Safety aspects of infliximab in inflammatory bowel disease patients - A retrospective cohort study in 100 patients of a German University Hospital

Background: Infliximab, a chimeric anti-tumour necrosis factor monoclonal antibody with potent anti-inflammatory effects, represents an effective treatment option in patients with severe inflammatory bowel disease (IBD). Serious side-effects of such an immunomodulating therapy are speculated and therefore we reviewed our clinical experience in a retrospective safety study looking upon a single cohort of 100 IBD patients from a large German University Hospital. Methods: 100 patients with severe Crohn's disease (n = 92), ulcerative colitis (n = 7) or indeterminate colitis (n = 1) treated with infliximab (5 mg/kg) from January 2000 to December 2003 were retrospectively analysed for acute and subacute adverse events by chart review. Results: Overall, infliximab therapy was generally well tolerated. No fatal complications, malignancies, autoimmune diseases, neurologic or cardiovascular complications were observed in the cohort during the study period. Overall, adverse events were observed in 10 patients: 2 patients showed an acute infusion reaction, 1 patient a serum sickness-like reaction, in 4 patients a bacterial or viral infection occurred, in 1 patient pancytopenia and 2 patients developed surgical complications. Only 6 patients with adverse events required admission to hospital. A case of tuberculosis after infliximab was not found. The lack of adverse side-effects was associated with young median age and infrequent comorbidities of the cohort. Conclusion: Regarding its strong immunomodulating capacity, infliximab appears to be an efficient and relatively safe therapeutic option for patients with severe IBD. However, the use of infliximab requires careful screening and close patient monitoring to identify patients at risk and the infrequent, but sometimes serious complications of infliximab. Copyright (C) 2004 S. Karger AG, Basel

Baseline body mass index among children and adults undergoing allogeneic hematopoietic cell transplantation: clinical characteristics and outcomes

Obesity is an important public health problem that may influence the outcomes of hematopoietic cell transplantation (HCT). We studied 898 children and adults receiving first-time allogeneic hematopoietic stem cell transplants between 2004 and 2012. Pre-transplant body mass index (BMI) was classified as underweight, normal weight, overweight, or obese using the WHO classification, or age-adjusted BMI percentiles for children. The study population was predominantly Caucasian, and the median age was 51 years (5 months – 73 years). The cumulative 3-year incidence of non-relapse mortality (NRM) in underweight, normal weight, overweight, and obese patients was 20%, 19%, 20%, and 33%, respectively. Major causes of NRM were acute and chronic graft-versus-host disease (GVHD). The corresponding incidence of relapse was 30%, 41%, 37%, and 30%, respectively. Three-year overall survival was 59%, 48%, 47%, and 43%, respectively. Multivariate analysis showed that obesity was associated with higher NRM (HR 1.43, p=0.04), and lower relapse (HR 0.65, p=0.002). Pre-transplant plasma levels of ST2 and TNFR1 biomarkers were significantly higher in obese compared with normal weight patients (p=0.04 and p=0.05, respectively). The increase in NRM observed in obese patients was partially offset by lower incidence of relapse with no difference in overall survival

Einfluss von Cd-, Cu- und Zn-Kontaminationen auf die mikrobielle Population und Respiration in bewässerten Kastanozems in SE-Georgien

Das Untersuchungsgebiet befindet sich etwa 80 km südlich der Hauptstadt Tiflis im Mashavera-Tal in SE-Georgien. Aufgrund kontinentaler Klimabedingungen (504 mm) werden die intensiv landwirtschaftlich genutzten Böden mit Wasser aus dem Mashavera-Fluss bewässert. Der Fluss ist stark mit spurenmetallhaltigen (Cd, Cu, Zn) Schwebstoffen belastet, die aus Erosionsprozessen von Abraumhalden und Abwassereinleitungen der Flotationsanlagen einer NE-Metallmine stammen. Hierdurch werden die bewässerten Böden im Mashavera-Tal großflächig mit Cd, Cu und Zn belastet. Im Rahmen der Untersuchungen wurden die Auswirkungen der Spurenmetallbelastung auf die Lebensraumfunktion der Böden geprüft. Die im Mashavera-Tal anthropogen verursachte Cd-, Cu- und Zn-Kontamination der landwirtschaftlich genutzten Böden wirkt sich negativ auf die untersuchten mikrobiellen Parameter aus. Auf stark belasteten Flächen ist ein deutlicher Rückgang der mikrobiellen Respiration zu verzeichen. Zudem zeigt sich eine geringere Diversität in der bakteriellen Populationsstruktur in stark belasteten Bodenproben

Auswirkungen des Buntemetallbergbaus im Mashavera-Tal (Georgien) auf Bodenfunktionen und Möglichkeiten der in-situ Sanierung

Bie Böden des Mashavera-Tals (SE-Georgien) werden seit Jahrzehnten mit durch Buntmetallbergbau belastetet Wassser des Flusses Mashavera bewässert. Die daraus resultierenden hohen Cd, Cu und Zn Gehalte der Oberböden stellen ein erhebliches Belastungspotenzial für die Nahrungskette dar. Im Gefäßversuch gelang es durch Zugabe von Divergan® (ein Polyvinylpyrrolidon)die Spurenmetalle in schwer mobilisierbare Fraktionen zu überführen und dadurch die Pflanzenaufnahme zu reduzieren. Ob das Verfahren auch als Sanierungsstrategie im Mashavera-Tal anwendbar ist, muss aber zunächst noch im Feldversuch getestet werden

TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis

Although tumor necrosis factor (α) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate–induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis

Clinical narrative analytics challenges

Precision medicine or evidence based medicine is based on the extraction of knowledge from medical records to provide individuals with the appropriate treatment in the appropriate moment according to the patient features. Despite the efforts of using clinical narratives for clinical decision support, many challenges have to be faced still today such as multilinguarity, diversity of terms and formats in different services, acronyms, negation, to name but a few. The same problems exist when one wants to analyze narratives in literature whose analysis would provide physicians and researchers with highlights. In this talk we will analyze challenges, solutions and open problems and will analyze several frameworks and tools that are able to perform NLP over free text to extract medical entities by means of Named Entity Recognition process. We will also analyze a framework we have developed to extract and validate medical terms. In particular we present two uses cases: (i) medical entities extraction of a set of infectious diseases description texts provided by MedlinePlus and (ii) scales of stroke identification in clinical narratives written in Spanish

Effect of liver transplantation on inflammatory bowel disease in patients with primary sclerosing cholangitis

This report investigates the influence of liver transplantation and concomitant immunosuppression on the course of progression of inflammatory bowel disease (IBD) and discusses statistical methodology appropriate for such settings. The data on 303 patients who underwent liver transplantation for primary sclerosing cholangitis (PSC) were analyzed using person-time analysis and Cox regression, with the duration of IBD as the time variable and transplantation as a segmented time-dependent covariate, to take into account both posttransplant and pretransplant history of IBD. The need for colectomy and appearance of colorectal cancer were taken as outcome measures. The only significant risk factor in the multivariate model for colectomy was transplantation itself, which increased the risk of colectomy due to intractable disease (Wald statistic; P =. 001). None of the variables available for analysis were found to influence the risk of colon cancer significantly. Graphs showing the dependence of the instantaneous risk of cancer on the time from onset of IBD and its independence from the latter in the case of colectomy are presented. The use of a unique statistical methodology described for the first time in this setting led us to the somewhat surprising conclusion that transplantation and concomitant use of immunosuppression accelerate the progression of IBD. At the same time, transplantation does not affect the incidence of colorectal cancer. These results confirm the findings of some recent studies and can potentially shed new light on the disease pathogenesis

Correct quantum chemistry in a minimal basis from effective Hamiltonians

We describe how to create ab-initio effective Hamiltonians that qualitatively describe correct chemistry even when used with a minimal basis. The Hamiltonians are obtained by folding correlation down from a large parent basis into a small, or minimal, target basis, using the machinery of canonical transformations. We demonstrate the quality of these effective Hamiltonians to correctly capture a wide range of excited states in water, nitrogen, and ethylene, and to describe ground and excited state bond-breaking in nitrogen and the chromium dimer, all in small or minimal basis sets

Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population

BackgroundTo better understand the associations between a history of tobacco use and survival outcomes, cigarette use was prospectively surveyed in 687 previously untreated patients with cancer of the oral cavity (n = 271), oropharynx (n = 257), larynx (n = 135), or hypopharynx (n = 24).MethodsKaplan–Meier and Cox models explored the associations of tobacco use intensity (packs/day), duration (years of use), and timing before diagnosis with overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS).ResultsCigarette use duration, timing, and intensity were significant predictors for all outcomes in univariate analysis. Never smoking and pack‐years were not significantly associated with outcomes after adjustment for prognostic factors, such as stage, comorbidities, and human papillomavirus (HPV) status, which were strongly associated with clinical outcomes.ConclusionThe findings confirm the association between smoking history and survival and the importance of clinical variables in evaluating smoking as a prognostic factor. Timing, intensity, and duration of cigarette use should be considered with other prognostic factors when considering risk stratification for treatment planning. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1810–1820, 2016Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134806/1/hed24515.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134806/2/hed24515_am.pd

The ELIXIR Human Copy Number Variations Community:building bioinformatics infrastructure for research

Copy number variations (CNVs) are major causative contributors both in the genesis of genetic diseases and human neoplasias. While 'High-Throughput' sequencing technologies are increasingly becoming the primary choice for genomic screening analysis, their ability to efficiently detect CNVs is still heterogeneous and remains to be developed. The aim of this white paper is to provide a guiding framework for the future contributions of ELIXIR's recently established h uman CNV Community, with implications beyond human disease diagnostics and population genomics. This white paper is the direct result of a strategy meeting that took place in September 2018 in Hinxton (UK) and involved representatives of 11 ELIXIR Nodes. The meeting led to the definition of priority objectives and tasks, to address a wide range of CNV-related challenges ranging from detection and interpretation to sharing and training. Here, we provide suggestions on how to align these tasks within the ELIXIR Platforms strategy, and on how to frame the activities of this new ELIXIR Community in the international context