Endoscopic trans-oral outlet reduction after bariatric surgery is safe and effective for dumping syndrome.

BACKGROUND: Dumping syndrome (DS) is a common complication of bariatric surgery. Treatments include dietary and behavioral changes, as well as pharmacotherapy and revision surgery. All can be costly or hard to adhere to. In recent years, evidence accumulates in favor of endoscopic trans-oral outlet reduction (TORe) as an effective treatment for DS, targeting the pathophysiology of rapid gastric clearance. The objective of this study is to assess the safety and efficacy of TORe for DS in a single referral center. METHODS: Patients after bariatric surgery suffering DS were followed, and data were retrospectively analyzed. Diagnosis and post-procedural assessment of DS were made clinically using Sigstad score. During the procedure, the anastomotic rim was cauterized. Afterwards, 2 non-interrupted "8-figure" sutures were placed, resulting in imbrication of additional gastric tissue on top of the anastomosis and narrowing to <1 cm at the end of the procedure. Patients were instructed to keep a liquid diet for 14 days and follow-up continued for 6 months. RESULTS: Between 8/2018 and 9/2019 TORe was carried out in 13 patients (M:F = 3:10) with mean age of 45.1 (range 25-56) and BMI of 33.5 (range 28.1-40.3). Average time since recent surgery was 5.5 years (range 1-9). Mean pre-procedure anastomosis diameter was 25.2 mm (range 15-30) and was reduced to a mean of 5.6 mm (range 5-10). Three patients (23%) were admitted overnight due to inability to drink which resolved spontaneously. No major complications were reported. At 6 months, the Sigstad score was significantly reduced (19.4 ± 3.6 vs 5.2 ± 5.5, P < 0.001), and 11/13 (85%) of patients had a complete resolution of their dumping symptoms. In addition, BMI decreased by a mean of 2.3 kg/m2 (-1 to 7.5, p = 0.002). CONCLUSION: TORe is a safe and effective treatment for patients suffering dumping syndrome and should be considered early in the treatment of DS.

Fecal Transplantation for Treatment of Clostridium Difficile Infection in Elderly and Debilitated Patients.

BACKGROUND: Fecal microbiota transplantation (FMT) is a new technique recently introduced to treat recurrent Clostridium difficile infection (CDI). Little is known about the efficacy and risks of FMT in elderly and ill patients. AIM: To investigate FMT efficacy in ill and elderly patients compared to conventional treatment. METHODS: The study comprised two groups of patients between 2012 and 2016 with recurrent CDI at two medical centers in Israel. The study group received FMT and the controls conventional therapy. The primary end points were CDI recurrence, length of hospitalization, and short-term survival. RESULTS: Thirty-four patients altogether, (21 females, mean age 82 years) participated, 11 received FMT and 23 controls. Demographics and clinical characteristics were similar between the two groups. Comorbidity indexes, i.e., Charlson index was high in both groups. In the FMT group, 10/11 (90%) patients showed clinical improvement 3 days after initiating treatment compared to 9/23 (39%) in the control group, p = 0.02. Survival at 2 months did not differ between the groups (FMT 54%, Control 50%, p = 0.816), but mean survival in the FMT group was higher than in the control (12 vs. 4 months, respectively, p = 0.015). Two significant adverse events from the FMT group included suspected aspirations, both occurring during gastroscopy route of administration. CONCLUSIONS: FMT is effective for elderly and very ill patients. Safety is a concern, but is rare even in patients with much comorbidity. Colonoscopy may be the preferred route of FMT infusion.

Crohn's Disease Exclusion Diet for the Treatment of Crohn's Disease: Real-World Experience from a Tertiary Center.

The Crohn's Disease (CD) exclusion diet (CDED) has been shown to induce remission in pediatric and adult patients with CD. In this retrospective cohort study, we describe our real-world experience with the CDED at the inflammatory bowel disease (IBD) unit of the Tel Aviv Medical Center between 2018-2021. CD patients with multiple clinical presentations and disease phenotypes who initiated the diet were included. Indications for treatment, medical and nutritional data were collected from dietician clinic visits and medical records. Clinical and biomarker responses were determined. The CDED was recommended to 220 CD patients. Seventy-two patients were included in the analysis for a clinically active disease (n = 48) or for remission maintenance (n = 24). Among patients with a clinically active disease, 62.5% of patients achieved clinical remission at week 6 and at week 12. A positive association between high adherence to the CDED and clinical remission at week 12 was observed (adjusted OR = 7.6, 95% CI 1.07-55.2, p = 0.043). Among patients treated for remission maintenance, remission at week 12 was maintained among 83.3% of patients. We conclude that the CDED may be a promising intervention for multiple CD presentations and indications. These findings should be further validated in larger, prospective, controlled studies.

Short-term effectiveness and safety of tofacitinib in ulcerative colitis - real world data from tertiary medical centers in Israel.

BACKGROUND: We sought to define the effectiveness and safety of tofacitinib in a real-world (RW) cohort of Israeli patients with moderate to severe ulcerative colitis (UC). METHODS: This was a multi-center retrospective observational cohort study (2019-2020) to assess the effectiveness and safety of tofacitinib induction and maintenance therapy up to 26 weeks. Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3 points, and SCCAI ≤2 or a PMS ≤1, respectively. RESULTS: We included 73 patients, 47% male; median age 26 years [IQR: 19.5-39.5], disease duration 7 years [IQR: 2.5-14.5], follow-up 7.1 months [IQR: 3-12], 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant corticosteroids (CS). Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months [IQR 3.4-16]. Overall, response, remission, and CS-free-remission were achieved in 47.6%, 20.6%, and 17.5% of patients, respectively. At early maintenance (week 26), response, remission, and CS-free-remission were achieved in 65%, 22.5%, and 20% of patients, respectively. At week 26, tofacitinib 10 mg BID was still used in 43%. Seventeen patients (23.2%) had an adverse event including herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. CONCLUSIONS: Tofacitinib was effective in achieving CS-free-remission in about 1/5 of highly biologics -experienced patients with UC. Despite a considerable proportion of patients maintained on tofacitinib 10 mg bid, it was well tolerated and safe. Earlier positioning of tofacitinib in the therapeutic algorithm may result in improved outcomes.

Faecal Proteases from Pouchitis Patients Activate Protease Activating Receptor-2 to Disrupt the Epithelial Barrier.

BACKGROUND AND AIMS: The pathogenesis of pouch inflammation may involve epithelial barrier disruption. We investigated whether faecal proteolytic activity is increased during pouchitis and results in epithelial barrier dysfunction through protease activating receptor [PAR] activation, and assessed whether the intestinal microbiome may be the source of the proteases. METHODS: Faecal samples were measured for protease activity using a fluorescein isothiocyanate [FITC]-casein florescence assay. Caco-2 cell monolayers were exposed to faecal supernatants to assess permeability to FITC-dextran. Tight junction protein integrity and PAR activation were assessed by immunoblot and immunofluorescence. A truncated PAR2 protein in Caco-2 cells was achieved by stable transfection using CRISPR/Cas9 plasmid. PAR2 activation in pouch biopsies was examined using antibodies directed to the N-terminus of the protein. Microbial composition was analysed based on 16S rRNA gene sequence analysis. RESULTS: Ten pouchitis patients, six normal pouch [NP] patients and nine healthy controls [HC] were recruited. The pouchitis patients exhibited a 5.19- and 5.35-fold higher faecal protease [FP] activity [p ≤ 0.05] compared to the NP and HC participants, respectively. The genus Haemophilus was positively associated with FP activity [R = 0.718, false discovery rate < 0.1]. Faecal supernatants from pouchitis patients activated PAR2 on Caco-2 monolayers, disrupted tight junction proteins and increased epithelial permeability. PAR2 truncation in Caco-2 abrogated faecal protease-mediated permeability. Pouch biopsies obtained from pouchitis patients, but not from NP patients, displayed PAR2 activation. CONCLUSIONS: Protease-producing bacteria may increase faecal proteolytic activity that results in pouch inflammation through disruption of tight junction proteins and increased epithelial permeability in a PAR2-dependent manner. This mechanism may initiate or propagate pouch inflammation.

The effect of a multispecies probiotic on microbiota composition in a clinical trial of patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Although probiotics are increasingly used in irritable bowel syndrome (IBS), their mechanism of action has not been elucidated sufficiently. We aimed to evaluate the impact of a multispecies probiotic on enteric microbiota composition in women with diarrhea-predominant-IBS (IBS-D) and to determine whether these effects are associated with changes in IBS symptoms or inflammatory markers. METHODS: In a double-blind, placebo-controlled study, Rome III IBS-D women completed a two-week run-in period and eligible women were assigned at random to a probiotic capsule (BIO-25) or an indistinguishable placebo, twice daily for 8 weeks. IBS symptoms and stool consistency were rated daily by visual analogue scales and the Bristol stool scale. High sensitivity C-reactive protein, fecal calprotectin and microbial composition were tested at baseline and at 4 and 8 weeks. Microbial sequencing of the 16S rRNA was performed and data were analyzed to compare patients who responded to treatment with those who did not. KEY RESULTS: 172 IBS-D patients were recruited and 107 eligible patients were allocated to the intervention (n = 54) or placebo (n = 53) group. Compared to placebo, BIO-25 did not result in changes in microbial diversity or taxa proportions, except for higher relative proportions of Lactobacillus in the BIO-25 group (P = 0.002). Symptomatic responders to BIO-25 showed a reduction in the proportion of Bilophila(P = 0.003) posttreatment. Patients with beneficial inflammatory-marker changes had higher baseline proportions of Faecalibacterium(P = 0.03), Leuconostoc (P = 0.03), and Odoribacter (P = 0.05) compared to corresponding non-responders. CONCLUSIONS & INFERENCES: Identifying patients with a more amenable microbiome at treatment initiation may result in better treatment response.