Mechanism-Based Treatment Strategies for IBD: Cytokines, Cell Adhesion Molecules, JAK Inhibitors, Gut Flora, and More

Background Although TNF inhibitors revolutionized the therapy of inflammatory bowel disease (IBD), we have been reaching a point where other therapies with different mechanisms of action are necessary. A rising number of elderly IBD patients with contraindications to established therapies and a growing group of patients losing response to anti-TNF therapy compel us to find safer, better-tolerated, and, ideally, personalized treatment options. However, in order to choose the right drug to fit a patient, it is indispensable to understand the pathomechanism involved in IBD. Summary The aim of this review is to explain the inflammatory signaling pathways in IBD and how to inhibit them with current and future therapeutic approaches. Next to biologic agents targeting inflammatory cytokines (anti-TNF agents, anti-IL-12/-23 agents, and specific inhibitors of IL-23), biologics blocking leukocyte trafficking to the gut (anti-integrin antibodies) are available nowadays. More recently, small molecules inhibiting the JAK-STAT pathway (JAK inhibitors) or preventing lymphocyte trafficking (sphingosine-1-phosphate modulators) have been approved or are under investigation. Furthermore, modifying the microbiota has potential therapeutic effects on IBD, and autologous hematopoietic or mesenchymal stem cell transplantation may be considered for a highly selected group of IBD patients. Key Message Physicians should understand the different mechanisms of action of the potential therapies for IBD to select the right drug for the right patient

Molecular characterization, toxin detection and resistance testing of human clinical Clostridium difficile isolates from Lebanon

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen’s occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area

Endemic Gastrointestinal Anthrax in 1960s Lebanon: Clinical Manifestations and Surgical Findings

Anthrax is an ancient disease caused by the gram-positive Bacillus anthracis; recently, it has gained much attention because of its potential use in biologic warfare. Anthrax infection occurs in three forms: cutaneous, inhalational, and gastrointestinal. The last type results from ingestion of poorly cooked contaminated meat. Intestinal anthrax was widely known in Lebanon in the 1960s, when a series of >100 cases were observed in the Bekaa Valley. We describe some of these cases, introduce the concept of the surgical management of advanced intestinal anthrax, and describe some of the approaches for treatment

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Quality Metrics and Indicators in Colonoscopy

Colonoscopy is the preferred method for colorectal cancer screening. However, despite significant advances, the examination remains subject to limitations and variability amongst different practitioners. This calls for the need for objective quality indicators to ensure the optimal use of the modality. Three major priority quality measures have been identified that include adenoma detection rate (ADR), cecal intubation, and adherence to surveillance guidelines. ADR is the best-studied metric correlating with outcomes including post-colonoscopy colon cancer, but has inherent limitations such as the potential for corruptibility. Other important quality indicators include the quality of bowel preparation and colonoscopy withdrawal time. All these quality measures are interrelated and an improvement in any of them would help in increasing the power of colonoscopy as a screening tool, as well as decreasing its economic burden and potentially improving adherence to screening guidelines