Five years of fecal microbiota transplantation-an update of the Israeli experience

AIM To evaluate and describe the efficacy of fecal microbiota transplantation(FMT) for Clostridium difficile infection(CDI) in a national Israeli cohort.METHODS All patients who received FMT for recurrent(recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients' medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success(at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT(cessation of diarrhea within 7 d) and recurrence at 6 mo.RESULTS There were 111 FMTs for CDI, with a median age of 70 years [interquartile range(IQR): 53-82], and 42%(47) males. Fifty patients(45%) were treated via the lower gastrointestinal(LGI, represented only by colonoscopy) route, 37(33%) via capsules, and 24(22%) via the upper gastrointestinal(UGI) route. The overall success rate was 87.4%(97 patients), with no significant difference between routes of administration(P = 0.338). In the univariant analysis, FMT success correlated with milder disease(P = 0.01), ambulatory setting(P < 0.05) and lower Charlson comorbidity score(P < 0.05). In the multivariant analysis, only severe CDI [odd ratio(OR) = 0.14, P < 0.05] and inpatient FMT(OR = 0.19, P < 0.05) were each independently inversely related to FMT success. There were 35(32%) patients younger than 60 years of age, and 14(40%) of them had a background of inflammatory bowel disease.CONCLUSION FMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.

Inflammatory bowel disease patient profiles are related to specific information needs: A nationwide survey

BACKGROUND Inflammatory bowel diseases(IBD) is a heterogenous, lifelong disease, with an unpredictable and potentially progressive course, that may impose negative psychosocial impact on patients.While informed patients with chronic illness have improved adherence and outcomes, previous research showed that the majority of IBD patients receive insufficient information regarding their disease.The large heterogeneity of IBD and the wide range of information topics makes a one-size fits all knowledge resource overwhelming and cumbersome.We hypothesized that different patient profiles may have different and specific information needs, the identification of which will allow building personalized computer-based information resources in the future.AIM To evaluate the scope of disease-related knowledge among IBD patients and determine whether different patient profiles drive unique information needs.METHODS We conducted a nationwide survey addressing hospital-based IBD clinics.A Total of 571 patients completed a 28-item questionnaire, rating the amount of information received at time of diagnosis and the importance of information, as perceived by participants, for a newly diagnosed patient, and for the participants themselves, at current time.We performed an exploratory factor analysis of the crude responses aiming to create a number of representative knowledge domains(factors), and analyzed the responses of a set of 15 real-life patient profiles generated by the study team.RESULTS Participants gave low ratings for the amount of information received at disease onset(averaging 0.9/5) and high ratings for importance, both for the newly diagnosed patients(mean 4.2/5) and for the participants themselves at current time(mean 3.5/5).Factor analysis grouped responses into six informationdomains.The responses of selected profiles, compared with the rest of the participants, yielded significant associations(defined as a difference in rating of >0.5 points with a P < 0.05).Patients with active disease showed a higher interest in work-disability, stress-coping, and therapy-complications.Patients newly diagnosed at age > 50, and patients with long-standing disease(> 10 years)showed less interest in work-disability.Patients in remission with mesalamine or no therapy showed less interest in all domains except for nutrition and long-term complications.CONCLUSION We demonstrate unmet patient information needs.Analysis of various patient profiles revealed associations with specific information topics, paving the way for building patient-tailored information resources.

Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: Results of a phase Ⅰ clinical trial

AIM: To evaluate safety and possible efficacy of induction of oral immune regulation using colitis extracted proteins (CEP) in Crohn's disease (CD) subjects. METHODS: Ten CDs were treated orally with autologous CEP thrice weekly for 16 wk. Subjects were monitored for CDAI and IBDQ. Immune modulatory effect was assessed by T-lymphocyte FACS analysis, CEP-specific IFNγ ELISPOT assay and cytokine levels. RESULTS: Induction of oral immune regulation significantly ameliorated disease activity. All (10/10) subjects had clinical response (CDAI≤70) and 7/10 achieved clinical remission (CDAI≤150). Significant increase in mean IBDQ score was noted (134±9 vs 164±12). No treatment-related adverse events were noted. High levels of CEP-specific IFNγ spot forming colonies were detected in five subjects prior to treatment and in all five, a marked decrease was observed. The CD4+/CD8+ lymphocyte ratio and peripheral NKT cell numbers increased significantly, in 7/10 and in 5/10 subjects, respectively. Significant increase in serum IL-10 and IL-4 levels was observed in 7/10 subjects during treatment period. CONCLUSION: Immune regulation via oral administration of CEP is a safe and possibly effective treatment for subjects with moderate CD and may provide means of antigen-specific immune modulation.

Factors associated with surgery in patients with intra-abdominal fistulizing Crohn's disease

AIM To characterize radiological and clinical factors associated with subsequent surgical intervention in Crohn's disease(CD) patients with intra-abdominal fistulae.METHODS From a cohort of 1244 CD patients seen over an eight year period(2006 to 2014), 126 patients were identified as having intra-abdominal fistulae, and included in the study. Baseline patient information was collected from the medical records. Imaging studies were assessed for: anatomic type and number of fistulae; diameter of the inflammatory conglomerate; length of diseased bowel; presence of a stricture with pre-stenotic dilatation; presence of an abscess; lymphadenopathy; and the degree of bowel enhancement. Multivariate analysis for the prediction of abdominal surgery was calculated via Generalized Linear Models.RESULTS In total, there were 193 fistulae in 132 patients, the majority(52%) being entero-enteric. Fifty-nine(47%) patients underwent surgery within one year of the imaging study, of which 36(29%) underwent surgery within one month. Radiologic features that were associated with subsequent surgery included: multiple fistulae(P = 0.009), presence of stricture(P = 0.02), and an entero-vesical fistula(P = 0.01). Evidence of an abscess, lymphadenopathy, or intense bowel enhancement as well as C-reactive protein levels was not associated with an increased rate of surgery. Patients who were treated after the imaging study with combination immunomodulatory and anti-TNF therapy had significantly lower rates of surgery(P = 0.01). In the multivariate analysis, presence of a stricture [RR 4.5(1.23-16.3), P = 0.02] was the only factor that increased surgery rate.CONCLUSION A bowel stricture is the only factor predicting an increased rate of surgery. Radiological parameters may guide in selecting treatment options in patients with fistulizing CD.

Enigma of primary aortoduodenal fistula

A diagnosis of primary aortoenteric fistula is difficult to make despite a high level of clinical suspicion. It should be considered in any elderly patient who presents with upper gastrointestinal bleeding in the context of a known abdominal aortic aneurysm. We present the case of young man with no history of abdominal aortic aneurysm who presented with massive upper gastrointestinal bleeding. Initial misdiagnosis led to a delay in treatment and the patient succumbing to the illness. This case is unique in that the fistula formed as a result of complex atherosclerotic disease of the abdominal aorta, and not from an aneurysm.

Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

Background:Family studies support a genetic predisposition to inflammatory bowel diseases(IBD),but known genetic variants only partially explain the disease heritability.Families withmultiple affected individuals potentially harbour rare and highimpact causal variants.Long regions of homozygosity due to recent inbreedingmay increase the risk of individuals bearing homozygous loss-of-function variants.This study aimed to identify rare and homozygous genetic variants contributing to IBD.Methods:Four families with known consanguinity and multiple cases of IBD were recruited.In a family-specific analysis,we utilised homozygosity mapping complemented by whole-exome sequencing.Results:We detected a single region of homozygosity shared by Crohn’s disease cases from a family of Druze ancestry,spanning 2.6Mb containing the NOD2 gene.Whole-exome sequencing did not identify any potentially damaging variants within the region,suggesting that non-coding variation may be involved.In addition,affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1,WHAMM,DENND3,and C5.Conclusion:This study examined the potential contribution of rare,high-impact homozygous variants in consanguineous families with IBD.While the analysis was not designed to achieve statistical significance,our findings highlight genes or loci that warrant further research.Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn’s disease.