterine serous carcinoma may not be applicable. Copyright © 2013 Elsevier Inc. All rights reserved.

Fluid-Structure Interaction Modeling of Intracranial Aneurysm Hemodynamics: Effects of Different Assumptions

NASA Astrophysics Data System (ADS)

Rajabzadeh Oghaz, Hamidreza; Damiano, Robert; Meng, Hui

2015-11-01

Intracranial aneurysms (IAs) are pathological outpouchings of cerebral vessels, the progression of which are mediated by complex interactions between the blood flow and vasculature. Image-based computational fluid dynamics (CFD) has been used for decades to investigate IA hemodynamics. However, the commonly adopted simplifying assumptions in CFD (e.g. rigid wall) compromise the simulation accuracy and mask the complex physics involved in IA progression and eventual rupture. Several groups have considered the wall compliance by using fluid-structure interaction (FSI) modeling. However, FSI simulation is highly sensitive to numerical assumptions (e.g. linear-elastic wall material, Newtonian fluid, initial vessel configuration, and constant pressure outlet), the effects of which are poorly understood. In this study, a comprehensive investigation of the sensitivity of FSI simulations in patient-specific IAs is investigated using a multi-stage approach with a varying level of complexity. We start with simulations incorporating several common simplifications: rigid wall, Newtonian fluid, and constant pressure at the outlets, and then we stepwise remove these simplifications until the most comprehensive FSI simulations. Hemodynamic parameters such as wall shear stress and oscillatory shear index are assessed and compared at each stage to better understand the sensitivity of in FSI simulations for IA to model assumptions. Supported by the National Institutes of Health (1R01 NS 091075-01).

Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up.

PubMed

Katrangi, Waddah; Grebe, Stephan K G; Algeciras-Schimnich, Alicia

2017-10-26

While thyroglobulin autoantibodies (TgAb) can result in false low serum thyroglobulin (Tg) immunoassay (IA) measurements, they might also be indicators of disease persistence/recurrence. Hence, accurate TgAb measurement, in addition to Tg quantification, is crucial for thyroid cancer monitoring. We compared the analytical and clinical performance of four commonly used TgAb IAs. We measured Tg by mass spectrometry (Tg-MS) and by four pairs of Tg and TgAb IAs (Beckman, Roche, Siemens, Thermo) in 576 samples. Limit of quantitation (LOQ) and manufacturers' upper reference interval cut-off (URI) were used for comparisons. Clinical performance was assessed by receiving operator characteristics (ROC) curve analysis. Quantitative and qualitative agreement between TgAb-IAs was moderate with R2 of 0.20-0.70 and κ from 0.41-0.66 using LOQ and 0.47-0.71 using URI. In samples with TgAb interference, detection rates of TgAb were similar using LOQ and URI for Beckman, Siemens, and Thermo, but much lower for the Roche TgAb-IA when the URI was used. In TgAb positive cases, the ROC areas under the curve (AUC) for the TgAb-IAs were 0.59 (Beckman), 0.62 (Siemens), 0.59 (Roche), and 0.59 (Thermo), similar to ROC AUCs achieved with Tg. Combining Tg and TgAb measurements improved the ROC AUCs compared to Tg or TgAb alone. TgAb-IAs show significant qualitative and quantitative differences. For 2 of the 4 TgAb-IAs, using the LOQ improves the detection of interfering TgAbs. All assays showed suboptimal clinical performance when used as surrogate markers of disease, with modest improvements when Tg and TgAb were combined.

Endosonographic and manometric evaluation of internal anal sphincter in patients with chronic anal fissure and its correlation with clinical outcome after topical glyceryl trinitrate therapy.

PubMed

Pascual, Marta; Pera, Miguel; Courtier, Ricard; Gil, Mariá José; Parés, David; Puig, Sonia; Andreu, Montserrat; Grande, Luis

2007-08-01

Anorectal pressure studies have demonstrated internal anal sphincter (IAS) hypertonia in patients with chronic anal fissure. It is unknown however, if these changes in IAS function are associated with any abnormality in sphincter morphology. The first aim was to investigate the clinical characteristics and the manometric and endosonographic findings of the IAS in a cohort of patients with chronic anal fissure. The second aim was to investigate the association between these findings and the outcome with topical Glyceryl trinitrate (GTN) therapy. All patients who presented with chronic anal fissure from November 1999 to May 2004 were included after failure of conservative therapy. Anorectal manometry and anal endosonography were performed before treatment with 0.2% GTN ointment twice daily was initiated. Patients were evaluated after 8 weeks. One hundred and twenty-four patients (66 women, mean age, 45.2 +/- 14.8 years) were included. Hypertonia of the IAS was found in 84 (68%) patients. The mean maximum IAS thickness was 3.6 +/- 0.76 mm (1.6-5.5). An abnormally thick IAS, adjusted by age, was observed in 113 (91.1%) patients. We found no correlation between resting pressure and IAS thickness (r = 0.074; p = 0.41). At 8 weeks, 52 patients (42%) had healed with complete symptoms resolution. No statistically significant differences were observed when clinical features and manometric and endosonographic findings were compared between healing and no-healing fissures. The majority of patients with chronic anal fissure present an abnormally thick IAS. Clinical, manometric and endosonographic features had no association with outcome after GTN treatment.

Low-Dose Acetylsalicylic Acid in Treating Patients With Stage I-III Non-Small Cell Lung Cancer

ClinicalTrials.gov

2017-06-29

Adenocarcinoma of the Lung; Recurrent Non-small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

Hypofractionated Radiation Therapy in Preventing Recurrence in Patients With Breast Cancer After Surgery

ClinicalTrials.gov

2018-02-08

Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7

The Effect of Simvastatin on Breast Cancer Cell Growth in Women With Stage I-II Breast Cancer

ClinicalTrials.gov

2018-03-02

Invasive Breast Carcinoma; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

Enhanced Quitline Intervention in Smoking Cessation for Patients With Non-Metastatic Lung Cancer

ClinicalTrials.gov

2017-05-25

Limited Stage Small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Tobacco Use Disorder

Is a More Comprehensive Surgery Necessary in Patients With Uterine Serous Carcinoma?

PubMed

Touhami, Omar; Trinh, Xuan-Bich; Gregoire, Jean; Sebastianelli, Alexandra; Renaud, Marie-Claude; Grondin, Katherine; Plante, Marie

2015-09-01

Uterine serous carcinoma (USC) is an aggressive histologic subtype of endometrial cancer that shares similarities to serous ovarian cancer, with a propensity for spread to the upper abdomen, a high recurrence rate, and a poor prognosis. The aim of this study was to determine whether the traditional surgical staging procedure for endometrial cancer was adequate for USC or whether a more extensive surgery, similar to the staging procedure for ovarian cancer, needs to be performed. Specifically, the roles of omentectomy and sentinel lymph node (SLN) mapping were evaluated. We retrospectively identified cases of presumed clinical stage I USC at our institution from April 2005 to March 2014. Medical records were reviewed for the following information: age at diagnosis, preoperative imaging, operative findings, surgical procedure, and final histology with definitive International Federation of Gynecology and Obstetrics stage. A total of 39 patients with presumed clinical stage I USC were identified. According to the final pathology report, the surgical stage was as follows: 17 stage IA (44%), 8 stage IB (20%), 3 stage II (8%), 2 stage IIIA (5%), 6 stage IIIC1 (15%), 1 IIIC2 (3%), and 2 stage IVB (5%). Therefore, 14 patients (36%) were surgically upstaged, but none of the patients had their clinical disease upstaged by virtue of finding microscopic metastatic disease in an otherwise normal-looking omentum. Sentinel lymph node mapping was performed in 19 patients (42%). Sensitivity and negative predictive value of SLN mapping were 100% when at least 1 SLN was identified. The detection of microscopic disease in radiologically and clinically normal-appearing omentum seems to be rare in USC. Sentinel lymph node mapping seems to be valuable in the serous subtype of endometrial cancer. A less extensive surgery may be possible in patients with USC as it seems to provide the same information as a more extensive surgery.

[A century of teaching research and medico-legal assistance in Iaşi].

PubMed

Scripcaru, G

1982-01-01

On September 15, 1982, the Medico-Legal Department of the Institute of Medicine and Pharmacy of Iaşi will celebrate one hundred years of activity reflected in the instruction of a great number of generations of physicians, forensic physicians and lawyers to say nothing of the remarkable services brought to the Courts of Law and public medical assistance in Moldavia. The organization of university and medical education in Iaşi had to face implicitly the problem of teaching forensic medicine. This subject was tought for the first time in 1860 at the Faculty of Law of the "Al. I. Cuza" University of Iaşi by I. Ciurea. He started teaching forensic medicine at the Faculty of Medicine in 1882. Professor I. Ciurea was specially sent abroad on the purpose of "studying medicine applied to Law". This stage of evolvement and development of the medico-legal studies in Iaşi is associated today with the names of I. Ciurea, George Bogdan, Gr. T. Popa and N. Bălan. Through their activity, publications and genuine scholarship they succeeded in founding a real scientific school of forensic medicine in Iaşi. At the some time they asserted this subject both on the national and international level. An outstanding stage in the development of the forensic medicine in Iaşi was its increasing application to questions of civil and 'criminal law, especially in court proceedings. This stage is brilliantly represented through the teaching, scientific activity and medico-legal assistance given by M. Kernbach. Nowadays we are actively implied in a new stage of development of the forensic studies. This is the period of the epistemological affirmation of the forensic medicine in Iaşi. Its main task is the elaboration of epistemological models for the majority of the law questions which require the rigour of scientific truth. New discoveries have been made in keeping with the natural progress of forensic medicine in all its branches. Within the process of elaboration of new and more reliable criteria of judgement, all knowledge acquired was epistemologically systematized. The one hundred years of medico-legal teaching at the Institute of Medicine and Pharmacy of Iaşi signifies in fact more things at the same time: 170 years since the first medico-legal certificate had been emitted in Moldavia; 150 years since the first medico-legal autopsy; 118 years since the organization of the teaching of forensic medicine at the Faculty of Law; 91 years since I. Ciurea's death; 52 years since the death of G. Bogdan; and last but not least, 30 years since the organization of the system of medico-legal assistance in our socialist society. All these events, the remarkable achievements of the past, constitute an impetus to the prospective development of forensic medicine in Iaşi, with the goal of obtaining an ever increasing coefficient of scientific accuracy of the medico-legal act as well as to the permanent contribution of forensic medicine to medical assistance and public sanity.

Clinical Variables Correlated with Numbers of Intra-arterial Nimodipine Infusion in Patients with Medically Refractory Cerebral Vasospasm

PubMed Central

Kim, Sang-Young; Kim, Ki-Hong; Cho, Jae-Hoon

2015-01-01

Objective The objective of this study was to find out the clinical variables correlated with repeated intra-arterial (IA) nimodipine infusions in patients with medically refractory cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH). Materials and Methods During the 36 months between January 2011 and December 2013, 275 patients were treated at our institute for SAH due to a ruptured intracranial aneurysm. Of the 275 patients, 26 patients (9.5%) met the inclusion criteria. For each patient, a retrospective review of their medical records was conducted. Results Eleven patients underwent a single IA nimodipine infusion and 15 patients underwent more than two IA nimodipine infusions. Multiple IA nimodipine infusion patients had poor improvement (2 of 15 patients, 13.3%) in Glasgow coma scale (GCS) scores after the first IA nimodipine infusion compared to patients of single IA nimodipine infusion (6 of 11 patients, 54.6%) (p = 0.038). The mean middle cerebral artery (MCA) Lindegaard ratio of multiple IA nimodipine infusion patients was 4.3 ± 1.1 after the first IA nimodipine infusion (p = 0.039). In multiple IA nimodipine infusion patients, CV occurred more often bilaterally (p = 0.035) and distally (p = 0.001). More vessel segments were affected in multiple IA nimodipine infusion patients (3.1 ± 1.0) (p < 0.001). Conclusion The following factors correlated with multiple IA nimodipine infusions: 1) no improvement in GCS after the IA nimodipine infusion; 2) no decrease of MCA velocity on transcranial doppler over 50 cm/s or Lindegaard ratio over 4.3 after the IA nimodipine infusion; 3) distal, bilateral, or diffuse involvement of CV. PMID:26523251

Follow-up Findings in a Turkish Girl with Pseudohypoparathyroidism Type Ia Caused by a Novel Heterozygous Mutation in the GNAS Gene.

PubMed

Şahin, Sezgin; Hiort, Olaf; Thiele, Susanne; Evliyaoğlu, Olcay; Tüysüz, Beyhan

2017-03-01

Pseudohypoparathyroidism type Ia (PHP-Ia) is characterized by multihormone resistance and an Albright hereditary osteodystrophy (AHO) phenotype. It is caused by heterozygous mutations in GNAS gene. Clinical and biochemical findings of a female PHP-Ia patient were evaluated from age of diagnosis (6.5 years) to 14.5 years of age. The patient had short stature, brachydactyly, and subcutaneous heterotopic ossifications. Serum calcium and phosphorus levels were normal, but parathyroid hormone levels were high. Based on the typical clinical findings of AHO phenotype and biochemical findings, she was diagnosed as having PHP-Ia. A novel heterozygous mutation (c.128T>C) was found in the GNAS gene. Follow-up examinations revealed resistance to thyroid-stimulating hormone and a bioinactive growth hormone. Clinicians should take into consideration PHP-Ia in patients referred with short stature, and patients with an AHO phenotype must be further evaluated for hormone resistance, GNAS gene mutation, Gsα activity. To our knowledge, this is the first case report describing bioinactive growth hormone in PHP-Ia.

The transcriptional landscape of Rhizoctonia solani AG1-IA during infection of soybean as defined by RNA-seq

PubMed Central

Copley, Tanya R.; Duggavathi, Raj

2017-01-01

Rhizoctonia solani Kühn infects most plant families and can cause significant agricultural yield losses worldwide; however, plant resistance to this disease is rare and short-lived, and therefore poorly understood, resulting in the use of chemical pesticides for its control. Understanding the functional responses of this pathogen during host infection can help elucidate the molecular mechanisms that are necessary for successful host invasion. Using the pathosystem model soybean-R. solani anastomosis group AG1-IA, we examined the global transcriptional responses of R. solani during early and late infection stages of soybean by applying an RNA-seq approach. Approximately, 148 million clean paired-end reads, representing 93% of R. solani AG1-IA genes, were obtained from the sequenced libraries. Analysis of R. solani AG1-IA transcripts during soybean invasion revealed that most genes were similarly expressed during early and late infection stages, and only 11% and 15% of the expressed genes were differentially expressed during early and late infection stages, respectively. Analyses of the differentially expressed genes (DEGs) revealed shifts in molecular pathways involved in antibiotics biosynthesis, amino acid and carbohydrate metabolism, as well as pathways involved in antioxidant production. Furthermore, several KEGG pathways were unique to each time point, particularly the up-regulation of genes related to toxin degradation (e.g., nicotinate and nicotinamid metabolism) at onset of necrosis, and those linked to synthesis of anti-microbial compounds and pyridoxine (vitamin B6) biosynthesis 24 h.p.o. of necrosis. These results suggest that particular genes or pathways are required for either invasion or disease development. Overall, this study provides the first insights into R. solani AG1-IA transcriptome responses to soybean invasion providing beneficial information for future targeted control methods of this successful pathogen. PMID:28877263

Improvement of sidestream dark field imaging with an image acquisition stabilizer.

PubMed

Balestra, Gianmarco M; Bezemer, Rick; Boerma, E Christiaan; Yong, Ze-Yie; Sjauw, Krishan D; Engstrom, Annemarie E; Koopmans, Matty; Ince, Can

2010-07-13

In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging. The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared. Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 +/- 0.15 N without vs. 0.62 +/- 0.05 N with the IAS, p < 0.001). The IAS ensured an increased duration of a stable image sequence (8 +/- 2 s without vs. 42 +/- 8 s with the IAS, p < 0.001). The time required to obtain a stable image sequence was similar with and without the IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 +/- 5 s without vs. 67 +/- 14 s with the IAS, p = 0.006). The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the microscopic field of view. The IAS improved both axial and lateral SDF image stability and thereby increased the critical force required to induce pressure artifacts. The IAS ensured a significantly increased duration of maintaining a stable image sequence.

Juvenile granulosa cell ovarian tumor: a case report and review of literature.

PubMed

Sivasankaran, Sujatha; Itam, Paul; Ayensu-Coker, Leslie; Sanchez, Judith; Egler, Rachel A; Anderson, Matthew L; Brandt, Mary L; Dietrich, Jennifer E

2009-10-01

Juvenile granulosa cell tumors (JGCT) are rare ovarian tumors that frequently present with precocious puberty. Presentation in infants less than a year of age is also rare. We describe a 10-month-old infant who presented with both premature thelarche and adrenarche due to JGCT. Laboratory evaluation revealed classic elevation of estradiol and inhibin B, and less classic elevation of total and free testosterone. Oophorectomy and staging resulted in a diagnosis of Stage IA JGCT. Survival rates are >95% among patients diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late as 48 months. Therefore, tumor surveillance is warranted for patients with even a Stage IA JGCT and involves monitoring serial inhibin B levels along with intermittent imaging.

Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery

ClinicalTrials.gov

2018-02-12

Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; HER2-positive Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer

Fludeoxyglucose F-18-PET in Planning Lung Cancer Radiation Therapy

ClinicalTrials.gov

2018-04-19

Stage I Lung Cancer; Stage I Non-Small Cell Lung Cancer AJCC v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Lung Cancer; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7

[Characteristics of morphological manifestations of anaphylactic shock in response to the administration of pharmaceutical preparations encountered in the practice of forensic medical expert-histologist].

PubMed

Denisova, O P; Kul'bitskiĭ, B N; Putintsev, V A; Bogomolova, I N; Bogomolov, D V

2012-01-01

The authors report the results of a forensic medical investigation of 6 cases of death associated with the administration of pharmaceutical products documented by forensic medical experts of the Russian Centre of Forensic Medical Expertise. The results of the study are compared with the clinical data and summarized using the methods of tanatogenetic analysis. The following main clinical variants of iatrogenic anaphylactic shock (IAS) are distinguished: bronchospastic IAS (n = 1), asphyxic IAS (n = 1), hemodynamic IAS (n = 3), and combined (bronchospastic plus hemodynamic) IAS (n = 1). The signs of all these variants are described allowing for their diagnostics and differentiation diagnostics. These data can be used for the purpose of forensic medical diagnostics and elucidation of the mechanisms of tanatogenesis.

Clinical, pathological, and radiological characteristics of solitary ground-glass opacity lung nodules on high-resolution computed tomography.

PubMed

Qiu, Zhi-Xin; Cheng, Yue; Liu, Dan; Wang, Wei-Ya; Wu, Xia; Wu, Wei-Lu; Li, Wei-Min

2016-01-01

Lung nodules are being detected at an increasing rate year by year with high-resolution computed tomography (HRCT) being widely used. Ground-glass opacity nodule is one of the special types of pulmonary nodules that is confirmed to be closely associated with early stage of lung cancer. Very little is known about solitary ground-glass opacity nodules (SGGNs). In this study, we analyzed the clinical, pathological, and radiological characteristics of SGGNs on HRCT. A total of 95 resected SGGNs were evaluated with HRCT scan. The clinical, pathological, and radiological characteristics of these cases were analyzed. Eighty-one adenocarcinoma and 14 benign nodules were observed. The nodules included 12 (15%) adenocarcinoma in situ (AIS), 14 (17%) minimally invasive adenocarcinoma (MIA), and 55 (68%) invasive adenocarcinoma (IA). No patients with recurrence till date have been identified. The positive expression rates of anaplastic lymphoma kinase and ROS-1 (proto-oncogene tyrosine-protein kinase ROS) were only 2.5% and 8.6%, respectively. The specificity and accuracy of HRCT of invasive lung adenocarcinoma were 85.2% and 87.4%. The standard uptake values of only two patients determined by 18F-FDG positron emission tomography/computed tomography (PET/CT) were above 2.5. The size, density, shape, and pleural tag of nodules were significant factors that differentiated IA from AIS and MIA. Moreover, the size, shape, margin, pleural tag, vascular cluster, bubble-like sign, and air bronchogram of nodules were significant determinants for mixed ground-glass opacity nodules (all P <0.05). We analyzed the clinical, pathological, and radiological characteristics of SGGNs on HRCT and found that the size, density, shape, and pleural tag of SGGNs on HRCT are found to be the determinant factors of IA. In conclusion, detection of anaplastic lymphoma kinase expression and performance of PET/CT scan are not routinely recommended.

Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual.

PubMed

Gershenwald, Jeffrey E; Scolyer, Richard A; Hess, Kenneth R; Sondak, Vernon K; Long, Georgina V; Ross, Merrick I; Lazar, Alexander J; Faries, Mark B; Kirkwood, John M; McArthur, Grant A; Haydu, Lauren E; Eggermont, Alexander M M; Flaherty, Keith T; Balch, Charles M; Thompson, John F

2017-11-01

Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors "microscopic" and "macroscopic" for regional node metastasis are redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472-492. © 2017 American Cancer Society. © 2017 American Cancer Society.

Melanoma Staging: Evidence-Based Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual

PubMed Central

Gershenwald, Jeffrey E.; Scolyer, Richard A.; Hess, Kenneth R.; Sondak, Vernon K.; Long, Georgina V.; Ross, Merrick I.; Lazar, Alexander J.; Faries, Mark B.; Kirkwood, John M.; McArthur, Grant A.; Haydu, Lauren E.; Eggermont, Alexander M. M.; Flaherty, Keith T.; Balch, Charles M.; Thompson, John F.

2018-01-01

To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8–1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent”; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA–IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. PMID:29028110

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Soyama, Hiroaki; Aoyama, Tadashi; Ishibashi, Hiroki; Kato, Kento; Iwahashi, Hideki; Matuura, Hiroko; Yoshikawa, Tomoyuki; Suzuki, Ayako; Hirata, Junko; Furuya, Kenichi

2017-01-01

Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. © 2017 S. Karger AG, Basel.

EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer

ClinicalTrials.gov

2013-01-15

Primary Peritoneal Cavity Cancer; Stage I Endometrial Carcinoma; Stage I Ovarian Epithelial Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage II Ovarian Epithelial Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

Impact of centralized diagnostic review on quality of initial staging in Hodgkin lymphoma: experience of the German Hodgkin Study Group.

PubMed

Bröckelmann, Paul J; Goergen, Helen; Fuchs, Michael; Kriz, Jan; Semrau, Robert; Baues, Christian; Kobe, Carsten; Behringer, Karolin; Eichenauer, Dennis A; von Tresckow, Bastian; Klimm, Beate; Halbsguth, Teresa; Wongso, Diana; Plütschow, Annette; Haverkamp, Heinz; Dietlein, Markus; Eich, Hans T; Stein, Harald; Diehl, Volker; Borchmann, Peter; Engert, Andreas

2015-11-01

Accurate clinical staging is crucial for adequate risk-adapted treatment in Hodgkin lymphoma (HL) to prevent patients from under- or over-treatment. Within the latest German Hodgkin Study Group trial generation, diagnostic findings such as histopathology, computerized tomography imaging and clinical risk factors were re-evaluated by expert panels. Here, we retrospectively analysed 5965 patients and identified 399 in who major discordant findings changed their first-line treatment allocation. Histopathology review did not confirm the initial diagnosis of HL in 87 patients. Treatment allocation was revised in 312 of the remaining 5878 patients: 176 were assigned to a higher and 128 to a lower risk group, respectively; the correct treatment group remained unclear in 8 patients. Cases of revised treatment allocation accounted for 9·8%, 6·0%, 0·8%, and 14·8% of patients initially assigned to the HD13, HD14, HD15 trials and stage IA lymphocyte-predominant HL project, respectively. Most revisions were due to wrong application of clinical stage (20·5% of 312 patients with revised treatment group), histological subtype (9·0%) or the risk factors ≥3 involved areas (46·8%) or large mediastinal mass (9·3%). In conclusion, centralized review by experienced experts changed risk-adapted first-line treatment in a relevant proportion of HL patients. Quality control measures clearly improve the accuracy of treatment and should be implemented in clinical practice. © 2015 John Wiley & Sons Ltd.

Risk Factors for the Rupture of Intracranial Aneurysms Using Computed Tomography Angiography.

PubMed

Wang, Guang-Xian; Wen, Li; Yang, Liu; Zhang, Qi-Chuang; Yin, Jin-Bo; Duan, Chun-Mei; Zhang, Dong

2018-02-01

To study the clinical and morphologic characteristics associated with risk factors for the rupture of intracranial aneurysms (IAs). A total of 1115 consecutive patients with 1282 IAs were reviewed from August 2011 to February 2016. The patients and IAs were divided into ruptured and unruptured groups. Based on the clinical and morphologic findings, the risk factors for IA rupture were assessed using statistical methods. Age, hypertension, diabetes mellitus, and cerebral atherosclerosis were associated with ruptured IAs. IAs located in the anterior cerebral artery, the anterior communicating artery, the posterior communicating artery, and the internal carotid artery were associated with ruptured IAs. Ruptures were also associated with arterial bifurcations, irregular aneurysm shapes, and all continuous data, except neck width. Binary logistic regression showed that IAs located at bifurcations (odds ratio [OR], 1.804), with irregular shapes (OR, 4.677), with high aspect ratios (ARs) (OR, 5.037) or with small mean diameters (MDs) (OR, 0.495) are more prone to rupture. Receiver operating characteristic analysis showed that the threshold values of the AR and MD were 1 and 3.70 mm, respectively. Morphologic characteristics, such as being located at bifurcations, being irregularly shaped, having a high AR (>1), and having a small MD (<3.70 mm), were better predictors of rupture. Copyright © 2017 Elsevier Inc. All rights reserved.

Intracranial aneurysms in patients with coarctation of the aorta: a prospective magnetic resonance angiographic study of 100 patients.

PubMed

Connolly, Heidi M; Huston, John; Brown, Robert D; Warnes, Carole A; Ammash, Naser M; Tajik, A Jamil

2003-12-01

To determine the frequency of intracranial aneurysms (IAs) detected in patients with coarctation of the aorta (CoA) with use of magnetic resonance angiography. From January 1, 1980, to September 30, 2002, 277 adult patients with CoA were seen at the Mayo Clinic in Rochester, Minn, and were invited to participate in a study to detect IAs. Of these 277 patients (mean +/- SD age, 41.6 +/- 16.5; 70 men), 100 underwent cranial magnetic resonance angiography. Ten patients had an IA (95% confidence interval, 5%-18%), with a mean diameter of 3.5 mm (range, 2.0-8.0 mm). The frequency of IA was significantly higher than that predicted in the general population (10% vs 2%; P < .001). One patient had surgical intervention. No clinical or geographical differences were found between patients with CoA and IA and patients with CoA and no IA. The frequency of IA among patients with CoA is approximately 5-fold that of the general population. Although no risk factors were identified in this cohort, additional prospective evaluation is warranted. These data suggest that noninvasive cerebral imaging to screen for IA should be considered in patients with CoA.

Kindness Interventions in Enhancing Well-Being in Breast Cancer Survivors

ClinicalTrials.gov

2018-06-18

Cancer Survivor; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7

Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

ClinicalTrials.gov

2018-04-09

Estrogen Receptor Positive; Postmenopausal; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7

Nivolumab, Cisplatin, and Pemetrexed Disodium or Gemcitabine Hydrochloride in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer That Can Be Removed by Surgery

ClinicalTrials.gov

2018-03-02

Non-Squamous Non-Small Cell Lung Carcinoma; Stage I Non-Small Cell Lung Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Non-Small Cell Lung Carcinoma; Stage II Non-Small Cell Lung Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer

[The efficacy and safety of stereotactic radiotherapy for non-resectable non-small cell lung cancer].

PubMed

Futamura, Yohei; Sawa, Toshiyuki; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Iida, Takayoshi; Marui, Tsutomu

2010-11-01

Stereotactic radiotherapy (SRT) has recently been used for the treatment of small lung tumors. We retrospectively evaluated the efficacy and safety of SRT for non-small cell lung cancer (NSCLC) treated in our hospital. Between October 2007 and December 2009, 31 tumors of 29 patients were treated by SRT (mean age, 75 years: stage IA, n=13; stage IB, n=5; stage IIIA, n=1; stage IIIB, n=1; recurrence, n=11). All of the patients completed the treatment. In one patient who had radiation pneumonitis before SRT, a progression of pulmonary fibrosis was observed, and treated with steroid therapy. In evaluable 29 tumors of 27 patients, the recurrence rates are 11/29 (37.9%). Median progression free survival time was 8 months. The recurrence rate and median progression free survival time of stage IA and IB subgroups were 4/17 (23.5%) and 12 months, respectively. SRT is thought to be a safe and effective treatment for stage I NSCLC. For patients with stage I NSCLC, SRT can be a complemental therapy for surgical resection.

Results of the two incidence screenings in the National Lung Screening Trial.

PubMed

Aberle, Denise R; DeMello, Sarah; Berg, Christine D; Black, William C; Brewer, Brenda; Church, Timothy R; Clingan, Kathy L; Duan, Fenghai; Fagerstrom, Richard M; Gareen, Ilana F; Gatsonis, Constantine A; Gierada, David S; Jain, Amanda; Jones, Gordon C; Mahon, Irene; Marcus, Pamela M; Rathmell, Joshua M; Sicks, JoRean

2013-09-05

The National Lung Screening Trial was conducted to determine whether three annual screenings (rounds T0, T1, and T2) with low-dose helical computed tomography (CT), as compared with chest radiography, could reduce mortality from lung cancer. We present detailed findings from the first two incidence screenings (rounds T1 and T2). We evaluated the rate of adherence of the participants to the screening protocol, the results of screening and downstream diagnostic tests, features of the lung-cancer cases, and first-line treatments, and we estimated the performance characteristics of both screening methods. At the T1 and T2 rounds, positive screening results were observed in 27.9% and 16.8% of participants in the low-dose CT group and in 6.2% and 5.0% of participants in the radiography group, respectively. In the low-dose CT group, the sensitivity was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9% at T1; at T2, the positive predictive value increased to 5.2%. In the radiography group, the sensitivity was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8% at T1; both the sensitivity and the positive predictive value increased at T2. Among lung cancers of known stage, 87 (47.5%) were stage IA and 57 (31.1%) were stage III or IV in the low-dose CT group at T1; in the radiography group, 31 (23.5%) were stage IA and 78 (59.1%) were stage III or IV at T1. These differences in stage distribution between groups persisted at T2. Low-dose CT was more sensitive in detecting early-stage lung cancers, but its measured positive predictive value was lower than that of radiography. As compared with radiography, the two annual incidence screenings with low-dose CT resulted in a decrease in the number of advanced-stage cancers diagnosed and an increase in the number of early-stage lung cancers diagnosed. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2013-10-30

under the following clinical trial protocol: o S1203: A Randomized Phase III Study of Standard Cytarabine plus Daunorubicin (7+3) Therapy or Idarubicin...with High Dose Cytarabine (IA) versus IA with Vorinostat (IA+V) in Younger Patients with Previously Untreated Acute Myeloid Leukemia (AML) o

Insightfulness and later infant attachment in clinically depressed and nonclinical mothers.

PubMed

Ramsauer, Brigitte; Lotzin, Annett; Quitmann, Julia H; Becker-Stoll, Fabienne; Tharner, Anne; Romer, Georg

2014-01-01

The aim of this pilot study was to investigate the relationship between maternal insightfulness and sensitivity and subsequent infant attachment security and disorganization in clinically depressed and nonclinical mother-infant groups. Nineteen depressed mothers with infants ages 3 to 11 months participated in this study. Twenty nonclinical mother-infant dyads were matched to the clinical sample according to infant sex and age. Maternal depression was assessed using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (American Psychiatric Association, 1994), insightfulness using the Insightfulness Assessment (IA), and sensitivity using the Maternal Sensitivity Scales (M.D.S. Ainsworth, 1969). IA classifications and subscales were considered separately. Later infant attachment was assessed by the Strange Situation Procedure (M.D.S. Ainsworth, M.C. Blehar, E. Waters, & S. Wall, 1978). Depressed mothers tended to have less securely attached children than did nonclinical mothers. Within the clinical sample, the insightfulness categories correlated slightly moderately with attachment security, but were not related to attachment disorganization. Within the nonclinical sample, the IA categories were slightly moderately associated with attachment security and with disorganization. On IA subscales, relationship patterns differed in clinically depressed and nonclinical mother-infant dyads. These findings provide the first evidence of the predictive power of the IA categorization and subscales on subsequent infant attachment. They also may allow the development of different foci of intervention for enhancing insightful caregiving. © 2014 Michigan Association for Infant Mental Health.

Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control.

PubMed

Peeks, Fabian; Steunenberg, Thomas A H; de Boer, Foekje; Rubio-Gozalbo, M Estela; Williams, Monique; Burghard, Rob; Rajas, Fabienne; Oosterveer, Maaike H; Weinstein, David A; Derks, Terry G J

2017-09-01

To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose-6-phosphatase (G6Pase). Descriptive retrospective study of longitudinal clinical and biochemical data and long-term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM-analysis graphs were constructed. Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM-analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long-term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis). Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM-analysis can facilitate single-patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.

Nomogram predicting response after chemoradiotherapy in rectal cancer using sequential PETCT imaging: a multicentric prospective study with external validation.

PubMed

van Stiphout, Ruud G P M; Valentini, Vincenzo; Buijsen, Jeroen; Lammering, Guido; Meldolesi, Elisa; van Soest, Johan; Leccisotti, Lucia; Giordano, Alessandro; Gambacorta, Maria A; Dekker, Andre; Lambin, Philippe

2014-11-01

To develop and externally validate a predictive model for pathologic complete response (pCR) for locally advanced rectal cancer (LARC) based on clinical features and early sequential (18)F-FDG PETCT imaging. Prospective data (i.a. THUNDER trial) were used to train (N=112, MAASTRO Clinic) and validate (N=78, Università Cattolica del S. Cuore) the model for pCR (ypT0N0). All patients received long-course chemoradiotherapy (CRT) and surgery. Clinical parameters were age, gender, clinical tumour (cT) stage and clinical nodal (cN) stage. PET parameters were SUVmax, SUVmean, metabolic tumour volume (MTV) and maximal tumour diameter, for which response indices between pre-treatment and intermediate scan were calculated. Using multivariate logistic regression, three probability groups for pCR were defined. The pCR rates were 21.4% (training) and 23.1% (validation). The selected predictive features for pCR were cT-stage, cN-stage, response index of SUVmean and maximal tumour diameter during treatment. The models' performances (AUC) were 0.78 (training) and 0.70 (validation). The high probability group for pCR resulted in 100% correct predictions for training and 67% for validation. The model is available on the website www.predictcancer.org. The developed predictive model for pCR is accurate and externally validated. This model may assist in treatment decisions during CRT to select complete responders for a wait-and-see policy, good responders for extra RT boost and bad responders for additional chemotherapy. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

ClinicalTrials.gov

2016-02-18

Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Comparison of the Effectiveness of Radiofrequency Ablation With Stereotactic Body Radiation Therapy in Inoperable Stage I Non-Small Cell Lung Cancer: A Systemic Review and Pooled Analysis.

PubMed

Bi, Nan; Shedden, Kerby; Zheng, Xiangpeng; Kong, Feng-Ming Spring

2016-08-01

To performed a systematic review and pooled analysis to compare clinical outcomes of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for the treatment of medically inoperable stage I non-small cell lung cancer. A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS) and local tumor control rates (LCRs) and adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. The LCR (95% confidence interval) at 1, 2, 3, and 5 years for RFA was 77% (70%-85%), 48% (37%-58%), 55% (47%-62%), and 42% (30%-54%) respectively, which was significantly lower than that for SBRT: 97% (96%-98%), 92% (91%-94%), 88% (86%-90%), and 86% (85%-88%) (P<.001). These differences remained significant after correcting for stage IA and age (P<.001 at 1 year, 2 years, and 3 years; P=.04 at 5 years). The effect of RFA was not different from that of SBRT on OS (P>.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, whereas that for SBRT (grade ≥3) was radiation pneumonitis, occurring in 2% of patients. Compared with RFA, SBRT seems to have a higher LCR but similar OS. More studies with larger sample sizes are warranted to validate such findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of the Effectiveness of Radiofrequency Ablation With Stereotactic Body Radiation Therapy in Inoperable Stage I Non-Small Cell Lung Cancer: A Systemic Review and Pooled Analysis

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

Bi, Nan; Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; Shedden, Kerby

Purpose: To performed a systematic review and pooled analysis to compare clinical outcomes of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for the treatment of medically inoperable stage I non-small cell lung cancer. Methods and Materials: A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS) and local tumor control rates (LCRs) and adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. Results: Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. The LCR (95%more » confidence interval) at 1, 2, 3, and 5 years for RFA was 77% (70%-85%), 48% (37%-58%), 55% (47%-62%), and 42% (30%-54%) respectively, which was significantly lower than that for SBRT: 97% (96%-98%), 92% (91%-94%), 88% (86%-90%), and 86% (85%-88%) (P<.001). These differences remained significant after correcting for stage IA and age (P<.001 at 1 year, 2 years, and 3 years; P=.04 at 5 years). The effect of RFA was not different from that of SBRT on OS (P>.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, whereas that for SBRT (grade ≥3) was radiation pneumonitis, occurring in 2% of patients. Conclusions: Compared with RFA, SBRT seems to have a higher LCR but similar OS. More studies with larger sample sizes are warranted to validate such findings.« less

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA.

PubMed

Ooki, Akira; Maleki, Zahra; Tsay, Jun-Chieh J; Goparaju, Chandra; Brait, Mariana; Turaga, Nitesh; Nam, Hae-Seong; Rom, William N; Pass, Harvey I; Sidransky, David; Guerrero-Preston, Rafael; Hoque, Mohammad Obaidul

2017-11-15

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC). Experimental Design: Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. Results: A methylation panel of 6 genes ( CDO1, HOXA9, AJAP1, PTGDR, UNCX , and MARCH11 ) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR , and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes. Conclusions: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. Clin Cancer Res; 23(22); 7141-52. ©2017 AACR . ©2017 American Association for Cancer Research.

Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency.

PubMed

Dósa, Edit; Heltai, Krisztina; Radovits, Tamás; Molnár, Gabriella; Kapocsi, Judit; Merkely, Béla; Fu, Rongwei; Doolittle, Nancy D; Tóth, Gerda B; Urdang, Zachary; Neuwelt, Edward A

2017-10-03

Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall quality of life. The blood-labyrinth barrier is somewhat permeable to cisplatin, and sensory hair cells and cochlear supporting cells are highly sensitive to this toxic drug. Several chemoprotective agents such as N-acetylcysteine (NAC) were utilized experimentally to avoid these potentially serious and life-long side effects, although no clinical phase I trial was performed before. The purpose of this study was to establish the maximum tolerated dose (MTD) and pharmacokinetics of both intravenous (IV) and intra-arterial (IA) NAC in adults with chronic kidney disease to be used in further trials on oto- and nephroprotection in pediatric patients receiving platinum therapy. Due to ethical considerations in pediatric tumor patients, we used a clinical population of adults with non-neoplastic disease. Subjects with stage three or worse renal failure who had any endovascular procedure were enrolled in a prospective, non-randomized, single center trial to determine the MTD for NAC. We initially aimed to evaluate three patients each at 150, 300, 600, 900, and 1200 mg/kg NAC. The MTD was defined as one dose level below the dose producing grade 3 or 4 toxicity. Serum NAC levels were assessed before, 5 and 15 min post NAC. Twenty-eight subjects (15 men; mean age 72.2 ± 6.8 years) received NAC IV (N = 13) or IA (N = 15). The first participant to experience grade 4 toxicity was at the 600 mg/kg IV dose, at which time the protocol was modified to add an additional dose level of 450 mg/kg NAC. Subsequently, no severe NAC-related toxicity arose and 450 mg/kg NAC was found to be the MTD in both IV and IA groups. Blood levels of NAC showed a linear dose response (p < 0.01). Five min after either IV or IA NAC MTD dose administration, serum NAC levels reached the 2-3 mM concentration which seemed to be nephroprotective in previous preclinical studies. In adults with kidney impairment, NAC can be safely given both IV and IA at a dose of 450 mg/kg. Additional studies are needed to confirm oto- and nephroprotective properties in the setting of cisplatin treatment. Clinical Trial Registration URL: https://eudract.ema.europa.eu . Unique identifier: 2011-000887-92.

Immunoassay screening in urine for synthetic cannabinoids - an evaluation of the diagnostic efficiency.

PubMed

Franz, Florian; Angerer, Verena; Jechle, Hanna; Pegoro, Melanie; Ertl, Harald; Weinfurtner, Georg; Janele, David; Schlögl, Christian; Friedl, Matthias; Gerl, Stefan; Mielke, Reinhard; Zehnle, Ralf; Wagner, Matthias; Moosmann, Bjoern; Auwärter, Volker

2017-08-28

The abuse of synthetic cannabinoids (SCs) as presumed legal alternative to cannabis poses a great risk to public health. For economic reasons many laboratories use immunoassays (IAs) to screen for these substances in urine. However, the structural diversity and high potency of these designer drugs places high demands on IAs regarding cross-reactivity of the antibodies used and detection limits. Two retrospective studies were carried out in order to evaluate the capability of two homogenous enzyme IAs for the detection of currently prevalent SCs in authentic urine samples. Urine samples were analyzed utilizing a 'JWH-018' kit and a 'UR-144' kit. The IA results were confirmed by an up-to-date liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) screening method covering metabolites of 45 SCs. The first study (n=549) showed an 8% prevalence of SCs use (LC-MS/MS analysis) among inpatients of forensic-psychiatric clinics, whereas all samples were tested negative by the IAs. In a second study (n=200) the combined application of both IAs led to a sensitivity of 2% and a diagnostic accuracy of 51% when applying the recommended IA cut-offs. Overall, 10 different currently prevalent SCs were detected in this population. The results can be explained by an insufficient cross-reactivity of the antibodies towards current SCs in combination with relatively high detection limits of the IAs. In light of the presented study data it is strongly recommended not to rely on the evaluated IA tests for SCs in clinical or forensic settings. For IA kits of other providers similar results can be expected.

REVIEW-ARTICLE Intermediate alleles of Huntington's disease HTT gene in different populations worldwide: a systematic review.

PubMed

Apolinário, T A; Paiva, C L A; Agostinho, L A

2017-04-05

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by a dynamic mutation due to the expansion of CAG repeats in the HTT gene (4p16.3). The considered normal alleles have less than 27 CAG repeats. Intermediate alleles (IAs) show 27 to 35 CAG repeats and expanded alleles have more than 35 repeats. The IAs apparently have shown a normal phenotype. However, there are some reported associations between individuals that bear an IA and clinical HD signs, such as behavioral disturbs. The association of IAs with the presence of clinical signs gives clinical relevance to these patients. We emphasized the importance of determining the frequency of IA alleles in the general population as well as in HD families. Therefore, the aim of this study was to conduct a systematic review, in order to investigate the frequency of IAs in the overall chromosomes of different ethnic groups and of families with HD history worldwide as well as the frequency of individuals who bear the intermediate alleles. We searched indexed articles from the following electronic databases: U.S. National Library of Medicine and the National Institutes of Health (PubMed), Pubmed Central (PMC) and Virtual Health Library (VHL). Therefore, 488 articles were obtained and, of these, 33 had been published in more than one database. We accepted the article of only one database and ended up with 455 articles for this review. The frequency of IAs within the chromosomes of the general population ranged from 0.45 to 8.7% and of individuals with family history of HD ranged from 0.05 to 5.1%. The higher frequency of IAs in the general population (8.7%) was found in one Brazilian cohort.

Complete Versus Incomplete Angiography Prior to Percutaneous Coronary Intervention in ST-Elevation Myocardial Infarction.

PubMed

Stiver, Kevin; Gao, Xu; Shreenivas, Satya; Boudoulas, Konstantinos Dean; Mazzaferri, Ernie; Makki, Nader; Lilly, Scott M

2017-08-01

Shorter reperfusion times in ST-elevation myocardial infarction (STEMI) are associated with improved survival. Prehospital strategies have been developed to minimize door-to-balloon (DTB) time, but few strategies within the catheterization laboratory itself have been evaluated. Incomplete angiography (IA) prior to percutaneous coronary intervention (PCI) is undertaken in clinical practice as a means to further reduce DTB time. We sought to determine whether or not those with STEMI who underwent IA prior to PCI had different preprocedural characteristics or post-PCI outcomes. We retrospectively reviewed patients presenting to our institution between March 2013 and December 2015. Clinical, demographic, and angiographic data were reviewed. The frequency, predictors, and outcomes among those who received IA vs complete angiography (CA) prior to PCI were compared with analysis of variance. Two hundred fifty-six patients were identified; 68 patients (26.6%) underwent IA and 188 patients (73.4%) had CA prior to PCI. Patients who received IA were younger, but no other preprocedural factors were predictive of IA. The practice of IA did vary by operator (range, 0%-47%; P<.01). DTB times were shorter in the IA group (28.1 min vs 37.3 min; P<.01). Overall outcomes, including peak troponin values, length of stay, in-hospital mortality, and discharge ejection fraction did not differ between the groups. IA is associated with shorter DTB times, although in this population was not associated with improvements in short-term outcomes.

Stereotactic Ablative Radiotherapy for stage I histologically proven non-small cell lung cancer: an Italian multicenter observational study.

PubMed

Ricardi, Umberto; Frezza, Giovanni; Filippi, Andrea Riccardo; Badellino, Serena; Levis, Mario; Navarria, Piera; Salvi, Fabrizio; Marcenaro, Michela; Trovò, Marco; Guarneri, Alessia; Corvò, Renzo; Scorsetti, Marta

2014-06-01

Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials. We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3-8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival). Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS). The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

PubMed

Nomelini, Rosekeila Simões; da Silva, Taísa Morete; Tavares Murta, Beatriz Martins; Murta, Eddie Fernando Candido

2012-01-01

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Chemotherapy With or Without Trastuzumab After Surgery in Treating Women With Invasive Breast Cancer

ClinicalTrials.gov

2018-06-26

Estrogen Receptor Negative; Estrogen Receptor Positive; HER2/Neu Positive; Progesterone Receptor Negative; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

Talimogene Laherparepvec and Radiation Therapy in Treating Patients With Newly Diagnosed Soft Tissue Sarcoma That Can Be Removed by Surgery

ClinicalTrials.gov

2018-05-23

FNCLCC Sarcoma Grade 2; FNCLCC Sarcoma Grade 3; Leiomyosarcoma; Liposarcoma; Stage I Soft Tissue Sarcoma AJCC v7; Stage IA Soft Tissue Sarcoma AJCC v7; Stage IB Soft Tissue Sarcoma AJCC v7; Stage II Soft Tissue Sarcoma AJCC v7; Stage IIA Soft Tissue Sarcoma AJCC v7; Stage IIB Soft Tissue Sarcoma AJCC v7; Undifferentiated Pleomorphic Sarcoma

Patients with non-substance-related disorders report a similar profile of childhood trauma experiences compared to heroin-dependent patients.

PubMed

Schwaninger, Philipp V; Mueller, Sandra E; Dittmann, Rebecca; Poespodihardjo, Renanto; Vogel, Marc; Wiesbeck, Gerhard A; Walter, Marc; Petitjean, Sylvie A

2017-04-01

Exposure to traumatic events is common among patients with substance use disorders (SUD). In patients with non-substance-related disorders, especially with gambling disorders (GD) and internet addiction (IA), traumatic childhood experiences have not been investigated extensively. The objective of this study was to compare trauma histories in patients with GD and IA to patients with heroin dependence. Cross-sectional surveys including the childhood trauma questionnaire (CTQ) and clinical data among 107 participants; 59 patients with non-substance-related disorders (GD [n = 39]; IA [n = 20]) were compared to 28 patients prescribed injectable heroin for opioid dependence in heroin-assisted treatment (HAT) and to a healthy control group (HC) (n = 20). The findings revealed a high prevalence of trauma exposure in all three clinical groups, with 74.4% of patients with GD, 80.0% of patients with IA, and 93.0% of patients in HAT compared to 40% in HC. All three groups (GD, IA, HAT) reported significantly higher levels of "emotional neglect" compared to HC. The results provide clinically relevant information suggesting that the burden of childhood traumatic experiences may be as common in patients with GD and IA as in patients with heroin dependence. These findings could pose an important starting-point for treatment. (Am J Addict 2017;26:215-220). © 2017 American Academy of Addiction Psychiatry.

Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial)

ClinicalTrials.gov

2018-06-19

Breast Adenocarcinoma; Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIIB Breast Cancer AJCC v7

Treatment with insulin analogs and prevalence of cardiovascular complications in patients with type 1 diabetes.

PubMed

Hasslacher, Christoph; Lorenzo Bermejo, Justo

2017-11-01

A lower incidence of cardiovascular events has been reported in type 2 diabetes patients treated with insulin analogs (IAs). Corresponding data on people affected by type 1 diabetes are not available yet. We investigated demographic and clinical data from 509 type 1 diabetics, who were treated in an outpatient clinic from 2006 to 2012. Multiple logistic regression was used to investigate the relationship between the type of insulin treatment and the prevalence of cardiovascular (CV) complications, that is, presence of coronary heart, cerebrovascular and peripheral arterial diseases, adjusting for potential confounders. Results from multiple logistic regression revealed that patients with impaired renal function [estimated glomerular filtration rate (eGFR) < 90 ml/min] show lower CV complication rates when treated with IAs (25%) compared with patients treated with human insulin (HI; 28%) and HI/IA (38%, p = 0.06). CV complication rates in the complete patient collective amounted to 17% (IA), 21% (HI) and 21% (HI/IA, p = 0.08). Examination of CV complications according to the type of IA revealed the lowest complication rates in type 1 diabetics treated with insulin lispro (5.9%) and glargine (16%). However, complication rate differences among insulin treatments did not reach statistical significance. The present cross-sectional study shows a borderline significantly lower CV morbidity in people with type 1 diabetes and impaired renal function when treated with IA compared with HI treatment after adjustment for multiple potential confounders [odds ratio (OR) = 0.78, which translates into a 22% lower complication rate]. Validation of these preliminary findings in confirmatory, prospective studies may have important clinical implications.

The association between Internet addiction and personality disorders in a general population-based sample.

PubMed

Zadra, Sina; Bischof, Gallus; Besser, Bettina; Bischof, Anja; Meyer, Christian; John, Ulrich; Rumpf, Hans-Jürgen

2016-12-01

Background and aims Data on Internet addiction (IA) and its association with personality disorder are rare. Previous studies are largely restricted to clinical samples and insufficient measurement of IA. Methods Cross-sectional analysis data are based on a German sub-sample (n = 168; 86 males; 71 meeting criteria for IA) with increased levels of excessive Internet use derived from a general population sample (n = 15,023). IA was assessed with a comprehensive standardized interview using the structure of the Composite International Diagnostic Interview and the criteria of Internet Gaming Disorder as suggested in DSM-5. Impulsivity, attention deficit hyperactivity disorder, and self-esteem were assessed with the widely used questionnaires. Results Participants with IA showed higher frequencies of personality disorders (29.6%) compared to those without IA (9.3%; p < .001). In males with IA, Cluster C personality disorders were more prevalent than among non-addicted males. Compared to participants who had IA only, lower rates of remission of IA were found among participants with IA and additional cluster B personality disorder. Personality disorders were significantly associated with IA in multivariate analysis. Comorbidity of IA and personality disorders must be considered in prevention and treatment.

Predictors of response to intra-articular steroid injection in psoriatic arthritis.

PubMed

Eder, Lihi; Chandran, Vinod; Ueng, Joanna; Bhella, Sita; Lee, Ker-Ai; Rahman, Proton; Pope, Angela; Cook, Richard J; Gladman, Dafna D

2010-07-01

To assess the effectiveness of IA corticosteroid (IAS) injections in PsA and to determine the association between macrophage migration inhibition factor (MIF) gene polymorphism and response to IAS injections. A cohort analysis of PsA patients who were followed prospectively was performed. Clinical response was defined as no tenderness or effusion in the injected joint at 3 months. Relapse was defined as re-occurrence of joint pain or effusion. MIF 173C > G genotyping (rs755622) was performed. Two hundred and twenty patients with 245 IAS injections were included in the study. The probability of responding at 3 months was 41.6%. Within 12 months, 25.5% of the joints relapsed. Clinical factors that were associated with response included duration of psoriasis [Odds ratio (OR) 1.03] and the use of MTX or anti-TNF agents at the time of injection (OR 2.68). Factors that were associated with relapse included injection into large joints (OR 4.58) and elevated sedimentation rate (OR 15.0), whereas absence of clinical and/or radiographic damage (OR 0.23) and duration of PsA (OR 0.92) reduced risk of relapse. MIF polymorphism was not associated with clinical response, but was associated with relapse (OR 3.2). On multivariate analysis including clinical covariates, the association between MIF polymorphism and relapse was lost. IAS injections are effective in PsA. MIF gene polymorphism is associated with relapse. However, this effect is explained by clinical variables that reflect disease activity, suggesting that MIF gene polymorphism influences inflammatory activity.

Stereotactic Body Radiation Therapy Followed by Surgery in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer

ClinicalTrials.gov

2017-12-28

Stage I Non-Small Cell Lung Cancer AJCC v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-05-03

Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-12-16

Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Lungscape: resected non-small-cell lung cancer outcome by clinical and pathological parameters.

PubMed

Peters, Solange; Weder, Walter; Dafni, Urania; Kerr, Keith M; Bubendorf, Lukas; Meldgaard, Peter; O'Byrne, Kenneth J; Wrona, Anna; Vansteenkiste, Johan; Felip, Enriqueta; Marchetti, Antonio; Savic, Spasenija; Lu, Shun; Smit, Egbert; Dingemans, Anne-Marie; Blackhall, Fiona H; Baas, Paul; Camps, Carlos; Rosell, Rafael; Stahel, Rolf A

2014-11-01

The Lungscape project was designed to address the impact of clinical, pathological, and molecular characteristics on outcome in resected non-small- cell lung cancer (NSCLC). A decentralized biobank with fully annotated tissue samples was established. Selection criteria for participating centers included sufficient number of cases, tissue microarray building capability, and documented ethical approval. Patient selection was based on availability of comprehensive clinical data, radical resection between 2003 and 2009 with adequate follow-up, and adequate quantity and quality of formalin-fixed tissue. Fifteen centers contributed 2449 cases. The 5-year overall survival (OS) was 69.6% and 63.6% for stages IA and IB, 51.6% and 47.7% for stages IIA and IIB, and 29.0% and 13.0% for stages IIIA and IIIB, respectively (p < 0.001). Median and 5-year relapse-free survival (RFS) were 52.8 months and 47.3%, respectively. Distant relapse was recorded for 44.4%, local for 26.0%, and both for 16.9% of patients. Based on multivariate analysis for the OS, RFS, and time to relapse, the factors significantly associated with all of them are performance status and pathological stage. The aim of this report is to present the results from Lungscape, the first large series reporting on NSCLC surgical outcome measured not only by OS but also by RFS and time to relapse and including multivariate analysis by significant clinical and pathological prognostic parameters. As tissue from all patients is preserved locally and is available for detailed molecular investigations, Lungscape provides an excellent basis to evaluate the influence of molecular parameters on the disease outcome after radical resection, besides providing an overview of the molecular landscape of stage I to III NSCLC.

A clinical study and meta-analysis of carotid stenosis with coexistent intracranial aneurysms.

PubMed

Yang, Ximeng; Lu, Jun; Wang, Junjie; Wang, Lijun; Qi, Peng; Hu, Shen; Chen, Kunpeng; Wang, Daming

2018-06-01

Carotid stenosis (CS) and intracranial aneurysms (IAs) may concur in one person. We studied the prevalence of IAs in CS patients in our retrospectively collected database and systematically reviewed this issue. Five hundred and fifty-seven CS (≥50%) patients confirmed by DSA in our hospital from 2010-06 to 2015-06 were screened for coexistent IAs. After searching the related literatures from English and Chinese journal literature databases, a meta-analysis was performed to pool the prevalence of CS with coexistent IAs. Subgroup analyses were performed to explore the causes of heterogeneity among studies. IAs were detected in 98(17.0%) out of the 577 CS patients. 12 literatures and the present study including a total of 6965 CS patients and 446 cases with coexistent IAs. The pooled prevalence of CS with coexistent IAs was 6.3% (95%CI: 4.2-8.3%) in all the CS patients. The pooled RR for female to male CS patients to have coexistent IAs was 1.67 (95%CI: 1.34-2.08, P = 0.000). 3 studies and the present study were carried out in Asian countries with a pooled prevalence of 10.8% (95%CI: 5.3-16.3%); 6 studies in European countries with 3.0% (95%CI: 2.2-3.7%); and 3 studies in USA with 6.0% (95%CI: 2.2-9.7%). There was a statistically significant difference between the three subgroups (P < 0.001). The prevalence of IAs in CS patients seems higher in our clinical study and the meta-analysis than in the general population and previously reported. The eastern and the women CS patients have a higher risk for coexistent IAs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Flexitouch® Home Maintenance Therapy or Standard Home Maintenance Therapy in Treating Patients With Lower-Extremity Lymphedema Caused by Treatment for Cervical Cancer, Vulvar Cancer, or Endometrial Cancer

ClinicalTrials.gov

2014-12-29

Lymphedema; Stage 0 Cervical Cancer; Stage 0 Uterine Corpus Cancer; Stage 0 Vulvar Cancer; Stage I Uterine Corpus Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vulvar Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Stage IVB Vulvar Cancer

Radiofrequency Tagged Surgery in Treating Patients With Breast Cancer

ClinicalTrials.gov

2018-06-18

Positive Axillary Lymph Node; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7

Transcriptomic evidence for involvement of reactive oxygen species in Rhizoctonia solani AG1 IA sclerotia maturation

PubMed Central

Wang, Haode; Ma, Zhoujie; Gai, Xiaotong; Sun, Yanqiu; He, Shidao; Liu, Xian; Wang, Yanfeng; Xuan, Yuanhu

2018-01-01

Rhizoctonia solani AG1 IA is a soil-borne fungal phytopathogen that can significantly harm crops resulting in economic loss. This species overwinters in grass roots and diseased plants, and produces sclerotia that infect future crops. R. solani AG1 IA does not produce spores; therefore, understanding the molecular mechanism of sclerotia formation is important for crop disease control. To identify the genes involved in this process for the development of disease control targets, the transcriptomes of this species were determined at three important developmental stages (mycelium, sclerotial initiation, and sclerotial maturation) using an RNA-sequencing approach. A total of 5,016, 6,433, and 5,004 differentially expressed genes (DEGs) were identified in the sclerotial initiation vs. mycelial, sclerotial maturation vs. mycelial, and sclerotial maturation vs. sclerotial initiation stages, respectively. Moreover, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses showed that these DEGs were enriched in diverse categories, including oxidoreductase activity, carbohydrate metabolic process, and oxidation-reduction processes. A total of 12 DEGs were further verified using reverse transcription quantitative PCR. Among the genes examined, NADPH oxidase 1 (NOX1) and superoxide dismutase (SOD) were highly induced in the stages of sclerotial initiation and maturation. In addition, the highest reactive oxygen species (ROS) production levels were detected during sclerotial initiation, and enzyme activities of NOX1, SOD, and catalase (CAT) matched with the gene expression profiles. To further evaluate the role of ROS in sclerotial formation, R. solani AG1 IA was treated with the CAT inhibitor aminotriazole and H2O2, resulting in the early differentiation of sclerotia. Taken together, this study provides useful information toward understanding the molecular basis of R. solani AG1 IA sclerotial formation and maturation, and identified the important role of ROS in these processes. PMID:29938140

Worse Prognosis for Stage IA Lung Cancer Patients with Smoking History and More Severe Chronic Obstructive Pulmonary Disease.

PubMed

Yoshida, Yukihiro; Kage, Hidenori; Murakawa, Tomohiro; Sato, Yasunori; Ota, Satoshi; Fukayama, Masashi; Nakajima, Jun

2015-01-01

This retrospective study examined whether the severity of chronic obstructive lung disease (COPD) affects surgical outcomes. The subjects were 243 consecutive patients who underwent lobectomy for clinical stage IA lung cancer from 1999 to 2008 in our hospital. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading system was used to classify the severity of COPD in smokers. Among the 149 smokers, 62 were diagnosed with COPD (25 as GOLD 1, 33 as GOLD 2, and 4 as GOLD 3). In univariate analysis, postoperative pulmonary complications were associated with male sex and more severe COPD. The frequencies were 17.1% in non-COPD, 24.0% in GOLD 1-COPD, and 46.0% in GOLD 2/3-COPD smokers (p = 0.0006). In univariate analysis, older age, smoking history, higher smoking pack-years and more severe COPD were associated with poor relapse-free survival. Relapse-free survival at five years was 80.7%, 66.9%, and 61.3% in non-COPD, GOLD 1-COPD, and GOLD 2/3-COPD smokers, respectively (p = 0.0005). Multivariate analyses showed that only GOLD 2/3-COPD was associated with postoperative pulmonary complications and relapse-free survival. Inhaled bronchodilators were prescribed preoperatively to 24.3% of the GOLD 2/3-COPD group. Smokers with GOLD 2/3-COPD are at high risk for pulmonary complications and have an unfavorable long-term prognosis.

Adaptive designs in clinical trials.

PubMed

Bowalekar, Suresh

2011-01-01

In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

Biological signatures of asymptomatic extra- and intracranial atherosclerosis: the Barcelona-AsIA (Asymptomatic Intracranial Atherosclerosis) study.

PubMed

López-Cancio, Elena; Galán, Amparo; Dorado, Laura; Jiménez, Marta; Hernández, María; Millán, Mónica; Reverté, Silvia; Suñol, Anna; Barallat, Jaume; Massuet, Anna; Alzamora, Maria Teresa; Dávalos, Antonio; Arenillas, Juan Francisco

2012-10-01

Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects >50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Our findings show distinct clinical and biological profiles in subclinical ICAD and extracranial atherosclerotic disease. Insulin resistance emerged as an important molecular pathway involved in the development of ICAD from its asymptomatic stage.

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

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

Gunther, Jillian R.; Fanale, Michelle A.; Reddy, Jay P.

Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicitiesmore » were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease.« less

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation.

PubMed

Gunther, Jillian R; Fanale, Michelle A; Reddy, Jay P; Akhtari, Mani; Smith, Grace L; Pinnix, Chelsea C; Milgrom, Sarah A; Yehia, Zeinab Abou; Allen, Pamela K; Osborne, Eleanor M; Mawlawi, Osama; Dabaja, Bouthaina S

2016-09-01

The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia revealed by crystallographic and small-angle X-ray scattering analysis.

PubMed

Smith, Clyde A; Toth, Marta; Weiss, Thomas M; Frase, Hilary; Vakulenko, Sergei B

2014-10-01

Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and enterococcal pathogens is primarily conferred by the bifunctional enzyme AAC(6')-Ie-APH(2'')-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6')-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2'')-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2'')-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6')-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6')-Ie enzyme is joined to APH(2'')-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2'')-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6')-Ie-APH(2'')-Ia enzyme.

A follow-up study of neonatal interatrial shunt with echocardiography until twelve to fifteen months of age.

PubMed

Ho, Chi-Lin; Jan, Sheng-Ling; Lin, Ming-Chih; Fu, Yun-Ching

2008-12-01

To assess the incidence and natural history of full-term neonates with interatrial shunt (IAS). A follow-up study of 1389 neonates who received screening echocardiography between 2003 and 2006. Babies with IAS at 2 to 4 days of life underwent follow-up echocardiography at 2 to 4 months, 6 to 9 months and 12 to 15 months of age until closure of IAS. The ratio of IAS was 68.3% initially. No significant demographic differences were identified between infants with and without initial IAS. Among 949 neonates with initial IAS, 84.5% infants had a left-to-right interatrial shunt, 13.5% had bidirectional shunt and 2% had predominantly right-to-left shunt. The persistence rate of IAS at 12 to 15 months of age was 3.8% (44/1166). The initial size of IAS ranged from 1.2 to 7.7mm (4.3+/-1.1 mm) detected by color Doppler flow mapping and cases were divided into three groups: small (< or =5 mm), medium (5 to 8 mm) and large group (> or =8 mm). There were 74.6% infants in the small group and 25.4% in the medium group initially. The neonates in the initial small group would always see their IAS close or else they would remain in the small group. Those in the final medium and large size groups always came from the initial medium group. The late closure rate of IAS was 93.9% of infants with initial IAS. The closure curves of initial small and medium sized groups were significantly different, and their late closure rates were 95.1% and 90.4%, respectively. IAS was very common during early neonatal stage, but most cases would close after 1 year. The late closure rate of initial IAS was different if using a cutpoint of 5 mm.

Prognostic importance of pleural attachment status measured by pretreatment CT images in patients with stage IA lung adenocarcinoma: measurement of the ratio of the interface between nodule and neighboring pleura to nodule surface area

NASA Astrophysics Data System (ADS)

Kawata, Y.; Niki, N.; Kusumoto, M.; Ohmatsu, H.; Aokage, K.; Ishii, G.; Matsumoto, Y.; Tsuchida, T.; Eguchi, K.; Kaneko, M.

2018-02-01

Screening for lung cancer with low-dose computed tomography (CT) has led to increased recognition of small lung cancers and is expected to increase the rate of detection of early-stage lung cancer. Major concerns in the implementation of the CT screening of large populations include determining the appropriate management of pulmonary nodules found on a scan. The identification of patients with early-stage lung cancer who have a higher risk for relapse and who require more aggressive surveillance has been a target of intense investigation. This study was performed to investigate whether image features of internal intensity in combination with surrounding structure characteristics are associated with an increased risk of relapse in patients with stage IA lung adenocarcinoma. We focused on pleural attachment status which is one of morphological characteristics associated with prognosis in three-dimensional thoracic CT images.

Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis.

PubMed

Ciurtin, Coziana; Wyszynski, Karol; Clarke, Robert; Mouyis, Maria; Manson, Jessica; Marra, Giampiero

2016-10-01

Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation.

The association between Internet addiction and personality disorders in a general population-based sample

PubMed Central

Zadra, Sina; Bischof, Gallus; Besser, Bettina; Bischof, Anja; Meyer, Christian; John, Ulrich; Rumpf, Hans-Jürgen

2016-01-01

Background and aims Data on Internet addiction (IA) and its association with personality disorder are rare. Previous studies are largely restricted to clinical samples and insufficient measurement of IA. Methods Cross-sectional analysis data are based on a German sub-sample (n = 168; 86 males; 71 meeting criteria for IA) with increased levels of excessive Internet use derived from a general population sample (n = 15,023). IA was assessed with a comprehensive standardized interview using the structure of the Composite International Diagnostic Interview and the criteria of Internet Gaming Disorder as suggested in DSM-5. Impulsivity, attention deficit hyperactivity disorder, and self-esteem were assessed with the widely used questionnaires. Results Participants with IA showed higher frequencies of personality disorders (29.6%) compared to those without IA (9.3%; p < .001). In males with IA, Cluster C personality disorders were more prevalent than among non-addicted males. Compared to participants who had IA only, lower rates of remission of IA were found among participants with IA and additional cluster B personality disorder. Personality disorders were significantly associated with IA in multivariate analysis. Discussion and conclusion: Comorbidity of IA and personality disorders must be considered in prevention and treatment. PMID:28005417

Phase I study of stereotactic body radiation therapy for centrally located stage IA non-small cell lung cancer (JROSG10-1).

PubMed

Kimura, Tomoki; Nagata, Yasushi; Harada, Hideyuki; Hayashi, Shinya; Matsuo, Yukinori; Takanaka, Tsuyoshi; Kokubo, Masaki; Takayama, Kenji; Onishi, Hiroshi; Hirakawa, Koichi; Shioyama, Yoshiyuki; Ehara, Takeshi

2017-10-01

To investigate the maximum tolerated dose (MTD) and recommended dose (RD) of stereotactic body radiation therapy (SBRT) for centrally located stage IA non-small cell lung cancer (NSCLC). Five dose levels, ranging from of 52 to 68 Gy in eight fractions, were determined; the treatment protocol began at 60 Gy (level 3). Each dose level included 10 patients. Levels 1-2 were indicated if more than four patients exhibited dose-limiting toxicity (DLT), which was defined as an occurrence of a grade 3 (or worse) adverse effect within 12 months after SBRT initiation. MTD was defined as the lowest dose level at which more than four patients exhibited DLT. Ten patients were enrolled in the level 3 study. One patient was considered unsuitable because of severe emphysema. Therefore, nine patients were evaluated and no patient exhibited DLT. The level 3 results indicated that we should proceed to level 4 (64 Gy). However, due to the difficulty involved in meeting the dose constraints, further dose escalation was not feasible and the MTD was found to be 60 Gy. The RD of SBRT for centrally located stage IA NSCLC was 60 Gy in eight fractions.

Exploring the statistical and clinical impact of two interim analyses on the Phase II design with option for direct assignment.

PubMed

An, Ming-Wen; Mandrekar, Sumithra J; Edelman, Martin J; Sargent, Daniel J

2014-07-01

The primary goal of Phase II clinical trials is to understand better a treatment's safety and efficacy to inform a Phase III go/no-go decision. Many Phase II designs have been proposed, incorporating randomization, interim analyses, adaptation, and patient selection. The Phase II design with an option for direct assignment (i.e. stop randomization and assign all patients to the experimental arm based on a single interim analysis (IA) at 50% accrual) was recently proposed [An et al., 2012]. We discuss this design in the context of existing designs, and extend it from a single-IA to a two-IA design. We compared the statistical properties and clinical relevance of the direct assignment design with two IA (DAD-2) versus a balanced randomized design with two IA (BRD-2) and a direct assignment design with one IA (DAD-1), over a range of response rate ratios (2.0-3.0). The DAD-2 has minimal loss in power (<2.2%) and minimal increase in T1ER (<1.6%) compared to a BRD-2. As many as 80% more patients were treated with experimental vs. control in the DAD-2 than with the BRD-2 (experimental vs. control ratio: 1.8 vs. 1.0), and as many as 64% more in the DAD-2 than with the DAD-1 (1.8 vs. 1.1). We illustrate the DAD-2 using a case study in lung cancer. In the spectrum of Phase II designs, the direct assignment design, especially with two IA, provides a middle ground with desirable statistical properties and likely appeal to both clinicians and patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessing the quality of the ecological component of English Environmental Statements.

PubMed

Drayson, Katherine; Wood, Graham; Thompson, Stewart

2015-09-01

Environmental Impact Assessment (EIA) is a key tool to help ensure sustainable built development in more than 200 countries worldwide. Ecology is frequently a component of EIA and early reviews of Ecological Impact Assessment (EcIA) chapters identified scope for improvement at almost every stage of the EcIA process, regardless of country. However, there have been no reviews of UK EcIA chapters since 2000, despite important changes in biodiversity and planning legislation, policy and guidance. In addition, no UK EcIA chapter reviews have attempted to assign a grade or score to EcIA chapters (as has been done for reviews of US, Finnish and Indian EcIA chapters). Furthermore, no EcIA chapter reviews have attempted to use a scoring system to identify which variables determine EcIA chapter information content, beyond straightforward comparisons of EcIA chapters before and after the introduction of guidelines. A variant of the Biodiversity Assessment Index (BAI) was used to assign scores between zero and one to EcIA chapters based on a series of 47 questions drawn from EU legislation and professional guidance. 112 EcIA chapters for proposed developments that were subsequently granted planning permission in England were assessed. The mean BAI score was less than 0.5, indicating the presence of considerable information gaps in the majority of EcIA chapters. Of 13 predictor variables identified as having the potential to affect EcIA chapter quality, 10 were identified as significantly related to the BAI scores. A backward stepwise Generalized Linear Model identified the use of professional guidance, the ecological consultancy type and the length of the EcIA chapter as having the greatest combined explanatory power. As a result, several recommendations are made to help improve future EcIA chapter content, including formal EcIA chapter review, publicising the professional guidance to consultants, the provision of training and the introduction of an accreditation scheme for consultants involved in EcIA This approach could be replicated in other countries that conduct EIA. Context-dependent EcIA chapter review criteria (as in this paper) would help to identify targeted recommendations for improvement. Alternatively, a global set of review criteria could highlight areas of best practice that could then be exported to other countries. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity.

PubMed

Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel

2017-03-01

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Percutaneous thermal ablation for stage IA non-small cell lung cancer: long-term follow-up.

PubMed

Narsule, Chaitan K; Sridhar, Praveen; Nair, Divya; Gupta, Avneesh; Oommen, Roy G; Ebright, Michael I; Litle, Virginia R; Fernando, Hiran C

2017-10-01

Surgical resection is the most effective curative therapy for non-small cell lung cancer (NSCLC). However, many patients are unable to tolerate resection secondary to poor reserve or comorbid disease. Radiofrequency ablation (RFA) and microwave ablation (MWA) are methods of percutaneous thermal ablation that can be used to treat medically inoperable patients with NSCLC. We present long-term outcomes following thermal ablation of stage IA NSCLC from a single center. Patients with stage IA NSCLC and factors precluding resection who underwent RFA or MWA from July 2005 to September 2009 were studied. CT and PET-CT scans were performed at 3 and 6 month intervals, respectively, for first 24 months of follow-up. Factors associated with local progression (LP) and overall survival (OS) were analyzed. Twenty-one patients underwent 21 RFA and 4 MWA for a total of 25 ablations. Fifteen patients had T1a and six patients had T1b tumors. Mean follow-up was 42 months, median survival was 39 months, and OS at three years was 52%. There was no significant difference in median survival between T1a nodules and T1b nodules (36 vs . 39 months, P=0.29) or for RFA and MWA (36 vs . 50 months, P=0.80). Ten patients had LP (47.6%), at a median time of 35 months. There was no significant difference in LP between T1a and T1b tumors (22 vs . 35 months, P=0.94) or RFA and MWA (35 vs . 17 months, P=0.18). Median OS with LP was 32 months compared to 39 months without LP (P=0.68). Three patients underwent repeat ablations. Mean time to LP following repeat ablation was 14.75 months. One patient had two repeat ablations and was disease free at 40-month follow-up. Thermal ablation effectively treated or controlled stage IA NSCLC in medically inoperable patients. Three-year OS exceeded 50%, and LP did not affect OS. Therefore, thermal ablation is a viable option for medically inoperable patients with early stage NSCLC.

Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

ClinicalTrials.gov

2018-02-15

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

Clinical Manifestations of Cryptosporidiosis and Identification of a New Cryptosporidium Subtype in Patients From Sonora, Mexico.

PubMed

Urrea-Quezada, Alejandro; González-Díaz, Mariana; Villegas-Gómez, Isaac; Durazo, María; Hernández, Jesús; Xiao, Lihua; Valenzuela, Olivia

2018-05-01

The aim of this study was to identify the clinical manifestations of cryptosporidiosis and the distribution of Cryptosporidium spp. and subtypes in children in Sonora, Mexico. Two subtypes of C. parvum, including IIaA15G2R1 and IIcA5G3a, and 6 subtypes of Cryptosporidium hominis, including IaA14R3, IaA15R3, IbA12G3, IdA23, IeA11G3T3, and a new subtype IaA14R11, were identified. Cryptosporidium as an etiologic agent for acute gastroenteritis is discussed.

BmprIa is required in mesenchymal tissue and has limited redundant function with BmprIb in tooth and palate development

PubMed Central

Li, Lu; Lin, Minkui; Wang, Ying; Cserjesi, Peter; Chen, Zhi; Chen, YiPing

2010-01-01

The BMP signaling plays a pivotal role in the development of craniofacial organs, including the tooth and palate. BmprIa and BmprIb encode two type I BMP receptors that are primarily responsible for BMP signaling transduction. We investigated mesenchymal tissue-specific requirement of BmprIa and its functional redundancy with BmprIb during the development of mouse tooth and palate. BmprIa and BmprIb exhibit partially overlapping and distinct expression patterns in the developing tooth and palatal shelf. Neural crest specific inactivation of BmprIa leads to formation of an unusual type of anterior clefting of the secondary palate, an arrest of tooth development at the bud/early cap stages, and severe hypoplasia of the mandible. Defective tooth and palate development is accompanied by the down-regulation of BMP responsive genes and reduced cell proliferation levels in the palatal and dental mesenchyme. To determine if BmprIb could substitute for BmprIa during tooth and palate development, we expressed a constitutively active form of BmprIb (caBmprIb) in the neural crest cells in which BmprIa was simultaneously inactivated. We found that substitution of BmprIa by caBmprIb in neural rest cells rescues the development of molars and maxillary incisor, but the rescued teeth exhibit a delayed odontoblast and ameloblast differentiation. In contrast, caBmprIb fails to rescue the palatal and mandibular defects including the lack of lower incisors. Our results demonstrate an essential role for BmprIa in the mesenchymal component and a limited functional redundancy between BmprIa and BmprIb in a tissue specific manner during tooth and palate development. PMID:21034733

Genetic association study identifies a functional CNV in the WWOX gene contributes to the risk of intracranial aneurysms.

PubMed

Fan, Jin; Sun, Wen; Lin, Min; Yu, Ke; Wang, Jian; Duan, Dan; Zheng, Bo; Yang, Zhenghui; Wang, Qingsong

2016-03-29

Intracranial aneurysms (IAs) accounts for 85% of hemorrhagic stroke. Genetic factors have been known to play an important role in the development of IAs. A functional CNV (CNV-67048) of human WW domain-containing oxidoreductase (WWOX), which has been identified as a tumor suppressor gene in multiple cancers, was identified to be associated with gliomas risk previously. Here, we hypothesized that the CNV-67048 could also affect susceptibility of IAs. Based on a two-stage, case- control study with a total of 976 patients of IAs and 1,200 matched healthy controls, we found the effect size for per copy deletion was 1.35 (95% CI = 1.16-1.57; Ptrend = 1.18 × 10-4). Compared with the individuals having no deletion, significantly higher risk of IAs was detected for both subjects carrying 1 copy deletion (OR = 1.24, 95% CI = 1.02-1.52) and subjects carrying 2 copy deletion (OR = 1.77, 95% CI = 1.24-2.53). Real-time PCR was used to confirm the abnormal expression of WWOX in tissues of IA patients and influence of genotypes of CNV-67048. The expression level of WWOX in IA tissues was significantly lower than that in corresponding normal tissues (P = 0.004), and the deletion genotypes of CNV-67048 have lower WWOX mRNA levels in both tumor tissues and border tissues (P < 0.01). Our data suggests that the deletion genotypes of CNV-67048 in WWOX predispose their carriers to IAs, which might be a genetic biomarker to predict risk of IAs in Chinese.

Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

ClinicalTrials.gov

2017-05-03

Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Long-term results of CT-guided percutaneous radiofrequency ablation of inoperable patients with stage Ia non-small cell lung cancer: A retrospective cohort study.

PubMed

Huang, Bing-Yang; Li, Xin-Min; Song, Xiao-Yong; Zhou, Jun-Jun; Shao, Zhuang; Yu, Zhi-Qi; Lin, Yi; Guo, Xin-Yu; Liu, Da-Jiang; Li, Lu

2018-05-01

This study was performed to retrospectively evaluate the 10-year overall survival (OS), progression-free survival (PFS), and local control rates of patients with inoperable stage Ia non-small cell lung cancer (NSCLC) who underwent computed tomography (CT)-guided radiofrequency ablation (RFA) in a single center. Fifty patients with inoperable NSCLC underwent RFA between 2004 and 2016. Thoracic surgeons evaluated the patients and performed RFA under CT guidance. Follow-up CT and positron emission tomography/CT scans were obtained. Local control rates and recurrence patterns were analyzed. Seventy-three lesions in 50 patients (M:F = 22:28; median age: 73 years; range: 52-82 years) were treated with CT-guided RFA. The mean lesion size was 2.2 cm (range: 1-3 cm). No procedure-related deaths occurred. Low-grade fever was the most common post-ablation complication, with an incidence rate of 36%. The 1-, 2-, 3-, 5-, and 10-year OS rates of patients with Ia NSCLC were 96.0%, 86.5%, 67.1%, 36.3%, and 1%, respectively, and the 1-, 2-, 3-, and 5-year PFS rates were 94.0%, 77.5%, 43.5%, and 10.8%, respectively. The most common pattern of recurrence was local, and 15 patients with recurrence were treated with repeat RFA. Tumor size <2.0 cm was associated with a significantly improved 3-year survival rate of 78.9%. CT-guided RFA is feasible and well tolerated by inoperable patients with inoperable stage Ia NSCLC. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

The use of biomarkers and molecular methods for the earlier diagnosis of invasive aspergillosis in immunocompromised patients.

PubMed

Ambasta, Anshula; Carson, Julie; Church, Deirdre L

2015-08-01

Invasive aspergillosis (IA) is an opportunistic infection that is often life threatening in the immunocompromised host. Early diagnosis is critical, especially given the efficacy and availability of several new anti-fungal therapies. Current (2008) diagnostic criteria have limited ability to detect early infection and are aimed at establishing disease. Although histopathology and culture techniques have traditionally been used to make a proven diagnosis of IA, their dependence on tissue samples and slow turnaround times hamper early confirmation of IA. Serologic detection of circulating galactomannan and 1,3-β-D-glucan fungal biomarkers show promise for improving the diagnosis of IA, and their use is included in the EORTC/MSG diagnostic criteria for IA. Numerous studies have evaluated the diagnostic performance of these two biomarkers and shown that they have suboptimal sensitivity when used alone for early diagnosis of proven IA. Currently available molecular assays also suffer from a lack of standardization. Evaluation of the use of different combinations of test methods to enhance diagnostic accuracy is also being done but prompt, accurate diagnosis of IA remains a clinical and diagnostic challenge. The clinical validity and limitations of biomarkers and current molecular methods for the early diagnosis of IA are summarized in this review with respect to the different patient populations at risk for this serious infection. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Interpreting survival data from clinical trials of surgery versus stereotactic body radiation therapy in operable Stage I non-small cell lung cancer patients.

PubMed

Samson, Pamela; Keogan, Kathleen; Crabtree, Traves; Colditz, Graham; Broderick, Stephen; Puri, Varun; Meyers, Bryan

2017-01-01

To identify the variability of short- and long-term survival outcomes among closed Phase III randomized controlled trials with small sample sizes comparing SBRT (stereotactic body radiation therapy) and surgical resection in operable clinical Stage I non-small cell lung cancer (NSCLC) patients. Clinical Stage I NSCLC patients who underwent surgery at our institution meeting the inclusion/exclusion criteria for STARS (Randomized Study to Compare CyberKnife to Surgical Resection in Stage I Non-small Cell Lung Cancer), ROSEL (Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer), or both were identified. Bootstrapping analysis provided 10,000 iterations to depict 30-day mortality and three-year overall survival (OS) in cohorts of 16 patients (to simulate the STARS surgical arm), 27 patients (to simulate the pooled surgical arms of STARS and ROSEL), and 515 (to simulate the goal accrual for the surgical arm of STARS). From 2000 to 2012, 749/873 (86%) of clinical Stage I NSCLC patients who underwent resection were eligible for STARS only, ROSEL only, or both studies. When patients eligible for STARS only were repeatedly sampled with a cohort size of 16, the 3-year OS rates ranged from 27 to 100%, and 30-day mortality varied from 0 to 25%. When patients eligible for ROSEL or for both STARS and ROSEL underwent bootstrapping with n=27, the 3-year OS ranged from 46 to 100%, while 30-day mortality varied from 0 to 15%. Finally, when patients eligible for STARS were repeatedly sampled in groups of 515, 3-year OS narrowed to 70-85%, with 30-day mortality varying from 0 to 4%. Short- and long-term survival outcomes from trials with small sample sizes are extremely variable and unreliable for extrapolation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

How close are we to customizing chemotherapy in early non-small cell lung cancer?

PubMed Central

Ioannidis, Georgios; Georgoulias, Vassilis; Souglakos, John

2011-01-01

Although surgery is the only potentially curative treatment for early-stage non-small cell lung cancer (NSCLC), 5-year survival rates range from 77% for stage IA tumors to 23% in stage IIIA disease. Adjuvant chemotherapy has recently been established as a standard of care for resected stage II-III NSCLC, on the basis of large-scale clinical trials employing third-generation platinum-based regimens. As the overall absolute 5-year survival benefit from this approach does not exceed 5% and potential long-term complications are an issue of concern, the aim of customized adjuvant systemic treatment is to optimize the toxicity/benefit ratio, so that low-risk individuals are spared from unnecessary intervention, while avoiding undertreatment of high-risk patients, including those with stage I disease. Therefore, the application of reliable prognostic and predictive biomarkers would enable to identify appropriate patients for the most effective treatment. This is an overview of the data available on the most promising clinicopathological and molecular biomarkers that could affect adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine practice. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information warranting further validation. On the other hand, real-time quantitative polymerase-chain reaction strategy involving relatively small number of genes offers a practical alternative, with high cross-platform performance. Although data extrapolation from the metastatic setting should be cautious, the concept of personalized, pharmacogenomics-guided chemotherapy for early NSCLC seems feasible, and is currently being evaluated in randomized phase 2 and 3 trials. The mRNA and/or protein expression levels of excision repair cross-complementation group 1, ribonucleotide reductase M1 and breast cancer susceptibility gene 1 are among the most potential biomarkers for early disease, with stage-independent prognostic and predictive values, the clinical utility of which is being validated prospectively. Inter-assay discordance in determining the biomarker status and association with clinical outcomes is noteworthing. PMID:21904580

Maternal immune activation and abnormal brain development across CNS disorders.

PubMed

Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

2014-11-01

Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.

Is There Convincing Evidence that Intermediate Repeats in the HTT Gene Cause Huntington's Disease?

PubMed

Oosterloo, Mayke; Van Belzen, Martine J; Bijlsma, Emilia K; Roos, Raymund A C

2015-01-01

Huntington's disease (HD) is a neurodegenerative disease associated with a CAG repeat expansion in the Huntingtin (HTT) gene. A trinucleotide size between 27 and 35 is considered 'intermediate' and not to cause symptoms and signs of HD. There are articles claiming otherwise, however publishing only the cases that have a HD phenotype introduces a significant publication bias. Our objective is to determine if there is convincing evidence that intermediate repeats (IA) cause HD. Previously published case reports on HTT intermediate repeat sizes and all cases from the Netherlands with an IA were reviewed for clinical symptoms and signs. Four patients had a clinical presentation of Huntington's disease and an IA out of ten reported cases in literature. Between 2001 and 2012, 1,690 patients were tested for HD in the Netherlands. One case out of 60 with an IA had a phenotype resembling HD, but had already been published in a case report. Given the high background frequency of intermediate alleles in several populations, the possibility of developing HD would have huge implications for 1-7% of the normal population. It is possible that IAs present as an endophenotype with the potential of subsequent clinical manifestations. However, given the scarcity of convincing cases, the lack of convincing biological evidence for pathogenicity of intermediate alleles, and many genes still to be discovered for HD mimics, we find that it is premature to claim that IAs can cause HD. We recommend systematic follow up of this group of individuals and if possible brain pathology for confirmation or exclusion of HD.

Tolerance of Sulfolobus SMV1 virus to the immunity of I-A and III-B CRISPR-Cas systems in Sulfolobus islandicus.

PubMed

Guo, Tong; Han, Wenyuan; She, Qunxin

2018-04-09

Sulfolobus islandicus Rey15A encodes one type I-A and two type III-B systems, all of which are active in mediating nucleic acids interference. However, the effectiveness of each CRISPR system against virus infection was not tested in this archaeon. Here we constructed S. islandicus strains that constitutively express the antiviral immunity from either I-A, or III-B, or I-A plus III-B systems against SMV1 and tested the response of each host to SMV1 infection. We found that, although both CRISPR immunities showed a strongly inhibition to viral DNA replication at an early stage of incubation, the host I-A CRISPR immunity gradually lost the control on virus proliferation, allowing accumulation of cellular viral DNA and release of a large number of viral particles. In contrast, the III-B CRISPR immunity showed a tight control on both viral DNA replication and virus particle formation. Furthermore, the SMV1 tolerance to the I-A CRISPR immunity did not result from the occurrence of escape mutations, suggesting the virus probably encodes an anti-CRISPR protein (Acr) to compromise the host I-A CRISPR immunity. Together, this suggests that the interplay between viral Acrs and CRISPR-Cas systems in thermophilic archaea could have shaped the stable virus-host relationship currently seen for many archaeal viruses.

Mucinous Cystadenocarcinoma Co-Existing with Mature Cystic Teratoma : A Rare Case Report

PubMed Central

Yeshvanth, Sunil Kumar; Shrinivas, Teerthanath; Agrawal, Tanu; Shetty, Jayaprakash K

2015-01-01

Co-existence of mucinous cystadenocarcinoma with mature cystic teratoma in the same ovary is very rare. We report a case in a 48-year-old female who presented with left abdominal mass. CT scan revealed a heterogeneous enhancing left ovarian mass lesion. Clinical diagnosis of complex ovarian cyst was made, later underwent laparotomy and histologically diagnosed as mucinous cystadenocarcinoma (grade 2) co-existing with benign cystic teratoma, stage Ia (FIGO) of the left ovary. Six months after surgery, the patient is doing well without any recurrence or metastasis. Hence, histopathological examination plays a significant role in accurate diagnosis and management of the patient. So, we should be aware of these rare co-existent tumours and meticulous dissection should be done to look for any synchronous tumours or malignant areas; since management and prognosis will vary significantly depending upon the microscopic type and stage. PMID:26393136

Computer-assisted adjuncts for aneurysmal morphologic assessment: toward more precise and accurate approaches

NASA Astrophysics Data System (ADS)

Rajabzadeh-Oghaz, Hamidreza; Varble, Nicole; Davies, Jason M.; Mowla, Ashkan; Shakir, Hakeem J.; Sonig, Ashish; Shallwani, Hussain; Snyder, Kenneth V.; Levy, Elad I.; Siddiqui, Adnan H.; Meng, Hui

2017-03-01

Neurosurgeons currently base most of their treatment decisions for intracranial aneurysms (IAs) on morphological measurements made manually from 2D angiographic images. These measurements tend to be inaccurate because 2D measurements cannot capture the complex geometry of IAs and because manual measurements are variable depending on the clinician's experience and opinion. Incorrect morphological measurements may lead to inappropriate treatment strategies. In order to improve the accuracy and consistency of morphological analysis of IAs, we have developed an image-based computational tool, AView. In this study, we quantified the accuracy of computer-assisted adjuncts of AView for aneurysmal morphologic assessment by performing measurement on spheres of known size and anatomical IA models. AView has an average morphological error of 0.56% in size and 2.1% in volume measurement. We also investigate the clinical utility of this tool on a retrospective clinical dataset and compare size and neck diameter measurement between 2D manual and 3D computer-assisted measurement. The average error was 22% and 30% in the manual measurement of size and aneurysm neck diameter, respectively. Inaccuracies due to manual measurements could therefore lead to wrong treatment decisions in 44% and inappropriate treatment strategies in 33% of the IAs. Furthermore, computer-assisted analysis of IAs improves the consistency in measurement among clinicians by 62% in size and 82% in neck diameter measurement. We conclude that AView dramatically improves accuracy for morphological analysis. These results illustrate the necessity of a computer-assisted approach for the morphological analysis of IAs.

Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-01-05

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

The Prevalence of Internet Addiction among a Japanese Adolescent Psychiatric Clinic Sample with Autism Spectrum Disorder And/or Attention-Deficit Hyperactivity Disorder: A Cross-Sectional Study

ERIC Educational Resources Information Center

So, Ryuhei; Makino, Kazunori; Fujiwara, Masaki; Hirota, Tomoya; Ohcho, Kozo; Ikeda, Shin; Tsubouchi, Shouko; Inagaki, Masatoshi

2017-01-01

Extant literature suggests that autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are risk factors for internet addiction (IA). The present cross-sectional study explored the prevalence of IA among 132 adolescents with ASD and/or ADHD in a Japanese psychiatric clinic using Young's Internet Addiction Test. The…

Computed Tomography Angiography Evaluation of Risk Factors for Unstable Intracranial Aneurysms.

PubMed

Wang, Guang-Xian; Gong, Ming-Fu; Wen, Li; Liu, Lan-Lan; Yin, Jin-Bo; Duan, Chun-Mei; Zhang, Dong

2018-03-19

To evaluate risk factors for instability in intracranial aneurysms (IAs) using computed tomography angiography (CTA). A total of 614 consecutive patients diagnosed with 661 IAs between August 2011 and February 2016 were reviewed. Patients and IAs were divided into stable and unstable groups. Along with clinical characteristics, IA characteristics were evaluated by CTA. Multiple logistic regression analysis was used to identify the independent risk factors associated with unstable IAs. Receiver operating characteristic (ROC) curve analysis was performed on the final model, and optimal thresholds were obtained. Patient age (odds ratio [OR], 0.946), cerebral atherosclerosis (CA; OR, 0.525), and IAs located at the middle cerebral artery (OR, 0.473) or internal carotid artery (OR, 0.512) were negatively correlated with instability, whereas IAs with irregular shape (OR, 2.157), deep depth (OR, 1.557), or large flow angle (FA; OR, 1.015) were more likely to be unstable. ROC analysis revealed threshold values of age, depth, and FA of 59.5 years, 4.25 mm, and 87.8°, respectively. The stability of IAs is significantly affected by several factors, including patient age and the presence of CA. IA shape and location also have an impact on the stability of IAs. Growth into an irregular shape, with a deep depth, and a large FA are risk factors for a change in IAs from stable to unstable. Copyright © 2018 Elsevier Inc. All rights reserved.

Expression characteristics of BMP2, BMPR-IA and Noggin in different stages of hair follicle in yak skin.

PubMed

Song, Liang-Li; Cui, Yan; Yu, Si-Jiu; Liu, Peng-Gang; Liu, Jun; Yang, Xue; He, Jun-Feng; Zhang, Qian

2018-05-01

Bone morphogenetic protein 2 (BMP2), BMP receptor-IA (BMPR-IA), and the BMP2 antagonist Noggin are important proteins involved in regulating the hair follicle (HF) cycle in skin. In order to explore the expression profiles of BMP2, BMPR-IA, and Noggin in the HF cycle of yak skin, we collected adult yak skin in the telogen, proanagen, and midanagen phases of HFs and evaluated gene and protein expression by real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. qRT-PCR and western blotting results showed that BMP2 and BMPR-IA expression levels were highest in the telogen of HFs and higher than that of Noggin in the same phase. The expression of Noggin was significantly higher in proanagen and midanagen phases of HFs than in the telogen phase, with the highest expression observed in the proanagen phase. Moreover, the expression of Noggin in the proanagen phase was significantly higher than those of BMP2 and BMPR-IA during the same phase. Immunohistochemistry results showed that BMP2, BMPR-IA, and Noggin were expressed in the skin epidermis, sweat glands, sebaceous glands, HF outer root sheath, and hair matrix. In summary, the characteristic expression profiles of BMP2, BMPR-IA, and Noggin suggested that BMP2 and BMPR-IA had inhibitory effects on the growth of HFs in yaks, whereas Noggin promoted the growth of yak HFs, mainly by affecting skin epithelial cell activity. These results provide a basis for further studies of HF development and cycle transition in yak skin. Copyright © 2017. Published by Elsevier Inc.

Association between hemodynamic modifications and clinical outcome of intracranial aneurysms treated using flow diverters

NASA Astrophysics Data System (ADS)

Paliwal, Nikhil; Damiano, Robert J.; Davies, Jason M.; Siddiqui, Adnan H.; Meng, Hui

2017-03-01

Treatment of intracranial aneurysms (IAs) has been revolutionized by the advent of endovascular Flow Diverters (FDs), which disrupt blood flow within the aneurysm to induce pro-thrombotic conditions, and serves as a scaffold for endothelial ingrowth and arterial remodeling. Despite good clinical success of FDs, complications like incomplete occlusion and post-treatment rupture leading to subarachnoid hemorrhage have been reported. In silico computational fluid dynamic analysis of the pre- and post-treated geometries of IA patients can shed light on the contrasting blood hemodynamics associated with different clinical outcomes. In this study, we analyzed hemodynamic modifications in 15 IA patients treated using a single FD; 10 IAs were completely occluded (successful) and 5 were partially occluded (unsuccessful) at 12-month follow-up. An in-house virtual stenting workflow was used to recapitulate the clinical intervention on these cases, followed by CFD to obtain pre- and post-treatment hemodynamics. Bulk hemodynamic parameters showed comparable reductions in both groups with average inflow rate and aneurysmal velocity reduction of 40.3% and 52.4% in successful cases, and 34.4% and 49.2% in unsuccessful cases. There was a substantial reduction in localized parameter like vortex coreline length and Energy Loss for successful cases, 38.2% and 42.9% compared to 10.1% and 10.5% for unsuccessful cases. This suggest that for successfully treated IAs, the localized complex blood flow is disrupted more prominently by the FD as compared to unsuccessful cases. These localized hemodynamic parameters can be potentially used in prediction of treatment outcome, thus aiding the clinicians in a priori assessment of different treatment strategies.

Association between hemodynamic modifications and clinical outcome of intracranial aneurysms treated using flow diverters.

PubMed

Paliwal, Nikhil; Damiano, Robert J; Davies, Jason M; Siddiqui, Adnan H; Meng, Hui

2017-02-11

Treatment of intracranial aneurysms (IAs) has been revolutionized by the advent of endovascular Flow Diverters (FDs), which disrupt blood flow within the aneurysm to induce pro-thrombotic conditions, and serves as a scaffold for endothelial ingrowth and arterial remodeling. Despite good clinical success of FDs, complications like incomplete occlusion and post-treatment rupture leading to subarachnoid hemorrhage have been reported. In silico computational fluid dynamic analysis of the pre- and post-treated geometries of IA patients can shed light on the contrasting blood hemodynamics associated with different clinical outcomes. In this study, we analyzed hemodynamic modifications in 15 IA patients treated using a single FD; 10 IAs were completely occluded (successful) and 5 were partially occluded (unsuccessful) at 12-month follow-up. An in-house virtual stenting workflow was used to recapitulate the clinical intervention on these cases, followed by CFD to obtain pre- and post-treatment hemodynamics. Bulk hemodynamic parameters showed comparable reductions in both groups with average inflow rate and aneurysmal velocity reduction of 40.3% and 52.4% in successful cases, and 34.4% and 49.2% in unsuccessful cases. There was a substantial reduction in localized parameter like vortex coreline length and Energy Loss for successful cases, 38.2% and 42.9% compared to 10.1% and 10.5% for unsuccessful cases. This suggest that for successfully treated IAs, the localized complex blood flow is disrupted more prominently by the FD as compared to unsuccessful cases. These localized hemodynamic parameters can be potentially used in prediction of treatment outcome, thus aiding the clinicians in a priori assessment of different treatment strategies.

Pembrolizumab in Treating Patients With Triple-Negative Breast Cancer

ClinicalTrials.gov

2018-06-28

Estrogen Receptor Negative; HER2/Neu Negative; Invasive Breast Carcinoma; Progesterone Receptor Negative; Stage 0 Breast Cancer AJCC v6 and v7; Stage I Breast Cancer AJCC v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage III Breast Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Triple-Negative Breast Carcinoma

Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6′)-Ie-APH(2′′)-Ia revealed by crystallographic and small-angle X-ray scattering analysis

PubMed Central

Smith, Clyde A.; Toth, Marta; Weiss, Thomas M.; Frase, Hilary; Vakulenko, Sergei B.

2014-01-01

Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and entero­coccal pathogens is primarily conferred by the bifunctional enzyme AAC(6′)-Ie-APH(2′′)-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6′)-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2′′)-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6′)-Ie-APH(2′′)-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2′′)-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6′)-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6′)-Ie enzyme is joined to APH(2′′)-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2′′)-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6′)-Ie-APH(2′′)-Ia enzyme. PMID:25286858

Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes.

PubMed

Netzel, Brian C; Grebe, Stefan K G; Carranza Leon, B Gisella; Castro, M Regina; Clark, Penelope M; Hoofnagle, Andrew N; Spencer, Carole A; Turcu, Adina F; Algeciras-Schimnich, Alicia

2015-08-01

Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.

Aspergillus antigen testing in bone marrow transplant recipients

PubMed Central

Williamson, E; Oliver, D; Johnson, E; Foot, A; Marks, D; Warnock, D

2000-01-01

Aims—To assess the clinical usefulness of a commercial aspergillus antigen enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a commercial latex agglutination (LA) test. Methods—In total, 2026 serum samples from 104 bone marrow transplant recipients were tested. These comprised 67 sera from seven patients who had died with confirmed IA, 268 sera from nine patients who had died with suspected IA, and 1691 sera from 88 patients with no clinical, radiological, or microbiological signs of IA. Results—The ELISA was more sensitive than the LA test. All patients who were ELISA positive were also LA positive, and a positive LA result never preceded a positive ELISA. Twelve of 16 patients with confirmed or suspected IA were ELISA positive on two or more occasions, compared with 10 of 15 who were LA positive. ELISA was positive before LA in five patients (range, 2–14 days), and became positive on the same day in the remainder. Aspergillus antigen was detected by ELISA a median of 15 days before death (range, 4–233). Clinical and/or radiological evidence of IA was noted in all patients, and a positive ELISA was never the sole criterion for introduction of antifungal treatment. Two samples (one from each of two patients without IA) gave false positive results. Conclusions—The aspergillus ELISA is a specific indicator of invasive aspergillosis if the criterion of two positive samples is required to confirm the diagnosis. However, the test is insufficiently sensitive to diagnose aspergillosis before other symptoms or signs are apparent, and hence is unlikely to lead to earlier initiation of antifungal treatment. It is therefore unsuitable for screening of asymptomatic patients at risk of invasive aspergillosis, but does have a useful role in confirming the diagnosis in symptomatic patients. Key Words: invasive aspergillosis • aspergillus antigen • Platelia enzyme linked immunosorbent assay PMID:10889818

Combined treatment with immunoadsorption and rituximab leads to fast and prolonged clinical remission in difficult-to-treat pemphigus vulgaris.

PubMed

Behzad, M; Möbs, C; Kneisel, A; Möller, M; Hoyer, J; Hertl, M; Eming, R

2012-04-01

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune bullous disorder which is characterized by blisters and erosions of the skin and mucous membranes. A frequently applied first-line therapy for PV consists of systemic corticosteroids (CS) combined with immunosuppressive agents. In refractory cases, novel therapeutic strategies such as immunoadsorption (IA) and the anti-CD20 antibody rituximab (Rtx) aim at directly interfering with pathogenic autoantibodies (auto-Abs). To investigate the long-term efficacy of IA in combination with Rtx in patients with difficult-to-treat PV, we assessed the clinical response to treatment by monitoring the Autoimmune Bullous Skin Disorder Intensity Score, IgG auto-Abs against desmoglein 1 and 3 (Dsg1 and Dsg3) and the dose of systemic CS. We retrospectively analysed clinical and serological parameters of 10 patients with difficult-to-treat PV who received IA at 4-week intervals, followed by Rtx either twice at 1000 mg or four times at 375mg m(-2) . During a 12-month follow-up period, CS were tapered according to the individual clinical status. Six months after the first IA treatment eight of 10 patients were in complete remission on therapy while one patient showed a partial response and one patient was unresponsive to the treatment. At 12 months, six of eight patients were in complete remission on therapy, one patient showed stable disease and one patient had relapsed. Overall, anti-Dsg3 IgG and anti-Dsg1 IgG auto-Abs correlated well with the clinical activity and systemic CS were tapered gradually. The present findings show that the combination of IA and Rtx induces rapid clinical remission and long-term control in difficult-to-treat pemphigus. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Impulsive aggression and response inhibition in attention-deficit/hyperactivity disorder and disruptive behavioral disorders: Findings from a systematic review.

PubMed

Puiu, Andrei A; Wudarczyk, Olga; Goerlich, Katharina S; Votinov, Mikhail; Herpertz-Dahlmann, Beate; Turetsky, Bruce; Konrad, Kerstin

2018-04-22

Although impulsive aggression (IA) and dysfunctional response inhibition (RI) are hallmarks of attention-deficit/hyperactivity disorder (ADHD) and disrupted behavioral disorders (DBDs), little is known about their shared and distinct deviant neural mechanisms. Here, we selectively reviewed s/fMRI ADHD and DBD studies to identify disorder-specific and shared IA and RI aberrant neural mechanisms. In ADHD, deviant prefrontal and cingulate functional activity was associated with increased IA. Structural alterations were most pronounced in the cingulate cortex. Subjects with DBDs showed marked cortico-subcortical dysfunctions. ADHD and DBDs share similar cortico-limbic structural and functional alterations. RI deficits in ADHD highlighted hypoactivity in the dorso/ventro-lateral PFC, insula, and striatum, while the paralimbic system was primarily dysfunctional in DBDs. Across disorders, extensively altered cortico-limbic dysfunctions underlie IA, while RI was mostly associated with aberrant prefrontal activity. Control network deficits were evidenced across clinical phenotypes in IA and RI. Dysfunctions at any level within these cortico-subcortical projections lead to deficient cognitive-affective control by ascribing emotional salience to otherwise irrelevant stimuli. The clinical implications of these findings are discussed. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

ClinicalTrials.gov

2017-11-15

Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

Equipoise among recanalization strategies.

PubMed

Tomsick, T A; Khatri, P; Jovin, T; Demaerschalk, B; Malisch, T; Demchuk, A; Hill, M D; Jauch, E; Spilker, J; Broderick, J P

2010-03-30

Modern acute ischemic stroke therapy is based on the premise that recanalization and subsequent reperfusion are essential for the preservation of brain tissue and favorable clinical outcomes. We outline key issues that we think underlie equipoise regarding the comparative clinical efficacy of IV recombinant tissue-type plasminogen activator (rt-PA) and intra-arterial (IA) reperfusion therapies for acute ischemic stroke. On the one hand, IV rt-PA therapy has the benefit of speed with presumed lower rates of recanalization of large artery occlusions as compared to IA methods. More recent reports of major arterial occlusions treated with IV rt-PA, as measured by transcranial Doppler and magnetic resonance angiography, demonstrate higher rates of recanalization. Conversely, IA therapies report higher recanalization rates, but are hampered by procedural delays and risks, even failing to be applied at all in occasional patients where time to reperfusion remains a critical factor. Higher rates of recanalization in IA trials using clot-removal devices have not translated into improved patient functional outcome as compared to trials of IV therapy. Combined IV-IA therapy promises to offer advantages of both, but perhaps only when applied in the timeliest of fashions, compared to IV therapy alone. Where equipoise exists, randomizing subjects to either IV rt-PA therapy or IV therapy followed by IA intervention, while incorporating new interventions into the study design, is a rational and appropriate research approach.

Impact of the revised (2008) EORTC/MSG definitions for invasive fungal disease on the rates of diagnosis of invasive aspergillosis.

PubMed

Tsitsikas, Dimitris A; Morin, Amelie; Araf, Shamzah; Murtagh, Bernadine; Johnson, Gemma; Vinnicombe, Sarah; Ellis, Stephen; Suaris, Tamara; Wilks, Mark; Doffman, Sarah; Agrawal, Samir G

2012-07-01

Diagnosis of invasive aspergillosis (IA) remains a challenge as the clinical manifestations are not specific, and a histological diagnosis is often unfeasible. The 2002 European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria for classification of cases into possible, probable or proven were revised in 2008. Our objective was to analyze the impact of these revisions on the diagnosis of IA. A retrospective analysis of 589 high risk patient-episodes revealed that 125 of 155 'possible' (81%) and 12 of 16 'probable' (75%) cases of IA should be changed to 'non-classifiable' when the new criteria were applied. We concluded, as expected, that the 2008 EORTC/MSG revised definitions reduced the number of cases classified as 'possible' IA, but additionally, there has been a dramatic reduction in 'probable' cases. These changes have significant implications on the interpretation of clinical trial data based on EORTC/MSG classifications.

Development of molecularly imprinted polymers to block quorum sensing and inhibit bacterial biofilm formation.

PubMed

Ma, Luyao; Feng, Shaolong; de la Fuente-Nunez, Cesar; Hancock, Robert E W; Lu, Xiaonan

2018-05-16

Bacterial biofilms are responsible for most clinical infections and show increased antimicrobial resistance. In this study, molecularly imprinted polymers (MIPs) were developed to specifically capture prototypical quorum sensing autoinducers [i.e., N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12AHL)], interrupt quorum sensing, and subsequently inhibit biofilm formation of Pseudomonas aeruginosa, an important human nosocomial pathogen. The synthesis of MIPs was optimized by considering the amount and type of the functional monomers itaconic acid (IA) and 2-hydroxyethyl methacrylate (HEMA). IA-based MIPs showed high adsorption affinity towards 3-oxo-C12AHL with an imprinting factor of 1.68. Compared to IA-based MIPs, the adsorption capacity of HEMA-based MIPs was improved 5-fold. HEMA-based MIPs significantly reduced biofilm formation (by ~65%), while biofilm suppression by IA-based MIPs was neutralized due to increased bacterial attachment. The developed MIPs represent promising alternative biofilm intervention agents that can be applied to surfaces relevant to clinical settings and food processing equipment.

Urinary inorganic arsenic concentrations and semen quality of male partners of subfertile couples in Tokyo.

PubMed

Oguri, Tomoko; Yoshinaga, Jun; Toshima, Hiroki; Mizumoto, Yoshifumi; Hatakeyama, Shota; Tokuoka, Susumu

2016-01-01

Inorganic arsenic (iAs) has been known as a testicular toxicant in experimental rodents. Possible association between iAs exposure and semen quality (semen volume, sperm concentration, and sperm motility) was explored in male partners of couples (n = 42) who visited a gynecology clinic in Tokyo for infertility consultation. Semen parameters were measured according to WHO guideline at the clinic, and urinary iAs and methylarsonic acid (MMA), and dimethylarsinic acid concentrations were determined by liquid chromatography-hydride generation-ICP mass spectrometry. Biological attributes, dietary habits, and exposure levels to other chemicals with known effects on semen parameters were taken into consideration as covariates. Multiple regression analyses and logistic regression analyses did not find iAs exposure as significant contributor to semen parameters. Lower exposure level of subjects (estimated to be 0.5 μg kg(-1) day(-1)) was considered a reason of the absence of adverse effects on semen parameters, which were seen in rodents dosed with 4-7.5 mg kg(-1).

Clinical outcomes of stage I and IIA non-small cell lung cancer patients treated with stereotactic body radiotherapy using a real-time tumor-tracking radiotherapy system.

PubMed

Katoh, Norio; Soda, Itaru; Tamamura, Hiroyasu; Takahashi, Shotaro; Uchinami, Yusuke; Ishiyama, Hiromichi; Ota, Kiyotaka; Inoue, Tetsuya; Onimaru, Rikiya; Shibuya, Keiko; Hayakawa, Kazushige; Shirato, Hiroki

2017-01-05

To investigate the clinical outcomes of stage I and IIA non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT) using a real-time tumor-tracking radiotherapy (RTRT) system. Patterns-of-care in SBRT using RTRT for histologically proven, peripherally located, stage I and IIA NSCLC was retrospectively investigated in four institutions by an identical clinical report format. Patterns-of-outcomes was also investigated in the same manner. From September 2000 to April 2012, 283 patients with 286 tumors were identified. The median age was 78 years (52-90) and the maximum tumor diameters were 9 to 65 mm with a median of 24 mm. The calculated biologically effective dose (10) at the isocenter using the linear-quadratic model was from 66 Gy to 126 Gy with a median of 106 Gy. With a median follow-up period of 28 months (range 0-127), the overall survival rate for the entire group, for stage IA, and for stage IB + IIA was 75%, 79%, and 65% at 2 years, and 64%, 70%, and 50% at 3 years, respectively. In the multivariate analysis, the favorable predictive factor was female for overall survival. There were no differences between the clinical outcomes at the four institutions. Grade 2, 3, 4, and 5 radiation pneumonitis was experienced by 29 (10.2%), 9 (3.2%), 0, and 0 patients. The subgroup analyses revealed that compared to margins from gross tumor volume (GTV) to planning target volume (PTV) ≥ 10 mm, margins < 10 mm did not worsen the overall survival and local control rates, while reducing the risk of radiation pneumonitis. This multi-institutional retrospective study showed that the results were consistent with the recent patterns-of-care and patterns-of-outcome analysis of SBRT. A prospective study will be required to evaluate SBRT using a RTRT system with margins from GTV to PTV < 10mm.

Internet addiction and its correlates among high school students: a preliminary study from Ahmedabad, India.

PubMed

Yadav, Priyanka; Banwari, Girish; Parmar, Chirag; Maniar, Rajesh

2013-12-01

Internet addiction (IA) is an upcoming and less researched entity in psychiatry, especially in low and middle income countries. This is the first such effort to study IA amongst Indian school students of class 11th and 12th and to find its correlation with socio-educational characteristics, internet use patterns and psychological variables, namely depression, anxiety and stress. Six hundred and twenty one students of six English medium schools of Ahmedabad participated, of which 552 (88.9%) who completed forms were analyzed. Young's Internet Addiction Test and 21 item Depression Anxiety and Stress Scale were used to measure IA and psychological variables respectively. Logistic regression analysis was applied to find the predictors of IA. Sixty-five (11.8%) students had IA; it was predicted by time spent online, usage of social networking sites and chat rooms, and also by presence of anxiety and stress. Age, gender and self-rated academic performance did not predict IA. There was a strong positive correlation between IA and depression, anxiety and stress. IA may be a relevant clinical construct, and needs extensive research even in developing nations. All high school students suffering from depression, anxiety and stress must be screened for IA, and vice versa. Copyright © 2013 Elsevier B.V. All rights reserved.

Pipeline embolization device for intracranial aneurysm: a systematic review.

PubMed

Leung, G K K; Tsang, A C O; Lui, W M

2012-12-01

The pipeline embolization device (PED) is a new endovascular stent designed for the treatment of challenging intracranial aneurysms (IAs). Its use has been extended to nonruptured and ruptured IAs of a variety of configurations and etiologies in both the anterior and posterior circulations. We conducted a systematic review of ten eligible reports on its clinical efficacy and safety. There were 414 patients with 448 IAs. The majority of the IAs were large (40.2 %), saccular or blister-like (78.3 %), and were located mostly in the anterior circulation (83.5 %). The regimens of antiplatelet therapy varied greatly between and within studies. The mean number of the PED used was 2.0 per IA. Deployment was successful in around 95 % of procedures. Aneurysm obliteration was achieved in 82.9 % of IAs at 6-month. The overall incidences of periprocedural intracranial vascular complication rate and mortality rate were 6.3 and 1.5 %, respectively. The PED is a safe and effective treatment for nonruptured IAs. Its use in the context of acute subarachnoid hemorrhage (SAH) should be cautioned. Its main limitations include the need for prolonged antiplatelet therapy, as well as the potential risks of IA rupture and non-IA-related intracerebral hemorrhages (ICH). Future studies should aim at identifying factors that predispose to incomplete obliteration, delayed rupture, and thromboembolic complications.

Serum inter-alpha-trypsin inhibitor and matrix hyaluronan promote angiogenesis in fibrotic lung injury.

PubMed

Garantziotis, Stavros; Zudaire, Enrique; Trempus, Carol S; Hollingsworth, John W; Jiang, Dianhua; Lancaster, Lisa H; Richardson, Elizabeth; Zhuo, Lisheng; Cuttitta, Frank; Brown, Kevin K; Noble, Paul W; Kimata, Koji; Schwartz, David A

2008-11-01

The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627).

Osimertinib in Treating Participants With Stage I-IIIA EGFR-mutant Non-small Cell Lung Cancer Before Surgery

ClinicalTrials.gov

2018-04-27

EGFR (Epidermal Growth Factor Receptor) Exon 19 Deletion Mutation; EGFR NP_005219.2:p.L858R; EGFR NP_005219.2:p.T790M; Stage I Non-Small Cell Lung Cancer AJCC (American Joint Committee on Cancer) v7; Stage IA Non-Small Cell Lung Carcinoma AJCC v7; Stage IB Non-Small Cell Lung Carcinoma AJCC v7; Stage II Non-Small Cell Lung Cancer AJCC v7; Stage IIA Non-Small Cell Lung Carcinoma AJCC v7; Stage IIB Non-Small Cell Lung Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Early-stage central lung cancer and volumetric modulated arc therapy: a dosimetric case study with literature review.

PubMed

Valakh, Vladimir; Chan, Philip; D'Adamo, Karen; Micaily, Bizhan

2013-10-01

In the present article we review on the use of Volumetric Modulated Arc Therapy (VMAT) for a small lung nodule that was centrally located in close proximity to the mediastinal structures. An inoperable patient with central, clinical stage IA adenocarcinoma of the right lung was treated with external-beam radiation therapy of 52.5 Gy in 15 factions. A single 360° coplanar arc VMAT plan (360-VMAT) was used for treatment and compared to step-and-shoot Intensity Modulation Radiotherapy (IMRT) and a single 180° ipsilateral partial arc VMAT plan (180-VMAT). Planning Target Volume (PTV) coverage was not different, and 360-VMAT had the highest dose homogeneity. Both 360-VMAT and 180-VMAT reduced esophageal dose compared to IMRT. While IMRT had the lowest lung dose, all 3 plans achieved acceptable sparing of the lung. 180-VMAT had the highest dose conformity. Both 360-VMAT and 180-VMAT improved esophageal sparing compared to IMRT. Use of VMAT in early-stage, centrally located NSCLC is a promising treatment approach and merits additional investigation.

Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed by the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed by Surgery

ClinicalTrials.gov

2018-06-22

Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage I Pancreatic Cancer AJCC v6 and v7; Stage IA Pancreatic Cancer AJCC v6 and v7; Stage IB Pancreatic Cancer AJCC v6 and v7; Stage II Pancreatic Cancer AJCC v6 and v7; Stage IIA Pancreatic Cancer AJCC v6 and v7; Stage IIB Pancreatic Cancer AJCC v6 and v7

Differential effects of chromosome 9p21 variation on subphenotypes of intracranial aneurysm: site distribution.

PubMed

Nakaoka, Hirofumi; Takahashi, Tomoko; Akiyama, Koichi; Cui, Tailin; Tajima, Atsushi; Krischek, Boris; Kasuya, Hidetoshi; Hata, Akira; Inoue, Ituro

2010-08-01

Recently, a genome-wide association study identified associations between single nucleotide polymorphisms on chromosome 9p21 and risk of harboring intracranial aneurysm (IA). Aneurysm characteristics or subphenotypes of IAs, such as history of subarachnoid hemorrhage, presence of multiple IAs and location of IAs, are clinically important. We investigated whether the association between 9p21 variation and risk of IA varied among these subphenotypes. We conducted a case-control study of 981 cases and 699 controls in Japanese. Four single nucleotide polymorphisms tagging the 9p21 risk locus were genotyped. The OR and 95% CI were estimated using logistic regression analyses. Among the 4 single nucleotide polymorphisms, rs1333040 showed the strongest evidence of association with IA (P=1.5x10(-6); per allele OR, 1.43; 95% CI, 1.24-1.66). None of the patient characteristics (gender, age, smoking, and hypertension) was a significant confounder or effect modifier of the association. Subgroup analyses of IA subphenotypes showed that among the most common sites of IAs, the association was strongest for IAs of the posterior communicating artery (OR, 1.69; 95% CI, 1.26-2.26) and not significant for IAs in the anterior communicating artery (OR, 1.22; 95% CI, 0.96-1.57). When dichotomizing IA sites, the association was stronger for IAs of the posterior circulation-posterior communicating artery group (OR, 1.73; 95% CI, 1.32-2.26) vs the anterior circulation group (OR, 1.28; 95% CI, 1.07-1.53). Heterogeneity in these ORs was significant (P=0.032). The associations did not vary when stratifying by history of subarachnoid hemorrhage (OR, 1.42; 95% CI, 1.18-1.71 for ruptured IA; OR, 1.27; 95% CI, 1.00-1.62 for unruptured IA) or by multiplicity of IA (OR, 1.57; 95% CI, 1.21-2.03 for multiple IAs; OR, 1.36; 95% CI, 1.15-1.61 for single IA). Our results suggest that genetic influence on formation may vary between IA subphenotypes.

Prognostic impact of the level of nodal involvement: retrospective analysis of patients with advanced oral squamous cell carcinoma.

PubMed

Murakami, R; Nakayama, H; Semba, A; Hiraki, A; Nagata, M; Kawahara, K; Shiraishi, S; Hirai, T; Uozumi, H; Yamashita, Y

2017-01-01

We retrospectively evaluated the prognostic impact of the level of nodal involvement in patients with advanced oral squamous cell carcinoma (SCC). Between 2005 and 2010, 105 patients with clinical stage III or IV oral SCC had chemoradiotherapy preoperatively. Clinical (cN) and pathological nodal (pN) involvement was primarily at levels Ib and II. We defined nodal involvement at levels Ia and III-V as anterior and inferior extensions, respectively, and recorded such findings as extensive. With respect to pretreatment variables (age, clinical stage, clinical findings of the primary tumour, and nodal findings), univariate analysis showed that extensive cN was the only significant factor for overall survival (hazard ratio [HR], 3.27; 95% CI 1.50 to 7.13; p=0.001). Univariate analysis showed that all pN findings, including the nodal classification (invaded nodes, multiple, and contralateral) and extensive involvement were significant, and multivariate analysis confirmed that extensive pN (HR 4.71; 95% CI 1.85 to 11.97; p=0.001) and multiple pN (HR 2.59; 95% CI 1.10 to 6.09; p=0.029) were independent predictors of overall survival. Assessment based on the level of invaded neck nodes may be a better predictor of survival than the current nodal classification. Copyright © 2016 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

De novo Transcriptome Analysis of Rhizoctonia solani AG1 IA Strain Early Invasion in Zoysia japonica Root.

PubMed

Zhu, Chen; Ai, Lin; Wang, Li; Yin, Pingping; Liu, Chenglan; Li, Shanshan; Zeng, Huiming

2016-01-01

Zoysia japonica brown spot was caused by necrotrophic fungus Rhizoctonia solani invasion, which led to severe financial loss in city lawn and golf ground maintenance. However, little was known about the molecular mechanism of R. solani pathogenicity in Z. japonica. In this study we examined early stage interaction between R. solani AG1 IA strain and Z. japonica cultivar "Zenith" root by cell ultra-structure analysis, pathogenesis-related proteins assay and transcriptome analysis to explore molecular clues for AG1 IA strain pathogenicity in Z. japonica. No obvious cell structure damage was found in infected roots and most pathogenesis-related protein activities showedg a downward trend especially in 36 h post inoculation, which exhibits AG1 IA strain stealthy invasion characteristic. According to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database classification, most DEGs in infected "Zenith" roots dynamically changed especially in three aspects, signal transduction, gene translation, and protein synthesis. Total 3422 unigenes of "Zenith" root were predicted into 14 kinds of resistance (R) gene class. Potential fungal resistance related unigenes of "Zenith" root were involved in ligin biosynthesis, phytoalexin synthesis, oxidative burst, wax biosynthesis, while two down-regulated unigenes encoding leucine-rich repeat receptor protein kinase and subtilisin-like protease might be important for host-derived signal perception to AG1 IA strain invasion. According to Pathogen Host Interaction (PHI) database annotation, 1508 unigenes of AG1 IA strain were predicted and classified into 37 known pathogen species, in addition, unigenes encoding virulence, signaling, host stress tolerance, and potential effector were also predicted. This research uncovered transcriptional profiling during the early phase interaction between R. solani AG1 IA strain and Z. japonica, and will greatly help identify key pathogenicity of AG1 IA strain.

Treatment of early non-small cell lung cancer, stage IA, by image-guided robotic stereotactic radioablation--CyberKnife.

PubMed

Brown, William T; Wu, Xiaodong; Amendola, Beatriz; Perman, Mark; Han, Hoke; Fayad, Fahed; Garcia, Silvio; Lewin, Alan; Abitbol, Andre; de la Zerda, Alberto; Schwade, James G

2007-01-01

To evaluate the efficacy of using image-guided robotic stereotactic radioablation as an alternative treatment modality for patients with surgically resectable, but medically inoperable, T1 N0 M0, stage IA non-small cell lung cancer. Between January 2004 and May 2006, 19 patients, 11 women and 8 men ranging in age from 52 to 88 years, with stage IA non-small cell lung cancer were treated. Tumor volume ranged from 1.7 to 13 mL. Total doses ranged from 24 to 60 Gy delivered in 3 fractions. Eleven patients received 60 Gy. Real-time target localization was accomplished by radiographic detection of fiducial marker(s) implanted within the tumor combined with respiratory motion tracking. All patients tolerated radioablation well with fatigue as the main side effect. Fourteen patients are alive from 1 to 25 months posttreatment. Four patients died: 2 of comorbid disease and 2 of cancer progression (status post 60 and 55.5 Gy). Three patients developed grade I radiation pneumonitis. Two patients have stable disease. In 3 patients, cancer recurred in the planning treatment volume: in 2 patients after treatment with 60 Gy and in 1 patient after treatment with 55.5 Gy. One patient had local control in the target volume but developed metastasis to the ipsilateral hilum. Nine patients had a complete response and show no evidence of disease. In our early experience, stereotactic radioablation using the CyberKnife system appears to be a safe, minimally invasive, and effective modality for treating early stage lung cancer in patients with medically inoperable disease. Dose escalation and/or increasing the treatment volumes, with the aid of the high conformality of this technique, may help to achieve further improvements in these promising results.

Vibration-based angular speed estimation for multi-stage wind turbine gearboxes

NASA Astrophysics Data System (ADS)

Peeters, Cédric; Leclère, Quentin; Antoni, Jérôme; Guillaume, Patrick; Helsen, Jan

2017-05-01

Most processing tools based on frequency analysis of vibration signals are only applicable for stationary speed regimes. Speed variation causes the spectral content to smear, which encumbers most conventional fault detection techniques. To solve the problem of non-stationary speed conditions, the instantaneous angular speed (IAS) is estimated. Wind turbine gearboxes however are typically multi-stage gearboxes, consisting of multiple shafts, rotating at different speeds. Fitting a sensor (e.g. a tachometer) to every single stage is not always feasible. As such there is a need to estimate the IAS of every single shaft based on the vibration signals measured by the accelerometers. This paper investigates the performance of the multi-order probabilistic approach for IAS estimation on experimental case studies of wind turbines. This method takes into account the meshing orders of the gears present in the system and has the advantage that a priori it is not necessary to associate harmonics with a certain periodic mechanical event, which increases the robustness of the method. It is found that the MOPA has the potential to easily outperform standard band-pass filtering techniques for speed estimation. More knowledge of the gearbox kinematics is beneficial for the MOPA performance, but even with very little knowledge about the meshing orders, the MOPA still performs sufficiently well to compete with the standard speed estimation techniques. This observation is proven on two different data sets, both originating from vibration measurements on the gearbox housing of a wind turbine.

Stomatitis associated with mammalian target of rapamycin inhibition: A review of pathogenesis, prevention, treatment, and clinical implications for oral practice in metastatic breast cancer.

PubMed

Chambers, Mark S; Rugo, Hope S; Litton, Jennifer K; Meiller, Timothy F

2018-04-01

Patients with metastatic breast cancer may develop oral morbidities that result from therapeutic interventions. Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a common adverse event (AE), secondary to mTOR inhibitor therapy, that can have a negative impact on treatment adherence, quality of life, and health care costs. A multidisciplinary team approach is important to minimize mIAS and to maximize treatment benefits to patients with breast cancer. In this review, we discuss the pathophysiology, diagnosis, and natural history of mIAS. Current and new management strategies for the prevention and treatment of mIAS are described in the context of fostering a coordinated team care approach to optimizing patient care. The authors conducted a PubMed search from 2007 through 2017 using the terms "stomatitis," "mIAS," "everolimus," "mTOR," "metastatic breast cancer," and "oral care." They selected articles published in peer-reviewed journals that reported controlled trials and evidence-based guidelines. mIAS can be distinguished from mucositis caused by cytotoxic chemotherapy or radiotherapy on the basis of cause, clinical presentation, and treatment paradigms. Specific preventive and therapeutic management strategies can be implemented across the continuum of patient oral health care. Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

Intra-articular corticoid injection induces circulating glucocorticoid bioactivity and systemic immune activation in juvenile idiopathic arthritis.

PubMed

Rintamäki, H; Tamm, K; Vaarala, O; Sidoroff, M; Honkanen, V; Raivio, T; Jänne, Oa; Kolho, K-L

2011-01-01

To study the systemic effects of intra-articular (IA) glucocorticoid (GC) injections in juvenile idiopathic arthritis (JIA). The study group comprised 21 JIA patients being treated with IA methylprednisolone [MP (n = 15) or MP plus triamcinolone hexacetonide (THA) (n = 6)] prescribed on clinical indications. The systemic effect of MP was assessed by measuring circulating glucocorticoid bioactivity (GBA) with a recombinant cell transactivation assay 7 and 24 h after the IA injections, and after 2 months. The systemic immunological responses were studied with a novel assay for testing patient serum-induced changes in the secretion of interferon (IFN)-γ and interleukin (IL)-5 from target cells. Administration of IA GC induced serum GBA (p = 0.001) and suppressed circulating cortisol levels (p = 0.002) 7 h after the injection. Serum withdrawn 24 h after the IA injection induced less IL-5 secretion from mitogen-activated target cells when compared with pre-treatment sera (p = 0.036). This decrease in target cell T helper (Th)2 response (IL-5) was MP dose related (r = -0.550, p = 0.018). High IL-5 secretion from target cells prior to the IA injections was associated with good clinical outcome at 2 months, seen as a low number of active (p = 0.044) and restricted joints (p = 0.049). IA GC injections have systemic effects that are reflected in the serum as an immediate elevation of GBA, a decrease of endogenous cortisol as well as a suppressive effect of patient serum on target cell IL-5 secretion. These systemic effects may play a role in the attenuation of disease activity.

Analysis of Radiation Effects in Digital Subtraction Angiography of Intracranial Artery Stenosis.

PubMed

Guo, Chaoqun; Shi, Xiaolei; Ding, Xianhui; Zhou, Zhiming

2018-04-21

Intracranial artery stenosis (IAS) is the most common cause for acute cerebral accidents. Digital subtraction angiography (DSA) is the gold standard to detect IAS and usually brings excess radiation exposure to examinees and examiners. The artery pathology might influence the interventional procedure, causing prolonged radiation effects. However, no studies on the association between IAS pathology and operational parameters are available. A retrospective analysis was conducted on 93 patients with first-ever stroke/transient ischemic attack, who received DSA examination within 3 months from onset in this single center. Comparison of baseline characteristics was determined by 2-tailed Student's t-test or the chi-square test between subjects with and without IAS. A binary logistic regression analysis was performed to determine the association between IAS pathology and the items with a P value <0.05 in Student's t-test or chi-square test. There were 93 candidates (42 with IAS and 51 without IAS) in this study. The 2 groups shared no significance of the baseline characteristics (P > 0.05). We found a significantly higher total time, higher kerma area product, greater total dose, and greater DSA dose in the IAS group than in those without IAS (P < 0.05). A binary logistic regression analysis indicated the significant association between total time and IAS pathology (P < 0.05) but no significance in kerma area product, radiation dose, and DSA dose (P > 0.05). IAS pathology would indicate a prolonged total time of DSA procedure in clinical practice. However, the radiation effects would not change with pathologic changes. Copyright © 2018 Elsevier Inc. All rights reserved.

Serum Inter–α-Trypsin Inhibitor and Matrix Hyaluronan Promote Angiogenesis in Fibrotic Lung Injury

PubMed Central

Garantziotis, Stavros; Zudaire, Enrique; Trempus, Carol S.; Hollingsworth, John W.; Jiang, Dianhua; Lancaster, Lisa H.; Richardson, Elizabeth; Zhuo, Lisheng; Cuttitta, Frank; Brown, Kevin K.; Noble, Paul W.; Kimata, Koji; Schwartz, David A.

2008-01-01

Rationale: The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-α-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury. Objectives: To determine whether IaI promotes HA-mediated angiogenesis in tissue injury. Methods: An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined. Measurements and Main Results: IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC. Conclusions: Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627). PMID:18703791

Examination of Insert Ear Interaural Attenuation (IA)Values in Audiological Evaluations.

PubMed

Gumus, Nebi M; Gumus, Merve; Unsal, Selim; Yuksel, Mustafa; Gunduz, Mehmet

2016-12-01

The purpose of this study was to evaluate Interaural Attenuation (IA) in frequency base in the insert earphones that are used in audiological assessments. Thirty healthy subjects between 18-65 years of age (14 female and 16 male) participated in our study. Otoscopic examination was performed on all participants. Audiological evaluations were performed using the Interacoustics AC40 clinical audiometer and ER-3A insert earphones. IA value was calculated by subtracting good ear bone conduction hearing thresholds of the worst airway hearing threshold. In our measuring for 0.125-8.0 kHz frequency were performed in our audiometry device separately for each frequency. IA amount in the results we found in 1000 Hz and below frequencies about 75-110 dB range avarage is 89±5dB, in above 1000 Hz frequencies in 50-95 dB range and avarage it is changed to 69±5dB. According to the obtained findings the quantity of melting in the transition between the ears are increasing with the insert earphones. The insert earphone should be beside supraaural earphone that is routinely used in clinics. Difficult masking applications due to the increase in the value of IA can be easily done with insert earphones.

Predicting interatrial septum rotation: is the position of the heart or the direction of the coronary sinus reliable?: Implications for interventional electrophysiologists from CT studies.

PubMed

Sun, Huan; Wang, Yanjing; Zhang, Zhenming; Liu, Lin; Yang, Ping

2015-04-01

Determining the location of the interatrial septum (IAS) is crucial for cardiac electrophysiology procedures. Empirical methods of predicting IAS orientation depend on anatomical landmarks, including determining it from the direction of the coronary sinus (CS) and the position of the heart (e.g., vertical or transverse). However, the reliability of these methods for predicting IAS rotation warrants further study. The purpose of this study was to assess the clinical utility of the relationship between IAS orientation, CS direction, and heart position. Data from 115 patients undergoing coronary computed tomography (CT) angiography with no evidence of cardiac structural disease were collected and analyzed. Angulations describing IAS orientation, CS direction, and heart position were measured. The relationships between IAS orientation and each of the other two parameters were subsequently analyzed. The mean angulations for IAS orientation, CS direction, and heart position were 36.8 ± 7.3° (range 19.1-53.6), 37.7 ± 6.6° (range 21.3-50.1), and 37.1 ± 8.3° (range 19.2-61.0), respectively. We found a significant correlation between IAS orientation and CS direction (r = 0.928; P < 0.01), and the linear regression equation was drawn: IAS orientation = 2.01 + 1.03 × CS direction (r(2) = 0.86). No correlation was observed between IAS orientation and heart position (P = 0.86). In patients without structural heart disease, CS direction may be a reliable predictor of IAS orientation, and may serve as a helpful reference for clinicians during invasive electrophysiological procedures. Further study is warranted to clarify the relationship between IAS orientation and heart position. © 2015 Wiley Periodicals, Inc.

Inflammation-based scoring is a useful prognostic predictor of pulmonary resection for elderly patients with clinical stage I non-small-cell lung cancer.

PubMed

Miyazaki, Takuro; Yamasaki, Naoya; Tsuchiya, Tomoshi; Matsumoto, Keitaro; Kunizaki, Masaki; Taniguchi, Daisuke; Nagayasu, Takeshi

2015-04-01

The number of elderly lung cancer patients requiring surgery has been increasing due to the ageing society and less invasive perioperative procedures. Elderly people usually have various comorbidities, but there are few simple and objective tools that can be used to determine prognostic factors for elderly patients with clinical stage I non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the prognostic factors of surgically treated, over 80-year old patients with clinical stage I NSCLC. The preoperative data of 97 over 80-year old patients with clinical stage I NSCLC were collected at Nagasaki University Hospital from 1990 to 2012. As prognostic factors, inflammation-based scoring systems, including the Glasgow Prognostic Score (GPS) determined by serum levels of C-reactive protein and albumin, the neutrophil lymphocyte ratio (NLR) and the platelet lymphocyte ratio (PLR) were evaluated, as well as other clinicopathological factors, including performance status, body mass index, carcinoembryonic antigen, Charlson comorbidity index and type of surgical procedure. The median age was 82 (range, 80-93) years. There were 62 (64.0%) clinical stage IA cases and 35 IB cases. Operations included 64 (66.0%) lobectomies, 15 segmentectomies and 18 wedge resections. The pathological stage was I in 76 (78.4%) patients, II in 12 (12.4%), III in 8 (8.2%) and IV in 1 (1.0%). Twelve (12.4%) patients underwent mediastinal lymph node dissection. Overall survival and disease-specific 5-year survival rates were 55.5 and 70.0%, respectively. The average GPS score was 0.4 (0-2). Disease-specific 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (74.2%, 53.7%, respectively, P = 0.03). Overall 5-year survival was significantly longer with GPS 0 than with GPS 1-2. (59.7%, 43.1%, respectively, P = 0.005). Both the NLR (median value = 1.9) and the PLR (median value = 117) were not correlated with disease-specific and overall 5-year survival. On multivariate analysis, pathological stage I (P = 0.01) and GPS 0 (P = 0.04, hazard ratio: 2.13, 95% confidence interval 1.036-4.393) were significant prognostic factors. The preoperative GPS appears to be a useful predictor of overall survival and could be a simple prognostic tool for elderly patients with clinical stage I NSCLC. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Association of female sex and heart rate with increased arterial stiffness in patients with type 2 diabetes mellitus

PubMed Central

Kang, Min-Kyung; Yu, Jae Myung; Chun, Kwang Jin; Choi, Jaehuk; Choi, Seonghoon; Lee, Namho; Cho, Jung Rae

2017-01-01

Objective: This study aimed to evaluate the factors associated with increased arterial stiffness (IAS) measured by pulse wave velocity (PWV) and its clinical implications in patients with type 2 diabetes mellitus (DM). Methods: This was an observational, cross-sectional study. The ankle–brachial PWV was used to measure arterial stiffness, and 310 patients (mean age, 49±9 years; 180 men) with type 2 DM were divided into two groups according to the results of PWV: Group 1 (IAS; n=214) and Group 2 (normal arterial stiffness; n=96). Results: Patients in Group 1 were predominantly females (48% vs. 28%, p=0.001) and showed higher blood pressure and faster heart rate (HR). The glomerular filtration rate was lower and the urine microalbumin level was higher in patients with IAS. In multiple regression analysis, female sex and faster HR were independently associated with IAS. In subgroup analysis among female patients, prior stroke was more common in patients with IAS, and faster HR and increased postprandial 2-h C-peptide level were independently associated with IAS. Conclusion: Female sex and faster HR were independently associated with IAS in patients with type 2 DM. In a subgroup analysis among female patients, prior stroke was more common in patients with IAS, and faster HR and elevated postprandial 2-h C-peptide level were found to be independently associated with IAS. PMID:29145217

Immunoadsorption of anti-HLA antibodies for highly sensitized patients awaiting renal transplantation.

PubMed

Hiesse, C; Kriaa, F; Rousseau, P; Farahmand, H; Bismuth, A; Fries, D; Charpentier, B

1992-01-01

Fifteen end-stage renal disease patients with high titres of panel reactive (PRA) antibodies were treated with immunoadsorption (IA) on sepharose-bound protein A columns in order to remove anti-HLA antibodies and facilitate transplantation. Infectious complications were not observed after IA and transplantation, and the procedure was well tolerated. In spite of the use of adjunctive immunosuppressive treatment with cyclophosphamide and prednisolone, this method produced only variable effects in lowering panel reaction antibodies, and was hampered by high de novo resynthesis of anti-HLA antibodies. Patients whose pre-IA antibody titre was greater than or equal to 1:64 clearly did not benefit from the procedure, but other immunological criteria were not predictive of efficacy. Twelve patients were transplanted on the basis of a negative cross-match with current serum, historical sera being retrospectively tested. Surprisingly, seven patients received a well-matched graft with both pre- and post-IA negative cross-matching. Graft survival was 86% in this group. Conversely, in the group of five transplants which were performed in recipients having a positive historical cross-match with the donor, graft survival was only 40%. One patient died with a functional graft, and two grafts failed due to hyperacute humoral rejection. Humoral rejection in a third patient was successfully treated by a second IA course and administration of polyclonal IgG. We conclude that IA is a safe procedure for managing hyperimmunized transplant candidates. However, its efficacy remains variable, and a better definition of patients who should benefit from IA needs to be found.

Improved therapy-success prediction with GSS estimated from clinical HIV-1 sequences.

PubMed

Pironti, Alejandro; Pfeifer, Nico; Kaiser, Rolf; Walter, Hauke; Lengauer, Thomas

2014-01-01

Rules-based HIV-1 drug-resistance interpretation (DRI) systems disregard many amino-acid positions of the drug's target protein. The aims of this study are (1) the development of a drug-resistance interpretation system that is based on HIV-1 sequences from clinical practice rather than hard-to-get phenotypes, and (2) the assessment of the benefit of taking all available amino-acid positions into account for DRI. A dataset containing 34,934 therapy-naïve and 30,520 drug-exposed HIV-1 pol sequences with treatment history was extracted from the EuResist database and the Los Alamos National Laboratory database. 2,550 therapy-change-episode baseline sequences (TCEB) were assigned to test set A. Test set B contains 1,084 TCEB from the HIVdb TCE repository. Sequences from patients absent in the test sets were used to train three linear support vector machines to produce scores that predict drug exposure pertaining to each of 20 antiretrovirals: the first one uses the full amino-acid sequences (DEfull), the second one only considers IAS drug-resistance positions (DEonlyIAS), and the third one disregards IAS drug-resistance positions (DEnoIAS). For performance comparison, test sets A and B were evaluated with DEfull, DEnoIAS, DEonlyIAS, geno2pheno[resistance], HIVdb, ANRS, HIV-GRADE, and REGA. Clinically-validated cut-offs were used to convert the continuous output of the first four methods into susceptible-intermediate-resistant (SIR) predictions. With each method, a genetic susceptibility score (GSS) was calculated for each therapy episode in each test set by converting the SIR prediction for its compounds to integer: S=2, I=1, and R=0. The GSS were used to predict therapy success as defined by the EuResist standard datum definition. Statistical significance was assessed using a Wilcoxon signed-rank test. A comparison of the therapy-success prediction performances among the different interpretation systems for test set A can be found in Table 1, while those for test set B are found in Figure 1. Therapy-success prediction of first-line therapies with DEnoIAS performed better than DEonlyIAS (p<10-16). Therapy success prediction benefits from the consideration of all available mutations. The increase in performance was largest in first-line therapies with transmitted drug-resistance mutations.

The optimal protocol to reduce blood loss and blood transfusion after unilateral total knee replacement: Low-dose IA-TXA plus 30-min drain clamping versus drainage clamping for the first 3 h without IA-TXA.

PubMed

Park, Joo Hyun; Choi, Sung Wook; Shin, Eun Ho; Park, Myung Hoon; Kim, Myung Ku

2017-01-01

Although intraarticular tranexamic acid (IA-TXA) administration or drainage clamping are popular methods used to reduce blood loss after total knee replacement (TKR), the protocol remains controversial. We aimed (1) to establish new protocols through investigating whether two methods, that is, low-dose (500 mg) IA-TXA plus 30-min drain clamping and drainage clamping for the first 3 h without IA-TXA, can reduce blood loss and blood transfusion after unilateral TKR and (2) to make recommendations related to clinical application. This study, conducted from September 2014 to June 2016 related to enrolled 95 patients with primary osteoarthritis who were to have a unilateral cemented TKR, was nonrandomized and retrospective. In group A, the drain was released following tourniquet deflation. In group B, 500-mg TXA was injected into the knee joint via a drain tube after fascia closure and the drain was clamped for the first 30 min to prevent leakage. In group C, the drain was clamped for the first 3-h postoperation. Demographic characteristics and clinical data were collected, including the levels of hematocrit (Hct), the total blood loss (TBL), drained blood volume (BV), the amount of blood transfused, and any complications that developed. We found a significantly lower postoperative TBL, drained BV, decreasing Hct level, and less transfused BV in the IA-TXA injection group (group B) and the 3-h drainage clamping group (group C) compared to the conventional negative drainage group (group A; p < 0.001). There was no significant difference between groups B and C ( p = 0.99). The drainage clamping method can be safer than IA-TXA administration in patients with risk factor of venous thromboembolic complication. Furthermore, the IA-TXA administration can be more optimal than drainage clamping in patients with high bleeding tendency or lateral retinacular release during TKR, who would be concerned about postoperative wound complication.

The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry.

PubMed

Roli, L; Santi, D; Belli, S; Tagliavini, S; Cavalieri, S; De Santis, M C; Baraldi, E; Fanelli, F; Mezzullo, M; Granata, A R; Pagotto, U; Pasquali, R; Rochira, V; Carani, C; Simoni, M; Trenti, T

2017-08-01

Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.

Optimal Cut-Off Points on the Health Anxiety Inventory, Illness Attitude Scales and Whiteley Index to Identify Severe Health Anxiety

PubMed Central

Hedman, Erik; Lekander, Mats; Ljótsson, Brjánn; Lindefors, Nils; Rück, Christian; Andersson, Gerhard; Andersson, Erik

2015-01-01

Background Health anxiety can be viewed as a dimensional phenomenon where severe health anxiety in form of DSM-IV hypochondriasis represents a cut-off where the health anxiety becomes clinically significant. Three of the most reliable and used self-report measures of health anxiety are the Health Anxiety Inventory (HAI), the Illness Attitude Scales (IAS) and the Whiteley Index (WI). Identifying the optimal cut-offs for classification of presence of a diagnosis of severe health anxiety on these measures has several advantages in clinical and research settings. The aim of this study was therefore to investigate the HAI, IAS and WI as proximal diagnostic instruments for severe health anxiety defined as DSM-IV hypochondriasis. Methods We investigated sensitivity, specificity and predictive value on the HAI, IAS and WI using a total of 347 adult participants of whom 158 had a diagnosis of severe health anxiety, 97 had obsessive-compulsive disorder and 92 were healthy non-clinical controls. Diagnostic assessments were conducted using the Anxiety Disorder Interview Schedule. Results Optimal cut-offs for identifying a diagnosis of severe health anxiety was 67 on the HAI, 47 on the IAS, and 5 on the WI. Sensitivity and specificity were high, ranging from 92.6 to 99.4%. Positive and negative predictive values ranged from 91.6 to 99.4% using unadjusted prevalence rates. Conclusions The HAI, IAS and WI have very good properties as diagnostic indicators of severe health anxiety and can be used as cost-efficient proximal estimates of the diagnosis. PMID:25849477

Installation Restoration Program (IRP) Stage 3. McClellan Air Force Base. Operable Unit B. Preliminary Assessment Summary Report. Volume 1. Text, Appendix A & Part B. (Part 1)

DTIC Science & Technology

1991-10-01

reflect the official position of the Air Force. "Accezoi a - . . . .. . NT:S C2 I - DTIC IA .; Ui’avll’ .- -, JJstificatin. By Dist ... . Al-4 , t...6625 SA 23 2 52 sm 30 LEGEND -122 .ANEAC D 42T 20Go4 824O SA ITE a- CHI LI SAU r41E FEC Fiur -. LoctinGfENDusra S-124 RA IA N SO POnATION material...V V V V aS 00 Sn 1 0 - 1.I 5 V I4 . V V VV V V V - V v vV VV ’A NS 11V V V WV 0 0- 44m N 0 C4 90 1, - All IA 0 000000000000 000 00 A-1.00444.5

The healthcare utilization and cost of treating patients experiencing inappropriate implantable cardioverter defibrillator shocks: a propensity score study.

PubMed

Bhavnani, Sanjeev P; Giedrimiene, Dalia; Coleman, Craig I; Guertin, Danette; Azeem, Meena; Kluger, Jeffrey

2014-10-01

Inappropriate shocks (IASs) from implantable cardioverter defibrillators (ICDs) are associated with decreased quality of life, but whether they increase healthcare utilization and treatment costs is unknown. We sought to determine the impact of IASs on subsequent healthcare utilization and treatment costs. We conducted a case-control analysis of ICD patients at a single institution from 1997 to 2010 and who had ≥12 months of post-ICD implant follow-up. Cases included all patients experiencing an IAS during the first 12 months after implantation. Eligible control patients did not receive a shock of any kind during the 12 months after implantation. Propensity scores based on 36 covariates (area under curve = 0.78) were used to match cases to controls. We compared the rate (occurrences/person year [PY]) of healthcare utilization immediately following IAS to the end of the 12-month follow-up period to the rate in the no-shock group over 12 months of follow-up. We also compared 12-month postimplant treatment (outpatient clinic, emergency room, and hospitalization) costs in both groups. A total of 76 patients experiencing ≥1 IAS during the first 12 months after implant (contributing 48 PYs) were matched to 76 no-shock patients (contributing 76 PYs). Cardiovascular (CV)-related clinic visit and hospitalization rates were increased following an IAS compared to those not receiving a shock (4.0 vs 3.3 and 0.7 vs 0.5, respectively, P = 0.02 for both). CV-related emergency room visitation (0.15 vs 0.08) rates were also numerically higher following an IAS, but did not reach statistical significance (P = 0.26). Patients experiencing an IAS accrued greater treatment costs during the 12 months postimplant compared to no-shock patients ($13,973 ± $46,345 vs $6,790 ± $19,091, P = 0.001). Recipients of IAS utilize the healthcare system more frequently following an IAS than patients not experiencing a shock. This increased utilization results in higher costs of treating IAS patients during the 12 months postimplant. ©2014 Wiley Periodicals, Inc.

Consensus Report on Impulsive Aggression as a Symptom across Diagnostic Categories in Child Psychiatry: Implications for Medication Studies

ERIC Educational Resources Information Center

Jensen, Peter S.; Youngstrom, Eric A.; Steiner, Hans; Findling, Robert L.; Meyer, Roger E.; Malone, Richard P.; Carlson, Gabrielle A.; Coccaro, Emil F.; Aman, Michael G.; Blair, James; Dougherty, Donald; Ferris, Craig; Flynn, Laurie; Green, Evelyn; Hoagwood, Kimberly; Hutchinson, Janice; Laughren, Tom; Leve, Leslie D.; Novins, Douglas K.; Vitiello, Benedetto

2007-01-01

Objective: To determine whether impulsive aggression (IA) is a meaningful clinical construct and to ascertain whether it is sufficiently similar across diagnostic categories, such that parallel studies across disorders might constitute appropriate evidence for pursuing indications. If so, how should IA be assessed, pharmacological studies…

ADHD and personality: a meta-analytic review.

PubMed

Gomez, Rapson; Corr, Philip J

2014-07-01

We report a meta-analysis of up to 40 data sets that examined the personality dimensions in the Five-Factor Model (FFM) and the integrated Five-Factor Model (IFFM) in relation to ADHD symptom domains of inattention (IA) and hyperactivity/impulsivity (HI). The IFFM incorporated the dimensions of other personality models (in particular, those of Eysenck, Tellegen, and Cloninger, as well as the FFM). Major findings were: (1) IA and HI were both associated with low conscientious inhibition/conscientiousness, and low agreeable inhibition/agreeableness, and with high negative emotionality/neuroticism; (2) conscientious inhibition and conscientiousness were more strongly related to IA than HI; (3) agreeable inhibition and agreeableness were more strongly related to HI than IA; and (4) the association of conscientious inhibition and conscientiousness with HI was moderated by age group and source from where participants were recruited (associations were stronger in children than adults, and clinical samples than community samples). These findings are discussed in relation to single and multiple pathway theories, underlying factors and processes for the personality-ADHD link, and clinical implications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Infection of Mice, Ferrets, and Rhesus Macaques with a Clinical Mumps Virus Isolate

PubMed Central

Xu, Pei; Huang, Zhixiang; Gao, Xiudan; Michel, Frank J.; Hirsch, Gwen; Hogan, Robert J.; Sakamoto, Kaori; Ho, Wenzhe; Wu, Jianguo

2013-01-01

In recent years, many mumps outbreaks have occurred in vaccinated populations worldwide. The reasons for these outbreaks are not clear. Animal models are needed to investigate the causes of outbreaks and to understand the pathogenesis of mumps virus (MuV). In this study, we have examined the infection of three animal models with an isolate of mumps virus from a recent outbreak (MuV-IA). We have found that while both ferrets and mice generated humoral and cellular immune responses to MuV-IA infection, no obvious signs of illness were observed in these animals; rhesus macaques were the most susceptible to MuV-IA infection. Infection of rhesus macaques via both intranasal and intratracheal routes with MuV-IA led to the typical clinical signs of mumps 2 weeks to 4 weeks postinfection. However, none of the infected macaques showed any fever or neurologic signs during the experimental period. Mumps viral antigen was detected in parotid glands by immunohistochemistry (IHC). Rhesus macaques represent the best animal model for the study of mumps virus pathogenesis. PMID:23678169

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PubMed

Barton, M; Boyages, J; Crennan, E; Davis, S; Fisher, R J; Hook, C; Johnson, N; Joseph, D; Khoo, V; Liew, K H; Morgan, G; O'Brien, P; Pendlebury, S; Pratt, G; Quong, G; Roos, D E; Thornton, D; Trotter, G; Walker, Q; Wallington, M

1996-04-01

To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

A Laboratory-Based Evaluation of Four Rapid Point-of-Care Tests for Syphilis

PubMed Central

Causer, Louise M.; Kaldor, John M.; Fairley, Christopher K.; Donovan, Basil; Karapanagiotidis, Theo; Leslie, David E.; Robertson, Peter W.; McNulty, Anna M.; Anderson, David; Wand, Handan; Conway, Damian P.; Denham, Ian; Ryan, Claire; Guy, Rebecca J.

2014-01-01

Background Syphilis point-of-care tests may reduce morbidity and ongoing transmission by increasing the proportion of people rapidly treated. Syphilis stage and co-infection with HIV may influence test performance. We evaluated four commercially available syphilis point-of-care devices in a head-to-head comparison using sera from laboratories in Australia. Methods Point-of-care tests were evaluated using sera stored at Sydney and Melbourne laboratories. Sensitivity and specificity were calculated by standard methods, comparing point-of-care results to treponemal immunoassay (IA) reference test results. Additional analyses by clinical syphilis stage, HIV status, and non-treponemal antibody titre were performed. Non-overlapping 95% confidence intervals (CI) were considered statistically significant differences in estimates. Results In total 1203 specimens were tested (736 IA-reactive, 467 IA-nonreactive). Point-of-care test sensitivities were: Determine 97.3%(95%CI:95.8–98.3), Onsite 92.5%(90.3–94.3), DPP 89.8%(87.3–91.9) and Bioline 87.8%(85.1–90.0). Specificities were: Determine 96.4%(94.1–97.8), Onsite 92.5%(90.3–94.3), DPP 98.3%(96.5–99.2), and Bioline 98.5%(96.8–99.3). Sensitivity of the Determine test was 100% for primary and 100% for secondary syphilis. The three other tests had reduced sensitivity among primary (80.4–90.2%) compared to secondary syphilis (94.3–98.6%). No significant differences in sensitivity were observed by HIV status. Test sensitivities were significantly higher among high-RPR titre (RPR≥8) (range: 94.6–99.5%) than RPR non-reactive infections (range: 76.3–92.9%). Conclusions The Determine test had the highest sensitivity overall. All tests were most sensitive among high-RPR titre infections. Point-of-care tests have a role in syphilis control programs however in developed countries with established laboratory infrastructures, the lower sensitivities of some tests observed in primary syphilis suggest these would need to be supplemented with additional tests among populations where syphilis incidence is high to avoid missing early syphilis cases. PMID:24618681

Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care

ClinicalTrials.gov

2017-04-05

Adenocarcinoma of the Lung; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Squamous Cell Lung Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Ovarian Conservation and Overall Survival in Young Women With Early-Stage Cervical Cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D

2017-01-01

To identify predictors of ovarian conservation at hysterectomy and to examine the association of ovarian conservation and survival of young women with early-stage cervical cancer. This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program to identify hysterectomy-based surgically treated patients with stage I cervical cancer diagnosed between 1983 and 2012 (N=16,511). Multivariable models were used to identify independent factors associated with ovarian conservation. Among the subgroup of 9,419 women younger than 50 years of age with stage I disease, survival outcomes and causes of death were examined for 3,908 (41.5%) women who underwent ovarian conservation at hysterectomy without radiotherapy. On multivariable analysis, age younger than 50 years, stage IA disease, and squamous histology were independent factors associated with ovarian conservation (all, P<.001). Among 5,526 women younger than 50 years of age with stage IA disease who underwent hysterectomy without radiotherapy, overall survival was significantly higher in patients undergoing ovarian conservation than in those undergoing oophorectomy (20-year rate, 93.5% compared with 86.8%, P<.001); cervical cancer-specific survival was similar between the patients who underwent ovarian conservation and those who underwent oophorectomy (98.8% compared with 97.8%, P=.12). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.63, 95% confidence interval [CI] 0.49-0.82, P=.001) and was independently associated with lower cumulative risks of death resulting from cardiovascular disease (20-year cumulative rate, 1.2% compared with 3.3%, adjusted hazard ratio 0.47, 95% CI 0.26-0.86, P=.014) and other chronic disease (0.5% compared with 1.4%, adjusted hazard ratio 0.24, 95% CI 0.09-0.65, P=.005) compared with oophorectomy. Both cervical cancer-specific survival (20-year rate, 93.1% compared with 92.0%, P=.37) and overall survival (86.7% compared with 84.6%, P=.12) were similar between ovarian conservation and oophorectomy among 3,893 women younger than 50 years of age with stage IB disease who underwent hysterectomy without radiotherapy. Among young women with stage IA cervical cancer, ovarian conservation at hysterectomy is associated with decreased all-cause mortality including death resulting from cardiovascular disease and other chronic diseases.

Polycystic ovary syndrome: early diagnosis and intervention are necessary for fertility preservation in young women with endometrial cancer under 35 years of age.

PubMed

Okamura, Yoshinori; Saito, Fumitaka; Takaishi, Kiyomi; Motohara, Takeshi; Honda, Ritsuo; Ohba, Takashi; Katabuchi, Hidetaka

2017-01-01

Polycystic ovary syndrome (PCOS) is a significant risk factor for premenopausal endometrial cancer (EC) and/or atypical endometrial hyperplasia (AEH). The aim was to elucidate the clinical background and detailed menstrual history of EC and/or AEH in young women with PCOS. From January 2001 to December 2013, women under 35 years of age who had been diagnosed with EC and/or AEH and who had been treated at Kumamoto University Hospital, Japan, were recruited. The patients' clinical characteristics, clinical stages of EC and/or AEH, medication and operation methods, endocrine profiles, and menstrual history were assessed retrospectively. Of all the cases of EC and/or AEH, 25 (4.6%) were under 35 years of age. The mean age was 29.0 years and all the patients were nulligravida. The clinical stages of EC and/or AEH that were identified included: AEH (five cases), stage IA (18 cases), IB (one case), and IIIA (one case). Fourteen (56%) cases met the criteria for PCOS. Both the Body Mass Index and Homeostatic Model Assessment-insulin resistance were significantly higher in the patients with PCOS than in the patients without PCOS. Medroxyprogesterone acetate therapy was not effective for the patients with PCOS and they underwent a hysterectomy more often than the patients without PCOS. All the patients with PCOS exhibited irregular menstruation or amenorrhea, the mean duration of which was 13.1 years before PCOS and EC and/or AEH were diagnosed. Although both the patients with and without PCOS had irregular menstruation, the patients with PCOS were less likely to have fertility-sparing surgery than the patients without PCOS because they had more advanced disease or failed to respond to medroxyprogesterone acetate therapy.

[The impacts of the multidisciplinary team model on the length of stay and hospital expenses of patients with lung cancer].

PubMed

Zou, Jing; Xu, Xingxiang; Wang, Daxin; Xu, Jin; Gu, Wenju

2015-05-01

To explore the impacts of the multidisciplinary team model on the average length of stay and hospital expenses of patients with lung cancer. After the multidisciplinary team discussion, 97 patients with lung cancer were selected as the lung cancer group according to the enrollment and elimination criteria the control group was 97 patients with lung cancer managed without team discussion during the same period. All the patients were firstly diagnosed to have lung cancer from December 2011 to December 2013 in Subei People's Hospital. The length of stay, hospital expenses, stages of tumor, types of tumor, Zubrod-ECOG-WHO score, the form of payment, smoking history, sex and age of all the patients were collected. The difference in the average length of stay and hospital expenses between the 2 groups and the associated factors were analyzed by using χ² test, t test and multi-factor stepwise regression analysis. There were 68 males and 29 females with a mean age of (61 ± 9) years in the lung cancer group, while there were 73 males and 24 females with a mean age of (63 ± 10) years in the control group. There were no differences between the 2 groups in tumor staging, tumor types, Zubrod-ECOG-WHO score, the form of payment, smoking history, sex and age (χ² = 4.854, P = 0.563, χ² = 4.248, P = 0.097; χ² = 0.395, P = 0.821; χ² = 1.191, P = 0.554; χ² = 0.108, P = 0.977; χ² = 1.011, P = 0.389; χ² = 0.649, P = 0.519; P = 0.474, P = 0.845, respectively). The average hospital expenses (13 303 vs 16 553, Yuan) were lower and the length of stay (10.33 vs 12.49, days) was shorter in the lung cancer group as compared to the control group (t = 2.616, P = 0.010; t = 2.730, P = 0.007), especially so for the first clinical hospitalization (15 953 vs 19 485 yuan, t = 2.315, P = 0.022; 12.71 vs 14.75 days, t = 1.979, P = 0.049). The average length of stay and the tumor stages were the main factors associated with the average hospital expenses. Except for patients with the limited stage of small cell lung cancer, the average length of stay and hospital expenses showed a tendency to reduce in different stages of the lung cancer group. The hospital cost was lower and the length of stay shorter for patients with stages Ia-IIIa and IIIb-IV in the lung cancer group as compared to the control group (6 722 vs 8 188 yuan; 1.09 vs 2.65 days). The multidisciplinary team model was an effective measure to cut down the hospital expenses and shorten the length of stay of lung cancer patients, especially for the first hospitalization. Patients may benefit from the multidisciplinary team approach according to their stages. On the basis of reducing the hospital costs and the length of stay, it further reduced the gap of the length of stay and hospital expenses between patients with Ia-IIIa and IIIb-IV diseases, while patients with stage Ia-IIIa disease seemed to benefit more.

Identification of Undiagnosed Inflammatory Arthritis in a Community Health-Fair Screen

PubMed Central

Deane, Kevin D.; Striebich, Christopher C.; Goldstein, Barbara L.; Derber, Lezlie A.; Parish, Mark C.; Feser, Marie L.; Hamburger, Elaine M.; Brake, Stacey; Belz, Cindy; Goddard, James; Norris, Jill M.; Karlson, Elizabeth W.; Holers, V. Michael

2010-01-01

Purpose The primary goals of this study were: 1) to identify individuals with undiagnosed inflammatory arthritis (IA) and rheumatoid arthritis (RA) in a community health-fair screen, and 2) to establish in a health-fair setting the diagnostic accuracy of combinations of the Connective Tissue Disease Screening Questionnaire (CSQ) and autoantibody testing for IA. Methods Screening for IA/RA was performed at health-fair sites using a combination of CSQ, joint examination, rheumatoid factor (RF) and anti-cyclic citrullinated (anti-CCP) antibody testing. IA was defined as ≥1 swollen joint/s suggestive of synovitis on joint examination by a trained clinician. Results Six-hundred one subjects were screened; 51.0% participating because of joint symptoms (pain, stiffness, or swelling). Eighty-four subjects (14.0%) had ≥1 swollen joint/s designated as IA on joint examination. Of the 601 subjects screened, 9 (1.5%) had IA and met ≥4 of 7 American College of Rheumatology criteria for RA but had no prior diagnosis of RA, and 15 (2.5%) had IA and RF and/or anti-CCP positivity, suggesting early RA. The diagnostic accuracy of combinations of CSQ and autoantibody testing for the identification of IA yielded maximal sensitivity, specificity, positive and negative predictive values of 95.3%, 99.2%, 71.4%, and 97.7%, respectively. Conclusions Health-fair screening may be an effective approach for the identification of individuals with undiagnosed IA/RA. A combination of CSQ and autoantibody testing alone has clinically useful diagnostic accuracy for the detection of IA. Decisions regarding which methodology to use for future health-fair IA/RA screening will depend on goals of screening and funding. PMID:19950306

The Relationship between Smoking and Replicated Sequence Variants on Chromosomes 8 and 9 with Familial Intracranial Aneurysm

PubMed Central

Deka, Ranjan; Koller, Daniel L.; Lai, Dongbing; Indugula, Subba Rao; Sun, Guangyun; Woo, Daniel; Sauerbeck, Laura; Moomaw, Charles J.; Hornung, Richard; Connolly, E. Sander; Anderson, Craig; Rouleau, Guy; Meissner, Irene; Bailey-Wilson, Joan E.; Huston, John; Brown, Robert D.; Kleindorfer, Dawn O.; Flaherty, Matthew L.; Langefeld, Carl; Foroud, Tatiana; Broderick, Joseph P.

2010-01-01

Purpose To replicate the previous association of single nucleotide polymorphisms (SNPs) with risk of intracranial aneurysm (IA) and to examine the relationship of smoking with these variants and the risk of IA. Methods White probands with an IA from families with multiple affected members were identified by 26 clinical centers located throughout North America, New Zealand, and Australia. White controls free of stroke and IA were selected by random digit dialing from the Greater Cincinnati population. SNPs previously associated with IA on chromosome 2, 8, and 9 were genotyped using a TaqMan assay or were included in the Affymetrix 6.0 array that was part of a genome-wide association study of 406 IA cases and 392 controls. Logistic regression modeling tested whether the association of replicated SNPs with IA was modulated by smoking. Results The strongest evidence of association with IA was found with the 8q SNP rs10958409 (genotypic P = 9.2 × 10-5; allelic P = 1.3 × 10-5; OR = 1.86, 95% CI: 1.40−2.47). We also replicated association with both SNPs on chromosome 9p, rs1333040 and rs10757278, but were not able to replicate the previously reported association of the two SNPs on chromosome 2q. Statistical testing showed a multiplicative relationship between the risk alleles and smoking with regard to the risk of IA. Conclusion Our data provide complementary evidence that the variants on chromosome 8q and 9p are associated with IA and that the risk of IA in patients with these variants are greatly increased with cigarette smoking. PMID:20190001

A coil placement technique to treat intracranial aneurysm with incorporated artery.

PubMed

Luo, Chao-Bao; Chang, Feng-Chi; Lin, Chung-Jung; Guo, Wan-Yuo

2018-03-01

Endovascular coil embolization is an accepted treatment option for intracranial aneurysms. However, the coiling of aneurysms with an incorporated artery (IA) poses a high risk of IA occlusion. Here we report our experience of endovascular coil placement using a technique that avoids IA occlusion in aneurysms with IAs. Over a 6-year period, 185 patients harboring 206 intracranial aneurysms underwent endosaccular coiling. Forty-two of these patients with 45 aneurysms were treated by coil placement to avoid IAs occlusion. We assessed the anatomy of the aneurysms and IAs, technical feasibility of the procedure, and degree of aneurysm occlusion. Clinical and angiographic outcomes were assessed as well. Aneurysms were located in the supra-clinoid intracranial internal carotid artery (n = 24), anterior cerebral artery (n = 6), middle cerebral artery (n = 7), and vertebrobasilar artery (n = 8). The IA was at the aneurysm neck in 34 patients, body in 10, and dome in 1. Immediate post-coiling angiogram showed preservation of blood flow through the IA in all aneurysms. Coil compaction with aneurysmal regrowth was found in 7 of 36 patients having follow-up conventional angiography. One patient had an IA territory infarction after embolization. All 42 patients were followed up (mean: 21 months) and showed no re-bleeding. This technique is effective and safe in managing intracranial aneurysms with IAs. Although aneurysmal recurrence may occur in some aneurysms because of insufficient coiling, this technique is simpler to perform and requires less skill than other techniques. It can be an alternative option for treating some selected intracranial aneurysms with IAs. Copyright © 2017. Published by Elsevier Taiwan LLC.

Pharmacokinetics of escin Ia in rats after intravenous administration.

PubMed

Wu, Xiu-Jun; Cui, Xiang-Yong; Tian, Lian-tian; Gao, Feng; Guan, Xin; Gu, Jing-Kai

2014-10-28

Escin, a natural mixture of triterpene saponins, is commonly utilized for the treatment of chronic venous insufficiency, hemorrhoids, inflammation and edema. Escin Ia is the chief active ingredient in escin and plays key role in mediating its pharmacological effects. Adequate pharmacokinetic data are essential for proper application of escin agent in clinical practice. However, pharmacokinetic properties of escin Ia are still poorly understood and this conflicts with the growing use of escin agent over the years. The goal of this study is to investigate the pharmacokinetic behavior of escin Ia in rats after low, medium and high-dose intravenous administration. Wistar rats were divided into 3 groups (n=6 per group) and escin Ia was administered via the caudal vein at doses of 0.5, 1.0 and 2.0 mg/kg, respectively. Subsequently, the concentrations of escin Ia and its metabolite isoescin Ia, a positional isomer of escin Ia, in rats׳ plasma were measured by an established liquid chromatography tandem mass spectrometry (LC-MS/MS) method at various time points following the administration of the drug. Main pharmacokinetic parameters were calculated by non-compartmental analysis using the TopFit 2.0 software package (Thomae GmbH, Germany). After intravenous administration, the Cmax and AUC of escin Ia increased in a dose-proportional manner at the dose of 0.5 mg/kg and 1.0 mg/kg, while increased in a more than dose-proportional manner at the doses of 1.0 mg/kg and 2.0 mg/kg. The t₁/₂ was significantly longer with increased intravenous doses, while other parameters such as CL and Vd also exhibit disagreement among three doses. Taken together, our data showed dose-dependent pharmacokinetic profile of escin Ia in rats after intravenous administration at the doses of 0.5-2.0 mg/kg. After intravenous administration, escin Ia was rapidly and extensively converted to isoescin Ia. The results suggested dose-dependent pharmacokinetics of escin Ia at the doses of 0.5-2.0 mg/kg after intravenous administration. Escin Ia is isomerized to isoescin Ia rapidly and extensively regardless of the doses. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A rationally designed peptide IA-2-P2 against type 1 diabetes in streptozotocin-induced diabetic mice.

PubMed

Shen, Lili; Lu, Shiping; Huang, Dongcheng; Li, Guoliang; Liu, Kunfeng; Cao, Rongyue; Zong, Li; Jin, Liang; Wu, Jie

2017-05-01

Recent studies have investigated the potential of type 1 diabetes mellitus-related autoantigens, such as heat shock protein 60, to induce immunological tolerance or to suppress the immune response. A functional 24-residue peptide derived from heat shock protein 60 (P277) has shown anti-type 1 diabetes mellitus potential in experimental animals and in clinical studies, but it also carries a potential atherogenic effect. In this study, we have modified P277 to retain an anti-type 1 diabetes mellitus effect and minimize the atherogenic potential by replacing the P277 B epitope with another diabetes-associated autoantigen, insulinoma antigen-2 (IA-2), to create the fusion peptide IA-2-P2. In streptozotocin-induced diabetic C57BL/6J mice, the IA-2-P2 peptide displayed similar anti-diabetic effects to the control P277 peptide. Also, the IA-2-P2 peptide did not show atherogenic activity in a rabbit model. Our findings indicate the potential of IA-2-P2 as a promising vaccine against type 1 diabetes mellitus.

Antifungal prophylaxis with fluconazole in allogeneic stem cell transplantation recipients who had prior invasive aspergillosis with subsequent complete resolution by computed tomography.

PubMed

Akahoshi, Yu; Kimura, Shun-Ichi; Gomyo, Ayumi; Hayakawa, Jin; Tamaki, Masaharu; Harada, Naonori; Kusuda, Machiko; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Sato, Miki; Terasako-Saito, Kiriko; Kikuchi, Misato; Nakasone, Hideki; Kako, Shinichi; Kanda, Yoshinobu

2018-04-01

Consensus has yet to be reached regarding secondary prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT) with a complete resolution of invasive aspergillosis (IA) confirmed by chest computed tomography (CT). We retrospectively evaluated the feasibility of antifungal prophylaxis with fluconazole in allogeneic HSCT recipients who had previously developed IA which showed complete resolution as confirmed by chest CT before HSCT. Consecutive adult patients who underwent allogeneic HSCT at our institution and who had received fluconazole as systemic antifungal prophylaxis from June 2007 to January 2015 were included. We compared the clinical outcomes between patients with a past history of IA who showed a complete resolution of chest CT abnormalities (n = 13) and those without a previous history of IA (n = 137). The cumulative incidence of proven or probable IA was 8.8% in the group without a past history of IA and 0.0% in the group with a past history of IA (p = .268). The cumulative incidence of proven or probable invasive fungal disease (IFD) within 100 days after allogeneic HSCT was 10.9% in the group without a past history of IA and 15.4% in the group with a past history of IA (p = .647). Fluconazole was switched to anti-mould agents in two-thirds of the patients in each group by day 100 after HSCT. Fluconazole was confirmed to be an acceptable prophylactic agent early after allogeneic HSCT in appropriately selected patients.

Effect of lipid-lowering therapy on the progression of intracranial arterial stenosis.

PubMed

Tan, Teng-Yeow; Kuo, Yeh-Lin; Lin, Wei-Che; Chen, Ting-Yao

2009-02-01

Intracranial arterial stenosis (IAS) is a severe disease with a high recurrent stroke rate even under the best medical treatment. Statins have been demonstrated to prevent stroke and to slow or halt atherosclerosis progression. This study was performed to observe the effect of atorvastatin on the progression of IAS, explore the factors associated with atherosclerosis regression and the recurrent rate of stroke. A hospital-base observation study enrolled 40 stroke patients with middle cerebral artery (MCA) or/and basilar artery (BA) stenosis. All participants had hyperlipidemia and were given atorvastatin 40 mg per day for at least six months. IAS was assessed by magnetic resonance angiogram (MRA) at the time of enrollment and then at least six months later. The primary outcome was the progression of IAS. All patients were also given antiplatelet agents for stroke prevention. At the end of the study, 23 (58 %), 15 (38 %) and 2 (4 %) patients had regressed, stationary and progressed IAS, respectively. Females were likely to have regressed IAS. The recurrent stroke rate was 18 %. Among the 54 stenotic vessels, 29 (54 %) vessels were assessed as improvement in stenosis. Compared with other studies, more regressed, stationary IAS and less progressed IAS were found in our study. Female gender was likely to have regressed IAS after statin treatment. Further clinical outcome trials are required to assess the effects of such therapy on morbidity and mortality in this particular group of patients.

Inverse correlation between microtubule-associated protein 1A/1B-light chain 3 and p62/sequestosome-1 expression in the progression of cutaneous squamous cell carcinoma.

PubMed

Yoshihara, Nagisa; Takagi, Atsushi; Ueno, Takashi; Ikeda, Shigaku

2014-04-01

The expression of autophagy-related markers has occasionally been reported to correlate with the clinical stage of disease in patients with solid cancer, indicating autophagy activation. However, there have been no such reports for cutaneous squamous cell carcinoma. In this study, we investigated the expression levels of two autophagy-related markers, microtubule-associated protein IA/IB light chain 3 (LC3) and p62/sequestosome-1 (p62), in cutaneous squamous cell carcinoma specimens and assessed their correlation to clinicopathological factors in patients with this type of cancer. As a marker of the autophagosome, LC3 expression increases with autophagosome formation/accumulation, whereas p62 expression decreases due to selective degradation via autophagy. We performed immunostaining for LC3 and p62 in 50 cutaneous squamous cell carcinoma specimens obtained from patients treated by surgical resection, counted the number of cells that showed positive staining, and calculated the percentage of positive cells per low-power microscopic field. We next investigated the correlations between the expression levels of these markers and various clinicopathological factors. The results indicated that LC3 expression increased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.046). By contrast, the expression of p62 decreased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.001). These results suggest that autophagy becomes activated during disease progression in patients with cutaneous squamous cell carcinoma. © 2014 Japanese Dermatological Association.

Abdominal emergency in elderly: a case of small bowel obstruction and ischemia caused by bulky IA ovarian cancer.

PubMed

Assenza, M; Campana, G; Centonze, L; Simonelli, L; Romeo, V; Marchese, S; Andreoli, C; Modini, C

2013-01-01

Bowel obstruction resulting from colorectal and ovarian cancer is a serious and distressing complication of these malignancies. This may be caused by diffuse peritoneal carcinomatosis, bulky masses filling the pelvis and abdomen or postoperative adhesions, and should be carefully worked out by pre-operative imaging. We report the case of a small bowel obstruction and intestinal ischemia caused by a bulky (20x40 cm in diameter) cystic ovarian neoplasm that was found to be a stage IA G2 cystadenocarcinoma, successfully managed by uterus-sparing surgery.

Expression of miR-146a-5p in patients with intracranial aneurysms and its association with prognosis.

PubMed

Zhang, H-L; Li, L; Cheng, C-J; Sun, X-C

2018-02-01

The study aims to detect the association of miR-146a-5p with intracranial aneurysms (IAs). The expression of miR-146a-5p was compared from plasma samples between 72 patients with intracranial aneurysms (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed to analyze the relationship between miR-146a-5p expression and clinical data and overall survival (OS) time of IAs patients. Univariate and multivariate Cox proportional hazards have also been performed. Notably, higher miR-146a-5p expression was found in plasma samples from 72 patients with intracranial aneurysms (IAs) compared with 40 healthy controls. Higher miR-146a-5p expression was significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan-Meier survival analysis verified that higher miR-146a-5p expression predicted a shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs patients. Univariate and multivariate Cox proportional hazards demonstrated that higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk factors of OS in patients with intracranial aneurysms (IAs). MiR-146a-5p expression may serve as a biomarker for predicting prognosis in patients with IAs.

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

PubMed Central

Jung, In-Hye; Jung, Jinhong; Cho, Byungchul; Kwak, Jungwon; Je, Hyoung Uk; Choi, Wonsik; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung

2015-01-01

Purpose To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication. PMID:26157678

Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels.

PubMed

af Klint, Erik; Grundtman, Cecilia; Engström, Marianne; Catrina, Anca Irinel; Makrygiannakis, Dimitrios; Klareskog, Lars; Andersson, Ulf; Ulfgren, Ann-Kristin

2005-12-01

To investigate whether intraarticular (IA) glucocorticoid (GC) therapy diminishes synovial cell infiltration, vascularity, expression of proinflammatory cytokines, and adhesion molecule levels in patients with chronic arthritides. Thirty-one patients with chronic arthritides received a single IA injection of triamcinolone hexacetonide to treat active large-joint inflammation. Synovial biopsy specimens were obtained with arthroscopic guidance before and 9-15 days after injection. The presence of T lymphocytes, macrophages, intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), the pan-endothelial marker CD31, and the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor (TNF), and high mobility group box chromosomal protein 1 (HMGB-1) was studied by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction. IA GC treatment resulted in good clinical response in 29 of 31 joints. After therapeutic intervention, the number of synovial T lymphocytes declined, whereas the number of macrophages remained unchanged. Overall synovial protein expression of TNF, IL-1beta, extranuclear HMGB-1, VEGF, and ICAM-1 was reduced at followup tissue sampling, while no significant effects were observed regarding vascularity. In contrast, expression of IL-1alpha, VEGF, and cytoplasmic HMGB-1 protein in vascular endothelial cells was not affected. GC therapy down-regulated levels of messenger RNA encoding IL-1alpha and IL-1beta, but not TNF or HMGB-1. Synovial cell infiltration and proinflammatory cytokine expression were affected in a multifaceted manner by IA GC treatment. Marked reduction of synovial T lymphocytes, TNF, IL-1beta, extranuclear HMGB-1, ICAM-1, and VEGF occurred in association with beneficial clinical effects. Unexpectedly, macrophage infiltration and proinflammatory endothelial cytokine expression remained unchanged. These findings may reflect mechanisms controlling the transiency of clinical improvement frequently observed after IA GC injection.

Clinical and angiographic outcome after endovascular management of giant intracranial aneurysms.

PubMed

Jahromi, Babak S; Mocco, J; Bang, Jee A; Gologorsky, Yakov; Siddiqui, Adnan H; Horowitz, Michael B; Hopkins, L Nelson; Levy, Elad I

2008-10-01

Giant (>or=25 mm) intracranial aneurysms (IA) have an extremely poor natural history and continue to confound modern techniques for management. Currently, there is a dearth of large series examining endovascular treatment of giant IAs only. We reviewed long-term clinical and radiological outcome from a series of 39 consecutive giant IAs treated with endovascular repair in 38 patients at 2 tertiary referral centers. Data were evaluated in 3 ways: on a per-treatment session basis for each aneurysm, at 30 days after each patient's final treatment, and at the last known follow-up examination. Ten (26%) aneurysms were ruptured. At the last angiographic follow-up examination (21.5 +/- 22.9 months), 95% or higher and 100% occlusion rates were documented in 64 and 36% of aneurysms, respectively, with parent vessel preservation maintained in 74%. Stents were required in 25 aneurysms. Twenty percent of treatment sessions resulted in permanent morbidity, and death within 30 days occurred after 8% of treatment sessions. On average, 1.9 +/- 1.1 sessions were required to treat each aneurysm, with a resulting cumulative per-patient mortality of 16% and morbidity of 32%. At the last known clinical follow-up examination (mean, 24.8 +/- 24.8 months), 24 (63%) patients had Glasgow Outcome Scale scores of 4 or 5 ("good" or "excellent"), 10 patients had worsened neurological function from baseline (26% morbidity), and 11 had died (29% mortality). We present what is to our knowledge the largest series to date evaluating outcome after consecutive giant IAs treated with endovascular repair. Giant IAs carry a high risk for surgical or endovascular intervention. We hope critical and honest evaluation of treatment results will ensure continued improvement in patient care.

Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

PubMed

Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James

2017-01-01

Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.

Clinical characterization and molecular classification of 12 Korean patients with pseudohypoparathyroidism and pseudopseudohypoparathyroidism.

PubMed

Cho, S Y; Yoon, Y A; Ki, C-S; Huh, H J; Yoo, H-W; Lee, B H; Kim, G-H; Yoo, J-H; Kim, S-Y; Kim, S J; Sohn, Y B; Park, S W; Huh, R; Chang, M S; Lee, J; Kwun, Y; Maeng, S H; Jin, D-K

2013-10-01

Pseudohypoparathyroidism (PHP) is defined as resistance toward parathyroid hormones. PHP and pseudopseudohypoparathyroidism (PPHP) are rare disorders resulting from genetic and epigenetic aberrations within or upstream of the GNAS locus. This study investigated the clinical characteristics and performed a molecular analysis of PHP and PPHP. A total of 12 patients with (P)PHP from 11 unrelated families (4 with PHP-Ia, 6 with PHP-Ib, and 2 with PPHP) were characterized using both clinical and molecular methods. Clinical features included the presenting symptoms, Albright hereditary osteodystrophy features, and resistance to hormones. Comprehensive analysis of the GNAS and STX16 loci was undertaken to investigate the molecular defects underlying (P)PHP. All PHP-Ib patients displayed hypocalcemic symptoms. All PHP-Ia patients showed resistance toward TSH, in addition to PTH. In most patients with PHP, when the diagnosis of PHP was first established, hypocalcemia and hyperphosphatemia were associated with a significant increase in serum PTH levels. One patient with PHP-Ia was diagnosed with growth hormone deficiency and showed a good response to human recombinant growth hormone therapy. 6 patients with PHP-Ia and PPHP showed 5 different mutations in the GNAS gene. 5 patients with PHP-Ib displayed a loss of differentially methylated region (DMR) imprints of the maternal GNAS. One PHP-Ib patient showed a de novo microdeletion in STX16 and a loss of methylation of exon A/B on the maternal allele. No patients revealed paternal disomy among 4 patients with PHP-Ib. Identification of the molecular causes of PHP and PPHP explains their distinctive clinical features and enables confirmation of the diagnosis and exact genetic counseling. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.

Morpho-functional assessment of interatrial septum: a transesophageal echocardiographic study.

PubMed

Galzerano, D; Tuccillo, B; Lama, D; Paolisso, G; Mirra, G; Giasi, M

1995-08-01

Despite the increasing number of reports on lipomatous hypertrophy of interatrial septum, a standardization of measurement of the dimensions of the interatrial septum (IAS) in the different phases of cardiac cycle has not been reported. Moreover, no data on modification of thickness with age and in specific cardiac diseases are available. Our purpose was to study whether the changes of thickness and thinning of IAS may be related to age, left atrial dimension, cardiac cycle and different cardiac diseases. 248 patients (mean age 52.7 +/- 19.9 years) underwent transthoracic (TTE) and transesophageal (TEE) echocardiography. IAS was measured at the constant regions anterior and posterior to the fossa ovalis. IAS thickness (tk), thinning (th) and % thinning (% th) were measured. IAS thickness ranged from 4 to 13 mm at the time of ventricular end-systolic phase (mean 6.7 +/- 1.9 mm) and from 6 to 16 mm at the time of atrial systole (mean 9.9 +/- 1.8 mm); significant statistical difference between these values was found (P < 0.01). IAS thinning ranged from 1 to 7 mm (mean 3.42 +/- 1.8) while % IAS thinning from 18 to 76% (mean 36.53 +/- 16.36%). Statistical analysis showed a significant positive correlation between age and ventricular end-systolic thickness and atrial systolic thickness and thinning. An insignificant correlation was found between age and % IAS thinning and between left atrial dimension and IAS tk and th. Our results demonstrate that IAS thickness increases by age; no correlation exists between IAS thinning and age. There is no difference between IAS thickness and thinning in patients with or without cardiac disease. We believe that the thickness of IAS can be considered hypertrophic only if it exceeds the value of 15 mm during both ventricular end-systolic and atrial systolic phases of the cardiac cycle. IAS thickness and thinning might be an additional parameter to evaluate systolic atrial function particularly with regard to maintenance of synus rhythm after conversion from atrial fibrillation as well as to better understand its role in determining the filling of ventricles in different clinical conditions.

Effects of icotinib on early-stage non-small-cell lung cancer as neoadjuvant treatment with different epidermal growth factor receptor phenotypes.

PubMed

Wang, Tao; Liu, Yang; Zhou, Bin; Wang, Zhi; Liang, Naichao; Zhang, Yundong; Dong, Zhouhuan; Li, Jie

2016-01-01

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated efficacy in treating advanced non-small-cell lung cancer (NSCLC). Preliminary findings suggested that EGFR-TKIs might also be beneficial in neoadjuvant therapy in treating NSCLC. Therefore, this study aimed to evaluate the efficacy and safety of neoadjuvant therapy with icotinib in patients with early-stage NSCLC. We retrospectively reviewed the medical history of patients who were initially diagnosed with stage IA-IIIA NSCLC and were under icotinib administration before surgery between December 2011 and December 2014. Tumor assessment was conducted between the second and fourth week from initial icotinib treatment. The association between personal characteristics, smoking status, disease stage, EGFR mutation status, and clinical outcomes were investigated using multivariate logistic regression analysis. A total of 67 patients with NSCLC were reviewed, and approximately half (38/67) of them were identified as having EGFR-mutant tumors. The overall response rate of all patients was 26.7% at 2-4 weeks' assessment. Multivariate analysis showed that female sex (38.5% versus 10.7% in males, P=0.028) and EGFR mutation status (42.1% versus 6.9% in EGFR wild type, P=0.011) were independent predictive factors. The analysis also showed that the most common adverse effects were rash (43.3%) and dry skin (34.4%), which were tolerable. Icotinib induced clinical response with minimal toxicity as neoadjuvant treatment in early NSCLC, especially in patients with common EGFR mutations. Further studies are warranted to confirm our findings.

[Invasive aspergillosis in hematooncological patients: advantages and disadvantages of various diagnostic methods, treatment options and financial costs of therapy].

PubMed

Rácil, Z; Mayer, J; Kocmanová, I; Wagnerová, B; Winterová, J; Folber, F; Lengerová, M; Moulis, M; Zácková, D; Smardová, L; Janíková, A; Navrátil, M; Dvoráková, D; Vorlícek, J

2008-02-01

Invasive aspergillosis (IA) is a leading invasive fungal infection in hematooncological patients. The aim of this study was to analyse the incidence, diagnostic procedures and treatment of IA in hematooncological department in large hospital in the Czech Republic. A retrospective analysis of medical and laboratory records from patients hospitalised in our department with proven/probable IA between January 2000 and December 2006 was performed. 52 cases of IA in 51 patients were identified (17.3% proven IA/82.7% probable IA). Number of IA cases notably increased during study period (1 case of IA in 2000 vs 21 cases of IA in 2006) and majority of them was of nosocomial origin (61.5%). Pulmonary aspergillosis was diagnosed in 46 cases (88.5%). Patients treated for acute leukemia or undergoing allogeneic stem cell transplantation represent the group at the highest risk of IA (in total 52% of cases). Fever and signs of pulmonary involvement were the most common clinical signs of infection (presented in 92.3% and 69.2 cases respectively). Conventional diagnostic methods including autopsy were able to diagnose only 15 cases of IA (28.8%). In all other cases (71.2%) the diagnosis was done by detection of galactomannan (GM) in serum. Introduction of GM monitoring enabled erlier initiation of antifungal treatment by 4 days. Initial therapy of IA led to the treatment response (partial and complete) in 18 (34.6%) of infections--the highest percentage of response has been seen in voriconazole monotherapy group (42%) and when combination of voriconazole and caspofungin has been used (83%). Salvage therapy was initiated due to the failure of initial treatment in 21 (40.3%) of cases. Patients were treated mostly with combination ofvoriconazole and caspofungin and/or monotherapy with voriconazole has been used with treatment response 55% and 50% respectively. Introduction of new antifungal drugs together with increased number of patients with IA led to the marked increase of total costs spent on treatment of IA per year--from 11,5 thousands CZK in 2000 to 6,2 millions CZK in 2006. IA is the most frequent cause of infection-related mortality in patients with haematological malignancies. Routine use of non-culture base methods in diagnosis of IA together with treatment using new, effective antifungals can improve prognosis of patients with this life threatening infection.

A blinded determination of H0 from low-redshift Type Ia supernovae, calibrated by Cepheid variables

NASA Astrophysics Data System (ADS)

Zhang, Bonnie R.; Childress, Michael J.; Davis, Tamara M.; Karpenka, Natallia V.; Lidman, Chris; Schmidt, Brian P.; Smith, Mathew

2017-10-01

Presently, a >3σ tension exists between values of the Hubble constant H0 derived from analysis of fluctuations in the cosmic microwave background by Planck, and local measurements of the expansion using calibrators of Type Ia supernovae (SNe Ia). We perform a blinded re-analysis of Riess et al. (2011) to measure H0 from low-redshift SNe Ia, calibrated by Cepheid variables and geometric distances including to NGC 4258. This paper is a demonstration of techniques to be applied to the Riess et al. (2016) data. Our end-to-end analysis starts from available Harvard -Smithsonian Center for Astrophysics (CfA3) and Lick Observatory Supernova Search (LOSS) photometries, providing an independent validation of Riess et al. (2011). We obscure the value of H0 throughout our analysis and the first stage of the referee process, because calibration of SNe Ia requires a series of often subtle choices, and the potential for results to be affected by human bias is significant. Our analysis departs from that of Riess et al. (2011) by incorporating the covariance matrix method adopted in Supernova Legacy Survey and Joint Lightcurve Analysis to quantify SN Ia systematics, and by including a simultaneous fit of all SN Ia and Cepheid data. We find H_0 = 72.5 ± 3.1 ({stat}) ± 0.77 ({sys}) km s-1 Mpc-1with a three-galaxy (NGC 4258+LMC+MW) anchor. The relative uncertainties are 4.3 per cent statistical, 1.1 per cent systematic, and 4.4 per cent total, larger than in Riess et al. (2011) (3.3 per cent total) and the Efstathiou (2014) re-analysis (3.4 per cent total). Our error budget for H0 is dominated by statistical errors due to the small size of the SN sample, whilst the systematic contribution is dominated by variation in the Cepheid fits, and for the SNe Ia, uncertainties in the host galaxy mass dependence and Malmquist bias.

Intra-articular knee temperature changes: ice versus cryotherapy device.

PubMed

Warren, Todd A; McCarty, Eric C; Richardson, Airron L; Michener, Todd; Spindler, Kurt P

2004-03-01

Cryotherapy is commonly applied without research documenting the intra-articular (IA) temperature changes or subject discomfort between ice and a cryotherapy device. The null hypothesis is that no difference would be observed in IA temperature decline or subject tolerance between ice and the cryotherapy device in normal knees. Prospective, within-subject controlled clinical trial. Twelve subjects had IA temperature in suprapatellar pouch and skin recorded bilaterally after application of cryotherapy versus ice. Subject tolerance was recorded by 10-cm visual analog scale (VAS). Statistical evaluation was by Spearman's correlation analysis and paired, nonparametric Wilcoxon's signed rank test. Both significantly lowered (P < 0.001) skin and IA temperature with median decreases (ice/cryotherapy) at 30 (3.3 degrees C/2.2 degrees C), 60 (12.8 degrees C/7.1 degrees C), and 90 (15.2 degrees C/9.7 degrees C) minutes. However, ice lowered the IA temperature significantly more than the cryotherapy device (P < 0.001) and was more painful by VAS at 30 and 60 minutes (P < 0.01). Both methods produced large declines in skin and IA temperatures. However, ice was more effective yet resulted in higher pain scores. The authors hypothesize that IA temperatures below a threshold are associated with increased perceived pain.

Intermittent androgen suppression in the LuCaP 23.12 prostate cancer xenograft model.

PubMed

Buhler, K R; Santucci, R A; Royai, R A; Whitney, S C; Vessella, R L; Lange, P H; Ellis, W J

2000-04-01

Intermittent androgen suppression (IAS) has been proposed as a method of delaying the onset of androgen-independent growth in prostate cancer. While several pilot studies have demonstrated the feasibility of such a treatment, no study to date has defined the effect of IAS on survival. We developed an IAS protocol for mice bearing the LuCaP 23.12 human prostate cancer xenograft, with each cycle consisting of 1 week of androgen replacement with a testosterone pellet followed by 3 weeks of androgen withdrawal. Mice that responded to castration with a 40% or greater decrease in serum prostate-specific antigen (PSA) were randomized to treatment with either continuous androgen suppression (CAS) or IAS. Serum PSA, tumor volume, and overall survival were monitored. A total of 75 mice met the randomization criteria. There was no significant difference of survival between animals treated with CAS or IAS (185 vs. 239 days, P = 0.1835). Serum PSA showed evidence of cycling with hormonal manipulation. No cycling was noted in tumor volume. IAS is not associated with a decrease in survival compared to CAS, yet in patients may offer quality-of-life improvements. Further studies of IAS in the setting of Institutional Review Board (IRB) approved clinical trials should be encouraged. Prostate 43:63-70, 2000. Published 2000 Wiley-Liss, Inc.

Ginseng in Decreasing Cancer-Related Fatigue After Treatment in Cancer Survivors

ClinicalTrials.gov

2018-03-15

Cancer Survivor; Stage I Breast Cancer AJCC v7; Stage I Colon Cancer AJCC v6 and v7; Stage IA Breast Cancer AJCC v7; Stage IB Breast Cancer AJCC v7; Stage II Breast Cancer AJCC v6 and v7; Stage II Colon Cancer AJCC v7; Stage IIA Breast Cancer AJCC v6 and v7; Stage IIA Colon Cancer AJCC v7; Stage IIB Breast Cancer AJCC v6 and v7; Stage IIB Colon Cancer AJCC v7; Stage IIC Colon Cancer AJCC v7; Stage III Breast Cancer AJCC v7; Stage III Colon Cancer AJCC v7; Stage IIIA Breast Cancer AJCC v7; Stage IIIA Colon Cancer AJCC v7; Stage IIIB Breast Cancer AJCC v7; Stage IIIB Colon Cancer AJCC v7; Stage IIIC Breast Cancer AJCC v7; Stage IIIC Colon Cancer AJCC v7

Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients.

PubMed

Espitia, Olivier; Samson, Maxime; Le Gallou, Thomas; Connault, Jérôme; Landron, Cedric; Lavigne, Christian; Belizna, Cristina; Magnant, Julie; de Moreuil, Claire; Roblot, Pascal; Maillot, François; Diot, Elisabeth; Jégo, Patrick; Durant, Cécile; Masseau, A; Brisseau, Jean-Marie; Pottier, Pierre; Espitia-Thibault, Alexandra; Santos, Anabele Dos; Perrin, François; Artifoni, Mathieu; Néel, Antoine; Graveleau, Julie; Moreau, Philippe; Maisonneuve, Hervé; Fau, Georges; Serfaty, Jean-Michel; Hamidou, Mohamed; Agard, Christian

2016-06-01

The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis. Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening >2mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared. Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70 years, p=0.003) and comprised more past/current smokers (43 vs 15%, p=0.0007). Aortic aneurisms were more frequent (38% vs 20%, p=0.03), and aortic wall thickening was more pronounced in IA. During follow-up (median=34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p=0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p=0.02). Mean age, sex ratio, inflammatory parameters, and free of aortic aneurism survival were equivalent in patients with IA ≥ 60 years when compared to patients with GCA-related aortitis. IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients <60 years. Most patients with IA ≥ 60 years share many features with GCA-related aortitis. Copyright © 2016 Elsevier B.V. All rights reserved.

Reexamining the domain of hypochondriasis: comparing the Illness Attitudes Scale to other approaches.

PubMed

Fergus, Thomas A; Valentiner, David P

2009-08-01

The present study examined utility of the Illness Attitudes Scale (IAS; [Kellner, R. (1986). Somatization and hypochondriasis. New York: Praeger Publishers]) in a non-clinical college sample (N=235). Relationships among five recently identified IAS dimensions (fear of illness and pain, symptom effects, treatment experience, disease conviction, and health habits) and self-report measures of several anxiety-related constructs (health anxiety, body vigilance, intolerance of uncertainty, anxiety sensitivity, and non-specific anxiety symptoms) were examined. In addition, this study investigated the incremental validity of the IAS dimensions in predicting medical utilization. The fear of illness and pain dimension and the symptom effects dimension consistently shared stronger relations with the anxiety-related constructs compared to the other three IAS dimensions. The symptom effects dimension, the disease conviction dimension, and the health habits dimension showed incremental validity over the anxiety-related constructs in predicting medical utilization. Implications for the IAS and future conceptualizations of HC are discussed.

Results of Fertility-Sparing Surgery for Expansile and Infiltrative Mucinous Ovarian Cancers.

PubMed

Gouy, Sebastien; Saidani, Marine; Maulard, Amandine; Bach-Hamba, Slim; Bentivegna, Enrica; Leary, Alexandra; Pautier, Patricia; Devouassoux-Shisheboran, Mojgan; Genestie, Catherine; Morice, Philippe

2018-03-01

No series had been reported focusing on the results of fertility-sparing surgery in stage I mucinous ovarian cancers according to histotype (infiltrative vs. expansile). Investigating such outcomes was the aim of the present study. The present study was a retrospective analysis of patients treated conservatively with preservation of the uterus and contralateral ovary from 1976 to 2016. The pathology of the tumors was reviewed by two expert pathologists according to the 2014 World Health Organization (WHO) classification criteria. Oncologic and fertility results were analyzed. Twenty-one patients fulfilled the inclusion criteria, twelve with expansile and nine with infiltrative cancer. All patients had a unilateral tumor and underwent unilateral salpingo-oophorectomy in one-step ( n  = 6) or two-step ( n  = 15) surgeries. All but one had complete peritoneal staging surgery based on cytology, omentectomy, and random peritoneal biopsies. Ten had nodal staging surgery. The International Federation of Gynecology and Obstetrics stages were IA ( n  = 9), IC1 ( n  = 6), and IC2 ( n  = 6); the nuclear grades were grade 1 ( n  = 9), grade 2 ( n  = 5), and grade 3 ( n  = 1). Two patients recurred (one expansile and one infiltrative type) 19 and 160 months after surgery, respectively. One stage IA, nuclear grade 2 expansile tumor recurred on the spared ovary; the patient remains alive. The other stage IA infiltrative tumor recurred as peritoneal spread; the patient is alive with disease. Six patients became pregnant; four with expansile tumors and two with infiltrative tumors. The type of mucinous cancer has no impact on the oncologic outcome in this series of patients treated conservatively. Fertility-sparing surgery should be considered for early-stage infiltrative-type tumors. According to the most recently updated World Health Organization classification guidelines, mucinous cancers should be classified as either expansile or infiltrative. The infiltrative type has a poorer prognosis, but there are no data about the safety of fertility-sparing surgery (FSS) in this context. A collection of 21 cases reviewed by two expert pathologists this study is the first devoted to the conservative treatment of mucinous tumors according to both subtypes. The key result was that the type of mucinous cancer has no impact on the oncologic outcome; thus, FSS may be considered in both subtypes. © AlphaMed Press 2017.

Automated segmentation of the atrial region and fossa ovalis towards computer-aided planning of inter-atrial wall interventions.

PubMed

Morais, Pedro; Vilaça, João L; Queirós, Sandro; Marchi, Alberto; Bourier, Felix; Deisenhofer, Isabel; D'hooge, Jan; Tavares, João Manuel R S

2018-07-01

Image-fusion strategies have been applied to improve inter-atrial septal (IAS) wall minimally-invasive interventions. Hereto, several landmarks are initially identified on richly-detailed datasets throughout the planning stage and then combined with intra-operative images, enhancing the relevant structures and easing the procedure. Nevertheless, such planning is still performed manually, which is time-consuming and not necessarily reproducible, hampering its regular application. In this article, we present a novel automatic strategy to segment the atrial region (left/right atrium and aortic tract) and the fossa ovalis (FO). The method starts by initializing multiple 3D contours based on an atlas-based approach with global transforms only and refining them to the desired anatomy using a competitive segmentation strategy. The obtained contours are then applied to estimate the FO by evaluating both IAS wall thickness and the expected FO spatial location. The proposed method was evaluated in 41 computed tomography datasets, by comparing the atrial region segmentation and FO estimation results against manually delineated contours. The automatic segmentation method presented a performance similar to the state-of-the-art techniques and a high feasibility, failing only in the segmentation of one aortic tract and of one right atrium. The FO estimation method presented an acceptable result in all the patients with a performance comparable to the inter-observer variability. Moreover, it was faster and fully user-interaction free. Hence, the proposed method proved to be feasible to automatically segment the anatomical models for the planning of IAS wall interventions, making it exceptionally attractive for use in the clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

High prevalence of intracranial aneurysms in patients with aortic dissection or aneurysm: feasibility of extended aorta CT angiography with involvement of intracranial arteries.

PubMed

Lee, Dahye; Ahn, Sung Jun; Cho, Eun-Suk; Kim, Yong Bae; Song, Suk-Won; Jung, Woo Sang; Suh, Sang Hyun

2017-10-01

Previous studies have suggested a higher prevalence of intracranial aneurysms (IAs) in patients with aortic aneurysms (AAs). To carry out a preliminary study to evaluate the prevalence of IAs in these patients and the diagnostic feasibility of extended aorta CT angiography (CTA), including intracranial arteries as well as the aorta. We retrospectively reviewed all patients with a clinical diagnosis of AA or aortic dissection (AD) who had undergone aorta CTA as well as MR angiography, CTA, and/or DSA of the brain between 2009 and 2014. Since 2012, the extended aorta CTA protocol has been applied in these patients. Characteristics of IAs were classified with baseline clinical data. For quantitative and qualitative assessment by two independent raters, brain images obtained by extended aorta CTA and brain CTA were compared. The radiation dose of the two aorta protocols was compared. The prevalence of IA was 22.2% (35/158). All IAs were detected by extended aorta CTA, except one small aneurysm (<3 mm). The mean vascular attenuation value between brain images showed no difference (p=0.83), but the contrast-to-noise ratio was significantly lower in extended aorta CTA (p<0.001). In qualitative assessment, the interobserver agreement was substantial (k=0.79). For the radiation dose, the dose-length product of the extended aorta CTA increased with increment of the scan range (p=0.048). With a high prevalence of IAs in patients with ADs or AAs, extended aorta CTA could be used to evaluate aorta disease and IA in a single session. However, further prospective studies are needed to prove efficacy and safety of the extended aorta CTA protocol in patients with AAs or ADs. 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/.

[Clinical significance of detection of internal anal sphincter in children with functional constipation].

PubMed

Hou, Xiang-yu; Wang, Ling-yun; Wang, Wei-lin; Li, Yong; Bai, Yu-zuo

2011-10-01

To investigate the structural and functional changes of internal anal sphincter (IAS) in children with functional constipation (FC), and to evaluate the association between the thickness of IAS and the severity of clinical symptoms. A total of 35 children with FC(constipation group,17 with incontinence) between June 2008 and December 2008 at the Shengjing Hospital of China Medical University were evaluated using anal manometry and endosonography. These patients were compared to 23 hospitalized children who were excluded for digestive and endocrinal diseases(control group). A validated symptom score(SS) was used to assess the severity of symptoms. The sum of SS ranged between 0 and 65. Anorectal manometry showed reflex relaxation of IAS in response to distension of rectal balloon in all patients. Rectal perceptional threshold in FC group was significantly higher than that in the controls[(42.4 ± 19.5) ml vs.(29.1 ± 15.6) ml, P<0.05]. The lowest volume for inducing reflex relaxation of IAS was significantly higher than that in the controls [(55.6 ± 31.6) ml vs.(30.5 ±13.8) ml, P<0.05]. The thickening of IAS was noted in all the patients[(3.8 ± 1.7) mm vs.(2.5 ± 1.0) mm, P<0.05]. However, there was no significant difference between FC and control in median resting anal sphincter pressure[(170.8 ± 62.3) mm Hg vs. (161.3 ± 51.1) mm Hg, P>0.05]. The median symptom score was 9.3 ± 4.3 in the FC group. The thickness of IAS correlated significantly with total symptom severity score(r=0.407, P<0.05). There was no correlation between thickness of IAS and age, sex, or duration of disease(P>0.05). Structural and functional changes of internal anal sphincter exist in children with functional constipation. The thickness of internal anal sphincter correlates significantly with symptom severity.

The incidence of invasive aspergillosis among solid organ transplant recipients and implications for prophylaxis in lung transplants.

PubMed

Minari, A; Husni, R; Avery, R K; Longworth, D L; DeCamp, M; Bertin, M; Schilz, R; Smedira, N; Haug, M T; Mehta, A; Gordon, S M

2002-12-01

Invasive aspergillosis (IA) is associated with significant morbidity and mortality in solid organ transplant recipients but data on the incidence rates stratified by type of solid organ are limited. To describe the attack rates and incidence of IA in solid organ transplant recipients, and the impact of universal Aspergillus prophylaxis (aerosolized amphotericin B or oral itraconazole) in lung transplant recipients. The 2,046 patients who received solid organ transplants at the Cleveland Clinic Foundation from January 1990 through 1999 were studied. Cases were ascertained through computerized records of microbiology, cytology, and pathology reports. Definite IA was defined as a positive culture and pathology showing septate hyphae. Probable IA was clinical disease and either a positive culture or histopathology. Disseminated IA was defined as involvement of two or more noncontiguous anatomic sites. We identified 33 cases of IA (28% disseminated) in 2,046 patients (attack rate = 1.6%) for an incidence of 4.8 cases per 1,000 patient-years (33 cases/6,813 pt-years). Both the attack and the incidence rates were significantly higher for lung transplant recipients vs. other transplant recipients: lung 12.8% (24 cases/188 patients) or 40.5 cases/1,000-pt year vs. heart 0.4% (3/686) or 1.4 per 1,000-pt year vs. liver 0.7% (3/439) or 2.1 per 1,000-pt year vs. renal 0.4% (3/733) or 1.2 per 1,000-pt year (P < 0.01). The incidence of IA was highest during the first year after transplantation for all categories, but cases occurred after the first year of transplantation only in lung transplant recipients. The attack rate of IA in lung transplant recipients was significantly lower after institution of routine Aspergillus prophylaxis (4.9% vs. 18.2%, P < 0.05). The highest incidence and attack rate of invasive aspergillosis among solid organ transplant recipients occurs in lung transplant recipients and supports the routine use of Aspergillus prophylaxis for at least one year after transplantation in this group.

No. 360-Induced Abortion: Surgical Abortion and Second Trimester Medical Methods.

PubMed

Costescu, Dustin; Guilbert, Édith

2018-06-01

This guideline reviews evidence relating to the provision of surgical induced abortion (IA) and second trimester medical abortion, including pre- and post-procedural care. Gynaecologists, family physicians, nurses, midwives, residents, and other health care providers who currently or intend to provide and/or teach IAs. Women with an unintended or abnormal first or second trimester pregnancy. PubMed, Medline, and the Cochrane Database were searched using the key words: first-trimester surgical abortion, second-trimester surgical abortion, second-trimester medical abortion, dilation and evacuation, induction abortion, feticide, cervical preparation, cervical dilation, abortion complications. Results were restricted to English or French systematic reviews, randomized controlled trials, clinical trials, and observational studies published from 1979 to July 2017. National and international clinical practice guidelines were consulted for review. Grey literature was not searched. The quality of evidence in this document was rated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology framework. The summary of findings is available upon request. IA is safe and effective. The benefits of IA outweigh the potential harms or costs. No new direct harms or costs identified with these guidelines. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. All rights reserved.

Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial.

PubMed

Jäger, Susanne; Müller, Kai W; Ruckes, Christian; Wittig, Tobias; Batra, Anil; Musalek, Michael; Mann, Karl; Wölfling, Klaus; Beutel, Manfred E

2012-04-27

In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy. This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment. A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed. ClinicalTrials (NCT01434589).

Structure of the phosphotransferase domain of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia.

PubMed

Smith, Clyde A; Toth, Marta; Bhattacharya, Monolekha; Frase, Hilary; Vakulenko, Sergei B

2014-06-01

The bifunctional acetyltransferase(6')-Ie-phosphotransferase(2'')-Ia [AAC(6')-Ie-APH(2'')-Ia] is the most important aminoglycoside-resistance enzyme in Gram-positive bacteria, conferring resistance to almost all known aminoglycoside antibiotics in clinical use. Owing to its importance, this enzyme has been the focus of intensive research since its isolation in the mid-1980s but, despite much effort, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive. The structure of the Mg2GDP complex of the APH(2'')-Ia domain of the bifunctional enzyme has now been determined at 2.3 Å resolution. The structure of APH(2'')-Ia is reminiscent of the structures of other aminoglycoside phosphotransferases, having a two-domain architecture with the nucleotide-binding site located at the junction of the two domains. Unlike the previously characterized APH(2'')-IIa and APH(2'')-IVa enzymes, which are capable of utilizing both ATP and GTP as the phosphate donors, APH(2'')-Ia uses GTP exclusively in the phosphorylation of the aminoglycoside antibiotics, and in this regard closely resembles the GTP-dependent APH(2'')-IIIa enzyme. In APH(2'')-Ia this GTP selectivity is governed by the presence of a `gatekeeper' residue, Tyr100, the side chain of which projects into the active site and effectively blocks access to the adenine-binding template. Mutation of this tyrosine residue to a less bulky phenylalanine provides better access for ATP to the NTP-binding template and converts APH(2'')-Ia into a dual-specificity enzyme.

Identity Abuse as a Tactic of Violence in LGBTQ Communities: Initial Validation of the Identity Abuse Measure.

PubMed

Woulfe, Julie M; Goodman, Lisa A

2018-03-01

Intimate partner violence (IPV; i.e., physical, sexual, or psychological abuse by a current or former partner) remains a public health concern with devastating personal and societal costs. Lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals are also vulnerable to a dimension of IPV called identity abuse (IA); that is, abuse tactics that leverage systemic oppression to harm an individual. Yet, we know little about its relative prevalence in subgroups of the LGBTQ community. This study developed and evaluated a measure of IA, and explored its prevalence in a sample of 734 sexual minority adults. The sample included women (53.1%), men (27.4%), and transgender or gender nonconforming "TGNC" (19.3%) participants. The majority of participants identified as queer or pansexual (38.7%), then gay (23.6%), lesbian (22.8%), and bisexual (13.6%). Participants completed an online survey that included measures of IA and physical, sexual, and psychological abuse. The IA items formed a unidimensional factor structure with strong internal consistency and construct validity. Nearly one fifth of the sample (16.8%) experienced past year IA and 40.1% reported adult IA. Women experienced greater exposure to IA in adulthood than men, and TGNC participants reported higher rates of IA in adulthood and in the last year compared to their cisgender counterparts. The odds of queer or bisexual participants reporting IA in adulthood were almost three times higher than gay participants, and two times higher than lesbian participants. Findings have implications for advancing assessment of partner abuse in the LGBTQ community, LGBTQ-competent clinical care, and training of practitioners.

Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis.

PubMed

Zhai, Lin; Qiu, Lan-Yan; Zu, Yuan; Yan, Yan; Ren, Xiao-Zhuan; Zhao, Jun-Feng; Liu, Yu-Jiang; Liu, Ji-Bin; Qian, Lin-Xue

2015-04-21

To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P < 0.001). There were statistically significant negative correlations between FPP and Qp/Qa (r = -0.707, P < 0.001), and between FPP and Ip/Ia (r = -0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters.

Contrast-enhanced ultrasound for quantitative assessment of portal pressure in canine liver fibrosis

PubMed Central

Zhai, Lin; Qiu, Lan-Yan; Zu, Yuan; Yan, Yan; Ren, Xiao-Zhuan; Zhao, Jun-Feng; Liu, Yu-Jiang; Liu, Ji-Bin; Qian, Lin-Xue

2015-01-01

AIM: To explore the feasibility of non-invasive quantitative estimation of portal venous pressure by contrast-enhanced ultrasound (CEUS) in a canine model. METHODS: Liver fibrosis was established in adult canines (Beagles; n = 14) by subcutaneous injection of carbon tetrachloride (CCl4). CEUS parameters, including the area under the time-intensity curve and intensity at portal/arterial phases (Qp/Qa and Ip/Ia, respectively), were used to quantitatively assess the blood flow ratio of the portal vein/hepatic artery at multiple time points. The free portal venous pressures (FPP) were measured by a multi-channel baroreceptor using a percutaneous approach at baseline and 8, 16, and 24 wk after CCl4 injections in each canine. Liver biopsies were obtained at the end of 8, 16, and 24 wk from each animal, and the stage of the fibrosis was assessed according to the Metavir scoring system. A Pearson correlation test was performed to compare the FPP with Qp/Qa and Ip/Ia. RESULTS: Pathologic examination of 42 biopsies from the 14 canines at weeks 8, 16, and 24 revealed that liver fibrosis was induced by CCl4 and represented various stages of liver fibrosis, including F0 (n = 3), F1 (n = 12), F2 (n = 14), F3 (n = 11), and F4 (n = 2). There were significant differences in the measurements of Qp/Qa (19.85 ± 3.30 vs 10.43 ± 1.21, 9.63 ± 1.03, and 8.77 ± 0.96) and Ip/Ia (1.77 ± 0.37 vs 1.03 ± 0.12, 0.83 ± 0.10, and 0.69 ± 0.13) between control and canine fibrosis at 8, 16, and 24 wk, respectively (all P < 0.001). There were statistically significant negative correlations between FPP and Qp/Qa (r = -0.707, P < 0.001), and between FPP and Ip/Ia (r = -0.759, P < 0.001) in the canine fibrosis model. Prediction of elevated FPP based on Qp/Qa and Ip/Ia was highly sensitive, as assessed by the area under the receiver operating curve (0.866 and 0.895, respectively). CONCLUSION: CEUS is a potential method to accurately, but non-invasively, estimate portal venous pressure through measurement of Qp/Qa and Ip/Ia parameters. PMID:25914459

Role of phosphoinositide 3-kinase IA (PI3K-IA) activation in cardioprotection induced by ouabain preconditioning.

PubMed

Duan, Qiming; Madan, Namrata D; Wu, Jian; Kalisz, Jennifer; Doshi, Krunal Y; Haldar, Saptarsi M; Liu, Lijun; Pierre, Sandrine V

2015-03-01

Acute myocardial infarction, the clinical manifestation of ischemia-reperfusion (IR) injury, is a leading cause of death worldwide. Like ischemic preconditioning (IPC) induced by brief episodes of ischemia and reperfusion, ouabain preconditioning (OPC) mediated by Na/K-ATPase signaling protects the heart against IR injury. Class I PI3K activation is required for IPC, but its role in OPC has not been investigated. While PI3K-IB is critical to IPC, studies have suggested that ouabain signaling is PI3K-IA-specific. Hence, a pharmacological approach was used to test the hypothesis that OPC and IPC rely on distinct PI3K-I isoforms. In Langendorff-perfused mouse hearts, OPC was initiated by 4 min of ouabain 10 μM and IPC was triggered by 4 cycles of 5 min ischemia and reperfusion prior to 40 min of global ischemia and 30 min of reperfusion. Without affecting PI3K-IB, ouabain doubled PI3K-IA activity and Akt phosphorylation at Ser(473). IPC and OPC significantly preserved cardiac contractile function and tissue viability as evidenced by left ventricular developed pressure and end-diastolic pressure recovery, reduced lactate dehydrogenase release, and decreased infarct size. OPC protection was blunted by the PI3K-IA inhibitor PI-103, but not by the PI3K-IB inhibitor AS-604850. In contrast, IPC-mediated protection was not affected by PI-103 but was blocked by AS-604850, suggesting that PI3K-IA activation is required for OPC while PI3K-IB activation is needed for IPC. Mechanistically, PI3K-IA activity is required for ouabain-induced Akt activation but not PKCε translocation. However, in contrast to PKCε translocation which is critical to protection, Akt activity was not required for OPC. Further studies shall reveal the identity of the downstream targets of this new PI3K IA-dependent branch of OPC. These findings may be of clinical relevance in patients at risk for myocardial infarction with underlying diseases and/or medication that could differentially affect the integrity of cardiac PI3K-IA and IB pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural correlate of Internet use in patients undergoing psychological treatment for Internet addiction.

PubMed

Lai, Carlo; Altavilla, Daniela; Mazza, Marianna; Scappaticci, Silvia; Tambelli, Renata; Aceto, Paola; Luciani, Massimiliano; Corvino, Stefano; Martinelli, David; Alimonti, Flaminia; Tonioni, Federico

2017-06-01

The new version of Diagnostic and Statistical Manual of Mental Disorders (DSM-5th) proposed the Internet Gaming Disorder for the diagnosis of Internet addiction (IA) considering the neurobiological evidence of the craving. The aim was to test the neural correlate in response to the Internet cue in patients with IA. Sixteen males with IA diagnosis (clinical group) and 14 healthy male (control group) were recruited for an experimental visual task composed of Internet images and emotional images. During the visual presentation of Internet cue, electroencefalographic data were recorded using Net Station 4.5.1 with a 256-channels HydroCel Geodesic Sensor Net. Event-related potential (ERP) components and low-resolution electromagnetic tomography (sLoreta) were analysed. sLoreta analyses showed that patients from the clinical group presented a higher primary somatosensorial cortex and lower paralimbic, temporal and orbito-frontal activation in response to both Internet and emotional images compared to those of the control group. These results suggest that clinically recognized pathological use of Internet could be linked to dissociative symptoms.

Epidemiology of invasive aspergillosis and azole resistance in patients with acute leukaemia: the SEPIA Study.

PubMed

Koehler, Philipp; Hamprecht, Axel; Bader, Oliver; Bekeredjian-Ding, Isabelle; Buchheidt, Dieter; Doelken, Gottfried; Elias, Johannes; Haase, Gerhard; Hahn-Ast, Corinna; Karthaus, Meinolf; Kekulé, Alexander; Keller, Peter; Kiehl, Michael; Krause, Stefan W; Krämer, Carolin; Neumann, Silke; Rohde, Holger; La Rosée, Paul; Ruhnke, Markus; Schafhausen, Philippe; Schalk, Enrico; Schulz, Katrin; Schwartz, Stefan; Silling, Gerda; Staib, Peter; Ullmann, Andrew; Vergoulidou, Maria; Weber, Thomas; Cornely, Oliver A; Vehreschild, Maria J G T

2017-02-01

Invasive aspergillosis (IA) is a serious hazard to high-risk haematological patients. There are increasing reports of azole-resistant Aspergillus spp. This study assessed the epidemiology of IA and azole-resistant Aspergillus spp. in patients with acute leukaemia in Germany. A prospective multicentre cohort study was performed in German haematology/oncology centres. The incidence of probable and proven aspergillosis according to the revised EORTC/MSG criteria was assessed for all patients with acute leukaemia [acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL)]. Cases were documented into a web-based case report form, and centres provided data on standards regarding prophylactic and diagnostic measures. Clinical isolates were screened centrally for azole resistance and, if applicable, underlying resistance mechanisms were analysed. Between September 2011 and December 2013, 179 cases of IA [6 proven (3.4%) and 173 probable (96.6%)] were diagnosed in 3067 patients with acute leukaemia. The incidence of IA was 6.4% among 2440 AML patients and 3.8% among 627 ALL patients. Mortality at Day 84 was 33.8% (49/145) and attributable mortality was 26.9% (39/145). At Day 84, 53 patients (29.6%) showed a complete response, 25 (14.0%) a partial response and 17 (9.5%) a deterioration or failure. A total of 77 clinical Aspergillus fumigatus isolates were collected during the study period. Two episodes of azole-resistant IA (1.1%) were caused by a TR/L98H mutation in the cyp51A gene. With only two cases of IA due to azole-resistant A. fumigatus, a change of antifungal treatment practices in Germany does not appear warranted currently. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Immunoadsorption or plasma exchange in the treatment of autoimmune encephalitis: a pilot study.

PubMed

Heine, Josephine; Ly, Lam-Thanh; Lieker, Ina; Slowinski, Torsten; Finke, Carsten; Prüss, Harald; Harms, Lutz

2016-12-01

Therapeutic apheresis has emerged as a major treatment option for autoantibody-associated inflammatory diseases of the nervous system. This includes patients with autoimmune encephalitides caused by antibodies against neuronal proteins. Plasma exchange (PE) and immunoadsorption (IA) constitute two possibilities to eliminate pathogenic antibodies from patients' plasma, but their efficacy and safety has not been prospectively assessed in larger patient groups of autoimmune encephalitides. In a prospective observational case control study, we, therefore, investigated the disease courses and treatment effects of 21 patients with autoimmune encephalitis associated with NMDAR, LGI1, CASPR2, GAD, mGluR5 and Hu antibodies. Patients were randomly assigned to receive PE (n = 11) or IA (n = 10). Symptoms were evaluated using the modified Rankin Scale (mRS). Side effects or adverse events were recorded. Both interventions, IA (p = 0.014) and PE (p = 0.01), resulted in significant reduction of the median mRS. With IA, 60 % of the patients improved clinically by at least 1 mRS score, none worsened. PE led to a comparable symptom reduction in 67 % of the cases. During 83 PE sessions, three adverse events were documented, while no side effects occurred under IA. Symptom improvement was significantly associated with younger age (r = -0.58), but not with disease duration. Therapeutic apheresis was most effective for neuronal surface antigens (83.3 %), followed by intracellular-synaptic antigens (66.7 %). Both IA and PE resulted in moderate to marked clinical improvement, with a low rate of adverse events. Apheresis is well tolerated and effective also as first-line therapy in autoimmune encephalitis, particularly in patients with antibodies targeting neuronal surfaces.

Intermittent Auscultation in Labor: Could It Be Missing Many Pathological (Late) Fetal Heart Rate Decelerations? Analytical Review and Rationale for Improvement Supported by Clinical Cases

PubMed Central

Sholapurkar, Shashikant L.

2015-01-01

Intermittent auscultation (IA) of fetal heart rate (FHR) is recommended/preferred in low risk labors. Its usage even in developed countries is poised to increase because of perceived benefit of reduction in operative intervention and some disillusionment with the cardiotocography (CTG). Many national guidelines have stipulated regimes (frequency/timing) of IA based on level IV evidence. These tend to get faithfully and exactingly followed. It was observed that deliveries of many unexpectedly asphyxiated infants occurred despite rigorously performed and documented IA compliant with the guidelines. This triggered a reappraisal of the robustness of IA leading to this focused review supplemented by two anonymized cases. It concludes that the current methodology of IA may be flawed in that it poses a risk of missing many or most late (pathological) FHR decelerations, one of the foremost goals of IA. This is because many late decelerations reach their nadir before the end of the contraction. Thus the currently recommended auscultation of FHR for 60 seconds after the contraction by all national guidelines seemed to encompass their “recovery” phase and appeared to be misinterpreted as normal FHR or even as a reassuring accelerative pattern in the clinical practice. A recent recommendation of recording of the FHR as a single figure (rather than a range) does not remedy this anomaly and seems even less informative. It would be better to auscultate FHR before and after the contractions (or contraction to contraction) and take the FHR just before the contraction as the baseline FHR and interpret the FHR after contraction in the context of this baseline. This relatively simple improvement would detect most late FHR decelerations thus ameliorating the risk and significantly enhancing the patient safety. PMID:26566404

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption.

PubMed

Becker, Luis E; Siebert, Daniela; Süsal, Caner; Opelz, Gerhard; Leo, Albrecht; Waldherr, Rüdiger; Macher-Goeppinger, Stephan; Schemmer, Peter; Schaefer, Sebastian Markus; Klein, Katrin; Beimler, Jörg; Zeier, Martin; Schwenger, Vedat; Morath, Christian

2015-11-01

For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

Propionibacterium acnes populations involved in deep pathological samples and their dynamics along the cardiac surgical pathway.

PubMed

Romano-Bertrand, S; Beretta, M; Jean-Pierre, H; Frapier, J-M; Calvet, B; Parer, S; Jumas-Bilak, E

2015-02-01

Propionibacterium acnes belongs to the normal skin microbiota, but it is also responsible for acne vulgaris and causes serious infections such as endocarditis and surgical site infections (SSI). The P. acnes population is structured into phylogenetic groups, with phylotype I being associated with acne. Herein, we explore the link between phylotypes and clinical origins in a collection of P. acnes isolated from different body sites, involved in deep infections or healthcare-associated infections (HAI), with particular emphasis on strains from cardiac SSI. Cardiac SSI have been further studied in terms of P. acnes population dynamics during the care pathway. The recA and tly genes phylotypes were compared to hemolytic behavior, susceptibility to antimicrobial agents, and clinical origins. An original approach of recA polymerase chain reaction temporal temperature gel electrophoresis (PCR-TTGE) was developed and applied for the direct identification of P. acnes phylotypes in surgical samples, in order to assess their temporal dynamics during the surgical course. Our results underlined the preferential involvement of IA-2/IB and II phylogroups in HAI and SSI. Unlike IA and II, type IA-2/IB presented a gradual increase with the depth of sampling in the peroperative phase of cardiac surgery. Phylotypes IA and IA-2/IB were both predominant in scar tissues and on postoperative skin, suggesting a specific predisposition to recolonize skin. Particular association of the phylotype IA-2/IB with SSI and its propensity to colonize wounds in cardiac surgery was observed. We assumed that the follow-up of P. acnes phylotypes during pathological processes could give new clues for P. acnes pathogenicity.

Early invasive (FIGO stage IA) carcinoma of the cervix: a clinico-pathologic study of 476 cases.

PubMed

Elliott, P.; Coppleson, M.; Russell, P.; Liouros, P.; Carter, J.; MacLeod, C.; Jones, M.

2000-01-01

The clinical and histologic features of 476 tumors fitting the 1995 FIGO definition of stage IA cervical cancer, treated at a Sydney tertiary referral hospital between 1953 and 1992, are reviewed. Five-year follow-up was complete with a median of 10 years. The diagnosis was increasingly made by histologic examination of colposcopically directed cone biopsy. The majority (88%) of tumors were squamous. The proportion of both younger women (3 mm. Treatment was surgical in 99% and was increasingly more conservative as the study progressed with no apparent increase in treatment failure. From 1973 treatment by cone biopsy rose from 6.5 to 35%, by radical hysterectomy fell from 51 to 21% and by lymphadenectomy from 53 to 26%. Only one of 115 patients treated by cone biopsy died. Positive lymph nodes were detected in 1.7% of 180 patients undergoing lymphadenectomy. There were 16 recurrences (3.4%); six vaginal with no cancer deaths, nine pelvic and one distant, with nine deaths and three new cancers (two deaths). Univariate analysis suggests that older age, glandular tumors and those invading 3 mm were associated with more treatment failures and multivariate analysis showed that both conservative hysterectomy and the omission of lymphadenectomy are associated with higher recurrence rates with >3 mm invasion. The study failed to resolve the dilemma of predicting those tumors with a poor prognosis.

The feasibility of a group stress management Liver SMART intervention for patients with end-stage liver disease: A pilot study.

PubMed

Jutagir, Devika R; Saracino, Rebecca M; Cunningham, Amy; Foran-Tuller, Kelly A; Driscoll, Mary A; Sledge, William H; Emre, Sukru H; Fehon, Dwain C

2018-06-04

Structured, empirically supported psychological interventions are lacking for patients who require organ transplantation. This stage IA psychotherapy development project developed and tested the feasibility, acceptability, tolerability, and preliminary efficacy of an 8-week group cognitive behavioral stress management intervention adapted for patients with end-stage liver disease awaiting liver transplantation. Twenty-nine English-speaking United Network for Organ Sharing-registered patients with end-stage liver disease from a single transplantation center enrolled in 8-week, group cognitive-behavioral liver stress management and relaxation training intervention adapted for patients with end-stage liver disease. Patients completed pre- and postintervention surveys that included the Beck Depression Inventory II and the Beck Anxiety Inventory. Feasibility, acceptability, tolerability, and preliminary efficacy were assessed.ResultAttendance rate was 69.40%. The intervention was rated as "good" to "excellent" by 100% of participants who completed the postintervention survey in teaching them new skills to relax and to cope with stress, and by 94.12% of participants in helping them feel supported while waiting for a liver transplant. No adverse events were recorded over the course of treatment. Attrition was 13.79%. Anxious and depressive symptoms were not statistically different after the intervention.Significance of resultsThe liver stress management and relaxation training intervention is feasible, acceptable, and tolerable to end-stage liver disease patients within a transplant clinic setting. Anxious and depressive symptoms remained stable postintervention. Randomized controlled trials are needed to study the intervention's effectiveness in this population.

Are Internet use and video-game-playing addictive behaviors? Biological, clinical and public health implications for youths and adults.

PubMed

Yau, Yvonne H C; Crowley, Michael J; Mayes, Linda C; Potenza, Marc N

2012-09-01

Internet use and video-game playing are experiencing rapid growth among both youth and adult populations. Research suggests that a minority of users experience symptoms traditionally associated with substance-related addictions. Mental health professionals, policy makers and the general public continue to debate the issue of Internet addiction (IA) and problematic video-game playing (PVG). This review identifies existing studies into the clinical and biological characteristics of these disorders that may help guide decisions as to whether or not IA and PVG should be grouped together with substance use disorders (SUDs).

The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

PubMed

Lee, Young Mok; Pan, Chi-Jiunn; Koeberl, Dwight D; Mansfield, Brian C; Chou, Janice Y

2013-11-01

Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia. © 2013.

Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series.

PubMed

Kommoss, S; McConechy, M K; Kommoss, F; Leung, S; Bunz, A; Magrill, J; Britton, H; Kommoss, F; Grevenkamp, F; Karnezis, A; Yang, W; Lum, A; Krämer, B; Taran, F; Staebler, A; Lax, S; Brucker, S Y; Huntsman, D G; Gilks, C B; McAlpine, J N; Talhouk, A

2018-05-01

We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P = 0.001) and disease-specific (P = 0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

CB1 receptors in the formation of the different phases of memory-related processes in the inhibitory avoidance test in mice.

PubMed

Kruk-Slomka, Marta; Biala, Grażyna

2016-03-15

The endocannabinoid system, through the cannabinoid type 1 (CB1) and 2 (CB2) receptors modulates many physiological functions, including different aspects of memory-related processes. The aim of the present experiments was to explore the role of the endocannabinoid system, through CB1 receptors in the different stages of short-term (acquisition, retention and retrieval) and long-term (acquisition, consolidation and retrieval) memory-related responses, using the inhibitory avoidance (IA) test in mice. Our results revealed that an acute injection of oleamide (10 and 20mg/kg), a CB1 receptor agonist, impairs the short-term or/and long-term acquisition, retention/consolidation, retrieval memory and learning processes in the IA test in mice. In turn, in this test an acute injection of AM 251 (1 and 3mg/kg), a CB1 receptor antagonist, improves the short-term or/and long-term memory stages, described above. Moreover, this memory impairment induced by effective dose of oleamide (20mg/kg) is reversed by non-effective dose of AM 251 (0.25mg/kg) in the IA task, which proves the selectivity of oleamide to CB1 receptors and confirms that the CB1 receptor-related mechanism is one of the possible mechanisms, responsible for memory and learning responses. Obtained results provide clear evidence that the endocannabinoid system, through CB1 receptors, participates in the different stages of short- and long-term memory-related behavior. This knowledge may open in the future new possibilities for the development of CB-based therapies, especially for memory impairment human disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression

PubMed Central

Wechalekar, Mihir D.; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M.; Pitzalis, Costantino; Smith, Malcolm D.; Friedman, Joshua R.; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J.; Fearon, Ursula

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception. PMID:29489833

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

PubMed

Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Structure of the phosphotransferase domain of the bifunctional aminoglycoside-resistance enzyme AAC(6′)-Ie-APH(2′′)-Ia

PubMed Central

Smith, Clyde A.; Toth, Marta; Bhattacharya, Monolekha; Frase, Hilary; Vakulenko, Sergei B.

2014-01-01

The bifunctional acetyltransferase(6′)-Ie-phosphotransfer­ase(2′′)-Ia [AAC(6′)-Ie-APH(2′′)-Ia] is the most important aminoglycoside-resistance enzyme in Gram-positive bacteria, conferring resistance to almost all known aminoglycoside antibiotics in clinical use. Owing to its importance, this enzyme has been the focus of intensive research since its isolation in the mid-1980s but, despite much effort, structural details of AAC(6′)-Ie-APH(2′′)-Ia have remained elusive. The structure of the Mg2GDP complex of the APH(2′′)-Ia domain of the bifunctional enzyme has now been determined at 2.3 Å resolution. The structure of APH(2′′)-Ia is reminiscent of the structures of other aminoglycoside phosphotransferases, having a two-domain architecture with the nucleotide-binding site located at the junction of the two domains. Unlike the previously characterized APH(2′′)-IIa and APH(2′′)-IVa enzymes, which are capable of utilizing both ATP and GTP as the phosphate donors, APH(2′′)-Ia uses GTP exclusively in the phosphorylation of the aminoglycoside antibiotics, and in this regard closely resembles the GTP-dependent APH(2′′)-IIIa enzyme. In APH(2′′)-Ia this GTP selectivity is governed by the presence of a ‘gatekeeper’ residue, Tyr100, the side chain of which projects into the active site and effectively blocks access to the adenine-binding template. Mutation of this tyrosine residue to a less bulky phenylalanine provides better access for ATP to the NTP-binding template and converts APH(2′′)-Ia into a dual-specificity enzyme. PMID:24914967

Prevalence and predictors of intracranial aneurysms in patients with bicuspid aortic valve.

PubMed

Egbe, Alexander C; Padang, Ratnasari; Brown, Robert D; Khan, Arooj R; Luis, Sushil A; Huston, John; Akintoye, Emmanuel; Connolly, Heidi M

2017-10-01

To determine the prevalence and outcomes of intracranial aneurysm (IA) in patients with bicuspid aortic valve (BAV). Retrospective review of patients with BAV who underwent brain MR angiography at the Mayo Clinic from 1994 to 2013. There were 678 patients included in this study-mean age 57±13 years, men 480 (71%), mean follow-up 10±3 years (5913 patient-years). Coarctation of aorta (COA) was present in 154 (23%) patients.There were 59 IAs identified in 52 of 678 patients (7.7%). IA was present in 20/154 patients (12.9%) with COA and 32/524 patients (5.7%) without COA (p<0.001). For the patients without COA, female gender and right-left cusp fusion were risks factors for IA in women after adjustment for all potential variables (HR 1.76, CI 1.31 to 2.68, p=0.03). There was no significant trend in the risk for IA across age tertiles: age ≤40 years versus 41-60 years (HR 1.19, p=0.34), and age 41-60 years versus 61-80 years (HR 1.06, p=0.56).Among the 52 patients with IA, enlargement occurred in three patients (6%), rupture in two patients (4%) and four patients (8%) underwent coil embolisation. For the 626 patients without IA at baseline, no patient developed IA over 7±2 years of imaging follow-up. BAV is associated with a higher prevalence of IA compared to the general population, and this risk is higher in patients with COA, right-left cusp fusion and female gender. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Early results of immediate repair of obstetric third-degree tears: 65% are completely asymptomatic despite persistent sphincter defects in 61%.

PubMed

Hayes, J; Shatari, T; Toozs-Hobson, P; Busby, K; Pretlove, S; Radley, S; Keighley, M

2007-05-01

The outcome of immediate repair of obstetric third-degree tears is poorly documented. Immediate repair may give better functional results than delayed repair because scarring is reduced. This aim of this prospective study was to examine the early outcome of immediate repair of third-degree tears. A total of 121 women who had immediate repair of obstetric third-degree tears underwent interview, anal ultrasonography and anorectal physiology. At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%), had minor flatus incontinence or mild urgency causing no compromise to their quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair), eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a successful repair but a residual IAS defect), 43 (35%) had a residual defect in the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and EAS. Residual defects in either or both of the sphincters were associated with a significantly higher incidence of abnormal resting and squeeze anal pressures. Anal manometry had no correlation with symptoms. The highest proportion of severe incontinence was in those with an IAS defect alone (37%) and when there was a residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone had severe faecal incontinence. These results indicate a good outcome following immediate repair of third-degree obstetric tears and emphasize the role of the IAS in providing continence.

Preoperative Embolization to Improve the Surgical Management and Outcome of Juvenile Nasopharyngeal Angiofibroma (JNA) in a Single Center: 10-Year Experience.

PubMed

Lutz, J; Holtmannspötter, M; Flatz, W; Meier-Bender, A; Berghaus, A; Brückmann, H; Zengel, P

2016-12-01

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign neoplasm that occurs almost exclusively in the nasopharynx of adolescent male individuals. We performed a retrospective study to determine the efficacy and safety of preoperative embolization and the surgical outcome in patients with JNA in a single-center institution. Fifteen cases undergoing embolization and surgical treatment between April 2003 and February 2013 were evaluated retrospectively. The demographic data, clinical presentation, and treatment were reviewed including the kind of preoperative embolization and different surgical approaches performed. The parameters investigated were the amount of blood loss, the tumor stage, and the rates of recurrence. Subsequently, a comparison was made between patients who had undergone Onyx ® embolization versus those who had been embolized with the standard approach. In these 15 patients (mean age, 15 years), a total of 27 surgical procedures were performed. One patient was at stage Ia, two were at stage Ib, two were at stage IIa, six were at stage IIb, one was at stage IIc, and three were at stage IIIa based on the Radkowsky classification. All patients underwent preoperative embolization and subsequent surgery. The surgical approach and the embolization technique varied and evolved during time. The embolization procedure decreased the intraoperative blood loss to a minimum of 250 ml, and with the advent of intratumoral embolization, the rate of recurrence diminished. Preoperative Onyx ® embolization facilitates the shift in the treatment to endoscopic excision in selected patients, which reduces recurrence rates and overall morbidity.

Multinational evidence-based recommendations for pain management by pharmacotherapy in inflammatory arthritis: integrating systematic literature research and expert opinion of a broad panel of rheumatologists in the 3e Initiative

PubMed Central

Colebatch, Alexandra N.; Buchbinder, Rachelle; Edwards, Christopher J.; Adams, Karen; Englbrecht, Matthias; Hazlewood, Glen; Marks, Jonathan L.; Radner, Helga; Ramiro, Sofia; Richards, Bethan L.; Tarner, Ingo H.; Aletaha, Daniel; Bombardier, Claire; Landewé, Robert B.; Müller-Ladner, Ulf; Bijlsma, Johannes W. J.; Branco, Jaime C.; Bykerk, Vivian P.; da Rocha Castelar Pinheiro, Geraldo; Catrina, Anca I.; Hannonen, Pekka; Kiely, Patrick; Leeb, Burkhard; Lie, Elisabeth; Martinez-Osuna, Píndaro; Montecucco, Carlomaurizio; Østergaard, Mikkel; Westhovens, Rene; Zochling, Jane; van der Heijde, Désirée

2012-01-01

Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008–09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. Results. A total of 49 242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice. Conclusions. Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice. PMID:22447886

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis

PubMed Central

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Background and Objectives Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. Methods This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. Results There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. Conclusions This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. Clinical Trial Registration: ClinicalTrials.gov (NCT02343003). PMID:29095245

Management of cancer gallbladder found as a surprise on a resected gallbladder specimen.

PubMed

Misra, Mahesh Chandra; Guleria, Sandeep

2006-06-15

Carcinoma gallbladder is associated with an overall 5-year survival rate reported less than 5% due to late diagnosis. Advent of ultrasound scanning may help in detecting gallbladder polyps and an early gallbladder cancer. Excellent 5-year survival (up to 100%) has been reported for Stage Ia disease and the survival has significantly improved for Stage Ib, II, and III if appropriate re-operation is carried out soon after the incidental detection of gallbladder cancer. Laparoscopic cholecystectomy (LC) is contraindicated in the presence of gallbladder cancer. It is recommended to excise all laparoscopic port sites, at the time of re-operation. Re-operation for Stage II gallbladder cancer is associated with a 90-100% 3-year survival rate. Patients with Stage III and IV tumors also benefit from an extended cholecystectomy. Patients with bulky primary tumors without lymph node metastases (T4N0) seem to have a better prognosis than those with distant lymph node metastases, and should be treated aggressively. It is advantageous to perform the appropriate extent of surgery for gallbladder cancer at the initial operation. Heightened awareness of the presence of cancer and the knowledge of appropriate management are important. For patients whose cancer is an incidental finding on pathologic review, re-resection is indicated for all disease except Stage Ia. Radiotherapy and chemotherapy have not been found effective as an adjuvant or palliative therapy in gallbladder cancer. Copyright 2006 Wiley-Liss, Inc.

Prevention and diagnosis of invasive fungal disease in high-risk patients within an integrative care pathway.

PubMed

Barnes, Rosemary A; Stocking, Kate; Bowden, Sarah; Poynton, Matthew H; White, P Lewis

2013-09-01

The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

An extracellular factor regulating expression of the chromosomal aminoglycoside 2'-N-acetyltransferase of Providencia stuartii.

PubMed Central

Rather, P N; Parojcic, M M; Paradise, M R

1997-01-01

The chromosomal aac(2')-Ia gene in Providencia stuartii encodes a housekeeping 2'-N-acetyltransferase [AAC(2')-Ia] involved in the acetylation of peptidoglycan. In addition, the AAC(2')-Ia enzyme also acetylates and confers resistance to the clinically important aminoglycoside antibiotics gentamicin, tobramycin, and netilmicin. Expression of the aac(2')-Ia gene was found to be strongly influenced by cell density, with a sharp decrease in aac(2')-Ia mRNA accumulation as cells approached stationary phase. This decrease was mediated by the accumulation of an extracellular factor, designated AR (for acetyltransferase repressing)-factor. AR-factor was produced in both minimal and rich media and acted in a manner that was strongly dose dependent. The activity of AR-factor was also pH dependent, with optimal activity at pH 8.0 and above. Biochemical characterization of conditioned media from P. stuartii has shown that AR-factor is between 500 and 1,000 Da in molecular size and is heat stable. In addition, AR-factor was inactivated by a variety of proteases, suggesting that it may be a small peptide. PMID:9257754

Intraarticular triamcinolone hexacetonide injection in children with chronic arthritis: a survey of clinical practice.

PubMed

Yang, M H; Lee, W I; Chen, L C; Lin, S J; Huang, J L

1999-01-01

To assess the efficacy of the intraarticular steroid(IAS) injection in the management of arthritis and the possible related complications in children with chronic arthritis. We evaluated 11 children of chronic arthritis (4 girls and 7 boys), age of onset ranged from 2-13.6 years, who had persistent arthritis treated with IAS from November 1994 to June 1997. The results of injections showed that the beneficial effect was noted within one day to 2 weeks without significant adverse reactions, remission exceeding 6 months was seen in 10 of 11 patients (in 14 of 18 joints). According to subgroups of chronic arthritis, the remission rate of IAS injection in children with pauciarticular arthritis reached 100%. A significant fall in C-reactive protein (CRP) between pre- and post-IAS injection (p = 0.03), but there were no differences in hemoglobin (Hb), white blood cells (WBCs), thrombocytes (Plts), erythrocyte sedimentation rate (ESR) and osteocalcin level. No injection-related complications were found. In conclusion, the IAS injection was an effective and safe treatment in children with chronic arthritis with no obvious complications especially in pauciarticular arthritis.

Investigating the influence of haemodynamic stimuli on intracranial aneurysm inception.

PubMed

Chen, Haoyu; Selimovic, Alisa; Thompson, Harry; Chiarini, Alessandro; Penrose, Justin; Ventikos, Yiannis; Watton, Paul N

2013-07-01

We propose a novel method to reconstruct the hypothetical geometry of the healthy vasculature prior to intracranial aneurysm (IA) formation: a Frenet frame is calculated along the skeletonization of the arterial geometry; upstream and downstream boundaries of the aneurysmal segment are expressed in terms of the local Frenet frame basis vectors; the hypothetical healthy geometry is then reconstructed by propagating a closed curve along the skeleton using the local Frenet frames so that the upstream boundary is smoothly morphed into the downstream boundary. This methodology takes into account the tortuosity of the arterial vasculature and requires minimal user subjectivity. The method is applied to 22 clinical cases depicting IAs. Computational fluid dynamic simulations of the vasculature without IA are performed and the haemodynamic stimuli in the location of IA formation are examined. We observe that locally elevated wall shear stress (WSS) and gradient oscillatory number (GON) are highly correlated (20/22 for WSS and 19/22 for GON) with regions susceptible to sidewall IA formation whilst haemodynamic indices associated with the oscillation of the WSS vectors have much lower correlations.

Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young

PubMed Central

Lamb, Molly M.; Frederiksen, Brittni; Seifert, Jennifer A.; Kroehl, Miranda; Rewers, Marian; Norris, Jill M.

2015-01-01

Aims/hypothesis Dietary sugar intake may increase insulin production, stress the beta cells and increase the risk for islet autoimmunity (IA) and subsequent type 1 diabetes. Methods Since 1993, the Diabetes Autoimmunity Study in the Young (DAISY) has followed children at increased genetic risk for type 1 diabetes for the development of IA (autoantibodies to insulin, GAD or protein tyrosine phosphatase-like protein [IA2] twice or more in succession) and progression to type 1 diabetes. Information on intake of fructose, sucrose, total sugars, sugar-sweetened beverages, beverages with non-nutritive sweetener and juice was collected prospectively throughout childhood via food frequency questionnaires (FFQs). We examined diet records for 1,893 children (mean age at last follow-up 10.2 years); 142 developed IA and 42 progressed to type 1 diabetes. HLA genotype was dichotomised as high risk (HLA-DR3/4,DQB1*0302) or not. All Cox regression models were adjusted for total energy, FFQ type, type 1 diabetes family history, HLA genotype and ethnicity. Results In children with IA, progression to type 1 diabetes was significantly associated with intake of total sugars (HR 1.75, 95% CI 1.07–2.85). Progression to type 1 diabetes was also associated with increased intake of sugar-sweetened beverages in those with the high-risk HLA genotype (HR 1.84, 95% CI 1.25–2.71), but not in children without it (interaction p value = 0.02). No sugar variables were associated with IA risk. Conclusions/interpretation Sugar intake may exacerbate the later stage of type 1 diabetes development; sugar-sweetened beverages may be especially detrimental to children with the highest genetic risk of developing type 1 diabetes. PMID:26048237

Effects of a manualized short-term treatment of internet and computer game addiction (STICA): study protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background In the last few years, excessive internet use and computer gaming have increased dramatically. Salience, mood modification, tolerance, withdrawal symptoms, conflict, and relapse have been defined as diagnostic criteria for internet addiction (IA) and computer addiction (CA) in the scientific community. Despite a growing number of individuals seeking help, there are no specific treatments of established efficacy. Methods/design This clinical trial aims to determine the effect of the disorder-specific manualized short-term treatment of IA/CA (STICA). The cognitive behavioural treatment combines individual and group interventions with a total duration of 4 months. Patients will be randomly assigned to STICA treatment or to a wait list control group. Reliable and valid measures of IA/CA and co-morbid mental symptoms (for example social anxiety, depression) will be assessed prior to the beginning, in the middle, at the end, and 6 months after completion of treatment. Discussion A treatment of IA/CA will establish efficacy and is desperately needed. As this is the first trial to determine efficacy of a disorder specific treatment, a wait list control group will be implemented. Pros and cons of the design were discussed. Trial Registration ClinicalTrials (NCT01434589) PMID:22540330

Aspergillus fumigatus-Related Species in Clinical Practice

PubMed Central

Lamoth, Frédéric

2016-01-01

Aspergillus fumigatus is the main etiologic agent of invasive aspergillosis (IA). Other Aspergillus species belonging to the section Fumigati (A. fumigatus complex) may occasionally be the cause of IA. These strains are often misidentified, as they cannot be distinguished from A. fumigatus by conventional morphological analysis and sequencing methods. This lack of recognition may have important consequences as these A. fumigatus-related species often display some level of intrinsic resistance to azoles and other antifungal drugs. A. lentulus, A. udagawae, A. viridinutans, and A. thermomutatus (Neosartorya pseudofischeri) have been associated with refractory cases of IA. Microbiologists should be able to suspect the presence of these cryptic species behind a putative A. fumigatus isolate on the basis of some simple characteristics, such as defect in sporulation and/or unusual antifungal susceptibility profile. However, definitive species identification requires specific sequencing analyses of the beta-tubulin or calmodulin genes, which are not available in most laboratories. Multiplex PCR assays or matrix-assisted laser desorption ionization – time-of-flight mass spectrometry (MALDI-TOF MS) gave promising results for rapid and accurate distinction between A. fumigatus and other Aspergillus spp. of the section Fumigati in clinical practice. Improved diagnostic procedures and antifungal susceptibility testing may be helpful for the early detection and management of these particular IA cases. PMID:27242710

Aspergillus fumigatus-Related Species in Clinical Practice.

PubMed

Lamoth, Frédéric

2016-01-01

Aspergillus fumigatus is the main etiologic agent of invasive aspergillosis (IA). Other Aspergillus species belonging to the section Fumigati (A. fumigatus complex) may occasionally be the cause of IA. These strains are often misidentified, as they cannot be distinguished from A. fumigatus by conventional morphological analysis and sequencing methods. This lack of recognition may have important consequences as these A. fumigatus-related species often display some level of intrinsic resistance to azoles and other antifungal drugs. A. lentulus, A. udagawae, A. viridinutans, and A. thermomutatus (Neosartorya pseudofischeri) have been associated with refractory cases of IA. Microbiologists should be able to suspect the presence of these cryptic species behind a putative A. fumigatus isolate on the basis of some simple characteristics, such as defect in sporulation and/or unusual antifungal susceptibility profile. However, definitive species identification requires specific sequencing analyses of the beta-tubulin or calmodulin genes, which are not available in most laboratories. Multiplex PCR assays or matrix-assisted laser desorption ionization - time-of-flight mass spectrometry (MALDI-TOF MS) gave promising results for rapid and accurate distinction between A. fumigatus and other Aspergillus spp. of the section Fumigati in clinical practice. Improved diagnostic procedures and antifungal susceptibility testing may be helpful for the early detection and management of these particular IA cases.

Treatment Trends for Stage I Testicular Seminoma in an Equal-Access Medical System.

PubMed

Wingate, Jonathan T; Etzioni, Ruth; Macdonald, Dusten M; Brand, Timothy C

2016-10-01

The practice patterns for adjuvant therapies for stage I seminoma are rapidly evolving, and surveillance is currently preferred. How these recommendations have affected contemporary practice in an equal-access US population is unknown. A total of 436 men diagnosed with clinical stage IA-IB seminoma from 2001 to 2011 were identified in the Automated Central Tumor Registry (ACTUR). The ACTUR is the cancer registry system for the Department of Defense. Logistic regression models analyzed the association between patient characteristics and adjuvant therapy. Overall and recurrence-free survival were determined from Kaplan-Meier analysis. The use of adjuvant radiotherapy in this population decreased significantly from 2001 to 2011. In 2001, 83.9% of patients received radiotherapy compared with only 24.0% in 2011. During that period, a concomitant increase occurred in the use of chemotherapy from 0% to 38.0%. A later year of diagnosis was significantly associated with a greater rate of receiving chemotherapy relative to radiotherapy (P < .001 for 2006-2011 vs. 2001-2005; relative rate ratio, 19.3; 95% confidence interval [CI], 8.04-46.13). A later year of diagnosis was not significantly associated with the receipt of surveillance (P = .412 for 2006-2011 vs. 2001-2005; odds ratio, 0.83; 95% CI, 0.54-1.29). Black race or age was not significantly associated with adjuvant therapy. With a median follow-up period of 4.7 years, the 5-year overall and recurrence-free survival rates were 98.0% and 77.0%, respectively. The use of adjuvant radiotherapy has been replaced by chemotherapy for clinical stage I testicular seminoma in an equal-access system. The lack of an increase in active surveillance in our cohort might represent overtreatment of the population. Published by Elsevier Inc.

Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity.

PubMed

Romano, K D; Pugh, K J; Trifiletti, D M; Libby, B; Showalter, T N

In 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. From 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA-IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. Median followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. This comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Biomarker validation for intraductal papillary mucinous neoplasms of the pancreas | Division of Cancer Prevention

Cancer.gov

A critical component to successful cancer screening is the identification of a lesion for which intervention will result in prolonged survival or cure.The five-year survival of patients with resected stage IA pancreas cancer (the earliest identifiable lesion and |

Pilot scale experiment with MBR operated in intermittent aeration condition: analysis of biological performance.

PubMed

Capodici, M; Di Bella, G; Di Trapani, D; Torregrossa, M

2015-02-01

The effect of intermittent aeration (IA) on a MBR system was investigated. The study was aimed at analyzing different working conditions and the influence of different IA cycles on the biological performance of the MBR pilot plant, in terms of organic carbon and ammonium removal as well as extracellular polymeric substances (EPSs) production. The membrane modules were placed in a separate compartment, continuously aerated. This configuration allowed to disconnect from the filtration stage the biological phenomena occurring into the IA bioreactor. The observed results highlighted good efficiencies, in terms of organic carbon and ammonium removal. It was noticed a significant soluble microbial products (SMPs) release, likely related to the higher metabolic stress that anoxic conditions exerted on the biomass. However, the proposed configuration, with the membranes in a separate compartment, allowed to reduce the EPSs in the membrane tank even during the non-aerated phase, thus lowering fouling development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Iliac artery stenting in patients with poor distal runoff: Influence of concomitant infrainguinal arterial reconstruction.

PubMed

Timaran, Carlos H; Ohki, Takao; Gargiulo, Nicholas J; Veith, Frank J; Stevens, Scott L; Freeman, Michael B; Goldman, Mitchell H

2003-09-01

Inadequate infrainguinal runoff is considered an important risk factor for iliac stent failure. However, the influence of concomitant infrainguinal arterial reconstruction (CIAR) on iliac stent patency is unknown. This study evaluated the influence of CIAR on outcome of iliac angioplasty and stenting (IAS) in patients with poor distal runoff. Over 5 years (1996 to 2001), 68 IAS procedures (78 stents) were performed in 62 patients with poor distal runoff (angiographic runoff score >or=5). The SVS/AAVS reporting standards were followed to define outcome variables and risk factors. Data were analyzed with both univariate analysis (Kaplan-Meier method [K-M]) and regression analysis (Cox proportional hazards model). Indications for iliac artery stenting were disabling claudication (59%) and limb salvage (41%). Of the 68 procedures, IAS with CIAR was performed in 31 patients (46%), and IAS alone was performed in 37 patients (54%). Patients undergoing IAS with CIAR were older (P =.03) and had more extensive and multifocal iliac artery occlusive disease, with more TASC (TransAtlantic Inter-Society Consensus) type C lesions (P =.03), compared with patients undergoing IAS alone. No other significant differences in risk factors were noted. Runoff scores between patients undergoing IAS with CIAR and those undergoing IAS alone were not significantly different (median runoff scores, 6 [range, 5-8] and 7 [range, 5-9], respectively; P =.77). Primary stent patency rate at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, for patients undergoing IAS with CIAR, and was 76%, 66%, and 55%, respectively, for patients undergoing IAS. Univariate analysis revealed that primary stent patency rate was not significantly different between the 2 groups (K-M, log-rank test, P =.81). Primary graft patency rate for CIAR was 81%, 52%, and 46% at 1, 3, and 5 years, respectively. Performing CIAR did not affect primary iliac stent patency (relative risk, 1.1; 95% confidence interval, 0.49-2.47; P =.81). Overall, there was a trend toward improved limb salvage in patients undergoing IAS with CIAR, compared with those undergoing IAS alone (K-M, log rank test, P =.07). In patients undergoing IAS with poor distal runoff, CIAR does not improve iliac artery stent patency. Infrainguinal bypass procedures should therefore be reserved for patients who do not demonstrate clinical improvement and possibly for those with limb-threatening ischemia.

Management of complicated diverticulitis of the colon.

PubMed

Tochigi, Toru; Kosugi, Chihiro; Shuto, Kiyohiko; Mori, Mikito; Hirano, Atsushi; Koda, Keiji

2018-01-01

Diverticular disease of the colon occurs quite frequently in developed countries, and its prevalence has recently increased in Japan. The appearance of diverticulosis increases with age, although mostly remaining asymptomatic. Approximately 20% of cases require treatment. As the Western lifestyle and number of elderly people increase, the need for medical treatment also increases. Computed tomography (CT) is the gold standard for diagnosing diverticulitis. Complicated diverticulitis is classified by the size and range of abscess formation and the severity of the peritonitis. Each case should be classified based on clinical and computed tomography (CT) findings and then treated appropriately. Most patients with uncomplicated diverticulitis (stages 0-Ia) can be treated conservatively. Diverticulitis with a localized abscess (stages Ib-II) is generally resolved with conservative treatment. If the abscess is larger or conservative treatment fails, however, percutaneous drainage or surgery should be considered. Operative treatment is considered standard therapy for severe diverticulitis with perforation and generalized peritonitis (stages III-IV). Colonic diverticulitis treated conservatively frequently recurs. Elective surgery after recovery should be considered carefully and decisions made on a case-by-case basis. Because cases of colonic diverticulitis will undoubtedly increase in Japan, it is likely that we will be confronted with increasing numbers of treatment decisions. We therefore need to have a systematic strategy for treating the various stages of colonic diverticulitis appropriately. We herein review the management of complicated diverticulitis.

Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT(2″)-Ia.

PubMed

Cox, Georgina; Stogios, Peter J; Savchenko, Alexei; Wright, Gerard D

2015-01-06

The aminoglycosides are highly effective broad-spectrum antimicrobial agents. However, their efficacy is diminished due to enzyme-mediated covalent modification, which reduces affinity of the drug for the target ribosome. One of the most prevalent aminoglycoside resistance enzymes in Gram-negative pathogens is the adenylyltransferase ANT(2″)-Ia, which confers resistance to gentamicin, tobramycin, and kanamycin. Despite the importance of this enzyme in drug resistance, its structure and molecular mechanism have been elusive. This study describes the structural and mechanistic basis for adenylylation of aminoglycosides by the ANT(2″)-Ia enzyme. ANT(2″)-Ia confers resistance by magnesium-dependent transfer of a nucleoside monophosphate (AMP) to the 2″-hydroxyl of aminoglycoside substrates containing a 2-deoxystreptamine core. The catalyzed reaction follows a direct AMP transfer mechanism from ATP to the substrate antibiotic. Central to catalysis is the coordination of two Mg(2+) ions, positioning of the modifiable substrate ring, and the presence of a catalytic base (Asp86). Comparative structural analysis revealed that ANT(2″)-Ia has a two-domain structure with an N-terminal active-site architecture that is conserved among other antibiotic nucleotidyltransferases, including Lnu(A), LinB, ANT(4')-Ia, ANT(4″)-Ib, and ANT(6)-Ia. There is also similarity between the nucleotidyltransferase fold of ANT(2″)-Ia and DNA polymerase β. This similarity is consistent with evolution from a common ancestor, with the nucleotidyltransferase fold having adapted for activity against chemically distinct molecules. IMPORTANCE  : To successfully manage the threat associated with multidrug-resistant infectious diseases, innovative therapeutic strategies need to be developed. One such approach involves the enhancement or potentiation of existing antibiotics against resistant strains of bacteria. The reduction in clinical usefulness of the aminoglycosides is a particular problem among Gram-negative human pathogens, since there are very few therapeutic options for infections caused by these organisms. In order to successfully circumvent or inhibit the activity of aminoglycoside-modifying enzymes, and to thus rejuvenate the activity of the aminoglycoside antibiotics against Gram-negative pathogens, structural and mechanistic information is crucial. This study reveals the structure of a clinically prevalent aminoglycoside resistance enzyme [ANT(2″)-Ia] and depicts the molecular basis underlying modification of antibiotic substrates. Combined, these findings provide the groundwork for the development of broad-spectrum inhibitors against antibiotic nucleotidyltransferases. Copyright © 2015 Cox et al.

Structural and Molecular Basis for Resistance to Aminoglycoside Antibiotics by the Adenylyltransferase ANT(2″)-Ia

PubMed Central

Cox, Georgina; Stogios, Peter J.; Savchenko, Alexei

2015-01-01

ABSTRACT   The aminoglycosides are highly effective broad-spectrum antimicrobial agents. However, their efficacy is diminished due to enzyme-mediated covalent modification, which reduces affinity of the drug for the target ribosome. One of the most prevalent aminoglycoside resistance enzymes in Gram-negative pathogens is the adenylyltransferase ANT(2″)-Ia, which confers resistance to gentamicin, tobramycin, and kanamycin. Despite the importance of this enzyme in drug resistance, its structure and molecular mechanism have been elusive. This study describes the structural and mechanistic basis for adenylylation of aminoglycosides by the ANT(2″)-Ia enzyme. ANT(2″)-Ia confers resistance by magnesium-dependent transfer of a nucleoside monophosphate (AMP) to the 2″-hydroxyl of aminoglycoside substrates containing a 2-deoxystreptamine core. The catalyzed reaction follows a direct AMP transfer mechanism from ATP to the substrate antibiotic. Central to catalysis is the coordination of two Mg2+ ions, positioning of the modifiable substrate ring, and the presence of a catalytic base (Asp86). Comparative structural analysis revealed that ANT(2″)-Ia has a two-domain structure with an N-terminal active-site architecture that is conserved among other antibiotic nucleotidyltransferases, including Lnu(A), LinB, ANT(4′)-Ia, ANT(4″)-Ib, and ANT(6)-Ia. There is also similarity between the nucleotidyltransferase fold of ANT(2″)-Ia and DNA polymerase β. This similarity is consistent with evolution from a common ancestor, with the nucleotidyltransferase fold having adapted for activity against chemically distinct molecules. Importance   To successfully manage the threat associated with multidrug-resistant infectious diseases, innovative therapeutic strategies need to be developed. One such approach involves the enhancement or potentiation of existing antibiotics against resistant strains of bacteria. The reduction in clinical usefulness of the aminoglycosides is a particular problem among Gram-negative human pathogens, since there are very few therapeutic options for infections caused by these organisms. In order to successfully circumvent or inhibit the activity of aminoglycoside-modifying enzymes, and to thus rejuvenate the activity of the aminoglycoside antibiotics against Gram-negative pathogens, structural and mechanistic information is crucial. This study reveals the structure of a clinically prevalent aminoglycoside resistance enzyme [ANT(2″)-Ia] and depicts the molecular basis underlying modification of antibiotic substrates. Combined, these findings provide the groundwork for the development of broad-spectrum inhibitors against antibiotic nucleotidyltransferases. PMID:25564464

Are Internet use and video-game-playing addictive behaviors? Biological, clinical and public health implications for youths and adults

PubMed Central

Yau, Yvonne H. C.; Crowley, Michael J.; Mayes, Linda C.; Potenza, Marc N.

2013-01-01

Internet use and video-game playing are experiencing rapid growth among both youth and adult populations. Research suggests that a minority of users experience symptoms traditionally associated with substance-related addictions. Mental health professionals, policy makers and the general public continue to debate the issue of Internet addiction (IA) and problematic video-game playing (PVG). This review identifies existing studies into the clinical and biological characteristics of these disorders that may help guide decisions as to whether or not IA and PVG should be grouped together with substance use disorders (SUDs). PMID:24288435

Pathogenesis, Newly Recognized Etiologies, and Management of Idiopathic Anaphylaxis

PubMed Central

Kuhlen, James L.; Virkud, Yamini V.

2018-01-01

Idiopathic anaphylaxis (IA) is a life-threatening allergic disease and the most common diagnosis given to patients following an anaphylactic event. The inability of the healthcare provider and the patient to identify the trigger for anaphylaxis makes standard allergen avoidance measures ineffectual. IA is diagnosed after other causes of anaphylaxis have been excluded. Mast cell activation syndromes (MCAS), mastocytosis, IgE to galactose-alpha-1,3-galactose (α-gal), and certain medications have recently been recognized as causes of anaphylaxis that were previously labeled idiopathic. This review will describe the epidemiology and proposed theories of pathogenesis for IA, its diagnostic approach, its clinical management, and examine newly recognized disorders that were previously labeled as idiopathic anaphylaxis. PMID:25725228

Report on the ENIAC (Electronic Numerical Integrator and Computer)

DTIC Science & Technology

1946-06-01

3401070 •ra l!Oeelall Ia ~· C....te .. t ’ hla •ltsar ~nan •-•~an, four nl.,• uaoatat•d ’Clt’l ••ell dlllt, ’l’llet Ia, t<M>r nlaJtl npn .. ..,l...the· chronological order shDwn on PX-CJ.-306. • When the cyelinp, unit ring rcach~s stuge 11, · gate B27 opens t.e pass an on beat pulse, This...C(X;) ’ Stage clcv6n of’ the ring opens g~te B27 . This gate passes a pulsD f which sets the tlip-tlop E27. Thll negative output or the tUp-tlop

[Actual review of diagnostics and endovascular therapy of intracranial arterial stenoses].

PubMed

Gizewski, E R; Weber, R; Forsting, M

2011-02-01

Approximately 6 - 50% of all ischemic strokes are caused by intracranial arterial stenosis (IAS). Despite medical prevention, patients with symptomatic IAS have a high annual risk for recurrent ischemic stroke of about 12%, and up to 19% in the case of high-grade IAS (≥ 70%). Digital subtraction angiography remains the gold standard for the diagnosis and grading of IAS. However, noninvasive imaging techniques including CT angiography, MR angiography, or transcranial Doppler and duplex ultrasound examinations are used in the clinical routine to provide additional information about the brain structure and hemodynamic. However, for technical reasons, the grading of stenoses is sometimes difficult and inaccurate. To date, aspirin is recommended as the treatment of choice in the prevention of recurrent ischemic stroke in patients with IAS. IAS patients who suffer a recurrent ischemic stroke or transient ischemic attack while taking aspirin can be treated with endovascular stenting or angioplasty in specialized centers. The periprocedural complication rate of these endovascular techniques is about 2 - 7% at experienced neuro-interventional centers. The rate of re-stenosis is reported between 10 and 40% depending on patient age and stenosis location. Further randomized studies comparing medical secondary prevention and endovascular therapy are currently being performed. With regard to the improvement of endovascular methods and lower complication rates, the indication for endovascular therapy in IAS could be broadened especially for stenosis in the posterior circulation. © Georg Thieme Verlag KG Stuttgart · New York.

2009 Pandemic H1N1 Influenza Virus Causes Disease and Upregulation of Genes Related to Inflammatory and Immune Responses, Cell Death, and Lipid Metabolism in Pigs▿

PubMed Central

Ma, Wenjun; Belisle, Sarah E.; Mosier, Derek; Li, Xi; Stigger-Rosser, Evelyn; Liu, Qinfang; Qiao, Chuanling; Elder, Jake; Webby, Richard; Katze, Michael G.; Richt, Juergen A.

2011-01-01

There exists limited information about whether adaptation is needed for cross-species transmission of the 2009 pandemic H1N1 influenza virus (pH1N1). Here, we compare the pathogenesis of two pH1N1 viruses, one derived from a human patient (A/CA/04/09 [CA09]) and the other from swine (A/swine/Alberta/25/2009 [Alb09]), with that of the 1918-like classical swine influenza virus (A/swine/Iowa/1930 [IA30]) in the pig model. Both pH1N1 isolates induced clinical symptoms such as coughing, sneezing, decreased activity, fever, and labored breathing in challenged pigs, but IA30 virus did not cause any clinical symptoms except fever. Although both the pH1N1 viruses and the IA30 virus caused lung lesions, the pH1N1 viruses were shed from the nasal cavities of challenged pigs whereas the IA30 virus was not. Global gene expression analysis indicated that transcriptional responses of the viruses were distinct. pH1N1-infected pigs had an upregulation of genes related to inflammatory and immune responses at day 3 postinfection that was not seen in the IA30 infection, and expression levels of genes related to cell death and lipid metabolism at day 5 postinfection were markedly different from those of IA30 infection. These results indicate that both pH1N1 isolates are more virulent due in part to differences in the host transcriptional response during acute infection. Our study also indicates that pH1N1 does not need prior adaptation to infect pigs, has a high potential to be maintained in naïve swine populations, and might reassort with currently circulating swine influenza viruses. PMID:21900171

[Analysis of the therapeutic efficacy and prognosis for acute myeloid leukemia M2a patients treated by IA and DA regimens].

PubMed

Wang, Fan; Yuan, Hai-Long; Duan, Xian-Lin; Wang, Lei; Cao, Hai-Zhou; Xu, Jian-Li; Qu, Jian-Hua

2014-08-01

This study was purposed to compare the therapeutic efficacy and prognosis of acute myeloid leukemia M2a (AML-M2a) patients treated by idarubicin (IDA) combined with cytarabine (Ara-C) (IA) and daunorubicin (DNR) combined cytarabine (Ara-C) (DA) regimens. The clinical data of 65 patients with AML-M2a in our hospital were collected from May 2009 to May 2013 and analyzed. The results indicated the complete remission in IA group was slightly higher than that in DA group, there was no statistically significant difference(P > 0.05); leukocyte minimum value in IA group [(0.58 ± 0.40)×10(9)/L] was obviously lower than that in DA group [(0.99 ± 0.67)×10(9)/L] (P < 0.05); neutrophil minimum value in IA group [(0.19 ± 0.09)×10(9)/L] was significantly lower than that in DA group [(0.21 ± 0.16)×10(9)/L] (P < 0.05); the neutropenia duration in IA group (12.59 ± 5.31)d was much longer than that in DA group (9.17 ± 7.04)d (P < 0.05). The median survival time of patients in IA group was 36.67 months, which was obviously longer than that of patients in DA group (21.45 months) (P < 0.05). The lactate dehydrogenase (LDH) value and chemotherapy regimens were the independently risk factor affecting the prognosis of AML-M2a patients. It is concluded that as compared with DA regimen, the IA regimen can prolong the median survival time and has better long-term therapeutic efficacy, thus it can be used as the first chemotherapy regimen for treatment of AML-M2a.

Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME.

PubMed

Scheibenbogen, Carmen; Loebel, Madlen; Freitag, Helma; Krueger, Anne; Bauer, Sandra; Antelmann, Michaela; Doehner, Wolfram; Scherbakov, Nadja; Heidecke, Harald; Reinke, Petra; Volk, Hans-Dieter; Grabowski, Patricia

2018-01-01

Infection-triggered disease onset, chronic immune activation and autonomic dysregulation in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) point to an autoimmune disease directed against neurotransmitter receptors. We had observed elevated autoantibodies against ß2 adrenergic receptors, and muscarinic 3 and 4 acetylcholine receptors in a subset of patients. Immunoadsorption (IA) was shown to be effective in removing autoantibodies and improve outcome in various autoimmune diseases. 10 patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with IA with an IgG-binding column for 5 days. We assessed severity of symptoms as outcome parameter by disease specific scores. Antibodies were determined by ELISA and B cell phenotype by flow cytometry. IgG levels dropped to median 0.73 g/l (normal 7-16 g/l) after the 4th cycle of IA, while IgA and IgM levels remained unchanged. Similarly, elevated ß2 IgG antibodies rapidly decreased during IA in 9 of 10 patients. Also 6 months later ß2 autoantibodies were significantly lower compared to pretreatment. Frequency of memory B cells significantly decreased and frequency of plasma cells increased after the 4th IA cycle. A rapid improvement of symptoms was reported by 7 patients during the IA. 3 of these patients had long lasting moderate to marked improvement for 6-12+ months, 2 patients had short improvement only and 2 patients improved for several months following initial worsening. IA can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development. Data from our pilot trial warrants further studies in CFS/ME.

[The use of galactomannan detection in diagnosing invasive aspergillosis in hemato-oncological patients].

PubMed

Rácil, Z; Kocmanová, I; Wagnerová, B; Winterová, J; Lengerová, M; Moulis, M; Mayer, J

2008-01-01

PREMISES AND OBJECTIVES: Timely diagnosis is of critical importance for the prognosis of invasive aspergilosis (IA) patients. Over recent years, IA detection of galactomannan using the ELISA method has assumed growing importance. The objective of the study was to analyse the usability of the method in current clinical practice of a hemato-oncological ward. From May 2003 to October 2006, blood samples were taken from patients at IA risk to detect galactomannan (GM) in serum using the ELISA method. The patients who underwent the tests were classified by the probability of IA presence on the basis of the results of conventional diagnostic methods and section findings. A total of 11,360 serum samples from 911 adult patients were tested for GM presence. IA (probable/proven) was diagnosed in 42 (4.6%) of them. The rates of sensitivity, specificity, positive and negative predictive value of galactomannan detection for IA diagnosis in our ward were, respectively, 95.2%, 90.0%, 31.5% and 99.7%. The principal causes of the limited positive predictive value of the test were the high percentage of false-positive test results (mainly caused by concomitant administration of some penicillin antibiotics or Plasma-Lyte infusion solution), as well as the fact that a large percentage of patients we examined fell within the group of patients with hematological malignity with a very low prevalence of IA. GM detection in serum is associated with high sensitivity and excellent negative predictive value in IA diagnosis in hemato-oncological patients. Knowledge and elimination of possible causes of false-positive results as well as focusing the screening on patients at greatest risk of infection are necessary for an even better exploitation of the test.

Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitis.

PubMed

Zhao, Zhen-Hua; Hu, Liang-Hao; Ren, Hong-Bo; Zhao, An-Jing; Qian, Yang-Yang; Sun, Xiao-Tian; Su, Song; Zhu, Shu-Guang; Yu, Jin; Zou, Wen-Bin; Guo, Xiao-Rong; Wang, Lei; Li, Zhao-Shen; Liao, Zhuan

2017-09-01

Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort. In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the χ 2 test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis. In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P < .01). According to the M-ANNHEIM classification, the PEP incidences of CP at stages 0, I, II, III, and IV were 4.4%, 5.1%, 3.8%, 2.0%, and 2.0%, respectively. CP patients at stage Ia had the highest PEP incidence (8.0%) among all CP patients, significantly higher than that at stages Ib + Ic (3.9%) and II (3.8%). Female gender, history of acute pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor. Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression. (Clinical trial registration number: NCT02781987.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Prevention of atrial fibrillation by inter-atrial septum pacing guided by electrophysiological testing, in patients with delayed interatrial conduction.

PubMed

Manolis, A G; Katsivas, A G; Vassilopoulos, C; Koutsogeorgis, D; Louvros, N E

2002-04-01

Interatrial septum (IAS) pacing seems efficient in synchronizing atrial depolarization in patients (pts) with delayed inter-atrial conduction, but its clinical role in preventing atrial tachyarrhythmias is still debated. This study was conducted in order to evaluate the clinical efficacy of IAS pacing guided by pace mapping of the IAS, as an alternative treatment modality in pts with drug refractory paroxysmal atrial fibrillation (PAF). We evaluated 29 pts (13 male, 16 female, 60 +/- 11 years), with drug refractory PAF, normal sinus node function and prolonged inter-atrial conduction time (P wave 142 +/- 10 ms). Multipolar catheters were inserted and the electrograms from the high right atrium (HRA) and proximal, middle and distal coronary sinus (CS) were recorded. The IAS was paced from multiple sites. The site of IAS where the timing between HRA and distal CS was <20 ms was considered the most suitable for synchronizing the atria. This site was found to be superior to the CS os. near the fossa ovalis in all pts. An active fixation atrial lead was positioned at this site and a standard lead was placed in the right ventricle. During IAS pacing, the P wave duration decreased significantly to 107 +/- 15 ms (P<0.001). At implant, the atrial sensing was 2.3 +/- 0.7 mV, the atrial pacing threshold was 0.95 +/- 0.15 V (0.5 ms) and the impedance was 760 +/- 80 Ohm. We evaluated the pts during four periods of 3 months duration each. The first period (control) was before pacemaker implantation, while the pts were under antiarrhythmic treatment. During the subsequent two periods, we evaluated the clinical efficacy of IAS pacing to prevent PAF recurrences, in AAT (75 bpm) and AAIR (75-140 bpm) mode, with random selection of the order and after discontinuation of antiarrhythmic treatment. During the fourth period, the same AAIR mode was assessed, but antiarrhythmic drugs were also administered. We compared the arrhythmia free interval among the four periods. The proportion of atrial paced beats in AAIR pacing mode plus antiarrhythmics was significantly higher compared with the drug-free period in AAIR mode (57 +/- 9% and 49 +/- 9% respectively, P=0017) and with AAT pacing mode (44 +/- 10%,(, P<0.001). In AAT mode, the arrhythmia free interval was 24.2 +/- 5.1 days, while it was 26.2 +/- 5.7 days in AAIR mode. These intervals did not differ significantly from the pre-implantation period (24.1 +/- 6.3 days). The arrhythmia free interval in AAIR pacing in combination with antiarrhythmic drug therapy was 38.7 +/- 8.1 days and this was significantly longer than the previous periods (P<0.05). Atrial septal pacing in combination with antiarrhythmic drug therapy reduced the incidence of PAF in pts with prolonged inter-atrial conduction times. Pace mapping of the IAS is an attractive technique to assess the shortest atrial activation time between HRA and distal CS. Whether placement of the atrial lead based on the shortest HRA--distal CS time is the best place in the IAS to prevent PAF still remains to be proven.

Single Degenerate Models for Type Ia Supernovae: Progenitor's Evolution and Nucleosynthesis Yields

NASA Astrophysics Data System (ADS)

Nomoto, Ken'ichi; Leung, Shing-Chi

2018-06-01

We review how the single degenerate models for Type Ia supernovae (SNe Ia) works. In the binary star system of a white dwarf (WD) and its non-degenerate companion star, the WD accretes either hydrogen-rich matter or helium and undergoes hydrogen and helium shell-burning. We summarize how the stability and non-linear behavior of such shell-burning depend on the accretion rate and the WD mass and how the WD blows strong wind. We identify the following evolutionary routes for the accreting WD to trigger a thermonuclear explosion. Typically, the accretion rate is quite high in the early stage and gradually decreases as a result of mass transfer. With decreasing rate, the WD evolves as follows: (1) At a rapid accretion phase, the WD increase its mass by stable H burning and blows a strong wind to keep its moderate radius. The wind is strong enough to strip a part of the companion star's envelope to control the accretion rate and forms circumstellar matter (CSM). If the WD explodes within CSM, it is observed as an "SN Ia-CSM". (X-rays emitted by the WD are absorbed by CSM.) (2) If the WD continues to accrete at a lower rate, the wind stops and an SN Ia is triggered under steady-stable H shell-burning, which is observed as a super-soft X-ray source: "SN Ia-SSXS". (3) If the accretion continues at a still lower rate, H shell-burning becomes unstable and many flashes recur. The WD undergoes recurrent nova (RN) whose mass ejection is smaller than the accreted matter. Then the WD evolves to an "SN Ia-RN". (4) If the companion is a He star (or a He WD), the accretion of He can trigger He and C double detonations at the sub-Chandrasekhar mass or the WD grows to the Chandrasekhar mass while producing a He-wind: "SN Ia-He CSM". (5) If the accreting WD rotates quite rapidly, the WD mass can exceed the Chandrasekhar mass of the spherical WD, which delays the trigger of an SN Ia. After angular momentum is lost from the WD, the (super-Chandra) WD contracts to become a delayed SN Ia. The companion star has become a He WD and CSM has disappeared: "SN Ia-He WD". We update nucleosynthesis yields of the carbon deflagration model W7, delayed detonation model WDD2, and the sub-Chandrasekhar mass model to provide some constraints on the yields (such as Mn) from the comparison with the observations. We note the important metallicity effects on 58Ni and 55Mn.

Induced abortion - impact on a subsequent pregnancy in first-time mothers: a registry-based study.

PubMed

Holmlund, Susanna; Kauko, Tommi; Matomäki, Jaakko; Tuominen, Miia; Mäkinen, Juha; Rautava, Päivi

2016-10-24

To date, several studies concerning the effects of induced abortion (IA) on women's later psychosocial well-being and future delivery complications have been published. However, the lack of reports on woman's physical well-being during their first full-term pregnancy occurring after IA is what inspired the current study. Here, we evaluate the physical well-being and use of maternity services of first-time mothers with a history of IA. Finnish National Birth Registry data from 2008 to 2010 were linked with the Induced Abortion Registry data from 1983 to 2007. After excluding first-time mothers with a history of miscarriage, ectopic pregnancy or delivery, 57,406 mothers were eligible for the study, with 5,167 (9.0 %) having experienced prior IA. Data from the pregnancy follow-up visits were evaluated and compared between IA mothers and primiparous mothers. Women with IA had higher rates of smoking after the first trimester and were more likely to be overweight (body mass index >25 kg/m 2 ) than the control group mothers. A higher use of maternity health clinic (MHC) services, thrombosis prophylaxis and participation in a second trimester ultrasound and amniotic fluid sample testing were evident in IA mothers, whereas the likelihood of assisted fertilisation procedure(s) was elevated in the control group. A shorter interpregnancy interval (IPI) seemed to contribute to a late first MHC visit and first trimester serum screening test participation, a higher incidence of placenta samples and an increased presence of preeclampsia and maternal care for poor foetal growth. IA is associated with being overweight before the subsequent pregnancy and with smoking after the first trimester. More frequent pregnancy follow-up visits in the IA group may be due to greater participation in the placenta sample testing and use of thrombosis prophylaxis. No association between IA and preeclampsia, hypertension, gestational diabetes or preterm premature rupture of membranes was evident in the pregnancy parameters. According to our findings, experiencing IA decreased the need for fertilisation procedures before the next pregnancy when compared to primiparous mothers. Among the IA mothers, the short IPI seemed to contribute to the higher risk for preeclampsia and maternal care for poor foetal growth. However, more research is needed around the IPI before establishing its effect on later pregnancy.

Coexistence of obstructive sleep apnea worsens the overall outcome of intracranial aneurysm: a pioneer study.

PubMed

Bir, Shyamal C; Nanda, Anil; Cuellar, Hugo; Sun, Hai; Guthikonda, Bharat; Liendo, Cesar; Minagar, Alireza; Chernyshev, Oleg Y

2018-03-01

OBJECTIVE Obstructive sleep apnea (OSA) is associated with the progression of abdominal and thoracic aortic aneurysms. However, the role of OSA in the overall outcome of intracranial aneurysms (IAs) has not yet been established. Authors of this report investigated the role of OSA in the overall outcome of IAs. METHODS Radiological and clinical data on patients (from 2010 through 2015) with confirmed IA were retrospectively reviewed. Significant differences between the OSA and non-OSA groups were determined using a chi-square test. Logistic regression analysis was performed to identify the predictors of an unfavorable IA outcome. RESULTS Among the 283 patients with confirmed IAs, 45 patients (16%) were positively screened for OSA, a proportion that was significantly higher than the prevalence of OSA in nonaneurysmal neurosurgical patients (4%, p = 0.008). The percentage of patients with hypertension (p = 0.018), a body mass index ≥ 30 kg/m 2 (p < 0.0001), hyperlipidemia (p = 0.034), diabetes mellitus (p = 0.005), chronic heart disease (CHD; p = 0.024), or prior stroke (p = 0.03) was significantly higher in the OSA group than in the non-OSA group. Similarly, the percentage of wide-necked aneurysms (p = 0.00001) and patients with a poor Hunt and Hess Grade IV-V (p = 0.01) was significantly higher in the OSA group than in the non-OSA group. In addition, the percentage of ruptured aneurysms (p = 0.03) and vasospasms (p = 0.03) was significantly higher in the OSA group. The percentage of patients with poor modified Rankin Scale (mRS) scores (3-6) was significantly higher in the OSA group (p = 0.03). A separate cohort of patients with ruptured IAs showed similar results. In both univariate (p = 0.01) and multivariate (p = 0.04) regression analyses, OSA was identified as an individual predictor of an unfavorable outcome. In addition, hypertension and prior stroke were revealed as predictors of a poor IA outcome. CONCLUSIONS Complications of IA such as rupture and vasospasm are often the consequence of uncontrolled OSA. Overall outcome (mRS) of IAs is also affected by the co-occurrence of OSA. Therefore, the coexistence of OSA with IA affects the outcome of IAs. Obstructive sleep apnea is a risk factor for a poor outcome in IA patients.

Concurrent chemoradiotherapy with S-1 in patients with stage III-IV oral squamous cell carcinoma: A retrospective analysis of nodal classification based on the neck node level.

PubMed

Murakami, Ryuji; Semba, Akiko; Kawahara, Kenta; Matsuyama, Keiya; Hiraki, Akimitsu; Nagata, Masashi; Toya, Ryo; Yamashita, Yasuyuki; Oya, Natsuo; Nakayama, Hideki

2017-07-01

The aim of the present study was to retrospectively evaluate the treatment outcomes of concurrent chemoradiotherapy (CCRT) with S-1, an oral fluoropyrimidine anticancer agent, for advanced oral squamous cell carcinoma (SCC). The study population consisted of 47 patients with clinical stage III or IV oral SCC, who underwent CCRT with S-1. Pretreatment variables, including patient age, clinical stage, T classification, midline involvement of the primary tumor and nodal status, were analyzed as predictors of survival. In addition to the N classification (node-positive, multiple and contralateral), the prognostic impact of the level of nodal involvement was assessed. Nodal involvement was mainly observed at levels Ib and II; involvement at levels Ia and III-V was considered to be anterior and inferior extension, respectively, and was recorded as extensive nodal involvement (ENI). The 3-year overall survival (OS) and progression-free survival (PFS) rates were 37 and 27%, respectively. A finding of ENI was a significant factor for OS [hazard ratio (HR)=2.16; 95% confidence interval (CI): 1.03-4.55; P=0.038] and PFS (HR=2.65; 95% CI: 1.32-5.33; P=0.005); the 3-year OS and PFS rates in patients with vs. those without ENI were 23 vs. 50% and 9 vs. 43%, respectively. The other variables were not significant. Therefore, CCRT with S-1 may be an alternative treatment for advanced oral SCC; favorable outcomes are expected in patients without ENI.

Current State Of Proton And Carbon-Ion Radiotherapy At The Hyogo Ion Beam Medical Center (HIBMC)

NASA Astrophysics Data System (ADS)

Murakami, Masao; Demizu, Yusuke; Niwa, Yasue; Fujii, Osamu; Terashima, Kazuki; Mima, Masayuki; Miyawaki, Daisuke; Sasaki, Ryohei; Hishikawa, Yoshio; Abe, Mitsuyuki

2011-06-01

HIBMC is the world's first facility to be able to use both proton (PRT) and carbon-ion radiotherapy (CiRT). The medically dedicated synchrotron can accelerate protons up to 230 MeV and carbon ions up to 320 MeV. From April 2001 to March 2010, the facility treated 3275 patients, with 2487 patients treated using PRT and 788 using CiRT. Particle radiotherapy was delivered to patients suffering from malignant tumors originating in the head and neck (502 patients), lungs (330), liver (539), prostate (1283), and the bone & soft tissue (130). The clinical results are as follows: (1) H & N tumors: The 2-year overall survival (OS) rates of patients with olfactory neuroblastoma, mucoepidermoid cancer, adenoid cystic cancer, adenocarcinoma, squamous cell carcinoma, and malignant melanoma was 100%, 86%, 78%, 78%, 66%, and 62%, respectively. (2) Lung cancer: For all 80 patients, the 3-year OS rate was 75% (Stage IA: 74%; Stage IB: 76%) and local control (LC) rate was 82% (IA: 87%; IB: 77%). Grade 3 pulmonary toxicity was observed in only 1 patient. These results are comparable to those obtained by surgery, and indicate proton therapy and carbon-ion therapy are safe and effective for stage I lung cancer. (3) Liver cancer: The 5-year LC rate for 429 tumor patient was 90%, and the 5-year OS rate for 364 patients was 38%. These results seem equivalent to those obtained by surgery or radio-frequency ablation. (4) Prostate cancer: In 290 patients treated by proton radiotherapy, five patients died from other disease in the median follow-up period of 62 months. Biochemical disease-free survival and OS rate at 5 years was 88.2% and 96.5%, respectively. Our proton radiotherapy showed excellent OS and biochemical disease-free survival rates with minimum late morbidities. PRT VS CiRT: From our retrospective analysis, it seems that there is no significant difference in the LC and OS rate in H&N, lung and liver cancer between PRT and CiRT.

Current State Of Proton And Carbon-Ion Radiotherapy At The Hyogo Ion Beam Medical Center (HIBMC)

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

Murakami, Masao; Hishikawa, Yoshio; Demizu, Yusuke

2011-06-01

HIBMC is the world's first facility to be able to use both proton (PRT) and carbon-ion radiotherapy (CiRT). The medically dedicated synchrotron can accelerate protons up to 230 MeV and carbon ions up to 320 MeV. From April 2001 to March 2010, the facility treated 3275 patients, with 2487 patients treated using PRT and 788 using CiRT. Particle radiotherapy was delivered to patients suffering from malignant tumors originating in the head and neck (502 patients), lungs (330), liver (539), prostate (1283), and the bone and soft tissue (130). The clinical results are as follows: (1) H and N tumors: Themore » 2-year overall survival (OS) rates of patients with olfactory neuroblastoma, mucoepidermoid cancer, adenoid cystic cancer, adenocarcinoma, squamous cell carcinoma, and malignant melanoma was 100%, 86%, 78%, 78%, 66%, and 62%, respectively. (2) Lung cancer: For all 80 patients, the 3-year OS rate was 75%(Stage IA: 74%; Stage IB: 76%) and local control (LC) rate was 82%(IA: 87%; IB: 77%). Grade 3 pulmonary toxicity was observed in only 1 patient. These results are comparable to those obtained by surgery, and indicate proton therapy and carbon-ion therapy are safe and effective for stage I lung cancer. (3) Liver cancer: The 5-year LC rate for 429 tumor patient was 90%, and the 5-year OS rate for 364 patients was 38%. These results seem equivalent to those obtained by surgery or radio-frequency ablation. (4) Prostate cancer: In 290 patients treated by proton radiotherapy, five patients died from other disease in the median follow-up period of 62 months. Biochemical disease-free survival and OS rate at 5 years was 88.2% and 96.5%, respectively. Our proton radiotherapy showed excellent OS and biochemical disease-free survival rates with minimum late morbidities. PRT VS CiRT: From our retrospective analysis, it seems that there is no significant difference in the LC and OS rate in H and N, lung and liver cancer between PRT and CiRT.« less

Islet cell autoantibodies in African patients with Type 1 and Type 2 diabetes in Dar es Salaam Tanzania: a cross sectional study

PubMed Central

Lutale, JJK; Thordarson, H; Holm, PI; Eide, GE; Vetvik, K

2007-01-01

Background The aim of the present study was to assess the occurrence of glutamic acid decarboxylase autoantibodies (GADA) and insulinoma antigen 2 autoantibodies (IA2A) among patients of African origin in Dar es Salaam, Tanzania and to compare the occurrence of autoimmune mediated Type 1 diabetes with findings previously reported from the same place and from other African diabetic populations. Methods Two hundred and forty five patients from the diabetic clinic at Muhimbili Hospital were recruited for a cross sectional study. Patients were clinically classified into groups with Type 1 (T1D) and Type 2 diabetes (T2D); there were 94 patients with T1D and 151 with T2D. Autoantibodies for GAD and IA2 were measured with an assay based on radioligand binding. Fasting and random blood glucose, HbA1c, and C-peptide levels were also determined. Results Of the patients with T1D, 28 (29.8%) were GADA positive and 20 (21.3%) were IA2A positive. The overall occurrence of any autoantibody was 42.6%. The GAD and IA2 autoantibodies were detected more frequently among patients with T1D than among patients with T2D (P < 0.001). A higher autoantibody prevalence was observed with combined GADA and IA2A measurements compared to individual autoantibody measurements; 40 (42.6%) patients with T1D versus 11 (7.3%) with T2D had at least one positive autoantibody titer. There was no correlation between duration of disease and detection of autoantibodies in patients with T1D. There was a strong association with family history of diabetes among the autoantibody positive versus autoantibody negative patients with T1D (p < 0.01). Conclusion The prevalence of GAD and IA2 autoantibodies among African patients with T1D in Dar es Salaam was the same as that reported previously for South Africa and Ethiopia. It was much higher than the prevalence of islet cell autoantibodies (ICA) reported from the same clinic about 15 years ago. For unknown reasons the prevalence of pancreatic related autoantibodies in this African population is lower than the prevalence found among Caucasian populations. PMID:17963519

Estimation of the Mean Axon Diameter and Intra-axonal Space Volume Fraction of the Human Corpus Callosum: Diffusion q-space Imaging with Low q-values.

PubMed

Suzuki, Yuriko; Hori, Masaaki; Kamiya, Kouhei; Fukunaga, Issei; Aoki, Shigeki; VAN Cauteren, Marc

2016-01-01

Q-space imaging (QSI) is a diffusion-weighted imaging (DWI) technique that enables investigation of tissue microstructure. However, for sufficient displacement resolution to measure the microstructure, QSI requires high q-values that are usually difficult to achieve with a clinical scanner. The recently introduced "low q-value method" fits the echo attenuation to only low q-values to extract the root mean square displacement. We investigated the clinical feasibility of the low q-value method for estimating the microstructure of the human corpus callosum using a 3.0-tesla clinical scanner within a clinically feasible scan time. We performed a simulation to explore the acceptable range of maximum q-values for the low q-value method. We simulated echo attenuations caused by restricted diffusion in the intra-axonal space (IAS) and hindered diffusion in the extra-axonal space (EAS) assuming 100,000 cylinders with various diameters, and we estimated mean axon diameter, IAS volume fraction, and EAS diffusivity by fitting echo attenuations with different maximum q-values. Furthermore, we scanned the corpus callosum of 7 healthy volunteers and estimated the mean axon diameter and IAS volume fraction. Good agreement between estimated and defined values in the simulation study with maximum q-values of 700 and 800 cm(-1) suggested that the maximum q-value used in the in vivo experiment, 737 cm(-1), was reasonable. In the in vivo experiment, the mean axon diameter was larger in the body of the corpus callosum and smaller in the genu and splenium, and this anterior-to-posterior trend is consistent with previously reported histology, although our mean axon diameter seems larger in size. On the other hand, we found an opposite anterior-to-posterior trend, with high IAS volume fraction in the genu and splenium and a lower fraction in the body, which is similar to the fiber density reported in the histology study. The low q-value method may provide insights into tissue microstructure using a 3T clinical scanner within clinically feasible scan time.

A Mathematical Model of Intermittent Androgen Suppression for Prostate Cancer

NASA Astrophysics Data System (ADS)

Ideta, Aiko Miyamura; Tanaka, Gouhei; Takeuchi, Takumi; Aihara, Kazuyuki

2008-12-01

For several decades, androgen suppression has been the principal modality for treatment of advanced prostate cancer. Although the androgen deprivation is initially effective, most patients experience a relapse within several years due to the proliferation of so-called androgen-independent tumor cells. Bruchovsky et al. suggested in animal models that intermittent androgen suppression (IAS) can prolong the time to relapse when compared with continuous androgen suppression (CAS). Therefore, IAS has been expected to enhance clinical efficacy in conjunction with reduction in adverse effects and improvement in quality of life of patients during off-treatment periods. This paper presents a mathematical model that describes the growth of a prostate tumor under IAS therapy based on monitoring of the serum prostate-specific antigen (PSA). By treating the cancer tumor as a mixed assembly of androgen-dependent and androgen-independent cells, we investigate the difference between CAS and IAS with respect to factors affecting an androgen-independent relapse. Numerical and bifurcation analyses show how the tumor growth and the relapse time are influenced by the net growth rate of the androgen-independent cells, a protocol of the IAS therapy, and the mutation rate from androgen-dependent cells to androgen-independent ones.

Mass spectrometry and immunoassay: how to measure steroid hormones today and tomorrow.

PubMed

Taylor, Angela E; Keevil, Brian; Huhtaniemi, Ilpo T

2015-08-01

The recent onslaught of mass spectrometry (MS) to measurements of steroid hormones, including demands that they should be the only acceptable method, has confused clinicians and scientists who have relied for more than 40 years on a variety of immunoassay (IA) methods in steroid hormone measurements. There is little doubt that MS methods with their superior specificity will be the future method of choice in many clinical and research applications of steroid hormone measurement. However, the majority of steroid measurements are currently, and will continue to be, carried out using various types of IAs for several reasons, including their technical ease, cost and availability of commercial reagents. Speedy replacement of all IAs with MS is an unrealistic and unnecessary goal, because the availability of MS measurements is limited by cost, need of expensive equipment, technical demands and lack of commercial applications. Furthermore, IAs have multiple well-known advantages that vindicate their continuing use. The purpose of this article is to elucidate the advantages and limitations of the MS and IA techniques from two angles, i.e. promotion of MS and defence of IA. The purpose of the text is to give the reader an unbiased view about the current state and future trends of steroid analysis and to help him/her choose the correct assay method to serve his/her diagnostic and research needs. © 2015 European Society of Endocrinology.

Hemiparesis after Operation of Astrocytoma Grade II in Adults: Effects of Acupuncture on Sensory-Motor Behavior and Quality of Life

PubMed Central

Yu, Haibo; Schröder, Sven; Li, Zhifeng; Yang, Ying; Chen, Yu; Huang, Xingxian

2013-01-01

To evaluate the effect of acupuncture on hemiparesis and quality of life for adults with brain astrocytoma grade II, we conducted a randomized, observer-blinded clinical trial. Fifty-eight patients were randomized to standard rehabilitation (SR) therapy without acupuncture (n = 20), SR plus standard acupuncture (SA) (n = 19), and SR plus individualized acupuncture (IA) (n = 19). SA points were PC6, SP6, HT1, LU5, BL40, and ST36, while a special concept called “connecting and regulation Ren and Du” and “Jin-3-needling” served as IA. This treatment was individualized according to the clinical syndrome. The outcome was measured by the Barthel Index (BI), the Fugl-Meyer scale (FM), and the EORTC Core Quality of Life Questionnaire (QLQ-C30) with the Brain Cancer Module (BCM20). IA + SR reached significantly higher BI scores than SA + SR, which reached significantly higher BI scores than SR. IA + SR was significantly superior to SA + SR and to SR at the 8th week for the scores of FM motor and sensory assessments and most QLQ-C30-BCM20 items. In conclusion, the individualized acupuncture concept of “connecting and regulating Ren and Du” combined with “Jin-3-needling” offers a promising possibility for the treatment of hemiparesis due to astrocytoma, but further evaluation is mandatory. PMID:23864900

Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok

PubMed Central

Kroon, Eugène D.M.B.; Phanuphak, Nittaya; Shattock, Andrew J.; Fletcher, James L.K.; Pinyakorn, Suteeraporn; Chomchey, Nitiya; Akapirat, Siriwat; de Souza, Mark S.; Robb, Merlin L.; Kim, Jerome H.; van Griensven, Frits; Ananworanich, Jintanat; Wilson, David P.

2017-01-01

Abstract Introduction: Antiretroviral treatment (ART) reduces HIV transmission. Despite increased ART coverage, incidence remains high among men who have sex with men (MSM) in many places. Acute HIV infection (AHI) is characterized by high viral replication and increased infectiousness. We estimated the feasible reduction in transmission by targeting MSM with AHI for early ART. Methods: We recruited a cohort of 88 MSM with AHI in Bangkok, Thailand, who initiated ART immediately. A risk calculator based on viral load and reported behaviour, calibrated to Thai epidemiological data, was applied to estimate the number of onwards transmissions. This was compared with the expected number without early interventions. Results: Forty of the MSM were in 4th-generation AHI stages 1 and 2 (4thG stage 1, HIV nucleic acid testing (NAT)+/4thG immunoassay (IA)-/3rdG IA–; 4thG stage 2, NAT+/4thG IA+/3rdG IA–) while 48 tested positive on third-generation IA but had negative or indeterminate western blot (4thG stage 3). Mean plasma HIV RNA was 5.62 log10 copies/ml. Any condomless sex in the four months preceding the study was reported by 83.7%, but decreased to 21.2% by 24 weeks on ART. After ART, 48/88 (54.6%) attained HIV RNA <50 copies/ml by week 8, increasing to 78/87 (89.7%), and 64/66 (97%) at weeks 24 and 48, respectively. The estimated number of onwards transmissions in the first year of infection would have been 27.3 (95% credible interval: 21.7–35.3) with no intervention, 8.3 (6.4–11.2) with post-diagnosis behaviour change only, 5.9 (4.4–7.9) with viral load reduction only and 3.1 (2.4–4.3) with both. The latter was associated with an 88.7% (83.8–91.1%) reduction in transmission. Conclusions: Disproportionate HIV transmission occurs during AHI. Diagnosis of AHI with early ART initiation can substantially reduce onwards transmission. PMID:28691441

Does the COPD assessment test (CAT(TM)) questionnaire produce similar results when self- or interviewer administered?

PubMed

Agusti, A; Soler-Cataluña, J J; Molina, J; Morejon, E; Garcia-Losa, M; Roset, M; Badia, X

2015-10-01

The COPD assessment test (CAT) is a questionnaire that assesses the impact of chronic obstructive pulmonary disease (COPD) on health status, but some patients have difficulties filling it up by themselves. We examined whether the mode of administration of the Spanish version of CAT (self vs. interviewer) influences its scores and/or psychometric properties. Observational, prospective study in 49 Spanish centers that includes clinically stable COPD patients (n = 153) and patients hospitalized because of an exacerbation (ECOPD; n = 224). The CAT was self-administered (CAT-SA) or administered by an interviewer (CAT-IA) based on the investigator judgment of the patient's capacity. To assess convergent validity, the Saint George's Respiratory Disease Questionnaire (SGRQ) and the London Chest Activity of Daily Living (LCADL) instrument were also administered. Psychometric properties were compared across modes of administration. A total of 118 patients (31 %) completed the CAT-SA and 259 (69 %) CAT-IA. Multiple regression analysis showed that mode of administration did not affect CAT scores. The CAT showed excellent psychometric properties in both modes of administration. Internal consistency coefficients (Cronbach's alpha) were high (0.86 for CAT-SA and 0.85 for CAT-IA) as was test-retest reliability (intraclass correlation coefficients of 0.83 for CAT-SA and CAT-IA). Correlations with SGRQ and LCADL were moderate to strong both in CAT-SA and CAT-IA, indicating good convergent validity. Similar results were observed when testing longitudinal validity. The mode of administration does not influence CAT scores or its psychometric properties. Hence, both modes of administration can be used in clinical practice depending on the physician judgment of patient's capacity.

Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.

PubMed

Aranda, G; Careaga, M; Hanzu, F A; Patrascioiu, I; Ríos, P; Mora, M; Morales-Romero, B; Jiménez, W; Halperin, I; Casals, G

2016-10-01

Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

PubMed Central

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-01

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke. PMID:28091591

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia.

PubMed

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-16

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

NASA Astrophysics Data System (ADS)

Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

2017-01-01

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Comparative study between manual injection intraosseous anesthesia and conventional oral anesthesia.

PubMed

Peñarrocha-Oltra, D; Ata-Ali, J; Oltra-Moscardó, M-J; Peñarrocha-Diago, M-A; Peñarrocha, M

2012-03-01

To compare intraosseous anesthesia (IA) with the conventional oral anesthesia techniques. A simple-blind, prospective clinical study was carried out. Each patient underwent two anesthetic techniques: conventional (local infiltration and locoregional anesthetic block) and intraosseous, for respective dental operations. In order to allow comparison of IA versus conventional anesthesia, the two operations were similar and affected the same two teeth in opposite quadrants. A total of 200 oral anesthetic procedures were carried out in 100 patients. The mean patient age was 28.6±9.92 years. Fifty-five vestibular infiltrations and 45 mandibular blocks were performed. All patients were also subjected to IA. The type of intervention (conservative or endodontic) exerted no significant influence (p=0.58 and p=0.62, respectively). The latency period was 8.52±2.44 minutes for the conventional techniques and 0.89±0.73 minutes for IA - the difference being statistically significant (p<0.05). Regarding patient anesthesia sensation, the infiltrative techniques lasted a maximum of one hour, the inferior alveolar nerve blocks lasted between 1-3 hours, and IA lasted only 2.5 minutes - the differences being statistically significant (p≤0.0000, Φ=0.29). Anesthetic success was recorded in 89% of the conventional procedures and in 78% of the IA. Most patients preferred IA (61%)(p=0.0032). The two anesthetic procedures have been compared for latency, duration of anesthetic effect, anesthetic success rate and patient preference. Intraosseous anesthesia has been shown to be a technique to be taken into account when planning conservative and endodontic treatments.

Wrapping of intracranial aneurysms: Single-center series and systematic review of the literature.

PubMed

Perrini, Paolo; Montemurro, Nicola; Caniglia, Michele; Lazzarotti, Guido; Benedetto, Nicola

2015-01-01

Circumferential wrapping of the aneurysm wall with a variety of materials is a well-known therapeutic approach for the repair of unclippable intracranial aneurysms (IAs). Wrapping materials can stimulate foreign-body inflammatory reactions and parent artery narrowing with resultant ischemic stroke. In this study, a single-center retrospective review of the outcome with wrapping of IAs is presented beside an analysis of existing literature. For the institutional analysis, all patients who underwent wrapping of IAs in the last five years were analyzed. For the analysis of the literature, a MEDLINE search between 1990 and the present was performed for clinical series reporting wrapping of IAs. Specifically, the risk of rebleeding, cerebrovascular complications, and the incidence of granuloma formation were evaluated. Two hundred and ninety patients with IA were surgically treated in our department. Fifteen patients (5.2%) underwent wrapping of IA. Early parent artery narrowing occurred in one patient (6.7%) and was associated with ischemic stroke. Delayed cerebrovascular complications, including parent artery narrowing (one case), granuloma formation (one case), and fatal bleeding from an unruptured aneurysm, occurred in three patients (20%). For the review of the literature, 197 cases of wrapped aneurysms were collected. Bleeding after wrapping occurred in 16 (12%) of the patients with ruptured aneurysms. Acute ischemic complications were reported in 7 cases (3.5%) and granuloma formation was observed in 3 patients (1.5%). These data suggest that the microsurgical wrapping of IAs present a risk of ischemic complications and granuloma formation. Additionally, the rebleeding rate of ruptured aneurysms remains high, although still lower than the natural history of untreated ruptured aneurysms.

Adavosertib, External Beam Radiation Therapy, and Cisplatin in Treating Patients With Cervical, Vaginal, or Uterine Cancer

ClinicalTrials.gov

2018-06-06

Endometrioid Adenocarcinoma; Recurrent Cervical Carcinoma; Stage I Uterine Corpus Cancer AJCC v7; Stage I Vaginal Cancer AJCC v6 and v7; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Cervical Cancer AJCC v6 and v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage II Vaginal Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Cervical Cancer AJCC v6 and v7; Stage III Uterine Corpus Cancer AJCC v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIA Cervical Cancer AJCC v6 and v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7

Recent advances in intra-articular drug delivery systems for osteoarthritis therapy.

PubMed

Maudens, Pierre; Jordan, Olivier; Allémann, Eric

2018-05-21

Osteoarthritis (OA) is the most common degenerative disease of the joint. Despite many reports and numerous clinical trials, OA is not entirely understood, and there is no effective treatment available for this disease. To satisfy this unmet medical need, drug delivery systems (DDSs) containing disease-modifying OA drugs (DMOADs) for intra-articular (IA) administration are required to improve the health of OA patients. DDSs should provide controlled and/or sustained drug release, enabling long-term treatment with a reduced number of injections. This paper reviews the role and interaction among different tissues involved in OA and summarizes recent clinical trials and research on DDSs, focusing on small-molecule delivery. To achieve an ideal treatment, various key criteria have been identified to design and develop an IA DDS matching the clinical needs. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Evaluation of sphincter damage degree with anal endosonography for children with fecal incontinence].

PubMed

Sun, Xiaobing; Li, Dianguo; Wang, Ruoyi; Sun, Xiaogang; Liu, Qian

2014-03-01

To evaluate the application of anal endosonography in the morphology of internal anal sphincter (IAS), external anal sphincter (EAS) and puborectalis (PR) in order to provide necessary information for analysis of the etiology of fecal incontinence and formulation of the therapeutic schedule. From December 2010 to November 2012, 18 children of anorectal malformation (n=14) or Hirschsprung's disease(n=4) with fecal incontinence received anal endosonography. The morphology of IAS, EAS and PR was observed. The damage of anal sphincter was classified according to Starck criteria. Anorectal mamometry and anal clinical score were measured simultaneously. Spearman analysis was performed to examine the correlation of anal sphincter damage with anorectal mamometric score and anal clinical score. According to Starck criteria, anal sphincter damage was small in 11 children, moderate in 6, and severe in 1. PR damage was found in 4 cases. Starck score was positively correlated with manometric score(P<0.05), while not correlated with anal clinical score(P>0.05). Anal endosonography can clearly display the morphology of IAS, EAS and PR, and their integrity and damage degree. It is a very valuable technique to evaluate the anal sphincter of the children with fecal incontinence, which however can not reflect the function of anal sphincter and anal continence thoroughly.

Prospective, Multicenter, Randomized, Crossover Clinical Trial Comparing the Safety and Effectiveness of Cooled Radiofrequency Ablation With Corticosteroid Injection in the Management of Knee Pain From Osteoarthritis.

PubMed

Davis, Tim; Loudermilk, Eric; DePalma, Michael; Hunter, Corey; Lindley, David; Patel, Nilesh; Choi, Daniel; Soloman, Marc; Gupta, Anita; Desai, Mehul; Buvanendran, Asokumar; Kapural, Leonardo

2018-01-01

Osteoarthritis (OA) of the knee affects the aging population and has an associated influence on the health care system. Rigorous studies evaluating radiofrequency ablation for OA-related knee pain are lacking. This study compared long-term clinical safety and effectiveness of cooled radiofrequency ablation (CRFA) with intra-articular steroid (IAS) injection in managing OA-related knee pain. This is a prospective, multicenter, randomized trial with 151 subjects with chronic (≥6 months) knee pain that was unresponsive to conservative modalities. Knee pain (Numeric Rating Scale [NRS]), Oxford Knee Score, overall treatment effect (Global Perceived Effect), analgesic drug use, and adverse events were compared between CRFA and IAS cohorts at 1, 3, and 6 months after intervention. There were no differences in demographics between study groups. At 6 months, the CRFA group had more favorable outcomes in NRS: pain reduction 50% or greater: 74.1% versus 16.2%, P < 0.0001 (25.9% and 83.8% of these study cohorts, respectively, were nonresponders). Mean NRS score reduction was 4.9 ± 2.4 versus 1.3 ± 2.2, P < 0.0001; mean Oxford Knee Score was 35.7 ± 8.8 vs 22.4 ± 8.5, P < 0.0001; mean improved Global Perceived Effect was 91.4% vs 23.9%, P < 0.0001; and mean change in nonopioid medication use was CRFA > IAS (P = 0.02). There were no procedure-related serious adverse events. This study demonstrates that CRFA is an effective long-term therapeutic option for managing pain and improving physical function and quality of life for patients with painful knee OA when compared with IAS injection. ClinicalTrials.gov (NCT02343003).

Streptococcus agalactiae isolates of serotypes Ia, III and V from human and cow are able to infect tilapia.

PubMed

Chen, Ming; Wang, Rui; Luo, Fu-Guang; Huang, Yan; Liang, Wan-Wen; Huang, Ting; Lei, Ai-Ying; Gan, Xi; Li, Li-Ping

2015-10-22

Recent studies have shown that group B streptococcus (GBS) may be infectious across hosts. The purpose of this study is to investigate the pathogenicity of clinical GBS isolates with serotypes Ia, III and V from human and cow to tilapia and the evolutionary relationship among these GBS strains of different sources. A total of 27 clinical GBS isolates from human (n=10), cow (n=2) and tilapia (n=15) were analyzed using serotyping, multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Among them, 15 isolates were tested for their pathogenicity to tilapia. The results showed that five human GBS strains (2 serotype III, 2 serotype Ia and 1 serotype V) infected tilapia with mortality rate ranging from 56.67% to 100%, while the other five human GBS strains tested were unable to infect tilapia. In addition, two cow GBS strains C001 and C003 of serotype III infected tilapia. However, they had significantly lower pathogenicity than the five human strains. Furthermore, human GBS strains H005 and H008, which had very strong ability to infect tilapia, had the same PFGE pattern. MLST analysis showed that the five human and the two cow GBS strains that were able to infect tilapia belonged to clonal complexes CC19, CC23 and CC103. The study for the first time confirmed that human or cow GBS clonal complexes CC19, CC23 and CC103 containing strains with serotypes Ia, III and V could infect tilapia and induce clinical signs under experimental conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

PubMed

Altorki, Nasser K; Yip, Rowena; Hanaoka, Takaomi; Bauer, Thomas; Aye, Ralph; Kohman, Leslie; Sheppard, Barry; Thurer, Richard; Andaz, Shahriyour; Smith, Michael; Mayfield, William; Grannis, Fred; Korst, Robert; Pass, Harvey; Straznicka, Michaela; Flores, Raja; Henschke, Claudia I

2014-02-01

A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in diameter, the 10-year rates were 88% (95% confidence interval, 82-93) versus 84% (95% confidence interval, 73-96) (P = .45), and Cox survival analysis showed no significant difference between sublobar resection and lobectomy using either approach (P = .42 and P = .52, respectively). Sublobar resection and lobectomy have equivalent survival for patients with clinical stage IA non-small cell lung cancer in the context of computed tomography screening for lung cancer. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Engraftment of Human Mesenchymal Stem Cells in a Rat Photothrombotic Cerebral Infarction Model : Comparison of Intra-Arterial and Intravenous Infusion Using MRI and Histological Analysis

PubMed Central

Byun, Jun Soo; Kim, Jae Kyun; Jung, Jisung; Ha, Bon Chul; Park, Serah

2013-01-01

Objective This study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction. Methods Male Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2* weighted image (T2*WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining. Results Grafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2*WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups. Conclusion In a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain. PMID:24527188

Respiratory sinus arrhythmia reactivity of internet addiction abusers in negative and positive emotional states using film clips stimulation.

PubMed

Hsieh, Dai-Ling; Hsiao, Tzu-Chien

2016-07-04

People with internet addiction (IA) suffer from mental, physical, social, and occupational problems. IA includes psychological and physiological syndromes, and among the syndromes, emotion was suggested important mental and physiological expressions of IA. However, few physiologically emotional characters of IA were investigated. Autonomic nervous system (ANS) activity was a good link between IA and emotion, and respiratory sinus arrhythmia (RSA) gained from ANS was hypothesized related to IA. An emotional induction experiment using negative and positive emotional films was conducted to validate the hypotheses. Thirty-four participants recruited from college were classified into high-risk IA group (HIA) and low-risk IA group (LIA). The respiratory signals, ECG signals, and self-assessed emotional intensity were acquired. The relationship and difference between IA and RSA was tested using descriptive statistics and inferential statistics. The RSA values of HIA were lower than those of LIA both before and after the induction of positive and negative emotions. When participants experienced a negative emotion (anger or fear), their RSA values declined; the decline for HIA was greater than that for LIA. The RSA values of HIA participants before induction of fear, happiness, or surprise, statistically significantly differed from that after induction of those emotions, with p values of 0.007, 0.04 and 0.01 respectively. The difference between the changes in RSA values upon the induction of surprise of HIA and LIA was statistically significant difference (p = 0.03). The interaction between two IA groups among emotional induction states was statistically significant difference. RSA value here was the main variable that reflected ANS activity, and especially vagus nerve regulation. The results revealed that the changes in RSA values were biologically significantly different between HIA and LIA, especially when sadness, happiness, or surprise was induced. HIA people exhibited stronger RSA reactivity following negative emotion than LIA people, but the RSA reactivity following positive emotion was weaker. This study provides more physiological information about IA and assists further investigation on the regulation of the ANS for IA abusers. The results will benefit the further application, early detection, therapy, and even early prevention. Clinical trial registration details This study was approved by the Institution Review Board of the National Taiwan University Hospital, Hsinchu Branch (Hsinchu, Taiwan), under the research project: A study of interactions between cognition, emotion and physiology (contract no.100IRB-32).

Monitoring of clinical strains and environmental fungal aerocontamination to prevent invasive aspergillosis infections in hospital during large deconstruction work: a protocol study

PubMed Central

Loeffert, Sophie Tiphaine; Melloul, Elise; Dananché, Cédric; Hénaff, Laetitia; Bénet, Thomas; Cassier, Pierre; Dupont, Damien; Guillot, Jacques; Botterel, Françoise; Wallon, Martine; Gustin, Marie-Paule; Vanhems, Philippe

2017-01-01

Introduction Monitoring fungal aerocontamination is an essential measure to prevent severe invasive aspergillosis (IA) infections in hospitals. One central block among 32 blocks of Edouard Herriot Hospital (EHH) was entirely demolished in 2015, while care activities continued in surrounding blocks. The main objective was to undertake broad environmental monitoring and clinical surveillance of IA cases to document fungal dispersion during major deconstruction work and to assess clinical risk. Methods and analysis A daily environmental survey of fungal loads was conducted in eight wards located near the demolition site. Air was collected inside and outside selected wards by agar impact samplers. Daily spore concentrations were monitored continuously by volumetric samplers at a flow rate of 10 L.min-1. Daily temperature, wind direction and speed as well as relative humidity were recorded by the French meteorological station Meteociel. Aspergillus fumigatus strains stored will be genotyped by multiple-locus, variable-number, tandem-repeat analysis. Antifungal susceptibility will be assessed by E-test strips on Roswell Park Memorial Institute medium supplemented with agar. Ascertaining the adequacy of current environmental monitoring techniques in hospital is of growing importance, considering the rising impact of fungal infections and of curative antifungal costs. The present study could improve the daily management of IA risk during major deconstruction work and generate new data to ameliorate and redefine current guidelines. Ethics and dissemination This study was approved by the clinical research and ethics committees of EHH. PMID:29175886

Development and Validation of an Individualized Immune Prognostic Signature in Early-Stage Nonsquamous Non-Small Cell Lung Cancer.

PubMed

Li, Bailiang; Cui, Yi; Diehn, Maximilian; Li, Ruijiang

2017-11-01

The prevalence of early-stage non-small cell lung cancer (NSCLC) is expected to increase with recent implementation of annual screening programs. Reliable prognostic biomarkers are needed to identify patients at a high risk for recurrence to guide adjuvant therapy. To develop a robust, individualized immune signature that can estimate prognosis in patients with early-stage nonsquamous NSCLC. This retrospective study analyzed the gene expression profiles of frozen tumor tissue samples from 19 public NSCLC cohorts, including 18 microarray data sets and 1 RNA-Seq data set for The Cancer Genome Atlas (TCGA) lung adenocarcinoma cohort. Only patients with nonsquamous NSCLC with clinical annotation were included. Samples were from 2414 patients with nonsquamous NSCLC, divided into a meta-training cohort (729 patients), meta-testing cohort (716 patients), and 3 independent validation cohorts (439, 323, and 207 patients). All patients underwent surgery with a negative surgical margin, received no adjuvant or neoadjuvant therapy, and had publicly available gene expression data and survival information. Data were collected from July 22 through September 8, 2016. Overall survival. Of 2414 patients (1205 men [50%], 1111 women [46%], and 98 of unknown sex [4%]; median age [range], 64 [15-90] years), a prognostic immune signature of 25 gene pairs consisting of 40 unique genes was constructed using the meta-training data set. In the meta-testing and validation cohorts, the immune signature significantly stratified patients into high- vs low-risk groups in terms of overall survival across and within subpopulations with stage I, IA, IB, or II disease and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.72 [95% CI, 1.26-2.33; P < .001] to 2.36 [95% CI, 1.47-3.79; P < .001]) after adjusting for clinical and pathologic factors. Several biological processes, including chemotaxis, were enriched among genes in the immune signature. The percentage of neutrophil infiltration (5.6% vs 1.8%) and necrosis (4.6% vs 1.5%) was significantly higher in the high-risk immune group compared with the low-risk groups in TCGA data set (P < .003). The immune signature achieved a higher accuracy (mean concordance index [C-index], 0.64) than 2 commercialized multigene signatures (mean C-index, 0.53 and 0.61) for estimation of survival in comparable validation cohorts. When integrated with clinical characteristics such as age and stage, the composite clinical and immune signature showed improved prognostic accuracy in all validation data sets relative to molecular signatures alone (mean C-index, 0.70 vs 0.63) and another commercialized clinical-molecular signature (mean C-index, 0.68 vs 0.65). The proposed clinical-immune signature is a promising biomarker for estimating overall survival in nonsquamous NSCLC, including early-stage disease. Prospective studies are needed to test the clinical utility of the biomarker in individualized management of nonsquamous NSCLC.

LKB1 promotes cell survival by modulating TIF-IA-mediated pre-ribosomal RNA synthesis under uridine downregulated conditions

PubMed Central

Liu, Xiuju; Huang, Henry; Wilkinson, Scott C.; Zhong, Diansheng; Khuri, Fadlo R.; Fu, Haian; Marcus, Adam; He, Yulong; Zhou, Wei

2016-01-01

We analyzed the mechanism underlying 5-aminoimidazole-4-carboxamide riboside (AICAR) mediated apoptosis in LKB1-null non-small cell lung cancer (NSCLC) cells. Metabolic profile analysis revealed depletion of the intracellular pyrimidine pool after AICAR treatment, but uridine was the only nucleotide precursor capable of rescuing this apoptosis, suggesting the involvement of RNA metabolism. Because half of RNA transcription in cancer is for pre-ribosomal RNA (rRNA) synthesis, which is suppressed by over 90% after AICAR treatment, we evaluated the role of TIF-IA-mediated rRNA synthesis. While the depletion of TIF-IA by RNAi alone promoted apoptosis in LKB1-null cells, the overexpression of a wild-type or a S636A TIF-IA mutant, but not a S636D mutant, attenuated AICAR-induced apoptosis. In LKB1-null H157 cells, pre-rRNA synthesis was not suppressed by AICAR when wild-type LKB1 was present, and cellular fractionation analysis indicated that TIF-IA quickly accumulated in the nucleus in the presence of a wild-type LKB1 but not a kinase-dead mutant. Furthermore, ectopic expression of LKB1 was capable of attenuating AICAR-induced death in AMPK-null cells. Because LKB1 promotes cell survival by modulating TIF-IA-mediated pre-rRNA synthesis, this discovery suggested that targeted depletion of uridine related metabolites may be exploited in the clinic to eliminate LKB1-null cancer cells. PMID:26506235

LKB1 promotes cell survival by modulating TIF-IA-mediated pre-ribosomal RNA synthesis under uridine downregulated conditions.

PubMed

Liu, Fakeng; Jin, Rui; Liu, Xiuju; Huang, Henry; Wilkinson, Scott C; Zhong, Diansheng; Khuri, Fadlo R; Fu, Haian; Marcus, Adam; He, Yulong; Zhou, Wei

2016-01-19

We analyzed the mechanism underlying 5-aminoimidazole-4-carboxamide riboside (AICAR) mediated apoptosis in LKB1-null non-small cell lung cancer (NSCLC) cells. Metabolic profile analysis revealed depletion of the intracellular pyrimidine pool after AICAR treatment, but uridine was the only nucleotide precursor capable of rescuing this apoptosis, suggesting the involvement of RNA metabolism. Because half of RNA transcription in cancer is for pre-ribosomal RNA (rRNA) synthesis, which is suppressed by over 90% after AICAR treatment, we evaluated the role of TIF-IA-mediated rRNA synthesis. While the depletion of TIF-IA by RNAi alone promoted apoptosis in LKB1-null cells, the overexpression of a wild-type or a S636A TIF-IA mutant, but not a S636D mutant, attenuated AICAR-induced apoptosis. In LKB1-null H157 cells, pre-rRNA synthesis was not suppressed by AICAR when wild-type LKB1 was present, and cellular fractionation analysis indicated that TIF-IA quickly accumulated in the nucleus in the presence of a wild-type LKB1 but not a kinase-dead mutant. Furthermore, ectopic expression of LKB1 was capable of attenuating AICAR-induced death in AMPK-null cells. Because LKB1 promotes cell survival by modulating TIF-IA-mediated pre-rRNA synthesis, this discovery suggested that targeted depletion of uridine related metabolites may be exploited in the clinic to eliminate LKB1-null cancer cells.

Structure of the Antibiotic Resistance Factor Spectinomycin Phosphotransferase from Legionella pneumophila

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

Fong, D.; Lemke, C; Huang, J

2010-01-01

Aminoglycoside phosphotransferases (APHs) constitute a diverse group of enzymes that are often the underlying cause of aminoglycoside resistance in the clinical setting. Several APHs have been extensively characterized, including the elucidation of the three-dimensional structure of two APH(3{prime}) isozymes and an APH(2{double_prime}) enzyme. Although many APHs are plasmid-encoded and are capable of inactivating numerous 2-deoxystreptmaine aminoglycosides with multiple regiospecificity, APH(9)-Ia, isolated from Legionella pneumophila, is an unusual enzyme among the APH family for its chromosomal origin and its specificity for a single non-2-deoxystreptamine aminoglycoside substrate, spectinomycin. We describe here the crystal structures of APH(9)-Ia in its apo form, its binarymore » complex with the nucleotide, AMP, and its ternary complex bound with ADP and spectinomycin. The structures reveal that APH(9)-Ia adopts the bilobal protein kinase-fold, analogous to the APH(3{prime}) and APH(2{double_prime}) enzymes. However, APH(9)-Ia differs significantly from the other two types of APH enzymes in its substrate binding area and that it undergoes a conformation change upon ligand binding. Moreover, kinetic assay experiments indicate that APH(9)-Ia has stringent substrate specificity as it is unable to phosphorylate substrates of choline kinase or methylthioribose kinase despite high structural resemblance. The crystal structures of APH(9)-Ia demonstrate and expand our understanding of the diversity of the APH family, which in turn will facilitate the development of new antibiotics and inhibitors.« less

Psychiatric disorders in individuals diagnosed with infantile autism as children: a case control study.

PubMed

Mouridsen, Svend Erik; Rich, Bente; Isager, Torben; Nedergaard, Niels Jørgen

2008-01-01

The objective of this study was to compare the prevalence and types of psychiatric disorders in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with psychiatric disorders in 336 matched controls from the general population using data from the nationwide Danish Psychiatric Central Register. The average observation time was 32.5 years, and mean age at follow-up was 40.6 years (range 25-55 years). Of the 118 individuals with IA, 57 (48.3%) had been in contact with psychiatric hospitals (inpatient hospitalization or outpatient visits) during the follow-up period, compared with 20/336 (6.0%) in the control group (p < 0.0001). This observation should alert general psychiatrists to the possibility of additional treatable psychiatric disorders occurring in individuals with IA. Of the 118 individuals in the IA group, 20 individuals (17%) had been given a comorbid psychiatric diagnosis during the observation period, compared with 9 individuals (2.7%) in the control group. Of the subjects with IA, 3.4% had received a diagnosis of schizophrenia (F20) at least once since the index admission in childhood, 0.8% had been diagnosed with delusional disorder (F22), 0.8% with acute psychotic disorder (F23), and 1.6% with unspecified non-organic psychosis (F29). In the control group, 0.9% had been diagnosed with schizophrenia (p = 0.08). In the group with IA, 3.4% had received a diagnosis in the broad category of affective disorders compared with 1.2% in the control group (p = 0.21). Issues associated with using registers in the ascertainment of co-occurring psychiatric disorders in IA are discussed.

Revisiting the Nucleotide and Aminoglycoside Substrate Specificity of the Bifunctional Aminoglycoside Acetyltransferase(6′)-Ie/Aminoglycoside Phosphotransferase(2″)-Ia Enzyme*

PubMed Central

Frase, Hilary; Toth, Marta; Vakulenko, Sergei B.

2012-01-01

The bifunctional aminoglycoside-modifying enzyme aminoglycoside acetyltransferase(6′)-Ie/aminoglycoside phosphotransferase(2″)-Ia, or AAC(6′)-Ie/APH(2″)-Ia, is the major source of aminoglycoside resistance in Gram-positive bacterial pathogens. In previous studies, using ATP as the cosubstrate, it was reported that the APH(2″)-Ia domain of this enzyme is unique among aminoglycoside phosphotransferases, having the ability to inactivate an unusually broad spectrum of aminoglycosides, including 4,6- and 4,5-disubstituted and atypical. We recently demonstrated that GTP, and not ATP, is the preferred cosubstrate of this enzyme. We now show, using competition assays between ATP and GTP, that GTP is the exclusive phosphate donor at intracellular nucleotide levels. In light of these findings, we reevaluated the substrate profile of the phosphotransferase domain of this clinically important enzyme. Steady-state kinetic characterization using the phosphate donor GTP demonstrates that AAC(6′)-Ie/APH(2″)-Ia phosphorylates 4,6-disubstituted aminoglycosides with high efficiency (kcat/Km = 105-107 m−1 s−1). Despite this proficiency, no resistance is conferred to some of these antibiotics by the enzyme in vivo. We now show that phosphorylation of 4,5-disubstituted and atypical aminoglycosides are negligible and thus these antibiotics are not substrates. Instead, these aminoglycosides tend to stimulate an intrinsic GTPase activity of the enzyme. Taken together, our data show that the bifunctional enzyme efficiently phosphorylates only 4,6-disubstituted antibiotics; however, phosphorylation does not necessarily result in bacterial resistance. Hence, the APH(2″)-Ia domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme is a bona fide GTP-dependent kinase with a narrow substrate profile, including only 4,6-disubstituted aminoglycosides. PMID:23115238

Cerebrovascular complications and granuloma formation after wrapping or coating of intracranial aneurysms with cotton gauze and human fibrin adhesives: results from a single-center patient series over a 5-year period.

PubMed

Beitzke, Markus; Leber, Klaus A; Deutschmann, Hannes; Gattringer, Thomas; Poltrum, Birgit; Fazekas, Franz

2013-10-01

Reinforcement of intracranial aneurysms (IAs) by wrapping or coating is a well-established therapeutic approach to those IAs not amenable to any other definitive treatment, but has been associated with complications such as parent artery narrowing, granuloma formation, and ischemic stroke. The goal of this study was to systematically investigate cerebrovascular complications following this procedure. The authors' hospital database was searched for all patients who underwent wrapping or coating of IAs with cotton gauze and human fibrin adhesives between October 2006 and October 2011. The follow-up records of these patients were extracted, including regular clinical visits and vascular imaging. Five hundred sixty-seven patients were treated for IAs over the 5-year period: 303 patients underwent endovascular strategies and 264 underwent craniotomies. Wrapping or coating of IAs was performed in 20 patients (3.5%). Parent artery narrowing occurred in 5 (25%) of the 20 patients and was associated with major ischemic strokes in 4 patients and severe headache in another. Ischemic strokes were associated with parent artery narrowing, which occurred early postoperatively in 2 patients or was a consequence of granuloma formation in 2 patients 1 and 2 months after the procedure, respectively. These data should add to the awareness of significant cerebrovascular complications following wrapping or coating of IAs with cotton gauze and human fibrin adhesives and indicate that major ischemic strokes need to be included in the risk/benefit considerations during decision making for such treatment strategies. Patients who receive IA wrapping should be monitored and followed up closely for arterial narrowing and granuloma formation.

Comparative study between manual injection intraosseous anesthesia and conventional oral anesthesia

PubMed Central

Ata-Ali, Javier; Oltra-Moscardó, María J.; Peñarrocha-Diago, María; Peñarrocha, Miguel

2012-01-01

Objective: To compare intraosseous anesthesia (IA) with the conventional oral anesthesia techniques. Materials and methods: A simple-blind, prospective clinical study was carried out. Each patient underwent two anesthetic techniques: conventional (local infiltration and locoregional anesthetic block) and intraosseous, for res-pective dental operations. In order to allow comparison of IA versus conventional anesthesia, the two operations were similar and affected the same two teeth in opposite quadrants. Results: A total of 200 oral anesthetic procedures were carried out in 100 patients. The mean patient age was 28.6±9.92 years. Fifty-five vestibular infiltrations and 45 mandibular blocks were performed. All patients were also subjected to IA. The type of intervention (conservative or endodontic) exerted no significant influence (p=0.58 and p=0.62, respectively). The latency period was 8.52±2.44 minutes for the conventional techniques and 0.89±0.73 minutes for IA – the difference being statistically significant (p<0.05). Regarding patient anesthesia sensation, the infiltrative techniques lasted a maximum of one hour, the inferior alveolar nerve blocks lasted between 1-3 hours, and IA lasted only 2.5 minutes – the differences being statistically significant (p≤0.0000, Φ=0.29). Anesthetic success was recorded in 89% of the conventional procedures and in 78% of the IA. Most patients preferred IA (61%) (p=0.0032). Conclusions: The two anesthetic procedures have been compared for latency, duration of anesthetic effect, anesthetic success rate and patient preference. Intraosseous anesthesia has been shown to be a technique to be taken into account when planning conservative and endodontic treatments. Key words: Anesthesia, intraosseous, oral anesthesia, Stabident®, infiltrative, mandibular block. PMID:22143700

Pancreatic islet amyloidosis, β-cell apoptosis, and α-cell proliferation are determinants of islet remodeling in type-2 diabetic baboons

PubMed Central

Guardado-Mendoza, Rodolfo; Davalli, Alberto M.; Chavez, Alberto O.; Hubbard, Gene B.; Dick, Edward J.; Majluf-Cruz, Abraham; Tene-Perez, Carlos E.; Goldschmidt, Lukasz; Hart, John; Perego, Carla; Comuzzie, Anthony G.; Tejero, Maria Elizabeth; Finzi, Giovanna; Placidi, Claudia; La Rosa, Stefano; Capella, Carlo; Halff, Glenn; Gastaldelli, Amalia; DeFronzo, Ralph A.; Folli, Franco

2009-01-01

β-Cell dysfunction is an important factor in the development of hyperglycemia of type-2 diabetes mellitus, and pancreatic islet amyloidosis (IA) has been postulated to be one of the main contributors to impaired insulin secretion. The aim of this study was to evaluate the correlation of IA with metabolic parameters and its effect on islets of Langerhans remodeling and relative endocrine-cell volume in baboons. We sequenced the amylin peptide, determined the fibrillogenic propensities, and evaluated pancreatic histology, clinical and biochemical characteristics, and endocrine cell proliferation and apoptosis in 150 baboons with different metabolic status. Amylin sequence in the baboon was 92% similar to humans and showed superimposable fibrillogenic propensities. IA severity correlated with fasting plasma glucose (FPG) (r = 0.662, P < 0.001) and HbA1c (r = 0.726, P < 0.001), as well as with free fatty acid, glucagon values, decreased homeostasis model assessment (HOMA) insulin resistance, and HOMA-B. IA severity was associated with a decreased relative β-cell volume, and increased relative α-cell volume and hyperglucagonemia. These results strongly support the concept that IA and β-cell apoptosis in concert with α-cell proliferation and hypertrophy are key determinants of islets of Langerhans “dysfunctional remodeling” and hyperglycemia in the baboon, a nonhuman primate model of type-2 diabetes mellitus. The most important determinants of IA were age and FPG (R2 = 0.519, P < 0.0001), and different FPG levels were sensitive and specific to predict IA severity. Finally, a predictive model for islet amyloid severity was generated with age and FPG as required variables. PMID:19666551

Multiplex Touchdown PCR for Rapid Typing of the Opportunistic Pathogen Propionibacterium acnes

PubMed Central

Barnard, Emma; Nagy, István; Hunyadkürti, Judit; Patrick, Sheila

2015-01-01

The opportunistic human pathogen Propionibacterium acnes is composed of a number of distinct phylogroups, designated types IA1, IA2, IB, IC, II, and III, which vary in their production of putative virulence factors, their inflammatory potential, and their biochemical, aggregative, and morphological characteristics. Although multilocus sequence typing (MLST) currently represents the gold standard for unambiguous phylogroup classification and individual strain identification, it is a labor-intensive and time-consuming technique. As a consequence, we developed a multiplex touchdown PCR assay that in a single reaction can confirm the species identity and phylogeny of an isolate based on its pattern of reaction with six primer sets that target the 16S rRNA gene (all isolates), ATPase (types IA1, IA2, and IC), sodA (types IA2 and IB), atpD (type II), and recA (type III) housekeeping genes, as well as a Fic family toxin gene (type IC). When applied to 312 P. acnes isolates previously characterized by MLST and representing types IA1 (n = 145), IA2 (n = 20), IB (n = 65), IC (n = 7), II (n = 45), and III (n = 30), the multiplex displayed 100% sensitivity and 100% specificity for detecting isolates within each targeted phylogroup. No cross-reactivity with isolates from other bacterial species was observed. This multiplex assay will provide researchers with a rapid, high-throughput, and technically undemanding typing method for epidemiological and phylogenetic investigations. It will facilitate studies investigating the association of lineages with various infections and clinical conditions, and it will serve as a prescreening tool to maximize the number of genetically diverse isolates selected for downstream higher-resolution sequence-based analyses. PMID:25631794

Lipomatous hypertrophy of the interatrial septum in ECG-gated multislice computed tomography of the heart.

PubMed

Czekajska-Chehab, Elżbieta; Tomaszewska, Monika; Olchowik, Grażyna; Tomaszewski, Marek; Adamczyk, Piotr; Drop, Andrzej

2012-07-01

Lipomatous hypertrophy of the interatrial septum (LHIS) is a benign disorder characterized by fat accumulation in the interatrial septum (IAS). The purpose of the study was to analyze the incidental detection of LHIS in patients with various clinical conditions, referred to ECG-gated multislice computed tomography (ECG-MSCT) examinations of the heart. The ECG-MSCT examinations of 5786 patients (2839 women; 2947 men), were analyzed. The examinations were performed using 8-row (1015 patients) and 64-row (4771 patients) MSCT, in pre- and postcontrast scanning. We analyzed the shape of the IAS, density and maximal thickness of IAS, the thickness of the epicardial adipose tissue, and the degree of contact of IAS with the ascending aorta and superior vena cava. We also determined body mass index (BMI) in patients with LHIS. LHIS was detected in 56 (0.96%) patients, with an average age of 61.5±9.8 years. The mean BMI in the analyzed group was 30.1±4.86. During the end-diastolic phase the thickness of IAS was significantly higher (p<0.0001), and on average equaled 18.3 mm. The mean optical density of the IAS was conspicuously higher (p<0.0001) in post-contrast phase than in pre-contrast phase. The thickness of the epicardial adipose tissue in the region of the left atrioventricular groove was on average 15 mm. In all cases the dumbbell shape of IAS was observed. The incidental frequency of LHIS occurrence in patients diagnosed with the ECG-MSCT examinations is about 1%. In most subjects it is linked with a higher BMI and increased thickness of the epicardial adipose tissue.

Asia-Pacific University Network Formed to Integrate ESD and SD into Higher Education

ERIC Educational Resources Information Center

Tabucanon, Mario T.

2008-01-01

The United Nations University-Institute of Advanced Studies (UNU-IAS) has launched an initiative to build academic alliances among leading universities in the Asia-Pacific area to promote the sustainability paradigm in postgraduate education and research. The initiative, still in its formative stages, is called ProSPER.Net, which stands for…

"Loko i'a": Enriching Educational Waters for Hawaiian Children

ERIC Educational Resources Information Center

Sumida, Anna Y.

2005-01-01

In this article, the author proposes to offer a glimpse into the practical challenges of teaching literacy in a public school setting where students enter classrooms at various stages of reading readiness. The author begins with the case of Kahea, a kindergarten student reading at an emergent literacy level, as an illustration of some of the…

IAS Towards an HIV Cure Symposium: people focused, science driven: 18-19 July 2015, Vancouver, Canada.

PubMed

Fidler, Sarah; Thornhill, John; Malatinkova, Eva; Reinhard, Robert; Lamplough, Rosanne; Ananworanich, Jintanat; Chahroudi, Ann

2015-10-01

The International AIDS Society (IAS) convened the Towards an HIV Cure Symposium on 18-19 July 2015 in Vancouver, Canada, bringing together researchers and community to discuss the most recent advances in our understanding of HIV latency, reservoirs and a summary of the current clinical approaches towards an HIV cure. The symposium objectives were to: (1) gather researchers and stakeholders to present, review, and discuss the latest research towards an HIV cure; (2) promote cross-disciplinary global interactions between basic, clinical and social scientists; and (3) provide a platform for sharing information among scientists, clinicians, funders, media and civil society. The symposium examined basic molecular science and animal model data, and emerging and ongoing clinical trial results to prioritise strategies and determine the viral and immune responses that could lead to HIV remission without antiretroviral therapy. This report summarises some of the major findings discussed during the symposium.

Dual drive coexistence of EML4-ALK and TPM3-ROS1 fusion in advanced lung adenocarcinoma.

PubMed

Zhu, You-Cai; Liao, Xing-Hui; Wang, Wen-Xian; Xu, Chun-Wei; Zhuang, Wu; Wei, Jian-Guo; Du, Kai-Qi

2018-02-01

We report a case of concomitant EML4-ALK and TPM3-ROS1 fusion in non-small cell lung cancer (NSCLC) in a 47-year-old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T 1a N 0 M 0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein. Using next generation sequencing, we found that the tumor had concomitant EML4-ALK and TPM3-ROS1 fusion. No recurrence was observed during seven months of follow-up. Precise diagnostic techniques allow the detection of concomitant ROS1 fusion and other driver genes, including ALK or EGFR; therefore oncologists should consider this rare double mutation in NSCLC patients. Further exploration of treatment models is required to provide additional therapeutic options. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Cis-acting factors modulate stability of intermediate alleles for Huntington disease

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

Goldberg, Y.P.; Zeisler, J.; Thielmann, J.

1994-09-01

The genetic basis of Huntington disease (HD), a late-onset autosomal dominant neurodegenerative disorder, has recently been defined as a CAG trinucleotide expansion in a novel gene on 4p16.3. The CAG length in clinically normal people ranges from 9 to 37, with the vast majority of alleles (99%) containing less than 30 repeats. In contrast, HD patients have CAG lengths greater than 36 with the largest repeat reported to date being 121. Molecular analysis of sporadic cases of HD revealed that new mutations are not rare (3%), and arise from intermediate alleles (IAs). IAs are CAG alleles greater than that usuallymore » seen in the general population (>30), but less than that seen in patients with HD and occur with a frequency of approximately 1.5% of the general population (12/797). An important question is whether these IAs are also susceptible to expansion. In new mutation families, these IAs are unstable in passage through the male germline and in sporadic cases expand to the full mutation associated with the HD phenotype. On the 41 meioses analyzed in new mutation families, 61% were unstable. In contrast to IAs in the new mutation families, the IAs in the general population were predominately stable from one generation to the next. Comparison of the frequency of intergenerational stability between the general population and the new mutation families showed that IAs in the general population are considerably more stable than those in the new mutation families. In contrast to SCA 1 where sequence interruption is thought to play a role in CAG trinucleotide stability, sequence analysis of IAs both from the general population and the new mutation families failed to reveal any interruption of the CAG tracts. These findings suggest that while CAG size is an important factor, other cis-acting factors present in new mutation families but not in the general population are likely to be critical in conferring instability upon the CAG trinucleotide repeat.« less

Relationship between aneurysm wall enhancement and conventional risk factors in patients with unruptured intracranial aneurysms: A black-blood MRI study.

PubMed

Liu, Peng; Qi, Haikun; Liu, Aihua; Lv, Xianli; Jiang, Yuhua; Zhao, Xihai; Li, Rui; Lu, Bing; Lv, Ming; Chen, Huijun; Li, Youxiang

2016-10-01

Aneurysmal wall enhancement (AWE) has emerged as a new possible biomarker for depicting inflammation of the intracranial aneurysm (IA). However, the relationships of AWE with other risk factors are still unclear for unruptured IA. The purpose of this study was to investigate the association between AWE and other risk metrics. Forty-eight patients with unruptured saccular IAs diagnosed by digital subtraction angiography were recruited to undergo magnetic resonance (MR) black-blood imaging. AWE was evaluated using the pre- and post-contrast black-blood MR images. Univariate and multivariate logistic regression analysis was performed to investigate the association of AWE with other risk factors, including size, maximal neck width, parent vessel diameter, location, multiplicity, daughter sacs and other clinical factors. The prevalence of AWE in each ISUIA grade was reported and compared by Wilcoxon rank sum test. In total, 61 aneurysms were detected in 48 patients. Aneurysm size was found to be an independent risk factor associated with AWE (OR 2.46 per mm increase, 95% CI 1.34-4.51; p = 0.004). Patient age was independently and inversely associated with AWE (OR 0.898 per year increase, 95% CI 0.812-0.994; p = 0.037). Higher prevalence of AWE was observed in larger aneurysms (12%, 71.4%, 100%, and 100% of ISUIA grade 1-4 IAs have AWE, respectively). Notably, 12% of small IAs (size <7 mm) exhibited AWE. The IAs with AWE had significant higher ISUIA grade than the IAs without (p < 0.001, Wilcoxon rank sum test). The wall enhancement in contrast-enhanced black-blood MR images was independently associated with aneurysm size in unruptured IAs. However, some small unruptured aneurysms did exhibit wall enhancement, suggesting that AWE may provide additional aneurysm instability information to improve current size-based rupture risk evaluation metrics. © The Author(s) 2016.

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

Pan, Kuo-Chuan; Ricker, Paul M.; Taam, Ronald E., E-mail: kpan2@illinois.edu, E-mail: pmricker@illinois.edu, E-mail: r-taam@northwestern.edu

The progenitor systems of Type Ia supernovae (SNe Ia) are still under debate. Based on recent hydrodynamics simulations, non-degenerate companions in the single-degenerate scenario (SDS) should survive the supernova (SN) impact. One way to distinguish between the SDS and the double-degenerate scenario is to search for the post-impact remnant stars (PIRSs) in SN Ia remnants. Using a technique that combines multi-dimensional hydrodynamics simulations with one-dimensional stellar evolution simulations, we have examined the post-impact evolution of helium-rich binary companions in the SDS. It is found that these helium-rich PIRSs (He PIRSs) dramatically expand and evolve to a luminous phase (L {approx}more » 10{sup 4} L{sub Sun }) about 10 yr after an SN explosion. Subsequently, they contract and evolve to become hot blue-subdwarf-like (sdO-like) stars by releasing gravitational energy, persisting as sdO-like stars for several million years before evolving to the helium red-giant phase. We therefore predict that a luminous OB-like star should be detectable within {approx}30 yr after the SN explosion. Thereafter, it will shrink and become an sdO-like star in the central regions of SN Ia remnants within star-forming regions for SN Ia progenitors evolved via the helium-star channel in the SDS. These He PIRSs are predicted to be rapidly rotating (v{sub rot} {approx}> 50 km s{sup -1}) and to have high spatial velocities (v{sub linear} {approx}> 500 km s{sup -1}). Furthermore, if SN remnants have diffused away and are not recognizable at a later stage, He PIRSs could be an additional source of single sdO stars and/or hypervelocity stars.« less

Photometric classification of type Ia supernovae in the SuperNova Legacy Survey with supervised learning

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

Möller, A.; Ruhlmann-Kleider, V.; Leloup, C.

In the era of large astronomical surveys, photometric classification of supernovae (SNe) has become an important research field due to limited spectroscopic resources for candidate follow-up and classification. In this work, we present a method to photometrically classify type Ia supernovae based on machine learning with redshifts that are derived from the SN light-curves. This method is implemented on real data from the SNLS deferred pipeline, a purely photometric pipeline that identifies SNe Ia at high-redshifts (0.2 < z < 1.1). Our method consists of two stages: feature extraction (obtaining the SN redshift from photometry and estimating light-curve shape parameters)more » and machine learning classification. We study the performance of different algorithms such as Random Forest and Boosted Decision Trees. We evaluate the performance using SN simulations and real data from the first 3 years of the Supernova Legacy Survey (SNLS), which contains large spectroscopically and photometrically classified type Ia samples. Using the Area Under the Curve (AUC) metric, where perfect classification is given by 1, we find that our best-performing classifier (Extreme Gradient Boosting Decision Tree) has an AUC of 0.98.We show that it is possible to obtain a large photometrically selected type Ia SN sample with an estimated contamination of less than 5%. When applied to data from the first three years of SNLS, we obtain 529 events. We investigate the differences between classifying simulated SNe, and real SN survey data. In particular, we find that applying a thorough set of selection cuts to the SN sample is essential for good classification. This work demonstrates for the first time the feasibility of machine learning classification in a high- z SN survey with application to real SN data.« less

Invasive Scalp Melanoma: Role for Enhanced Detection Through Professional Training.

PubMed

Lovasik, Brendan P; Sharma, Ishna; Russell, Maria C; Carlson, Grant W; Delman, Keith A; Rizzo, Monica

2016-11-01

Scalp and neck melanomas (SNMs) have a relatively poor prognosis compared to other sites, and represent an anatomically challenging area for detection. The aim of this study was to identify the role of the hairdresser in detection of SNMs. A tertiary surgical oncology institutional database was retrospectively reviewed for all patients undergoing resection of a scalp, posterior neck, or retro auricular invasive primary melanoma between 2008 and 2014. SNMs accounted for 128 melanoma patients during the study period, with median age 66 years, 88 % male, and median Breslow thickness 1.55 mm. Hairdressers detected 10 % of all SNMs, with hairdresser-detected SNMs presenting 13 years younger (53 vs. 66 years, P = 0.015), and with a trend towards lower Breslow depth (1.15 vs. 1.63) and more frequent discovery in AJCC Stage Ia or Ib (66.7 % vs. 44.8 %) than otherwise-detected SNMs. Women with SNMs were 1.8-fold more likely than men to have their SNMs detected by a hairdresser (P = 0.001), and presented at higher AJCC clinical stage than men and required wider surgical resection margins (P = 0.011). Women with hairdresser-detected SNMs were younger, with lower Breslow thickness and lower AJCC Clinical Stage than women with otherwise-detected SNM. This study suggests that hairdressers play a critical role in detection of invasive primary scalp and neck melanoma, accounting for 10 % of all melanomas referred to a tertiary surgical oncology center. Quality improvement initiatives aimed at increasing early detection of scalp and neck melanoma should include members of the cosmetology community.

[Carcinoma of the uterine cervical canal. Staging and biometric assessment with magnetic resonance].

PubMed

Fischetti, S G; Politi, G; Lomeo, E; Garozzo, G; Di Leo, S; Nuciforo, G

1994-10-01

In uterine cervical canal carcinoma, the current clinical FIGO criteria often fail not only to differentiate stage IA2 from stage IB but also to demonstrate possible parametrial involvement. Moreover, the analysis of tumor volume and of the depth of neoplastic stromal invasion is not very reliable. The authors investigated MR accuracy in the definition of such variables: to this purpose, 24 patients with histologically confirmed endocervical adenocarcinoma were submitted to MRI, which was performed with an 0.5-T superconductive magnet. Sagittal and oblique transverse or sometimes coronal SE images, oriented so as to be perpendicular to longitudinal cervical major axis were obtained with T2 weighting (TR 1800 ms, TE 25-90 ms). MR data were correlated with pathologic findings. MR accuracy in demonstrating parametrial involvement was 92%, its sensitivity was 86% and specificity 97%. Volumetric MR data showed a high correlation (r = 0.970) with those derived from pathologic findings. In 92% of cases stromal invasion exceeded 5 mm. MRI, thanks to its high accuracy, should be included in diagnostic pretreatment protocols, even though FIGO criteria do not require it yet, especially in the presence of an endocervical adenocarcinoma. Moreover, the accurate definition of tumor volume can allow less extensive surgery with the same survival rates and fewer complications, which are frequently observed after radical hysterectomy.

Injectional anthrax at a Scottish district general hospital.

PubMed

Inverarity, D J; Forrester, V M; Cumming, J G R; Paterson, P J; Campbell, R J; Brooks, T J G; Carson, G L; Ruddy, J P

2015-04-01

This retrospective, descriptive case-series reviews the clinical presentations and significant laboratory findings of patients diagnosed with and treated for injectional anthrax (IA) since December 2009 at Monklands Hospital in Central Scotland and represents the largest series of IA cases to be described from a single location. Twenty-one patients who fulfilled National Anthrax Control Team standardized case definitions of confirmed, probable or possible IA are reported. All cases survived and none required limb amputation in contrast to an overall mortality of 28% being experienced for this condition in Scotland. We document the spectrum of presentations of soft tissue infection ranging from mild cases which were managed predominantly with oral antibiotics to severe cases with significant oedema, organ failure and coagulopathy. We describe the surgical management, intensive care management and antibiotic management including the first description of daptomycin being used to treat human anthrax. It is noted that some people who had injected heroin infected with Bacillus anthracis did not develop evidence of IA. Also highlighted are biochemical and haematological parameters which proved useful in identifying deteriorating patients who required greater levels of support and surgical debridement.

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

PubMed Central

Lee, Ye Seung; Kim, Hui Kwon; Kim, Hye Rim; Lee, Jong Yoon; Choi, Joong Wan; Bae, Eun Ju; Oh, Phil Soo; Park, Won Il; Ki, Chang Seok

2014-01-01

Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 (p.Gln213*). To our knowledge, this is a novel mutation in GNAS. PMID:25045367

Psychometric Evaluation and Norms for the Multidimensional Assessment of Interoceptive Awareness (MAIA) in a Clinical Eating Disorders Sample.

PubMed

Brown, Tiffany A; Berner, Laura A; Jones, Michelle D; Reilly, Erin E; Cusack, Anne; Anderson, Leslie K; Kaye, Walter H; Wierenga, Christina E

2017-09-01

Altered interoceptive awareness (IA) has been implicated in the pathophysiology of eating disorders; however, few comprehensive self-report measures of IA exist in eating disorders. The present study sought to validate the Multidimensional Assessment of Interoceptive Awareness (MAIA), originally developed to assess IA in individuals practicing mind-body therapies, in an eating disorder sample. Adult and adolescent patients (n = 376) completed assessments upon admission to a partial hospital programme. Analyses examined the factor structure of the MAIA, scale means, scale-scale correlations, internal consistency and construct validity. Analyses also examined associations between MAIA subscales and eating disorder symptoms. Results supported the original eight-factor structure of the MAIA. Internal consistency was acceptable, and the scales converged with associated measures. Importantly, Not Distracting, Self-regulation, Body Listening and Trusting were most strongly associated with eating disorder symptoms. Results support use of the MAIA among eating disorders and provide further support for the relevance of IA in eating disorders. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

A novel one-step real-time multiplex PCR assay to detect Streptococcus agalactiae presence and serotypes Ia, Ib, and III.

PubMed

Furfaro, Lucy L; Chang, Barbara J; Payne, Matthew S

2017-09-01

Streptococcus agalactiae is the leading cause of early-onset neonatal sepsis. Culture-based screening methods lack the sensitivity of molecular assays and do not indicate serotype; a potentially important virulence marker. We aimed to develop a multiplex PCR to detect S. agalactiae while simultaneously identifying serotypes Ia, Ib, and III; commonly associated with infant disease. Primers were designed to target S. agalactiae serotype-specific cps genes and the dltS gene. The assay was validated with 512 vaginal specimens from pregnant women. 112 (21.9%) were dltS positive, with 14.3%, 0.9%, and 6.3% of these identified as cps Ia, Ib, and III, respectively. Our assay is a specific and sensitive method to simultaneously detect S. agalactiae and serotypes Ia, Ib, and III in a single step. It is of high significance for clinical diagnostic applications and also provides epidemiological data on serotype, information that may be important for vaccine development and other targeted non-antibiotic therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemotherapy-induced alopecia in mice. Induction by cyclophosphamide, inhibition by cyclosporine A, and modulation by dexamethasone.

PubMed Central

Paus, R.; Handjiski, B.; Eichmüller, S.; Czarnetzki, B. M.

1994-01-01

We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs. One injection of CYP to mice with all back skin follicles in anagen VI induces severe alopecia that strikingly reproduces the follicle response, recovery, and histopathology seen in human CYP-IA. CYP dose-dependently induces abnormal follicular melanogenesis and dystrophic anagen or, in more severely damaged follicles, dystrophic catagen. Both dystrophy forms are followed by an extremely shortened telogen phase, but differ in the associated hair loss and in recovery patterns, which determines hair regrowth. This follicular response to CYP can be manipulated pharmacologically: systemic cyclosporine A shifts it toward a mild form of dystrophic anagen, thus retarding CYP-IA and prolonging "primary recovery". Topical dexamethasone, in contrast, forces follicles into dystrophic catagen, which augments CYP-IA, but accelerates the regrowth of normally pigmented hair ("secondary recovery"). Images Figure 2 Figure 3 Figure 4 Figure 6 Figure 7 Figure 8 Figure 10 PMID:8160773

Intelligent Structured Intermittent Auscultation (ISIA): evaluation of a decision-making framework for fetal heart monitoring of low-risk women

PubMed Central

2014-01-01

Background Research-informed fetal monitoring guidelines recommend intermittent auscultation (IA) for fetal heart monitoring for low-risk women. However, the use of cardiotocography (CTG) continues to dominate many institutional maternity settings. Methods A mixed methods intervention study with before and after measurement was undertaken in one secondary level health service to facilitate the implementation of an initiative to encourage the use of IA. The intervention initiative was a decision-making framework called Intelligent Structured Intermittent Auscultation (ISIA) introduced through an education session. Results Following the intervention, medical records review revealed an increase in the use of IA during labour represented by a relative change of 12%, with improved documentation of clinical findings from assessments, and a significant reduction in the risk of receiving an admission CTG (RR 0.75, 95% CI, 0.60 – 0.95, p = 0.016). Conclusion The ISIA informed decision-making framework transformed the practice of IA and provided a mechanism for knowledge translation that enabled midwives to implement evidence-based fetal heart monitoring for low risk women. PMID:24884597

Carbapenemase-producing Enterobacteriaceae: a 2-year surveillance in a hospital in Iaşi, Romania.

PubMed

Braun, Sascha D; Dorneanu, Olivia S; Vremeră, Teodora; Reißig, Annett; Monecke, Stefan; Ehricht, Ralf

2016-01-01

Limited information is currently available about the prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in Romania. Routine tests of 1,993 clinical isolates at a hospital in Iaşi yielded 46 isolates that were resistant to carbapenems. All 46 isolates were phenotypically and genotypically analyzed using VITEK-2 and DNA microarray-based assays. Isolates were assigned to Klebsiella pneumoniae and Enterobacter cloacae. For 39 isolates, carbapenem resistance was confirmed and 37 harbored at least one carbapenem resistance gene. Two isolates were probably resistant due to AmpC β-lactamases in combination with a porin loss. The overall concordance between detected phenotype and genotype was 95%. Our data show that carbapenemase-producing isolates with different underlying resistance mechanisms are still rare in Iaşi, but the global rise of CPE warrants intensified surveillance.

HIV single staging algorithm: integration and maximization of resources by reducing time between HIV diagnosis and treatment.

PubMed

Bennett, Berry; Hardy, Bonnie; Fordan, Sally; Haddock-Morilla, Lizzette; Rowlinson, Marie-Claire; Crowe, Susanne

2013-12-01

Early HIV diagnosis, linkage and engagement into care are vital to improved personal health outcomes. The initiation of antiretroviral therapy, with retention in care and drug adherence leads to viral load suppression, a significant decrease in HIV transmission rates and ultimately a reduction in HIV incidence rates. In the U.S only 51% of those diagnosed with HIV infection are retained in care and 28% have a suppressed viral load. Reducing the time and number of visits from HIV diagnosis to entry into care, has the potential to engage and treat an increased number of infected individuals. (1) Evaluate the feasibility of conducting HIV-1 supplemental testing concurrently with baseline clinical management testing; (2) to evaluate whether all tests could be completed and reported prior to the traditional posttest counseling appointment; (3) to monitor the return activity for posttest and medical provider appointments. Baseline CD4 and HIV-1 viral load tests were performed concurrently with an HIV-1/2 antibody immunoassay (IA) and HIV-1 Western blot (WB) on 105 individuals with preliminary positive rapid test results. Participating study-sites were located in high-risk, high-morbidity locations: a county jail, a county mobile unit and a county hospital emergency department. Based on the individual's self-reporting statement of "No" to a previous HIV diagnosis and the POC preliminary positive rapid test result, blood specimens were processed via the Single Staging Algorithm. Study site data and medical record review established time intervals between the rapid test and subsequent visits. Of the 105 individuals with HIV-1 preliminary positive rapid test results, 102 were confirmed positive with HIV-1 WB (plus 3rd generation IA repeatedly reactive) and one was confirmed by an HIV-1 WB indeterminate (gp160), HIV-1 Nucleic Acid Amplification Test (NAAT) reactive (an algorithm-defined early infection). The concordance between POC preliminary positive rapid tests and the confirmatory test of the single staging algorithm was 98%. Ninety-six (91%) HIV-1 baseline viral load test results and 82 (78%) CD4/CD8 absolute counts were performed and made available to the provider prior to posttest counseling. The average number of visits for posttest counseling at 14 days was 44.7% (range 37.9-56.5%) with an additional 31.1% (range 22.7-37.9%) returning within 30 days. The average number of clients that returned for the medical provider appointment was 55.4%. A high percentage of HIV-1 clinical management baseline results (78-91%) and 100% confirmatory diagnostic results were completed and reported prior to the traditional posttest counseling appointment. Additional data and analysis is needed to determine the impact of the Single Staging Algorithm on medical provider appointments if the posttest appointment is more than 30 days after the preliminary HIV diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimal Futility Interim Design: A Predictive Probability of Success Approach with Time-to-Event Endpoint.

PubMed

Tang, Zhongwen

2015-01-01

An analytical way to compute predictive probability of success (PPOS) together with credible interval at interim analysis (IA) is developed for big clinical trials with time-to-event endpoints. The method takes account of the fixed data up to IA, the amount of uncertainty in future data, and uncertainty about parameters. Predictive power is a special type of PPOS. The result is confirmed by simulation. An optimal design is proposed by finding optimal combination of analysis time and futility cutoff based on some PPOS criteria.

Survival after resection for lung cancer is the outcome that matters.

PubMed

Reed, Michael F; Molloy, Mark; Dalton, Erica L; Howington, John A

2004-11-01

Lung cancer is the leading cause of cancer mortality in the United States. Stage-specific survival is well documented in national data sets; however, there remains limited recording of longitudinal survival in individual centers. The VistA Surgery Package was employed to list operations performed by the thoracic surgery service at one Veterans Administration (VA) Medical Center. During a period of 107 months, 416 thoracic operations were performed, 211 of them for lung cancer. Stage distribution was 66% stage I, 18% stage II, 12% stage III, and 4% stage IV. During follow-up, 102 patients died, 57 of them from disease-specific causes. Median survival was 39 months for stage I. Disease-specific median survival was 83 months for stage I, and 5-year survival was 52% (72% for stage IA and 32% for stage IB). Pulmonary resection offers high disease-free survival for early-stage lung cancer. Decentralized hospital computer programming (DHCP) allows individual oncology programs to reliably measure survival. Use of this important outcome measure in quality improvement programs facilitates realistic counseling of patients and meaningful assessments of practice effectiveness.

Conjugal transfer of aac(6')Ie-aph(2″)Ia gene from native species and mechanism of regulation and cross resistance in Enterococcus faecalis MCC3063 by real time-PCR.

PubMed

Jaimee, G; Halami, P M

2017-09-01

High level aminoglycoside resistance (HLAR) in the lactic acid bacteria (LAB) derived from food animals is detrimental. The aim of this study was to investigate the localization and conjugal transfer of aminoglycoside resistance genes, aac(6')Ie-aph(2″)Ia and aph(3')IIIa in different Enterococcus species. The cross resistance patterns in Enterococcus faecalis MCC3063 to clinically important aminoglycosides by real time PCR were also studied. Southern hybridization experiments revealed the presence of aac(6')Ie-aph(2 ″ )Ia and aph(3')IIIa genes conferring HLAR in high molecular weight plasmids except in Lactobacillus plantarum. The plasmid encoded bifunctional aac(6')Ie-aph(2″)Ia gene was transferable from Enterococcus avium (n = 2), E. cecorum (n = 1), E. faecalis (n = 1) and Pediococcus lolii (n = 1) species into the recipient strain; E. faecalis JH2-2 by filter mating experiments thus indicating the possible risks of gene transfer into pathogenic strains. Molecular analysis of cross resistance patterns in native isolate of E. faecalis MCC3063 carrying aac(6')Ie-aph(2″)Ia and aph(3')IIIa gene was displayed by quantification of the mRNA levels in this study. For this, the culture was induced with increasing concentrations of gentamicin, kanamycin and streptomycin (2048, 4096, 8192, 16384 μg/mL) individually. The increasing concentrations of gentamicin and kanamycin induced the expression of the aac(6')Ie-aph(2″)Ia and aph(3')IIIa resistance genes, respectively. Interestingly, it was observed that induction with streptomycin triggered a significant fold increase in the expression of the aph(3')IIIa gene which otherwise was not known to modify the aminoglycoside. This is noteworthy as streptomycin was found to confer cross resistance to structurally unrelated kanamycin. Also, expression of the aph(3')IIIa gene when induced with streptomycin, revealed that bacteria harbouring this gene will be able to overcome streptomycin bactericidal action at specific concentrations. HLAR in E. faecalis MCC3063 may be due to the combined expression of both the aac(6')Ie-aph(2″)Ia and aph(3')IIIa genes which could be therapeutically challenging. A combined expression of both the genes in E. faecalis MCC3063 may yield HLAR which could be therapeutically challenging. The study highlights the significant alterations in the mRNA expression levels of aac(6')Ie-aph(2″)Ia and aph(3')IIIa in resistant pathogens, upon exposure to clinically vital aminoglycosides. Copyright © 2017 Elsevier Ltd. All rights reserved.

Induced adult stem (iAS) cells and induced transit amplifying progenitor (iTAP) cells-a possible alternative to induced pluripotent stem (iPS) cells?

PubMed

Heng, Boon Chin; Richards, Mark; Ge, Zigang; Shu, Yimin

2010-02-01

The successful derivation of iPSC lines effectively demonstrates that it is possible to reset the 'developmental clock' of somatic cells all the way back to the initial embryonic state. Hence, it is plausible that this clock may instead be turned back half-way to a less immature developmental stage that is more directly applicable to clinical therapeutic applications or for in vitro pharmacology/toxicology screening assays. Such a suitable developmental state is postulated to be either the putative transit amplifying progenitor stage or adult stem cell stage. It is hypothetically possible to reprogram mature and terminally differentiated somatic cells back to the adult stem cell or transit amplifying progenitor stage, in a manner similar to the derivation of iPSC. It is proposed that the terminology 'Induced Adult Stem Cells' (iASC) or 'Induced Transit Amplifying Progenitor Cells' (iTAPC) be used to described such reprogrammed somatic cells. Of particular interest, is the possibility of resetting the developmental clock of mature differentiated somatic cells of the mesenchymal lineage, explanted from adipose tissue, bone marrow and cartilage. The putative adult stem cell sub-population from which these cells are derived, commonly referred to as 'mesenchymal stem cells', are highly versatile and hold much therapeutic promise in regenerative medicine, as attested to by numerous human clinical trials and animal studies. Perhaps it may be appropriate to term such reprogrammed cells as 'Induced Mesenchymal Stem Cells' (iMSC) or as 'Induced Mesenchumal Progenitor Cells' (iMPC). Given that cells from the same organ/tissue will share some commonalities in gene expression, we hypothesize that the generation of iASC or iTAPC would be more efficient as compared to iPSC generation, since a common epigenetic program must exist between the reprogrammed cells, adult stem cell or progenitor cell types and terminally differentiated cell types from the same organ/tissue.

Interoceptive Processes in Anorexia Nervosa in the Time Course of Cognitive-Behavioral Therapy: A Pilot Study.

PubMed

Fischer, Dana; Berberich, Götz; Zaudig, Michael; Krauseneck, Till; Weiss, Sarah; Pollatos, Olga

2016-01-01

Previous studies report reduced interoceptive abilities in anorexia nervosa (AN) using various methods. Recent research suggests that different levels of interoceptive processes aiming at different subdomains of interoceptive abilities must be further distinguished as these levels can be differentially affected. Two important levels refer to interoceptive accuracy (IA) derived from objective performance tasks such as the heartbeat detection task and interoceptive sensibility (IS) as assessed by self-report. There is a lack of studies investigating both IA and IS in AN and examining them in the time course of therapy. The aim of this pilot study was to evaluate the different interoceptive processes - especially IA and IS - in the time course of therapy. Fifteen patients with AN (restricting type) from the Psychosomatic Clinic in Windach were investigated three times (T1, T2, T3) during a standardized cognitive-behavioral therapy and compared with 15 matched healthy controls assessed at Ulm University in a comparable design. All participants performed the heartbeat detection task examining IA and completed standard psychological assessments including an assessment of IS. Patients with AN showed a significantly decreased weight, higher levels of depression, and both reduced IA and IS compared to healthy controls at T1. Following therapy, patients recovered in terms of weight and depression symptomatology. A descriptive trend for recovering from IA and IS was observed. Our findings suggest that interoceptive deficits are present in recovered patients. Therefore, further investigations are needed with more patients, differentiating between relapsed and recovered patients, and more specific training methods to improve interoceptive processes.

Comparative performance of electrochemiluminescence immunoassay and EIA for HIV screening in a multiethnic region of China.

PubMed

Bi, Xiaohui; Ning, Hongxia; Wang, Tingting; Li, Dongdong; Liu, Yongming; Yang, Tingfu; Yu, Jiansheng; Tao, Chuanmin

2012-01-01

The recent approval of 4th generation HIV tests has forced many laboratories to decide whether to shift from 3rd to these tests. There are limited published studies on the comparative evaluation of these two different assays. We compare the performance of fourth-generation electrochemiluminescence immunoassay (ChIA) and third-generation enzyme linked immunosorbent assay (EIA) for human immunodeficiency virus (HIV) screening and gauge whether the shift from EIA to ChIA could be better in a multiethnic region of China. We identified a large number of routine specimens (345,492) using two different assays from Jan 2008 to Aug 2011 in a teaching hospital with high sample throughput. Of the 344,596 specimens with interpretable HIV test results, 526(0.23%) of 228,761 using EIA and 303(0.26%) of 115,835 using ChIA were HIV-1 positive. The false-positive rate of EIA was lower than that of ChIA [0.03% vs. 0.08%, odds ratio 0.33 (95% confidence interval 0.24, 0.45)]. The positive predictive value (PPV) of EIA (89.6%) was significantly higher than that of ChIA (76.1%) (<0.001), reflecting the difference between the two assays. The clinical sensitivities of two assays in this study were 99.64% for EIA and 99.88% for ChIA. Caution is needed before shifting from 3rd to 4th generation HIV tests. Since none of these tests are perfect, different geographic and ethnic area probably require different considerations with regard to HIV testing methods, taking into account the local conditions.

[Role of c+70g single nucleotide polymorphism of endothelin receptor a gene in the development of ischemic atherothrombotic stroke].

PubMed

Oleshko, Tetiana B; Obukhova, Olha A; Oleshko, Tetiana M; Matlai, Olha I; Sotnikov, Dmitriy D; Harbuzova, Viktoriia Yu

Endothelial dysfunction is the basic pathogenic development mechanism of ischemic atherothrombotic stroke (IAS). One of the reasons for changes of endothelin structure and properties and its receptor can be genetic polymorphism of their genes. Study of C+70G polymorphic variant associations of endothelin receptor A gene (EDNRA) with IAS development became the goal of research. Venous blood of 170 patients with IAS and 124 persons without cerebrovascular pathology was used for the research. The groups did not differ in the ratio of two sexes (P = 0,294 for the ?2-test), but the average age of the first group (76,7 ± 0,93 years) was significantly higher than that of the second one (P < 0,001). Determination of allelic variant of EDNRA gene by C+70G polymorphism was carried out using method of polymerase chain reaction with further analysis of restriction fragment length. As a result of the conducted genotyping, it has been discovered that homozygote correlation by the main allele (CC), heterozygotes (CG) and homozygotes by minor allele (GG) does not differ authentically in patients with IAS and control group (24.1 %, 57.6 %, 8.2 % against 29.0 %, 50.0 %, 21.0 %; ? = 0.426). It is shown that association of the studied genetic marker with the scope of brain damage, localization of atherothrombotic process, course severity, recurrence and neurological manifestations of IAS. There is no association between the C+70G polymorphism of the EDNRA gene and the development of IAS and its clinical characteristics.

Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants.

PubMed

Silvestri, Romano; Artico, Marino

2005-01-01

Indolyl aryl sulfones (IASs) are a potent class of NNRTIs developed from L-737,126, a lead agent discovered by Merck AG. IAS derivatives are endowed with inhibitory activities against wt HIV-1 in the low nanomolar concentration range. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of the aryl sulfonyl moiety furnished IAS derivatives such as 5-chloro- or 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide, which showed very potent and selective anti-HIV-1 activity against some mutants carrying NNRTI resistant mutations at positions 103 and 181 of the reverse transcriptase. IAS derivatives bearing 2-hydroxyethylcarboxyamide or 2-hydroxyethylcarboxyhydrazide groups at position 2 of the indole nucleus were more active than L-737,126 against the K103N-Y181C double mutant. A great improvement of antiviral activity against wt HIV-1 and resistant mutants was obtained by coupling 1-3 simple amino acids, such as glycine and alanine, in sequence, with the 3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carbonyl moiety. The transformation of the chain terminus into amide or hydrazide, produced short peptides with high selectivity and potent activity against wt HIV-1, and the viral mutants Y181C, K103N-Y181C and EFV(R). IAS having two halogen atoms at the indole showed potent inhibitory activity against the Y181C and the EFV(R) resistant mutant strains. In particular, the introduction of a fluorine atom at position 4 of the indole ring notably contributed to improve the antiviral activities against both wt and the related resistant mutants. 5-Nitro-IASs were highly active against wt HIV-1 and exhibited low cytotoxicity. Experimental data highlighted the class IAS derivatives as promising candidates for clinical trials.

Therapeutic effect of immunoadsorption and subsequent immunoglobulin substitution in patients with dilated cardiomyopathy: Results from the observational prospective Bad Berka Registry.

PubMed

Ohlow, Marc-Alexander; Brunelli, Michele; Schreiber, Matthias; Lauer, Bernward

2017-02-01

Elimination of cardiac autoantibodies, frequently detected in patients with dilated cardiomyopathy (DCM), with immunoadsorption (IA) improves functional capacity and left ventricular (LV) function. This study aimed to prospectively address this issue in a large cohort of unselected patients. Consecutive patients undergoing IA followed by IgG substitution were included. Clinical and echocardiographic parameters were assessed at baseline (BL) and 12-month follow-up (FU). Patients were classified as IA responders when ≥2 of the following criteria were achieved: improvement in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) ≥5 points, symptoms [≥1 New York Heart Association (NYHA) class], LV ejection fraction (EF) ≥10% or decrease in LV end-diastolic diameter (EDD) ≥10%, or N-terminal pro B-type natriuretic peptide (NT-pro-BNP) ≥50%. 93 patients (median age 61 years, LVEF 30%, duration of symptoms 14 months, 87% in NYHA class III/IV, >90% treated with β-blocker/angiotensin-converting enzyme inhibitor) were included. When the entire cohort was analyzed, a significant improvement in MLHFQ (50 vs. 26 points), NYHA-class (median 3.0 vs. 2.0), LVEF (30% vs. 38%), LVEDD (62 vs. 59mm), NT-pro-BNP (892 vs. 523pg/ml) was observed at FU (p<0.05 for all). 48% (n=43) were classified as responders. Those were characterized by a shorter disease duration (11 vs. 22 months), larger BL LVEDD (64 vs. 60mm), presence of >1 viral genome, and higher values of mononuclear inflammatory cells at endomyocardial biopsy. Sixteen (17.2%) patients experienced IA related complications. A positive response is observed in 48% of inflammatory DCM patients undergoing IA, and this translates into a significant improvement in clinical and echocardiographic parameters. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

[Indication for limited surgery on small lung cancer tumors measuring 1cm or less in diameter on preoperative computed tomography and long-term results].

PubMed

Togashi, K; Koike, T; Emura, I; Usuda, H

2008-07-01

Non-invasive lung cancers showed a good prognosis after limited surgery. But it is still uncertain about invasive lung cancers. We investigated the indications for limited surgery for small lung cancer tumors measuring 1 cm or less in diameter on preoperative computed tomography (CT). This study retrospectively analyzed of 1,245 patients who underwent complete resection of lung cancer between 1989 and 2004 in our hospital. Sixty-two patients (5%) had tumors measuring 1 cm or less in diameter. The probability of survival was calculated using the Kaplan-Meier method. All diseases were detected by medical checkup, 52 % of the patients were not definitively diagnosed with lung cancer before surgery. Adenocarcinoma was histologically diagnosed in 49 patients (79%). Other histologic types included squamous cell carcinoma (8), large cell carcinoma (1), small cell carcinoma (1), carcinoid (2), and adenosquamous cell carcinoma (1). Fifty-seven patients (92%) showed pathologic stage IA. The other stages were IB (2), IIA (1), and IIIB (2). There were 14 bronchioloalveolar carcinomas (25% of IA diseases). The 5-year survival rates of IA patients were 90%. The 5-year survival rate of patients with tumors measuring 1cm or less diameter was 91% after lobectomy or pneumonectomy, and 90% after wedge resection or segmentectomy. There were 3 deaths from cancer recurrence, while there were no deaths in 14 patients with bronchioloalveolar carcinoma After limited surgery, non-invasive cancer showed good long-term results, while invasive cancer showed a recurrence rate of 2.3% to 79% even though the tumor measured 1 cm or less in diameter on preoperative CT.

Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis.

PubMed

Friedmacher, Florian; Puri, Prem

2012-08-01

Internal anal sphincter (IAS) achalasia is a clinical condition with presentation similar to Hirschsprung's disease, but with the presence of ganglion cells on rectal suction biopsy (RSB). The diagnosis is made by anorectal manometry (ARM), which demonstrates the absence of the rectosphincteric reflex on rectal balloon inflation. The recommended treatment of choice is posterior IAS myectomy. Recently, intrasphincteric botulinum toxin (Botox) injection has been effectively used for treatment of IAS achalasia. The aim of this meta-analysis was to compare the efficacy of posterior IAS myectomy with intrasphincteric Botox injection for treatment of IAS achalasia. A systematic literature search for relevant articles was conducted using the following databases: MEDLINE( ® ), EMBASE(®), ISI Web of Science(SM) and the Cochrane Library. A meta-analysis was performed with the studies where IAS achalasia was diagnosed based on the results of ARM and RSB. Odds ratio (OR) with 95 % confidence intervals were calculated. Sixteen prospective and retrospective studies, published from 1973 to 2009, were identified. A total of 395 patients with IAS achalasia were included in this meta-analysis. Fifty-eight percent of patients underwent IAS myectomy and 42 % Botox injection. Regular bowel movements were significantly more frequent after IAS myectomy (OR 0.53, [95 % CI 0.29-0.99]; p = 0.04). There was no significant difference in continued use of laxatives or rectal enemas (OR 0.92, [95 % CI 0.34-2.53], p = 0.89) and in overall complication rates between both procedures (OR 0.68, [95 % CI 0.38-1.21]; p = 0.19). Looking at specific complications, the rate of transient faecal incontinence was significantly higher after Botox injection (OR 0.07, [95 % CI 0.01-0.54]; p < 0.01). Constipation and soiling were not significantly different between both procedures (OR 0.66, [95 % CI 0.30-1.48]; p = 0.31 and OR 0.24, [95 % CI 0.03-2.07]; p = 0.25). The rate of non-response was significantly higher after Botox injection (OR 0.52, [95 % CI 0.27-0.99]; p = 0.04). Subsequent surgical treatment was significantly more frequent after Botox injection (OR 0.18, [95 % CI 0.07-0.44]; p < 0.0001). Short- and long-term improvements were significantly more frequent after IAS myectomy (OR 0.56, [95 % CI 0.32-0.97]; p = 0.04 and OR 0.25, [95 % CI 0.15-0.41]; p < 0.0001). This meta-analysis indicates that in patients with IAS achalasia, posterior IAS myectomy appears to be a more effective treatment option compared to intrasphincteric Botox injection. After Botox injection, the rate of transient faecal incontinence, non-response and subsequent surgical procedures were significantly higher compared to IAS myectomy.

The Carnegie Supernova Project. I. Third Photometry Data Release of Low-redshift Type Ia Supernovae and Other White Dwarf Explosions

NASA Astrophysics Data System (ADS)

Krisciunas, Kevin; Contreras, Carlos; Burns, Christopher R.; Phillips, M. M.; Stritzinger, Maximilian D.; Morrell, Nidia; Hamuy, Mario; Anais, Jorge; Boldt, Luis; Busta, Luis; Campillay, Abdo; Castellón, Sergio; Folatelli, Gastón; Freedman, Wendy L.; González, Consuelo; Hsiao, Eric Y.; Krzeminski, Wojtek; Persson, Sven Eric; Roth, Miguel; Salgado, Francisco; Serón, Jacqueline; Suntzeff, Nicholas B.; Torres, Simón; Filippenko, Alexei V.; Li, Weidong; Madore, Barry F.; DePoy, D. L.; Marshall, Jennifer L.; Rheault, Jean-Philippe; Villanueva, Steven

2017-11-01

We present final natural-system optical (ugriBV) and near-infrared (YJH) photometry of 134 supernovae (SNe) with probable white dwarf progenitors that were observed in 2004-2009 as part of the first stage of the Carnegie Supernova Project (CSP-I). The sample consists of 123 Type Ia SNe, 5 Type Iax SNe, 2 super-Chandrasekhar SN candidates, 2 Type Ia SNe interacting with circumstellar matter, and 2 SN 2006bt-like events. The redshifts of the objects range from z=0.0037 to 0.0835; the median redshift is 0.0241. For 120 (90%) of these SNe, near-infrared photometry was obtained. Average optical extinction coefficients and color terms are derived and demonstrated to be stable during the five CSP-I observing campaigns. Measurements of the CSP-I near-infrared bandpasses are also described, and near-infrared color terms are estimated through synthetic photometry of stellar atmosphere models. Optical and near-infrared magnitudes of local sequences of tertiary standard stars for each supernova are given, and a new calibration of Y-band magnitudes of the Persson et al. standards in the CSP-I natural system is presented.

Intimate partner violence and repeat induced abortion in Italy: A cross sectional study.

PubMed

Citernesi, Angela; Dubini, Valeria; Uglietti, Anna; Ricci, Elena; Cipriani, Sonia; Parazzini, Fabio

2015-01-01

To investigate the impact of intimate partner violence (IPV) on the risk of repeat induced abortion (RIA), we compared IPV history among women with and without previous induced abortion (IA). All consecutive women aged 18 years or more requiring IA in 12 Italian abortion clinics were eligible for inclusion in the study. They were asked to fill in an anonymous, self-developed questionnaire assessing sociodemographic data and their history of different types of violence and related risk factors. The analysis included 1030 women, 624 (60.6%) of whom reported a previous IA. Past or current IPV was reported by 19.3%: 7.0% reported sexual violence, 11.3% physical abuse and 12.1% psychological abuse. Past or current IPV was reported by 22.3% of women with RIA and 14.8% of those undergoing their first IA (adjusted odds ratio 1.57, 95% confidence interval 1.07-2.30; p = 0.02). When we considered sexual, psychological and physical abuse separately, we found that any kind of abuse was more frequent in women with RIA than in women with no previous IA. This study underlines the impact of IPV on the risk of RIA and suggests the need for screening for IPV among women requiring abortion, in order to identify women at risk of RIA and to improve their general and reproductive health.

Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

PubMed

Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

2014-08-01

Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was abolished in rhIDUA-treated joints only. Intra-articular rhIDUA is well-tolerated and safe in the canine MPS I animal model. Qualitative and quantitative assessments indicate that IA-rhIDUA successfully reduces tissue and cellular GAG storage in synovium and articular cartilage, including cartilage deep to the articular surface, and eliminates inflammatory macrophages from synovial tissue. The MPS I canine IA-rhIDUA results suggest that clinical studies should be performed to determine if IA-rhIDUA is a viable approach to ameliorating refractory orthopedic disease in human MPS I. Copyright © 2014 Elsevier Inc. All rights reserved.

Genetic and environmental risk factors for rheumatoid arthritis.

PubMed

Deane, Kevin D; Demoruelle, M Kristen; Kelmenson, Lindsay B; Kuhn, Kristine A; Norris, Jill M; Holers, V Michael

2017-02-01

Multiple genetic and environmental factors have been associated with an increased risk for rheumatoid arthritis (RA). Of these, the strongest associations have been seen with female sex, a family history of RA, the genetic factor the "shared epitope," and exposure to tobacco smoke. There is also renewed interest in mucosal inflammation and microbial factors as contributors to the development of RA. However, the identification of a "preclinical" period of RA that can be defined as local or systemic autoimmunity as measured by autoantibodies and other biomarkers prior to the development of clinically apparent synovitis suggests that the risk factors for RA are acting long prior to first clinical evidence of IA. As such, a major challenge to the field will be to investigate the full spectrum of the development of RA, from initiation and propagation of autoimmunity during preclinical RA and transition to clinically apparent synovitis and classifiable RA, to determine which genetic and environmental factors are important at each stage of disease development. Understanding the exact role and timing of action of risk factors for RA is especially important given the advent of prevention trials in RA, and the hope that a full understanding of genetic and environmental factors in RA could lead to effective preventive interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of the Effect of a Single Intra-articular Injection of Allogeneic Neonatal Mesenchymal Stromal Cells Compared to Oral Non-Steroidal Anti-inflammatory Treatment on the Postoperative Musculoskeletal Status and Gait of Dogs over a 6-Month Period after Tibial Plateau Leveling Osteotomy: A Pilot Study.

PubMed

Taroni, Mathieu; Cabon, Quentin; Fèbre, Marine; Cachon, Thibaut; Saulnier, Nathalie; Carozzo, Claude; Maddens, Stéphane; Labadie, Fabrice; Robert, Clément; Viguier, Eric

2017-01-01

Compare the clinical and pressure walkway gait evolution of dogs after a tibial plateau leveling osteotomy (TPLO) for a cranial cruciate ligament rupture (CrCLR) and treatment with either a 1-month course of non-steroidal anti-inflammatory drugs (NSAIDs) or a single postoperative intra-articular (IA) injection of allogeneic neonatal mesenchymal stromal cells (MSCs). Prospective, double-blinded, randomized, controlled, monocentric clinical study. Sixteen client-owned dogs. Dogs with unilateral CrCLR confirmed by arthroscopy were included. Allogeneic neonatal canine MSCs were obtained from fetal adnexa retrieved after C-section performed on healthy pregnant bitches. The dogs were randomly allocated to either the "MSCs group," receiving an IA injection of MSCs after TPLO, followed by placebo for 1 month, or the "NSAIDs group," receiving IA equivalent volume of MSCs vehicle after TPLO, followed by oral NSAID for 1 month. One of the three blinded evaluators assessed the dogs in each group before and after surgery (1, 3, and 6 months). Clinical score and gait and bone healing process were assessed. The data were statistically compared between the two groups for pre- and postoperative evaluations. Fourteen dogs (nine in the MSCs group, five in the NSAIDs group) completed the present study. No significant difference was observed between the groups preoperatively. No local or systemic adverse effect was observed after MSCs injection at any time point considered. At 1 month after surgery, bone healing scores were significantly higher in the MSCs group. At 1, 3, and 6 months after surgery, no significant difference was observed between the two groups for clinical scores and gait evaluation. A single IA injection of allogeneic neonatal MSCs could be a safe and valuable postoperative alternative to NSAIDs for dogs requiring TPLO surgery, particularly for dogs intolerant to this class of drugs.

AC coupled three op-amp biopotential amplifier with active DC suppression.

PubMed

Spinelli, E M; Mayosky, M A

2000-12-01

A three op-amps instrumentation amplifier (I.A) with active dc suppression is presented. dc suppression is achieved by means of a controlled floating source at the input stage, to compensate electrode and op-amps offset voltages. This isolated floating source is built around an optical-isolated device using a general-purpose optocoupler, working as a photovoltaic generator. The proposed circuit has many interesting characteristics regarding simplicity and cost, while preserving common mode rejection ratio (CMRR) and high input impedance characteristics of the classic three op-amps I.A. As an example, a biopotential amplifier with a gain of 80 dB, a lower cutoff frequency of 0.1 Hz, and a dc input range of +/- 8 mV was built and tested. Using general-purpose op-amps, a CMRR of 105 was achieved without trimmings.

Clinical responsiveness of self-report functional assessment measures for children with juvenile idiopathic arthritis undergoing intraarticular corticosteroid injections.

PubMed

Brown, G Ted; Wright, F Virginia; Lang, Bianca A; Birdi, Nina; Oen, Kim; Stephens, Derek; McComas, Joan; Feldman, Brian M

2005-12-15

The Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Functional Assessment Report (JAFAR), and Juvenile Arthritis Functional Status Index (JASI) are widely used functional measures for juvenile idiopathic arthritis (JIA) that differ in content, format, and completion time. We compared the responsiveness and child-parent agreement of the JAFAR, CHAQ, and JASI in a prospective, multicenter study. Children and adolescents from 5 rheumatology centers were enrolled. Subjects were about to undergo therapy (intraarticular corticosteroid injections [IAS] and methotrexate or hip surgery (MTX/hip]) expected to produce a functional improvement. All subjects were studied before the intervention and at 6 weeks and 6 months posttreatment. At each study visit, the 3 measures were administered in randomized, balanced order to both parents and children. A total of 92 subjects (mean age 12.8 years) were enrolled in the study, 74 of which were in the IAS group. The responsiveness of all 3 measures was moderate to strong. The standardized response mean at 6 weeks for the IAS group on the JAFAR, CHAQ, and JASI was 0.41 (95% confidence interval [95% CI] 0.18, 0.64), 0.70 (95% CI 0.47, 0.93), and 0.36 (95% CI 0.13, 0.59), respectively. The CHAQ was somewhat more responsive to change at 6 weeks (IAS group: relative efficiency 0.34 [JAFAR], 0.27 [JASI]), but less responsive at 6 months (MTX/hip group: relative efficiency 5.1 [JAFAR], 3.9 [JASI]). All 3 questionnaires showed acceptable parent-child agreement, and overall, there were few differences between the 3 questionnaires. The functional outcome measures currently used for JIA are all adequately responsive for use in trials or in the clinic setting. The choice of which measure to use should therefore be based on the time available for completion, the intended clinical/research use, and the depth of content required.

Antibiotic therapy in preterm premature rupture of the membranes.

PubMed

Yudin, Mark H; van Schalkwyk, Julie; Eyk, Nancy Van

2009-09-01

To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. The Society of Obstetricians and Gynaecologists of Canada. 1. Following PPROM at < or = 32 weeks' gestation, antibiotics should be administered to women who are not in labour in order to prolong pregnancy and to decrease maternal and neonatal morbidity. (I-A) 2. The use of antibiotics should be gestational-age dependent. The evidence for benefit is greater at earlier gestational ages (< 32 weeks). (I-A) 3. For women with PPROM at > 32 weeks' gestation, administration of antibiotics to prolong pregnancy is recommended if fetal lung maturity can not be proven and/or delivery is not planned. (I-A) 4. Antibiotic regimens may consist of an initial parenteral phase followed by an oral phase, or may consist of only an oral phase. (I-A) 5. Antibiotics of choice are penicillins or macrolide antibiotics (erythromycin) in parenteral and/or oral forms. (I-A) In patients allergic to penicillin, macrolide antibiotics should be used alone. (III-B) 6. The following two regimens may be used (the two regimens were used in the largest PPROM randomized controlled trials that showed a decrease in both maternal and neonatal morbidity): (1) ampicillin 2 g IV every 6 hours and erythromycin 250 mg IV every 6 hours for 48 hours followed by amoxicillin 250 mg orally every 8 hours and erythromycin 333 mg orally every 8 hours for 5 days (I-A); (2) erythromycin 250 mg orally every 6 hours for 10 days (I-A) 7. Amoxicillin/clavulanic acid should not be used because of an increased risk of necrotizing enterocolitis in neonates exposed to this antibiotic. Amoxicillin without clavulanic acid is safe. (I-A) 8. Women presenting with PPROM should be screened for urinary tract infections, sexually transmitted infections, and group B streptococcus carriage, and treated with appropriate antibiotics if positive. (II-2B).

Reliable Diagnosis of Carnitine Palmitoyltransferase Type IA Deficiency by Analysis of Plasma Acylcarnitine Profiles.

PubMed

Heiner-Fokkema, M Rebecca; Vaz, Frédéric M; Maatman, Ronald; Kluijtmans, Leo A J; van Spronsen, Francjan J; Reijngoud, Dirk-Jan

2017-01-01

Carnitine palmitoyltransferase IA (CPT-IA) deficiency is an inherited disorder of the carnitine cycle (MIM #255120). Patients affected by this deficiency might be missed easily because of lack of specific and sensitive biochemical markers. In this study, sensitivity and specificity of plasma free carnitine (C0) and long-chain acylcarnitines (lc-ac: C16:0-, C16:1-, C18:0-, C18:1- and C18:2-ac) was evaluated, including the sum of lc-ac (∑lc-ac) and the molar ratios C0/(C16:0-ac+C18:0-ac) and C0/∑lc-ac. Nine plasma acylcarnitine profiles of 4 CPT-IA deficient patients were compared with profiles of 2,190 subjects suspected of or diagnosed with an inherited disorder of metabolism. Age-dependent reference values were calculated based on the patient population without a definite diagnosis of an inborn error of metabolism (n = 1,600). Sensitivity, specificity, and Receiver Operating Characteristic (ROC) curves were calculated based on samples of the whole patient population. Concentrations of C0 in plasma were normal in all CPT-IA deficient patient samples. ROC analyses showed highest diagnostic values for C18:0-ac, C18:1-ac, and ∑lc-ac (AUC 1.000) and lowest for C0 (AUC 0.738). Combining two markers, i.e., a plasma C18:1-ac concentration <0.05 μmol/L and a molar ratio of C0/(C16:0-ac+C18:0-ac) >587, specificity to diagnose CPT-IA deficiency increased to 99.3% compared with either C18:1-ac (97.4%) or C0/(C16:0-ac+C18:0-ac) (96.9%) alone, all at a sensitivity of 100%. Combination of a low concentration of C18:1-ac with a high molar ratio of C0/(C16:0-ac+C18:0-ac) ratio in plasma has high diagnostic value for CPT-IA deficiency. Patients with a clinical suspicion of CPT-IA deficiency can be diagnosed with this test combination.

Single administration of intra-articular bupivacaine in arthroscopic knee surgery: a systematic review and meta-analysis.

PubMed

Sun, Qi-Bin; Liu, Shi-Dong; Meng, Qin-Jun; Qu, Hua-Zheng; Zhang, Zheng

2015-02-10

Single administration of intra-articular (IA) bupivacaine for pain relief after arthroscopic knee surgery is effective, but its active duration and dose-response relationship is unclear. We conducted this meta-analysis to summarize all published randomized controlled trials (RCTs), thus providing the most recent information on the safety and efficacy of single-administration IA bupivacaine for pain relief after arthroscopic knee surgery, and to determine whether a dose-response relationship exists. A systematic electronic literature search (through April 2014) was conducted to identify those RCTs that addressed the safety and efficacy of a single administration of IA bupivacaine for pain management after arthroscopic knee surgery. Subgroup analysis was conducted to determine changes in visual analog scale (VAS) scores at seven postoperative time points. Meta-regression and subgroup analyses were carried out to assess the effects of various treatment factors on efficacy and to evaluate the dose-response relationship of bupivacaine. Weighted mean differences or relative risks were calculated and pooled using a random-effects model. Twenty-eight trials involving 1,560 patients who underwent arthroscopic knee surgery met the inclusion criteria. The trials were subject to medium risk of bias. VAS scores at 2, 4, 6, 12, and 24 h postoperatively were significantly lower, the number of patients requiring supplementary analgesia was smaller, and the time to first request for analgesia was longer in the IA bupivacaine group than in the placebo group. The analgesic effect of single-administration IA bupivacaine may be associated with the effect of concomitant administration of epinephrine and concentration of bupivacaine, and no dose-response relationship was identified. No significant difference in side effects was detected between groups. Current evidence shows that the use of single-administration IA bupivacaine is effective for postoperative pain management in patients undergoing arthroscopic knee surgery, with satisfactory short-term safety. Low-dose administration of IA bupivacaine 0.5% combined with epinephrine adjuvant in clinical practice should be performed. Additional high-quality RCTs with longer follow-up periods are required to examine the safety of single-administration IA bupivacaine.

Characterization of Specific Immune Responses to Different Aspergillus Antigens during the Course of Invasive Aspergillosis in Hematologic Patients

PubMed Central

Beauvais, Anne; Beau, Remi; Candoni, Anna; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Zanetti, Eleonora; Quadrelli, Chiara; Codeluppi, Mauro; Guaraldi, Giovanni; Pagano, Livio; Caira, Morena; Giovane, Cinzia Del; Maccaferri, Monica; Stefani, Alessandro; Morandi, Uliano; Tazzioli, Giovanni; Girardis, Massimo; Delia, Mario; Specchia, Giorgina; Longo, Giuseppe; Marasca, Roberto; Narni, Franco; Merli, Francesco; Imovilli, Annalisa; Apolone, Giovanni; Carvalho, Agostinho; Comoli, Patrizia; Romani, Luigina; Latgè, Jean Paul; Luppi, Mario

2013-01-01

Several studies in mouse model of invasive aspergillosis (IA) and in healthy donors have shown that different Aspergillus antigens may stimulate different adaptive immune responses. However, the occurrence of Aspergillus-specific T cells have not yet been reported in patients with the disease. In patients with IA, we have investigated during the infection: a) whether and how specific T-cell responses to different Aspergillus antigens occur and develop; b) which antigens elicit the highest frequencies of protective immune responses and, c) whether such protective T cells could be expanded ex-vivo. Forty hematologic patients have been studied, including 22 patients with IA and 18 controls. Specific T cells producing IL-10, IFN-γ, IL-4 and IL-17A have been characterized through enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p, SOD1p, α1–3glucan, β1–3glucan, galactomannan. Specific T cells were expanded through short term culture. Aspergillus-specific T cells producing non-protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-γ) have been detected to all the antigens only in IA patients. Lower numbers of specific T cells producing IL-4 and IL-17A have also been shown. Protective T cells targeted predominantly Aspergillus cell wall antigens, tended to increase during the IA course and to be associated with a better clinical outcome. Aspergillus-specific T cells could be successfully generated from the PB of 8 out of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus hyphae. Aspergillus specific T-cell responses contribute to the clearance of the pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens are those mainly targeted by protective immune responses. Cytotoxic specific T cells can be expanded from immunosuppressed patients even during the infection by using the above mentioned antigens. These findings may be exploited for immunotherapeutic purposes in patients with IA. PMID:24023936

Association Between Psychotropic and Cardiovascular Iatrogenic Alerts and Risk of Hospitalizations in Elderly People Treated for Dementia: A Self-Controlled Case Series Study Based on the Matching of 2 French Health Insurance Databases.

PubMed

Zerah, Lorene; Boddaert, Jacques; Leperre-Desplanques, Armelle; Bonnet-Zamponi, Dominique; Verny, Marc; Deligne, Jean; Boelle, Pierre-Yves

2017-06-01

Elderly people are at risk of repeated hospitalizations, some of which may be drug related and preventable. In 2011, a group of French healthcare experts selected 5 iatrogenic alerts (IAs), based on criteria identified in a literature search and from their professional experience, to assess the appropriateness of medication in elderly patients. Our objective was to examine the association between hospitalizations and IAs in elderly patients treated for Alzheimer disease who are particularly sensitive to adverse drug events. A 2-year (January 1, 2011, to December 31, 2012) longitudinal national database study, with a study design similar to self-controlled case series, was performed to analyze data on drug prescriptions and hospitalization. IAs were defined as (1) long half-life benzodiazepine; (2) antipsychotic drugs in patients with Alzheimer disease; (3) co-prescription of 3 or more psychotropic drugs; (4) co-prescription of 2 or more diuretics; and (5) co-prescription of 4 or more antihypertensive drugs. Data were obtained by matching of 2 French National Health Insurance Databases. France. All affiliates, aged ≥75 years, receiving treatment for Alzheimer disease, alive on January 1, 2011 were included. We calculated the relative increase in the number of hospitalizations in patients with IAs. The analysis was performed over four 6-month periods. A total of 10,754 patients were included. During the periods with IAs, hospitalization rates increased by 0.36/year compared with 0.23/year in the periods without for the same patient, and the number of hospitalizations doubled [proportional fold change = 1.9, 95% confidence interval (1.8, 2.1)]. We estimated that 22% [95% confidence interval (20%, 23%)] of all hospitalizations were associated with IAs, 80% of which were due to psychotropic IAs. The IAs could be used as a simple and clinically relevant tool by prescribing physicians to assess the appropriateness of the prescription in elderly patients treated for Alzheimer disease. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Invasive aspergillosis caused by Aspergillus terreus: an emerging opportunistic infection with poor outcome independent of azole therapy.

PubMed

Hachem, Ray; Gomes, Marisa Zenaide Ribeiro; El Helou, Gilbert; El Zakhem, Aline; Kassis, Christelle; Ramos, Elizabeth; Jiang, Ying; Chaftari, Anne-Marie; Raad, Issam I

2014-11-01

Invasive aspergillosis (IA) caused by Aspergillus terreus is a significant cause of morbidity and mortality in patients with haematological malignancy (HM). Very few data are available in this patient population to differentiate IA patients with A. terreus from those with non-terreus species of Aspergillus to compare outcomes. We retrospectively investigated 513 HM patients who were treated for either definite or probable IA between June 1993 and August 2012 in a cancer centre. We compared baseline characteristics, antifungal therapies and outcomes between patients infected with A. terreus (n = 96, 18.7%) and those infected with non-terreus Aspergillus species (n = 335, 65.3%). Eighty-one patients with mixed or unspecified Aspergillus infections were excluded. Breakthrough infections occurred more frequently in the A. terreus group (91% versus 77%, P = 0.009). A. terreus infection was associated with a lower rate of final response to antifungal therapy (21% versus 38%, P = 0.0015) and a higher rate of IA-associated mortality (51% versus 30%, P < 0.001). Multivariate analyses showed that these associations were independent of patients' clinical characteristics and the antifungal regimens they received. Factors independently associated with final response included treatment with azoles (OR 3.1, 95% CI 1.9-5.0, P < 0.0001) and Aspergillus species (A. terreus versus non-terreus Aspergillus species) (OR 0.5, 95% CI 0.3-0.98, P = 0.043). Additionally, Aspergillus species and treatment with azoles were independently associated with IA-associated mortality. A. terreus IA in HM patients was associated with worse outcome than IA caused by non-terreus Aspergillus species. Poor prognosis in patients with invasive A. terreus infections is independent of anti-Aspergillus azole-based treatment. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy 2014. This work is written by US Government employees and is in the public domain in the US.

Radiofrequency ablation of stage IA non-small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial.

PubMed

Dupuy, Damian E; Fernando, Hiran C; Hillman, Shauna; Ng, Thomas; Tan, Angelina D; Sharma, Amita; Rilling, William S; Hong, Kelvin; Putnam, Joe B

2015-10-01

This study evaluated the 2-year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non-small cell lung cancer (NSCLC) undergoing computed tomography (CT)-guided radiofrequency ablation (RFA) in a prospective, multicenter trial. Fifty-four patients (25 men and 29 women) with a median age of 76 years (range, 60-89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy-proven stage IA NSCLC and were deemed medically inoperable by a board-certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed. The overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence-free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors > 2 cm. In the 19 patients with local recurrence, 11 were re-treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years. RFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2-year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. © 2015 American Cancer Society.

Diabetes mellitus in a patient with glycogen storage disease type Ia: a case report.

PubMed

Cohn, Aviva; Ohri, Anupam

2017-11-12

Glycogen storage disease type Ia is a genetic disorder that is associated with persistent fasting hypoglycemia and the inability to produce endogenous glucose. The development of diabetes with glycogen storage disease is exceedingly rare. The underlying pathogenesis for developing diabetes in these patients is unclear, and there are no guidelines for treatment. We describe a case of a 34-year-old woman of South Asian descent with glycogen storage disease type Ia, who developed uncontrolled diabetes mellitus as a young adult. Hyperglycemia was noted after childbirth, and worsened years later. Treatment for diabetes was difficult due to risks of hypoglycemia from her underlying glycogen storage disease. With minimal hypoglycemic events, the patient's blood glucose improved with exercise in combination with a sodium-glucose co-transporter 2 inhibitor and an alpha glucosidase inhibitor. We report a rare case of diabetes in the setting of glycogen storage disease-Ia. Based on the literature, there appears to be a relationship between glycogen storage disease and metabolic syndrome, which likely plays a role in the pathogenesis. The management of glycemic control remains a clinical challenge, requiring management of both fasting hypoglycemia from glycogen storage disease, as well as post-prandial hyperglycemia from diabetes mellitus.

Internal anal sphincter: Clinical perspective.

PubMed

Kumar, Lalit; Emmanuel, Anton

2017-08-01

To summarise current knowledge of Internal anal sphincter. The internal anal sphincter (IAS) is the involuntary ring of smooth muscle in the anal canal and is the major contributor to the resting pressure in the anus. Structural injury or functional weakness of the muscle results in passive incontinence of faeces and flatus. With advent of new assessment and treatment modalities IAS has become an important topic for surgeons. This review was undertaken to summarise our current knowledge of internal anal sphincter and highlight the areas that need further research. The PubMed database was used to identify relevant studies relating to internal anal sphincter. The available evidence has been summarised and advantages and limitations highlighted for the different diagnostic and therapeutic techniques. Our understanding of the physiology and pharmacology of IAS has increased greatly in the last three decades. Additionally, there has been a rise in diagnostic and therapeutic techniques specifically targeting the IAS. Although these are promising, future research is required before these can be incorporated into the management algorithm. Copyright © 2016 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Evaluation of radiological and pathological prognostic factors in surgically-treated patients with bronchoalveolar carcinoma.

PubMed

Carretta, A; Canneto, B; Calori, G; Ceresoli, G L; Campagnoli, E; Arrigoni, G; Vagani, A; Zannini, P

2001-08-01

The incidence of adenocarcinoma and bronchoalveolar carcinoma has increased in recent years. The aim of this study was to retrospectively evaluate radiological and pathological factors affecting survival in patients with bronchoalveolar carcinoma (BAC) or BAC associated with adenocarcinoma who underwent surgical treatment. From May 1988 to September 1999, 49 patients with BAC or BAC and adenocarcinoma underwent surgical treatment. Complete resection was performed in 42 patients. In these patients the impact of the following factors on survival was evaluated: stage, TNM status, radiological and pathological findings (percentage of bronchoalveolar carcinoma in the tumour, presence or absence of sclerosing and mucinous patterns, vascular invasion and lymphocytic infiltration). Twenty-nine patients were male and 20 female. Mean age was 63 years. Five-year survival was 54%. Univariate analysis of the patients who underwent complete resection demonstrated a favourable impact on survival in stages Ia and Ib (P = 0.01) and in the absence of nodal involvement (P = 0.02) and mucinous patterns (P = 0.02). Mucinous pattern was also prognostically relevant at multivariate analysis (P = 0.02). In the 27 patients with stage Ia and Ib disease, univariate analysis demonstrated that the absence of mucinous pattern (P = 0.006) and a higher percentage of BAC (P = 0.01) favourably influenced survival. The latter data were also confirmed by multivariate analysis (P = 0.01). Surgical treatment of early-stage BAC and combined BAC and adenocarcinoma is associated with favourable results. However, the definition of prognostic factors is of utmost importance to improve the results of the treatment. In our series tumours of the mucinous subtype and with a lower percentage of BAC had a worse prognosis.

Chronological changes in lung cancer surgery in a single Japanese institution

PubMed Central

Nakamura, Haruhiko; Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

2017-01-01

Background The aim of this study was to evaluate the chronological changes in epidemiological factors and surgical outcomes in patients with lung cancer who underwent surgery in a single Japanese institution. Patients and methods A clinicopathological database of patients with lung cancer who underwent surgery with curative intent from January 1974 to December 2014 was reviewed. The chronological changes in various factors, including patient’s age, sex, histological type, tumor size, pathological stage (p-stage), surgical method, operative time, intraoperative blood loss, 30-day mortality, and postoperative overall survival (OS), were evaluated. Results A total of 1,616 patients were included. The numbers of resected patients, females, adenocarcinomas, p-stage IA patients, and age at the time of surgery increased with time, but tumor size decreased (all P<0.0001). Concerning surgical methods, the number of sublobar resections increased, but that of pneumonectomies decreased (P<0.0001). The mean operative time, intraoperative blood loss, and the postoperative 30-day mortality rate decreased (all P<0.0001). When the patients were divided into two groups (1974–2004 and 2005–2014), the 5-year OS rates for all patients and for p-stage IA patients improved from 44% to 79% and from 73% to 89%, respectively (all P<0.0001). The best 5-year OS rate was obtained for sublobar resection (73%), followed by lobectomy (60%), combined resection (22%), and pneumonectomy (21%; P<0.0001). Conclusion Changes in epidemiological factors, a trend toward less invasive surgery, and a remarkably improved postoperative OS were confirmed, which demonstrated the increasingly important role of surgery in therapeutic strategies for lung cancer. PMID:28331339

A breath fungal secondary metabolite signature to diagnose invasive aspergillosis.

PubMed

Koo, Sophia; Thomas, Horatio R; Daniels, S David; Lynch, Robert C; Fortier, Sean M; Shea, Margaret M; Rearden, Preshious; Comolli, James C; Baden, Lindsey R; Marty, Francisco M

2014-12-15

Invasive aspergillosis (IA) remains a leading cause of mortality in immunocompromised patients, in part due to the difficulty of diagnosing this infection. Using thermal desorption-gas chromatography/mass spectrometry, we characterized the in vitro volatile metabolite profile of Aspergillus fumigatus, the most common cause of IA, and other pathogenic aspergilli. We prospectively collected breath samples from patients with suspected invasive fungal pneumonia from 2011 to 2013, and assessed whether we could discriminate patients with proven or probable IA from patients without aspergillosis, as determined by European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus definitions, by direct detection of fungal volatile metabolites in these breath samples. The monoterpenes camphene, α- and β-pinene, and limonene, and the sesquiterpene compounds α- and β-trans-bergamotene were distinctive volatile metabolites of A. fumigatus in vitro, distinguishing it from other pathogenic aspergilli. Of 64 patients with suspected invasive fungal pneumonia based on host risk factors, clinical symptoms, and radiologic findings, 34 were diagnosed with IA, whereas 30 were ultimately diagnosed with other causes of pneumonia, including other invasive mycoses. Detection of α-trans-bergamotene, β-trans-bergamotene, a β-vatirenene-like sesquiterpene, or trans-geranylacetone identified IA patients with 94% sensitivity (95% confidence interval [CI], 81%-98%) and 93% specificity (95% CI, 79%-98%). In patients with suspected fungal pneumonia, an Aspergillus secondary metabolite signature in breath can identify individuals with IA. These results provide proof-of-concept that direct detection of exogenous fungal metabolites in breath can be used as a novel, noninvasive, pathogen-specific approach to identifying the precise microbial cause of pneumonia. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prevalence and long-term clinical significance of intracranial atherosclerosis after ischaemic stroke or transient ischaemic attack: a cohort study.

PubMed

Ovesen, Christian; Abild, Annemette; Christensen, Anders Fogh; Rosenbaum, Sverre; Hansen, Christine Krarup; Havsteen, Inger; Nielsen, Jens Kellberg; Christensen, Hanne

2013-10-21

We investigated the prevalence and long-term risk associated with intracranial atherosclerosis identified during routine evaluation. This study presents data from a prospective cohort of patients admitted to our stroke unit for thrombolysis evaluation. We included 652 with a final diagnosis of ischaemic stroke or transient ischaemic attack (TIA) from April 2009 to December 2011. All patients were acutely evaluated with cerebral CT and CT angiography (CTA). Acute radiological examinations were screened for intracranial arterial stenosis (IAS) or intracranial arterial calcifications (IAC). Intracranial stenosis was grouped into 30-50%, 50-70% and >70% lumen reduction. The extent of IAC was graded as number of vessels affected. Patients were followed until July 2013. Recurrence of an ischaemic event (stroke, ischaemic heart disease (IHD) and TIA) was documented through the national chart system. Poor outcome was defined as death or recurrence of ischaemic event. 101 (15.5%) patients showed IAS (70: 30-50%, 29: 50-70% and 16: >70%). Two-hundred and fifteen (33%) patients had no IAC, 339 (52%) in 1-2 vessels and 102 (16%) in >2 vessels. During follow-up, 53 strokes, 20 TIA and 14 IHD occurred, and 95 patients died. The risk of poor outcome was significantly different among different extents of IAS as well as IAC (log-rank test p<0.01 for both). In unadjusted analysis IAS and IAC predicted poor outcome and recurrent ischaemic event. When adjusted, IAS and IAC independently increased the risk of a recurrent ischaemic event (IAS: HR 1.67; CI 1.04 to 2.64 and IAC: HR 1.22; CI 1.02 to 1.47). Intracranial atherosclerosis detected during acute evaluation predicts an increased risk of recurrent stroke.

Value of the Definition of Severe Familial Hypercholesterolemia for Stratification of Heterozygous Patients.

PubMed

Pérez-Calahorra, Sofia; Sánchez-Hernández, Rosa María; Plana, Núria; Marco-Benedi, Victoria; Pedro-Botet, Juan; Almagro, Fátima; Brea, Angel; Ascaso, Juan Francisco; Lahoz, Carlos; Civeira, Fernando

2017-03-01

Familial hypercholesterolemia (FH) is characterized by high low-density lipoprotein (LDL) cholesterol with co-dominant transmission and high risk of cardiovascular disease (CVD), although with high variability among subjects. Currently, CVD stratification tools for heterozygous FH (HeFH) are not available. A definition of severe HeFH has been recently proposed by the International Atherosclerosis Society (IAS), but it has not been validated. Our study aims to see clinical characteristics and prevalence of CVD in subjects defined as severe HeFH by IAS criteria. Probable or definite HeFH introduced in the Dyslipidemia Registry of Spanish Arteriosclerosis Society were analyzed by the IAS criteria. Univariate and multivariate analysis was used to assess the association of CVD with the IAS criteria. About 1,732 HeFH cases were analyzed. Severe HeFH had higher prevalence of familial history of CVD, personal history of tendon xanthomas, LDL cholesterol, and CVD than nonsevere HeFH. A total of 656 (77.1%) and 441 (50.1%) of men and women, respectively, fulfilled the IAS criteria of severe HeFH. In the univariate analysis, subjects defined as severe HeFH showed odds ratio 3.016 (95% CI 3.136 to 4.257, p <0.001) for CVD. However, when traditional risk factors were included in the multivariate analysis, only the presence of cholesterol >400 mg/dl had a statistically significant association with CVD odds ratio 8.76 (95% CI 3.90 to 19.69, p <0.001). In conclusion, the IAS definition of severe HeFH is not significantly associated with CVD when adjusted for classic risk factors. Risk stratification in HeFH is an important issue, but the proposed criteria do not seem to solve this problem. Copyright © 2016 Elsevier Inc. All rights reserved.

Absolute activity quantitation from projections using an analytical approach: comparison with iterative methods in Tc-99m and I-123 brain SPECT

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Kijewski, M. F.; Moore, S. C.

2001-06-01

Estimates of SPECT activity within certain deep brain structures could be useful for clinical tasks such as early prediction of Alzheimer's disease with Tc-99m or Parkinson's disease with I-123; however, such estimates are biased by poor spatial resolution and inaccurate scatter and attenuation corrections. We compared an analytical approach (AA) of more accurate quantitation to a slower iterative approach (IA). Monte Carlo simulated projections of 12 normal and 12 pathologic Tc-99m perfusion studies, as well as 12, normal and 12 pathologic I-123 neurotransmission studies, were generated using a digital brain phantom and corrected for scatter by a multispectral fitting procedure. The AA included attenuation correction by a modified Metz-Fan algorithm and activity estimation by a technique that incorporated Metz filtering to compensate for variable collimator response (VCR), IA-modeled attenuation, and VCR in the projector/backprojector of an ordered subsets-expectation maximization (OSEM) algorithm. Bias and standard deviation over the 12 normal and 12 pathologic patients were calculated with respect to the reference values in the corpus callosum, caudate nucleus, and putamen. The IA and AA yielded similar quantitation results in both Tc-99m and I-123 studies in all brain structures considered in both normal and pathologic patients. The bias with respect to the reference activity distributions was less than 7% for Tc-99m studies, but greater than 30% for I-123 studies, due to partial volume effect in the striata. Our results were validated using I-123 physical acquisitions of an anthropomorphic brain phantom. The IA yielded quantitation accuracy comparable to that obtained with IA, while requiring much less processing time. However, in most conditions, IA yielded lower noise for the same bias than did AA.

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

PubMed

Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria; Arafah, Baha M

2017-09-01

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes

PubMed Central

Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria

2017-01-01

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients. PMID:29264578

Is combined use of intravenous and intraarticular tranexamic acid superior to intravenous or intraarticular tranexamic acid alone in total knee arthroplasty? A meta-analysis of randomized controlled trials.

PubMed

Mi, Bobin; Liu, Guohui; Lv, Huijuan; Liu, Yi; Zha, Kun; Wu, Qipeng; Liu, Jing

2017-04-18

Tranexamic acid (TXA) has been proven to be effective in reducing blood loss and transfusion rate after total knee arthroplasty (TKA) without increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE). Recently, an increasing number of studies have been interested in applying combined intravenous (IV) with intraarticular (IA) tranexamic acid in total knee arthroplasty. The purpose of this meta-analysis was to compare the blood loss and complications of combined TXA with IV TXA or IA TXA on TKA. Systematic search of literatures were conducted to identify related articles that were published in PubMed, MEDLINE, Embase, the Cochrane Library, SpringerLink, ClinicalTrials.gov, and Ovid from their inception to September 2016. All studies that compare blood loss and complications of combined TXA and IV TXA or IA TXA on TKA were included. Main outcomes were collected and analyzed by the Review Manager 5.3. Five studies were included in the present meta-analysis. There was significant difference in total blood loss and blood volume of drainage when compared combined TXA group with IV TXA group or IA TXA group (P < 0.05). There was no difference in transfusion rate and thromboembolic complications when comparing combined TXA with IV TXA or IA TXA alone (P > 0.05). Compared with administration of IA TXA or IV TXA alone on TKA, combined use of TXA has advantages in reducing total blood loss and blood volume of drainage without increasing the incidence of thromboembolic complications. We recommend combined TXA as the preferred option for patients undergoing TKA.

Prospective Biomarker Screening for Diagnosis of Invasive Aspergillosis in High-Risk Pediatric Patients

PubMed Central

Hafner, Julia; Mengoli, Carlo; Wirth, Clemens; Heussel, Claus Peter; Löffler, Claudia; White, P. Lewis; Ullmann, Andrew J.; Michel, Denise; Wiegering, Verena; Wölfl, Matthias; Schlegel, Paul Gerhardt; Einsele, Hermann; Springer, Jan; Eyrich, Matthias

2016-01-01

ABSTRACT Combined biomarker screening is increasingly used to diagnose invasive aspergillosis (IA) in high-risk patients. In adults, the combination of galactomannan (GM) and fungal DNA detection has proven to be beneficial in the diagnosis of IA. Data in purely pediatric cohorts are scarce. Here, we monitored 39 children shortly before and after allogeneic stem cell transplantation twice weekly by use of a commercial GM enzyme-linked immunosorbent assay (ELISA) and a PCR assay based on amplification of the pan-Aspergillus ITS1/5.8S ribosomal operon. In addition, clinical data were recorded and classification of IA was performed according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Among the 39 high-risk children, we identified 4 patients (10.3%) with probable and 2 (5.1%) with possible IA. All patients with probable IA were repeatedly positive for both tests (means of 9.5 and 6.8 positive GM and PCR samples, respectively), whereas both possible IA cases were detected by PCR. The sensitivity and specificity were, respectively, 67% and 89% for GM and 100% and 63% for PCR. Positive and negative predictive values were, respectively, 50% and 100% for GM and 27% and 100% for PCR. For the combined testing approach, both values were 100%. The number of positive samples seemed to be lower in patients undergoing antifungal therapy. Sporadically positive tests occurred in 12% (GM) and 42% (PCR) of unclassified patients. In summary, our data show that combined monitoring for GM and fungal DNA also results in a high diagnostic accuracy in pediatric patients. Future studies have to determine whether combined testing is suitable for early detection of subclinical disease and how antifungal prophylaxis impacts assay performance. PMID:27795339

Prospective Biomarker Screening for Diagnosis of Invasive Aspergillosis in High-Risk Pediatric Patients.

PubMed

Loeffler, Juergen; Hafner, Julia; Mengoli, Carlo; Wirth, Clemens; Heussel, Claus Peter; Löffler, Claudia; White, P Lewis; Ullmann, Andrew J; Michel, Denise; Wiegering, Verena; Wölfl, Matthias; Schlegel, Paul Gerhardt; Einsele, Hermann; Springer, Jan; Eyrich, Matthias

2017-01-01

Combined biomarker screening is increasingly used to diagnose invasive aspergillosis (IA) in high-risk patients. In adults, the combination of galactomannan (GM) and fungal DNA detection has proven to be beneficial in the diagnosis of IA. Data in purely pediatric cohorts are scarce. Here, we monitored 39 children shortly before and after allogeneic stem cell transplantation twice weekly by use of a commercial GM enzyme-linked immunosorbent assay (ELISA) and a PCR assay based on amplification of the pan-Aspergillus ITS1/5.8S ribosomal operon. In addition, clinical data were recorded and classification of IA was performed according to the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Among the 39 high-risk children, we identified 4 patients (10.3%) with probable and 2 (5.1%) with possible IA. All patients with probable IA were repeatedly positive for both tests (means of 9.5 and 6.8 positive GM and PCR samples, respectively), whereas both possible IA cases were detected by PCR. The sensitivity and specificity were, respectively, 67% and 89% for GM and 100% and 63% for PCR. Positive and negative predictive values were, respectively, 50% and 100% for GM and 27% and 100% for PCR. For the combined testing approach, both values were 100%. The number of positive samples seemed to be lower in patients undergoing antifungal therapy. Sporadically positive tests occurred in 12% (GM) and 42% (PCR) of unclassified patients. In summary, our data show that combined monitoring for GM and fungal DNA also results in a high diagnostic accuracy in pediatric patients. Future studies have to determine whether combined testing is suitable for early detection of subclinical disease and how antifungal prophylaxis impacts assay performance. Copyright © 2016 American Society for Microbiology.

Distribution of genes encoding resistance to aminoglycoside modifying enzymes in methicillin-resistant Staphylococcus aureus (MRSA) strains.

PubMed

Khosravi, Azar Dokht; Jenabi, Atefeh; Montazeri, Effat Abbasi

2017-12-01

Today Methicillin-Resistant Staphylococcus aureus (MRSA) have acquired multiple resistance to a wide range of antibiotics including aminoglycosides. So, this study was aimed to investigate the rate of aminoglycoside resistance and the frequency of aminoglycoside resistance mediated genes of aac(Ia)-2, aph(3)-IIIa and ant(4')-Ia among MRSA strains. A total of 467 staphylococci isolates were collected from various clinical samples. S. aureus strains were identified by standard culture and identification criteria and investigating of presence of 16S rRNA and nuc genes. Cefoxitin disk diffusion, and oxacillin-salt agar screening methods were used to detect the MRSA strains with subsequent molecular identification for the presence of mecA gene. Antibiotic susceptibility of MRSA strains against aminoglycoside antibiotics was evaluated by using agar disk diffusion method. Multiplex PCR for the presence of aac(Ia)-2, aph(3)-IIIa and ant(4')-Ia encoding genes for aminoglycosides were performed for MRSA strains. From total staphylococci tested isolates, 262 (56.1%) were identified as S. aureus, of which 161 (61.45%) were detected as MRSA and all comprised mecA gene. The resistance pattern of MRSA strains to aminoglycoside antibiotics were: gentamicin 136 (84.5%); amikacin 125 (77.6%); kanamycin 139 (86.3%); tobramycin 132 (82%); and neomycin 155 (96.3%). The frequency of aac(Ia)-2, aph(3)-IIIa, and ant(4')-Ia genes among MRSA strains, were 64%, 42% and 11.8% respectively. In conclusion, as MRSA strains are of great concern in human infections, the results of present study could provide a useful resource for health sectors for choosing appropriate antibiotics for the effective treatment of infections due to MRSA strains. Copyright © 2017. Published by Elsevier Taiwan.

Isoflurane depolarizes bronchopulmonary C neurons by inhibiting transient A-type and delayed rectifier potassium channels.

PubMed

Zhang, Zhenxiong; Zhuang, Jianguo; Zhang, Cancan; Xu, Fadi

2013-04-01

Inhalation of isoflurane (ISO), a widely used volatile anesthetic, can produce clinical tachypnea. In dogs, this response is reportedly mediated by bronchopulmonary C-fibers (PCFs), but the relevant mechanisms remain unclear. Activation of transient A-type potassium current (IA) channels and delayed rectifier potassium current (IK) channels hyperpolarizes neurons, and inhibition of both channels by ISO increases neural firing. Due to the presence of these channels in the cell bodies of rat PCFs, we determined whether ISO could stimulate PCFs to produce tachypnea in anesthetized rats, and, if so, whether this response resulted from ISO-induced depolarization of the pulmonary C neurons via the inhibition of IA and IK. We recorded ventilatory responses to 5% ISO exposure in anesthetized rats before and after blocking PCF conduction and the responses of pulmonary C neurons (extracellularly recorded) to ISO exposure. ISO-induced (1mM) changes in pulmonary C neuron membrane potential and IA/IK were tested using the perforated patch clamp technique. We found that: (1) ISO inhalation evoked a brief tachypnea (∼7s) and that this response disappeared after blocking PCF conduction; (2) the ISO significantly elevated (by 138%) the firing rate of most pulmonary C neurons (17 out of 21) in the nodose ganglion; and (3) ISO perfusion depolarized the pulmonary C neurons in the vitro and inhibited both IA and IK, and this evoked-depolarization was largely diminished after blocking both IA and IK. Our results suggest that ISO is able to stimulate PCFs to elicit tachypnea in rats, at least partly, via inhibiting IA and IK, thereby depolarizing the pulmonary C neurons. Copyright © 2013. Published by Elsevier B.V.

Predictors of course and outcome in hypochondriasis after cognitive-behavioral treatment.

PubMed

Hiller, Wolfgang; Leibbrand, Rolf; Rief, Winfried; Fichter, Manfred M

2002-01-01

Predictors of treatment outcome were evaluated in a clinical sample suffering from hypochondriasis. The sample consisted of 96 patients with hypochondriacal disorder according to DSM-IV or high syndrome scores on the Illness Attitude Scales (IAS) or Whiteley Index (WI). After intense inpatient cognitive-behavioral treatment (CBT), 60% of the patients were classified as responders because of substantial improvements or recovery from hypochondriacal symptomatology. Non-responders were characterized by a higher degree of pre-treatment hypochondriasis, more somatization symptoms and general psychopathology (SCL-90R), more dysfunctional cognitions related to bodily functioning, higher levels of psychosocial impairments, and more utilization of the health care system as indicated by the number of hospital days and costs for inpatient treatments and medication. No predictive value was found for sociodemographic variables, comorbidity with other mental disorders and chronicity. Multiple linear regression showed that pre-treatment variables significantly predicted IAS scores at post-treatment (R(2) = 0.59), changes during treatment (0.10), IAS scores at follow-up two years later (0.41) and changes between baseline and follow-up (0.25). The results demonstrate the relevance of various psychopathological variables and health care utilization as important indicators for outcome and further course of clinical hypochondriasis. Copyright 2002 S. Karger AG, Basel

Behavioral and Emotional Symptoms of Post-Institutionalized Children in Middle Childhood

PubMed Central

Wiik, Kristen L.; Loman, Michelle M.; Van Ryzin, Mark J.; Armstrong, Jeffrey M.; Essex, Marilyn J.; Pollak, Seth D.; Gunnar, Megan R.

2010-01-01

Background Experience in institutional/orphanage care has been linked to increased mental health problems. Research suggests children adopted from institutions experience specific difficulties related to inattention/overactivity. Evidence of internalizing and conduct problems relative to non-adopted peers has been found in early childhood and early adolescence, but problems may not differ from other adopted children. This study clarifies the understanding of behavioral and emotional symptoms of post-institutionalized (PI) children during middle childhood. Methods Eight to eleven-year-old PI children (n=68) and two comparison groups, children internationally adopted from foster care (n=74) and non-adopted children (n=76), and their parents completed the MacArthur Health and Behavior Questionnaire related to ADHD, externalizing, and internalizing symptoms. Group means for symptom level and number of children with symptoms above clinical cutoffs were compared. Results PI children displayed an increased level of ADHD symptoms per parent report. PI child and parent report indicated a higher number of PI children above clinical ADHD cutoff. Both groups of internationally adopted (IA) children had higher levels of externalizing symptoms relative to non-adopted children, with parent report indicating higher numbers of IA children above the externalizing clinical threshold. Informants differed in their report of internalizing symptoms. Parents indicated both IA groups displayed increased internalizing symptom levels and greater numbers above clinical threshold; however, children reported this to be true only for the PI group. Conclusions PI children differ from non-adopted peers across symptom domains in middle childhood. Whether these concerns were more broadly associated with international adoption rather than institutional care depended on symptom domain and informant. An understanding of this variability may be beneficial for treatment and intervention. PMID:20649913

Spallation reactions in shock waves at supernova explosions and related problems

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

Ustinova, G. K., E-mail: ustinova@dubna.net.ru

2013-05-15

The isotopic anomalies of some extinct radionuclides testify to the outburst of a nearby supernova just before the collapse of the protosolar nebula, and to the fact that the supernova was Sn Ia, i.e. the carbon-detonation supernova. A key role of spallation reactions in the formation of isotopic anomalies in the primordial matter of the Solar System is revealed. It is conditioned by the diffusive acceleration of particles in the explosive shock waves, which leads to the amplification of rigidity of the energy spectrum of particles and its enrichment with heavier ions. The quantitative calculations of such isotopic anomalies ofmore » many elements are presented. It is well-grounded that the anomalous Xe-HL in meteoritic nanodiamonds was formed simultaneously with nanodiamonds themselves during the shock wave propagation at the Sn Ia explosion. The possible effects of shock wave fractionation of noble gases in the atmosphere of planets are considered. The origin of light elements Li, Be and B in spallation reactions, predicted by Fowler in the middle of the last century, is argued. All the investigated isotopic anomalies give the evidence for the extremely high magnetohydrodynamics (MHD) conditions at the initial stage of free expansion of the explosive shock wave from Sn Ia, which can be essential in solution of the problem of origin of cosmic rays. The specific iron-enriched matter of Sn Ia and its MHD-separation in turbulent processes must be taking into account in the models of origin of the Solar System.« less

Clinical validation and applicability of different tipranavir/ritonavir genotypic scores in HIV-1 protease inhibitor-experienced patients.

PubMed

Saracino, Annalisa; Monno, Laura; Tartaglia, Alessandra; Tinelli, Carmine; Seminari, Elena; Maggiolo, Franco; Bonora, Stefano; Rusconi, Stefano; Micheli, Valeria; Lo Caputo, Sergio; Lazzaroni, Laura; Ferrara, Sergio; Ladisa, Nicoletta; Nasta, Paola; Parruti, Giustino; Bellagamba, Rita; Forbici, Federica; Angarano, Gioacchino

2009-07-01

Tipranavir, a non-peptidic protease inhibitor which shows in vitro efficacy against some HIV-1-resistant strains, can be used in salvage therapies for multi-experienced HIV patients due to its peculiar resistance profile including 21 mutations at 16 protease positions according to International AIDS Society (IAS). Other genotypic scores, however, which attribute a different weight to single amino-acid substitutions, have been recently proposed. To validate the clinical utility of four different genotypic scores for selecting tipranavir responders, the baseline resistance pattern of 176 HIV heavily experienced patients was correlated with virological success (HIV-RNA<50 copies/ml) after 24 weeks of a new treatment based on tipranavir/ritonavir. Virological suppression after 24 weeks was reached by 42.5% of patients. With univariate analysis, genotypic scores were all associated with outcome but showed a low accuracy with ROC analysis, with the weighted score (WS) by Scherer et al. demonstrating the best performance with an AUC of 68%. Only 52% of patients classified as susceptible (WS< or =3) responded to the new therapy. The following variables were significantly associated (p<0.05) to failure with multivariate analysis: WS, log peak of HIV-RNA, IAS mutations: L33F, I54AMV, Q58E, and non-IAS mutation: N37DES. On the contrary, the use of T20 in T20-naïve patients and the V82AFSI and F53LY non-IAS mutations were associated with virological success. The study suggests that even if the "weighted" scores are able to interpret correctly the antiretroviral resistance profile of multi-experienced patients, it is difficult to individuate a cut-off which can be easily applied to this population for discriminating responders.

ChIA-PET2: a versatile and flexible pipeline for ChIA-PET data analysis

PubMed Central

Li, Guipeng; Chen, Yang; Snyder, Michael P.; Zhang, Michael Q.

2017-01-01

ChIA-PET2 is a versatile and flexible pipeline for analyzing different types of ChIA-PET data from raw sequencing reads to chromatin loops. ChIA-PET2 integrates all steps required for ChIA-PET data analysis, including linker trimming, read alignment, duplicate removal, peak calling and chromatin loop calling. It supports different kinds of ChIA-PET data generated from different ChIA-PET protocols and also provides quality controls for different steps of ChIA-PET analysis. In addition, ChIA-PET2 can use phased genotype data to call allele-specific chromatin interactions. We applied ChIA-PET2 to different ChIA-PET datasets, demonstrating its significantly improved performance as well as its ability to easily process ChIA-PET raw data. ChIA-PET2 is available at https://github.com/GuipengLi/ChIA-PET2. PMID:27625391

Installation Restoration Program. Phase 2. Confirmation/Quantification. Stage 1. Air Force Plant 6, Cobb County, Georgia. Volume 3.

DTIC Science & Technology

1986-08-09

WATER ASSESSMENT PROGRAM AIR FOsEa PLANT 6, L0CKED-GEOCIA CONPANY MARIETTA, GMO IA PROJECT NO. 611059 WELL 4W-22 WELL 4W-23 WELL MW-24 WELL 4W-25 Dace...PROGRAMo PHASE II--CONFIRMATION/QUANTIFICATION 0STAGE I Final Report for AIR FORCE PLANT 6, COBB COUNTY, GA. U.S. AIR FORCE OCCUPATIONAL AND ENVIRONMENTAL...Con uet on reverse 4 necessary arc .entir’y ay )lcx "UrCer) I;;EL_0 GROUP I SUB-GROuP Air Force Plant , Hazardous materialsI oilS’ DeB Ground water, S

[A Retrospective Study of Mean Computed Tomography Value to Predict 
the Tumor Invasiveness in AAH and Clinical Stage Ia Lung Cancer].

PubMed

Wu, Hanran; Liu, Changqing; Xu, Meiqing; Xiong, Ran; Xu, Guangwen; Li, Caiwei; Xie, Mingran

2018-03-20

Recently, the detectable rate of ground-glass opacity (GGO ) was significantly increased, a appropriate diagnosis before clinic treatment tends to be important for patients with GGO lesions. The aim of this study is to validate the ability of the mean computed tomography (m-CT) value to predict tumor invasiveness, and compared with other measurements such as Max CT value, GGO size, solid size of GGO and C/T ratio (consolid/tumor ratio, C/T) to find out the best measurement to predict tumor invasiveness. A retrospective study was conducted of 129 patients who recieved lobectomy and were pathological confirmed as atypical adenomatous pyperplasia (AAH) or clinical stage Ia lung cance in our center between January 2012 and December 2013. Of those 129 patients, the number of patients of AAH, AIS, AIS and invasive adenocarcinoma were 43, 26, 17 and 43, respectively. We defined AAH and AIS as noninvasive cancer (NC), MIA and invasive adenocarcinoma were categorized as invasive cancer(IC). We used receiver operating characteristic (ROC) curve analysis to compare the ability to predict tumor invasiveness between m-CT value, consolidation/tumor ratio, tumor size and solid size of tumor. Multiple logistic regression analyses were performed to determine the independent variables for prediction of pathologic more invasive lung cancer. 129 patients were enrolled in our study (59 male and 70 female), the patients were a median age of (62.0±8.6) years (range, 44 to 82 years). The two groups were similar in terms of age, sex, differentiation (P>0.05). ROC curve analysis was performed to determine the appropriate cutoff value and area under the cure (AUC). The cutoff value of solid tumor size, tumor size, C/T ratio, m-CT value and Max CT value were 9.4 mm, 15.3 mm, 47.5%, -469.0 HU and -35.0 HU, respectively. The AUC of those variate were 0.89, 0.79, 0.82, 0.90, 0.85, respectively. When compared the clinical and radiologic data between two groups, we found the IC group was strongly associated with a high m-CT value, high Max CT value, high C/T ratio and large tumor size. Gender, solid tumor size, tumor size, C/T ratio, m-CT value and MaxCT value were selected factor for multivariate analysis, when using the preoperatively determined variables to predict the tumor invasiveness, revealed that tumor size, C/T ratio, m-CT value and Max CT value were independent predictive factors of IC. The musurements of Max CT value, GGO size, solid size of GGO and C/T ratio were significantly correlated with tumor invasiveness, and the evaluation of m-CT value is most useful musurement in predicting more invasive lung cancer.

The double-degenerate, super-Chandrasekhar nucleus of the planetary nebula Henize 2-428.

PubMed

Santander-García, M; Rodríguez-Gil, P; Corradi, R L M; Jones, D; Miszalski, B; Boffin, H M J; Rubio-Díez, M M; Kotze, M M

2015-03-05

The planetary nebula stage is the ultimate fate of stars with masses one to eight times that of the Sun (M(⊙)). The origin of their complex morphologies is poorly understood, although several mechanisms involving binary interaction have been proposed. In close binary systems, the orbital separation is short enough for the primary star to overfill its Roche lobe as the star expands during the asymptotic giant branch phase. The excess gas eventually forms a common envelope surrounding both stars. Drag forces then result in the envelope being ejected into a bipolar planetary nebula whose equator is coincident with the orbital plane of the system. Systems in which both stars have ejected their envelopes and are evolving towards the white dwarf stage are said to be double degenerate. Here we report that Henize 2-428 has a double-degenerate core with a combined mass of ∼1.76M(⊙), which is above the Chandrasekhar limit (the maximum mass of a stable white dwarf) of 1.4M(⊙). This, together with its short orbital period (4.2 hours), suggests that the system should merge in 700 million years, triggering a type Ia supernova event. This supports the hypothesis of the double-degenerate, super-Chandrasekhar evolutionary pathway for the formation of type Ia supernovae.

The Type Ia Supernova Rate and Delay-Time Distribution

NASA Astrophysics Data System (ADS)

Graur, Or

2013-11-01

The nature of the progenitor stellar systems of thermonuclear, or Type Ia, supernovae (SNe Ia) remains unknown. Unlike core-collapse (CC) SNe, which have been successfully linked, at least partially, to various types of massive stars, the progenitors of SNe Ia are to date undetected in pre-explosion images and the nature of these progenitors can only be probed using indirect methods. In this thesis, I present three SN surveys aimed at measuring the rates at which SNe Ia explode at different times throughout the Universe's history and in different types of galaxies. I use these rates to re-construct the SN Ia delay-time distribution (DTD), a function that connects between the star-formation history (SFH) of a specific stellar environment and its SN Ia rate, and I use it to constrain different progenitor models. In Chapter 1, I provide a brief introduction of the field. This is followed, in Chapter 2, by a description of the Subaru Deep Field (SDF) SN Survey. Over a period of three years between 2005-2008, the SDF was observed on four independent epochs with Suprime-Cam on the Subaru 8.2-m telescope, with two nights of exposure per epoch, in the R, i', and z' bands. In this survey, I discover 150 SNe out to redshift z ~ 2, including 27 SNe Ia in the range 1.0 < z < 1.5 and 10 in the range 1.5 < z < 2.0. The SN Ia rate measurements from this sample are consistent with those derived from the Hubble Space Telescope (HST) GOODS sample, but the overall uncertainty of the 1.5 < z < 2.0 measurement is a factor of 2 smaller, of 35-50%. Based on this sample, we find that the SN Ia rate evolution levels off at 1.0 < z < 2.0, but shows no sign of declining. Combining our SN Ia rate measurements and those from the literature, and comparing to a wide range of possible SFHs, the best-fitting DTD is a power law of the form Psi(t) ~ t^beta, with index beta = -1.1 ± 0.1 (statistical) ± 0.17 (systematic). By combining the contribution from CC SNe, based on the wide range of SFHs, with that from SNe Ia, calculated with the best-fitting DTD, we map the cosmic history of iron accumulation and predict that the mean present-day cosmic iron abundance is in the range Z_Fe = (0.09-0.37) Z_Fe,solar. Most SNe have been discovered in dedicated imaging surveys and have been classified by means of follow-up spectroscopy. However, it is also possible to combine the discovery and classification stages by means of a spectroscopic SN survey. In Chapter 3, I develop a method to detect SN spectra buried in galaxy spectra acquired by large-scale spectroscopic galaxy surveys. Applying this procedure to the ~700,000 galaxy spectra in the 7th Data Release of the Sloan Digital Sky Survey (SDSS) that have SFHs derived with the VErsatile SPectral Analysis code (VESPA), I detect 90 SNe Ia and 10 Type II SNe. I use the SN Ia sample to measure SN Ia rates per unit stellar mass and confirm, at the median redshift of the sample, z = 0.1, the inverse dependence on galaxy mass of the SN Ia rate per unit mass, previously reported by Li et al. (2011a) for a local sample. I further confirm, following Kistler et al. (2013), that this relation can be explained by the combination of galaxy "downsizing" and a power-law DTD with an index of -1. Finally, I use the SN sample, combined with the individual galaxy SFHs, to derive the late component of the DTD, finding a value consistent with previous derivations. Chapter 4 presents the near-final SN sample and SN Ia rates from the Cluster Lensing And Supernova survey with Hubble (CLASH). Using the Advanced Camera for Surveys and the Wide Field Camera 3 on HST, we image 25 galaxy clusters and blank fields of galaxies. I report a sample of 22 SNe discovered in the blank fields around 20 of the 25 galaxy clusters. Of these, 11 are classified as SNe Ia, including four SNe Ia at redshifts z > 1.2. I measure volumetric SN Ia rates out to redshift z = 1.8 and add the first upper limit on the SN Ia rate in the range 1.8 < z < 2.4. The results are consistent with the rates I measure in Chapter 2 and with those from the HST/GOODS survey. Together with the most accurate and precise measurements at redshifts z < 1, they result in a best-fitting power-law DTD with an index of -0.93 +0.05(0.11) -0.06(0.12) (statistical) +0.12 -0.08 (systematic). The results of Chapters 2-4, summarized in Chapter 5, join other recent evidence suggestive of the double-degenerate progenitor scenario. A power-law DTD with an index of ~-1 can be explained by the gravitational merger of two carbon-oxygen white dwarfs. However, this form of the DTD does not necessarily exclude other progenitor scenarios or the possibility that there is more than one SN Ia production channel. In Chapter 5, I describe ongoing and future work that addresses this problem. Specifically, it may be possible to infer the existence of multiple production channels by studying the prompt component of the DTD. This can be achieved either by measuring volumetric SN Ia rates at higher redshifts than presented here, or by measuring SN Ia rates per unit mass in low-mass, dwarf galaxies. I present an initial sample of four SNe Ia discovered among ~52,000 SDSS galaxy spectra using the procedure developed in Chapter 3. The rate measured with this sample is not accurate enough to distinguish between DTD models, but it shows that with a larger galaxy sample, such as is being acquired by future iterations of the SDSS, such distinction will be possible. Finally, I show in Chapter 5 initial results from a program to obtain spectroscopic redshifts for the SN host galaxies in Chapter 2 with the highest photometric-based redshifts. This will eventually reduce the systematic error in the high-redshift SN Ia rate.

Juvenile nasopharyngeal angiofibroma: vascular determinates for operative complications and tumor recurrence.

PubMed

Chan, Kenny H; Gao, Dexiang; Fernandez, Patrick G; Kingdom, Todd T; Kumpe, David A

2014-03-01

Operative complications and tumor recurrence in juvenile nasopharyngeal angiofibroma (JNA) are measurable and meaningful outcomes. This study aimed to assess the association of these two outcomes to various clinical indices and in particular, vascular determinates. Retrospective cohort study. An 18-year retrospective chart review of an academic tertiary center was undertaken. Data from clinical notes, imaging studies, and arteriograms were analyzed. Thirty-seven male (mean age, 14.4 years) patients were included in the study. Tumor stages included: IA (three), IB (three), IIA (14), IIB (three), IIC (five), IIIA (five), and IIIB (four). Four complications (cerebrospinal fluid leak, cerebral vascular accident, and two transient ocular defects) occurred. Eight recurrences occurred within 24 months following surgery. Complications were associated with estimated intraoperative blood loss (EBL) (P = .045). Tumor recurrence was associated with feeding vessels from the contralateral internal carotid artery (ICA) (P = .017). EBL was significantly associated with surgical technique used. EBL, tumor stage, and tumor vascular supply were significantly associated with each other. Vascular factors were associated with JNA complication and tumor recurrence. EBL might affect complications, and contralateral ICA as a feeding vessel might affect recurrence. EBL was influenced by procedure choice and was interrelated to size and vascular supply of the tumor. This study bolsters the need to decrease intraoperative blood loss by preoperative embolization and use of endoscopic removal techniques. Furthermore, when branches of the ICA are found to be feeding vessels, greater surgical attention for a dry surgical field is encouraged. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Integrated skin flash planning technique for intensity-modulated radiation therapy for vulvar cancer prevents marginal misses and improves superficial dose coverage.

PubMed

Dyer, Brandon A; Jenshus, Abriel; Mayadev, Jyoti S

2018-02-28

Radiation therapy (RT) plays a definitive role in locally advanced vulvar cancer, and in the adjuvant setting with high risk postoperative features after wide local excision. There is significant morbidity associated with traditional, large RT fields using 2D or 3D techniques, and the use of intensity-modulated radiation therapy (IMRT) in vulvar cancer is increasing. However, there remains a paucity of technical information regarding the prevention of a marginal miss during the treatment planning process. The use of an integrated skin flash (ISF) during RT planning can be used to account for anatomic variation, and intra- and interfraction motion seen during treatment. Herein we present the case of a patient with a T1aN0M0, Stage IA vulva cancer to illustrate the progressive vulvar swelling and lymph edema seen during treatment and retrospectively evaluate the dosimetric effects of using an ISF RT plan vs standard RT planning techniques. Standard planning techniques to treat vulvar cancer patients with IMRT do not sufficiently account for the change in patient anatomy and can lead to a marginal miss. ISF is an RT planning technique that can decrease the risk of a marginal miss and the technique is easily implemented during the planning stages of RT treatment. Furthermore, use of an ISF technique can improve vulvar clinical target volume coverage and plan homogeneity. Based on our experience, and this study, a 2-cm ISF is suggested to account for variations in daily clinical setup and changes in patient anatomy during treatment. Published by Elsevier Inc.

mTORC1 controls long-term memory retrieval.

PubMed

Pereyra, Magdalena; Katche, Cynthia; de Landeta, Ana Belén; Medina, Jorge H

2018-06-08

Understanding how stored information emerges is a main question in the neurobiology of memory that is now increasingly gaining attention. However, molecular events underlying this memory stage, including involvement of protein synthesis, are not well defined. Mammalian target of rapamycin complex 1 (mTORC1), a central regulator of protein synthesis, has been implicated in synaptic plasticity and is required for memory formation. Using inhibitory avoidance (IA), we evaluated the role of mTORC1 in memory retrieval. Infusion of a selective mTORC1 inhibitor, rapamycin, into the dorsal hippocampus 15 or 40 min but not 3 h before testing at 24 h reversibly disrupted memory expression even in animals that had already expressed IA memory. Emetine, a general protein synthesis inhibitor, provoked a similar impairment. mTORC1 inhibition did not interfere with short-term memory retrieval. When infused before test at 7 or 14 but not at 28 days after training, rapamycin impaired memory expression. mTORC1 blockade in retrosplenial cortex, another structure required for IA memory, also impaired memory retention. In addition, pretest intrahippocampal rapamycin infusion impaired object location memory retrieval. Our results support the idea that ongoing protein synthesis mediated by activation of mTORC1 pathway is necessary for long but not for short term memory.

The Effect of Intra-articular Corticosteroids on Articular Cartilage

PubMed Central

Wernecke, Chloe; Braun, Hillary J.; Dragoo, Jason L.

2015-01-01

Background: Intra-articular (IA) corticosteroid therapy has been used for the treatment of inflammation and pain in the knee since the 1950s. Purpose: To review the current literature on the effects of IA corticosteroids on articular cartilage. Study Design: Systematic review. Methods: A MEDLINE and SCOPUS database search was performed, and studies were selected for basic science and clinical trial research on corticosteroids with direct outcome measures of cartilage health. Preliminary searches yielded 1929 articles, and final analysis includes 40 studies. Results: Methylprednisolone, dexamethasone, hydrocortisone, betamethasone, prednisolone, and triamcinolone were reported to display dose-dependent deleterious effects on cartilage morphology, histology, and viability in both in vitro and in vivo models. The beneficial animal in vivo effects of methylprednisolone, hydrocortisone, and triamcinolone occurred at low doses (usually <2-3 mg/dose or 8-12 mg/cumulative total dose in vivo), at which increased cell growth and recovery from damage was observed; the single human clinical trial indicated a beneficial effect of triamcinolone. However, at higher doses (>3 mg/dose or 18-24 mg/cumulative total dose in vivo), corticosteroids were associated with significant gross cartilage damage and chondrocyte toxicity. Dose and time dependency of corticosteroid chondrotoxicity was supported in the in vitro results, however, without clear dose thresholds. Conclusion: Corticosteroids have a time- and dose-dependent effect on articular cartilage, with beneficial effects occurring at low doses and durations and detrimental effects at high doses and durations. Clinically, beneficial effects are supported for IA administration, but the lowest efficacious dose should be used. PMID:26674652

Lipid management among individuals with inflammatory arthritis in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

PubMed

Navarro-Millán, Iris; Gamboa, Christopher M; Curtis, Jeffrey R; Safford, Monika M

2018-01-01

Objective Hyperlipidemia guidelines do not currently identify inflammatory arthritis (IA) as a cardiovascular disease (CVD) risk factor. We compared hyperlipidemia treatment of individuals with and without IA (rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis) in a large national cohort. Methods Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were classified as having IA (without diabetes or hypertension); diabetes (but no IA); hypertension (but no diabetes or IA); or no IA, diabetes, or hypertension. Multivariable logistic regression models examined the odds of medical treatment among those with hyperlipidemia. Results Thirty-nine participants had IA, 5423 had diabetes, 7534 had hypertension, and 5288 had no diabetes, hypertension, or IA. The fully adjusted odds of treatment were similar between participants with IA and those without IA, hypertension, or diabetes. Participants with diabetes and no IA and participants with hypertension and no IA were twice as likely to be treated for hyperlipidemia as those without IA, diabetes, or hypertension. Conclusion Despite their higher CVD risk, patients with IA were as likely to be treated for hyperlipidemia as those without diabetes, hypertension, or IA. Lipid guidelines should identify IA as a CVD risk factor to improve CVD risk optimization in IA.

75 FR 16067 - Designation for the Champaign, IL; Emmett, MI; Davenport, IA; Enid, OK; Keokuk, IA; Marshall, MI...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

... the Champaign, IL; Emmett, MI; Davenport, IA; Enid, OK; Keokuk, IA; Marshall, MI; and Omaha, NE Areas... Iowa Davenport, IA (563-322-7149). 4/1/2010 3/31/2013 Additional Locations: Dubuque, IA; Muscatine, IA...: Catoosa, OK. Keokuk Keokuk, IA (319-524-6482). 4/1/2010 3/31/2013 Additional Location: Havana, IL...

Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance

PubMed Central

Stogios, Peter J.; Spanogiannopoulos, Peter; Evdokimova, Elena; Egorova, Olga; Shakya, Tushar; Todorovic, Nick; Capretta, Alfredo; Wright, Gerard D.; Savchenko, Alexei

2013-01-01

SYNOPSIS Activity of the aminoglycoside phosphotransferase APH(3’)-Ia leads to resistance to aminoglycoside antibiotics in pathogenic Gram-negative bacteria, and contributes to the clinical obsolescence of this class of antibiotics. One strategy to rescue compromised antibiotics such as aminoglycosides is targeting the enzymes that confer resistance with small molecules. Previously we demonstrated that eukaryotic protein kinase (ePK) inhibitors could inhibit APH enzymes, due to the structural similarity between these two enzyme families. However, limited structural information of enzyme-inhibitor complexes hindered interpretation of the results. As well, cross-reactivity of compounds between APHs and ePKs represents an obstacle to their use as aminoglycoside adjuvants to rescue aminoglycoside antibiotic activity. Here, we structurally and functionally characterize inhibition of APH(3’)-Ia by three diverse chemical scaffolds – anthrapyrazolone, 4-anilinoquinazoline and pyrazolopyrimidine (PP) – and reveal distinctions in the binding mode of anthrapyrazolone and PP compounds to APH(3’)-Ia versus ePKs. Using this observation, we identify PP-derivatives that select against ePKs, attenuate APH(3’)-Ia activity and rescue aminoglycoside antibiotic activity against a resistant E. coli strain. The structures presented here and these inhibition studies provide an important opportunity for structure-based design of compounds to target aminoglycoside phosphotransferases for inhibition, potentially overcoming this form of antibiotic resistance. PMID:23758273

A partial differential equation model and its reduction to an ordinary differential equation model for prostate tumor growth under intermittent hormone therapy.

PubMed

Tao, Youshan; Guo, Qian; Aihara, Kazuyuki

2014-10-01

Hormonal therapy with androgen suppression is a common treatment for advanced prostate tumors. The emergence of androgen-independent cells, however, leads to a tumor relapse under a condition of long-term androgen deprivation. Clinical trials suggest that intermittent androgen suppression (IAS) with alternating on- and off-treatment periods can delay the relapse when compared with continuous androgen suppression (CAS). In this paper, we propose a mathematical model for prostate tumor growth under IAS therapy. The model elucidates initial hormone sensitivity, an eventual relapse of a tumor under CAS therapy, and a delay of a relapse under IAS therapy, which are due to the coexistence of androgen-dependent cells, androgen-independent cells resulting from reversible changes by adaptation, and androgen-independent cells resulting from irreversible changes by genetic mutations. The model is formulated as a free boundary problem of partial differential equations that describe the evolution of populations of the abovementioned three types of cells during on-treatment periods and off-treatment periods. Moreover, the model can be transformed into a piecewise linear ordinary differential equation model by introducing three new volume variables, and the study of the resulting model may help to devise optimal IAS schedules.

Frequency of operative trauma to anal sphincters: evaluation with endoanal ultrasound.

PubMed

Stamatiadis, Apostolos; Konstantinou, Evangelos; Theodosopoulou, Eleni; Mamoura, Konstantinia

2002-01-01

Sphincter trauma after anorectal surgery is usually asymptomatic. Frequency of trauma cannot be established with the clinical examination only. The frequency of operative sphincter defects and their correlation with disorders of continence was evaluated with the endoanal ultrasound. This study includes 123 subjects who had undergone anorectal surgery in the past and were examined with endoanal ultrasound for various indications such as continence disorders, recurrent fistula, idiopathic perineal pain, or simple postoperative follow-up. No subjects had isolated external anal sphincter defects. Nineteen of 123 patients (15%) had minor or major continence disorders, 55 patients (45%) had no sphincter defects, 42 (34%) had only internal anal sphincter (IAS) defects, and 26 (21%) had simultaneously external and internal anal sphincter (EAS) defects. The incidence of IAS and EAS trauma after Milligan-Morgan hemorrhoidectomy was 1/18 (5.5%) and 0/18 respectively; after fistula repair, 24/42 (57%) and 12/42 (29%); and after anal dilatation, 13/17 (76%) and 4/17 (24%). Sixteen of 26 patients (62%) with EAS trauma and 51/68 patients (75%) with IAS trauma did not report any disorders of continence. In patients with two or more operations, the frequency of IAS trauma was 74%, 30% for EAS trauma, and 26% for continence disorders.

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system

PubMed Central

2017-01-01

Objective To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). Methods We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Results Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. Conclusion To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal. PMID:27670255

Dilatation and curettage is more accurate than endometrial aspiration biopsy in early-stage endometrial cancer patients treated with high dose oral progestin and levonorgestrel intrauterine system.

PubMed

Kim, Da Hee; Seong, Seok Ju; Kim, Mi Kyoung; Bae, Hyo Sook; Kim, Mi La; Yun, Bo Seong; Jung, Yong Wook; Shim, Jeong Yun

2017-01-01

To determine whether less invasive endometrial (EM) aspiration biopsy is adequately accurate for evaluating treatment outcomes compared to the dilatation and curettage (D&C) biopsy in early-stage endometrial cancer (EC) patients treated with high dose oral progestin and levonorgestrel intrauterine system (LNG-IUS). We conducted a prospective observational study with patients younger than 40 years who were diagnosed with clinical stage IA, The International Federation of Gynecology and Obstetrics grade 1 or 2 endometrioid adenocarcinoma and sought to maintain their fertility. The patients were treated with medroxyprogesterone acetate 500 mg/day and LNG-IUS. Treatment responses were evaluated every 3 months. EM aspiration biopsy was conducted after LNG-IUS removal followed D&C. The tissue samples were histologically compared. The diagnostic concordance rate of the two tests was examined with κ statistics. Twenty-eight pairs of EM samples were obtained from five patients. The diagnostic concordance rate of D&C and EM aspiration biopsy was 39.3% (κ value=0.26). Of the seven samples diagnosed as normal with D&C, three (42.8%) were diagnosed as normal by using EM aspiration biopsy. Of the eight samples diagnosed with endometrioid adenocarcinoma by using D&C, three (37.5%) were diagnosed with endometrioid adenocarcinoma by using EM aspiration biopsy. Of the 13 complex EM hyperplasia samples diagnosed with the D&C, five (38.5%) were diagnosed with EM hyperplasia by using EM aspiration biopsy. Of the samples obtained through EM aspiration, 46.4% were insufficient for histological evaluation. To evaluate the treatment responses of patients with early-stage EC treated with high dose oral progestin and LNG-IUS, D&C should be conducted after LNG-IUS removal.

Inferior Lumbar Triangle Hernia as a Rarely Report Cause of Low Back Pain: A Report of 4 Cases

DTIC Science & Technology

2010-01-01

FACPd,e,f aContracted Chiropractic Physician, Naval Hospital Pensacola, Naval Branch Health Clinic NATTC, Pensacola, FL 32508 bAdjunct Clinical Faculty...Palmer College of Chiropractic , Davenport, IA 52803 cAdjunct Clinical Faculty, National University of Health Sciences, Lombard, IL 60148 dPrimary...medical and chiropractic clinicians detect these conditions, and aid in appropriate management. © 2010 National University of Health Sciences

Relation between sedimentary framework and hydrogeology in the Guarani Aquifer System in São Paulo state, Brazil

NASA Astrophysics Data System (ADS)

Hirata, Ricardo; Gesicki, Ana; Sracek, Ondra; Bertolo, Reginaldo; Giannini, Paulo César; Aravena, Ramón

2011-04-01

This paper presents the results of a new investigation of the Guarani Aquifer System (SAG) in São Paulo state. New data were acquired about sedimentary framework, flow pattern, and hydrogeochemistry. The flow direction in the north of the state is towards the southwest and not towards the west as expected previously. This is linked to the absence of SAG outcrop in the northeast of São Paulo state. Both the underlying Pirambóia Formation and the overlying Botucatu Formation possess high porosity (18.9% and 19.5%, respectively), which was not modified significantly by diagenetic changes. Investigation of sediments confirmed a zone of chalcedony cement close to the SAG outcrop and a zone of calcite cement in the deep confined zone. The main events in the SAG post-sedimentary history were: (1) adhesion of ferrugineous coatings on grains, (2) infiltration of clays in eodiagenetic stage, (3) regeneration of coatings with formation of smectites, (4) authigenic overgrowth of quartz and K-feldspar in advanced eodiagenetic stage, (5) bitumen cementation of Pirambóia Formation in mesodiagenetic stage, (6) cementation by calcite in mesodiagenetic and telodiagenetic stages in Pirambóia Formation, (7) formation of secondary porosity by dissolution of unstable minerals after appearance of hydraulic gradient and penetration of the meteoric water caused by the uplift of the Serra do Mar coastal range in the Late Cretaceous, (8) authigenesis of kaolinite and amorphous silica in unconfined zone of the SAG and cation exchange coupled with the dissolution of calcite at the transition between unconfined and confined zone, and (9) authigenesis of analcime in the confined SAG zone. The last two processes are still under operation. The deep zone of the SAG comprises an alkaline pH, Na-HCO 3 groundwater type with old water and enriched δ 13C values (<-3.9), which evolved from a neutral pH, Ca-HCO 3 groundwater type with young water and depleted δ 13C values (>-18.8) close to the SAG outcrop. This is consistent with a conceptual geochemical model of the SAG, suggesting dissolution of calcite driven by cation exchange, which occurs at a relatively narrow front recently moving downgradient at much slower rate compared to groundwater flow. More depleted values of δ 18O in the deep confined zone close to the Paraná River compared to values of relative recent recharged water indicate recharge occur during a period of cold climate. The SAG is a "storage-dominated" type of aquifer which has to be managed properly to avoid its overexploitation.

Fertility conserving management of early cervical cancer: our experience of LLETZ and pelvic lymph node dissection.

PubMed

Lindsay, Rhona; Burton, Kevin; Shanbhag, Smruta; Tolhurst, Jenny; Millan, David; Siddiqui, Nadeem

2014-01-01

Presently, for those diagnosed with early cervical cancer who wish to conserve their fertility, there is the option of radical trachelectomy. Although successful, this procedure is associated with significant obstetric morbidity. The recurrence risk of early cervical cancer is low and in tumors measuring less than 2 cm; if the lymphatics are negative, the likelihood of parametrial involvement is less than 1%. Therefore, pelvic lymph nodes are a surrogate marker of parametrial involvement and radical excision of the parametrium can be omitted if they are negative. The aim of this study was to report our experience of the fertility conserving management of early cervical cancer with repeat large loop excision of the transformation zone and laparoscopic pelvic lymph node dissection. Between 2004 and 2011, a retrospective review of cases of early cervical cancer who had fertility conserving management within Glasgow Royal Infirmary was done. Forty-three patients underwent fertility conserving management of early cervical cancer. Forty were screen-detected cancers; 2 were stage IA1, 4 were stage IA2, and 37 were stage IB1. There were 2 central recurrences during the follow-up period. There have been 15 live children to 12 women and there are 4 ongoing pregnancies. To our knowledge, this is the largest case series described and confirms the low morbidity and mortality of this procedure. However, even within our highly select group, there have been 2 cases of central recurrent disease. We, therefore, are urging caution in the global adoption of this technique and would welcome a multicenter multinational randomized controlled trial.