Project description:BackgroundThe pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways.MethodsWe performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n = 4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data with a previous cohort of ulcerative colitis and Crohn's disease patients (n = 4 per group) to distinguish non-destructive from classic IBD.ResultsLC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation, and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD. Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared with CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation.ConclusionsWe conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.
Project description:Multiple tests are needed to diagnose a patient with noninfectious diarrhea. Some patients will be mistakenly labeled as diarrhea-predominant irritable bowel syndrome (IBS-D) because of nonspecific computed tomographic scans and grossly normal endoscopic findings. It is crucial to understand other less common pathologies to avoid these instances of misdiagnosis. This article focuses on microscopic colitis (MC), eosinophilic colitis (EC), and celiac disease. MC is an inflammatory condition of the colon that presents with two subtypes, only to be differentiated by histology. EC is a rare chronic inflammatory process. Depending on the extent of the disease, it can present with mild diarrhea, malabsorption, or at its worst, cause obstruction and perforation. Celiac disease affects the small bowel, but interestingly can present similarly to colitis. Both MC and EC respond to oral budesonide. Patients with celiac disease improve on gluten-free diets. These treatments are distinctly different from typical IBS-D care plans.
Project description:Chronic lymphocytic leukemia (CLL) is the most prevalent type of leukemia, affects mostly elderly CLL patients, and is incurable without allogeneic transplantation. Although classic chemo(immuno)therapy is still the standard of care for patients in need of treatment, this paradigm might change in the near future with the advent of new therapeutic agents targeting major pathogenic pathways in CLL.
Project description:BackgroundScabies is an intensely itchy parasitic infection of the skin caused by the Sarcoptes scabiei mite. It is a common public health problem with an estimated global prevalence of 300 million cases. Serious adverse effects have been reported for some drugs used to treat scabies.ObjectivesTo evaluate topical and systemic drugs for treating scabies.Search strategyIn February 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and INDMED. In March 2007, we also searched the grey literature and sources for registered trials. We also checked the reference lists of retrieved studies.Selection criteriaRandomized controlled trials of drug treatments for scabies.Data collection and analysisTwo authors independently assessed trial quality and extracted data. Results were presented as relative risks with 95% confidence intervals and data combined where appropriate.Main resultsTwenty small trials involving 2392 people were included. One trial was placebo controlled, 16 compared two or more drug treatments, two compared treatment regimens, and one compared different drug vehicles.Fewer treatment failures occurred by day seven with oral ivermectin in one small trial (55 participants). Topical permethrin appeared more effective than oral ivermectin (85 participants, 1 trial), topical crotamiton (194 participants, 2 trials), and topical lindane (753 participants, 5 trials). Permethrin also appeared more effective in reducing itch persistence than either crotamiton (94 participants, 1 trial) or lindane (490 participants, 2 trials). One small trial did not detect a difference between permethrin (a synthetic pyrethroid) and a natural pyrethrin-based topical treatment (40 participants). No significant difference was detected in the number of treatment failures between crotamiton and lindane (100 participants, 1 trial), lindane and sulfur (68 participants, 1 trial), benzyl benzoate and sulfur (158 participants, 1 trial), and benzyl benzoate and natural synergized pyrethrins (240 participants, 1 trial); all were topical treatments. No trials of malathion were identified. No serious adverse events were reported. A number of trials reported skin reactions in participants randomized to topical treatments. There were occasional reports of headache, abdominal pain, diarrhoea, vomiting, and hypotension.Authors' conclusionsTopical permethrin appears to be the most effective treatment for scabies. Ivermectin appears to be an effective oral treatment. More research is needed on the effectiveness of malathion, particularly when compared to permethrin, and on the management of scabies in an institutional setting and at a community level.
Project description:BackgroundInfection with the protozoan Entamoeba histolytica is common in low- and middle-income countries, and up to 100,000 people with severe disease die every year. Adequate therapy for amoebic colitis is necessary to reduce illness, prevent development of complicated disease and extraintestinal spread, and decrease transmission.ObjectivesTo evaluate antiamoebic drugs for treating amoebic colitis.Search methodsWe searched the available literature up to 22 March 2018. We searched the Cochrane Infectious Diseases Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, mRCT, and conference proceedings. We contacted individual researchers, organizations, and pharmaceutical companies, and we checked reference lists.Selection criteriaRandomized controlled trials of antiamoebic drugs given alone or in combination, compared with placebo or another antiamoebic drug, for treating adults and children with a diagnosis of amoebic colitis.Data collection and analysisTwo review authors independently assessed the eligibility and methodological quality of trials and extracted and analysed the data. We calculated clinical and parasitological failure rates and rates of relapse and adverse events as risk ratios (RRs) with 95% confidence intervals (CIs), using a random-effects model. We determined statistical heterogeneity and explored possible sources of heterogeneity using subgroup analyses. We carried out sensitivity analysis by using trial quality to assess the robustness of reported results.Main resultsIn total, 41 trials (4999 participants) met the inclusion criteria of this review. In this update, we added four trials to the 37 trials included in the first published review version. Thirty trials were published over 20 years ago. Only one trial used adequate methods of randomization and allocation concealment, was blinded, and analysed all randomized participants. Only one trial used an E histolytica stool antigen test, and two trials used amoebic culture.Tinidazole may be more effective than metronidazole for reducing clinical failure (RR 0.28, 95% CI 0.15 to 0.51; 477 participants, eight trials; low-certainty evidence) and is probably associated with fewer adverse events (RR 0.65, 95% CI 0.46 to 0.92; 477 participants, 8 trials; moderate-certainty evidence). Compared with metronidazole, combination therapy may result in fewer parasitological failures (RR 0.36, 95% CI 0.15 to 0.86; 720 participants, 3 trials; low-certainty evidence), but we are uncertain which combination is more effective than another. Evidence is insufficient to allow conclusions regarding the efficacy of other antiamoebic drugs.Authors' conclusionsCompared with metronidazole, tinidazole may be more effective in reducing clinical failure and may be associated with fewer adverse events. Combination drug therapy may be more effective for reducing parasitological failure compared with metronidazole alone. However, these results are based mostly on small trials conducted over 20 years ago with a variety of poorly defined outcomes. Tests that detect E histolytica more accurately are needed, particularly in countries where concomitant infection with other bacteria and parasites is common.
Project description:BACKGROUND: Lymphocytic colitis is characterised by chronic watery diarrhoea with normal endoscopic or radiological findings and microscopic evidence of pronounced infiltration of the colonic mucosa with lymphocytes. AIM: To investigate the long term clinical and histological evolution of the disease in a large group of patients with well characterised lymphocytic colitis. METHODS: Between 1986 and 1995 the histological diagnosis of lymphocytic colitis was obtained in 35 patients; 27 of these agreed to a follow up examination. All clinical, endoscopic, and histopathological records were reviewed at that time and the patients had a second endoscopic examination with follow up biopsies. RESULTS: The patients initially presented with the typical findings of lymphocytic colitis. After a mean (SD) follow up of 37.8 (27.5) months, diarrhoea subsided in 25 (93%) and histological normalisation was observed in 22 (82%) of the 27 patients. Progression from lymphocytic colitis to collagenous colitis was not observed. CONCLUSIONS: Lymphocytic colitis is characterised by a benign course with resolution of diarrhoea and normalisation of histology in over 80% of patients within 38 months. Considering the benign course of the disease, the potential benefit of any drug treatment should be carefully weighed against its potential side effects.
Project description:BackgroundPlacental abruption is an important cause of maternal and fetal mortality and morbidity.ObjectivesTo assess the effectiveness and safety of any intervention for the care of women and/or their babies following a diagnosis of placental abruption.Search strategyComprehensive electronic search of the Cochrane Pregnancy and Childbirth trials register. Date of last search: October 2002.Selection criteriaRandomised and 'quasi-randomised' trials that report clinically meaningful outcomes and present results on an intention to treat basis.Data collection and analysisIf eligible trials were to be identified, data will be extracted, unblinded, by the reviewer from all studies.Main resultsNo studies that met the inclusion criteria were identified.Reviewer's conclusionsThe clinical management of placental abruption has to rely on knowledge other than that obtained through randomised clinical trials.
Project description:Alkylators and nucleoside analogs were the main drugs for treatingchronic lymphoblastic leukemia (CLL), which have been replaced by monoclonal antibodies, such as rituximab in the past 10 years for refractory or relapsed CLL. The first-line immunochemotherapy regimen, rituximab combined with nucleoside analogs, significantly increased CLL patients' first-reaction rate and improved progression-free survival. Despite the long-lasting remissions by the use of chemoimmunotherapy, most CLL patients will relapse eventually. The obinutuzumab (GA101), an updated CD20 antibody, that is thought to achieve a more durable response with unique molecular and functional characteristics. Obinutuzumab is a humanized, monoclonal type II CD20 antibody modified by glycoengineering. The glycoengineered Fc portion enhances the binding affinity to the FcγRIII receptor on immune effector cells, resulting in increased antibody-dependent cellular cytotoxicity and phagocytosis. In addition, the type II antibody binding characteristics of obinutuzumab to CD20 lead to an efficient induction of direct non-apoptotic cell death. This review summarizes the results of clinical studies using obinutuzumab and looks forward to its further application in treating CLL clinically.