Fecal Diversion for Perianal Crohn Disease in the Era of Biologic Therapies: A Multicenter Study.

BACKGROUND: The natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics. METHODS: We performed a retrospective, multicenter study from 1999 to 2020. Patients who underwent fecal diversion for refractory PCD were stratified by diversion type (ostomy with or without proctectomy). Times to clinical and surgical outcomes were estimated using Kaplan-Meier methods, and the association with biologics was assessed using multivariable Cox proportional hazards models. RESULTS: Eighty-two patients, from 3 academic institutions, underwent a total of 97 fecal diversions: 68 diversions without proctectomy and 29 diversions with proctectomy. Perianal healing occurred more commonly after diversion with proctectomy than after diversion without proctectomy (83% vs 53%; P = 0.021). Among the patients who had 68 diversions without proctectomy, with a median follow-up of 4.9 years post-diversion (interquartile range, 1.66-10.19), 37% had sustained healing, 31% underwent surgery to restore bowel continuity, and 22% underwent proctectomy. Ostomy-free survival occurred in 21% of patients. Biologics were independently associated with avoidance of proctectomy (hazard ratio, 0.32; 95% confidence interval, 0.11-0.98) and surgery to restore bowel continuity (hazard ratio, 3.10; 95% confidence interval, 1.02-9.37), but not fistula healing. CONCLUSIONS: In this multicenter study, biologics were associated with bowel restoration and avoidance of proctectomy after fecal diversion without proctectomy for PCD; however, a minority of patients achieved sustained fistula healing after initial fecal diversion or after bowel restoration. These results highlight the refractory nature of PCD.

Folate intake, markers of folate status and oral clefts: An updated set of systematic reviews and meta-analyses.

BACKGROUND: There has been a longstanding debate about the role of folate in the etiology of orofacial clefts (OFCs). Studies of different measures of nutritional intake or folate status have been done to investigate the possible role of folate in the prevention of OFC. Only one knowledge synthesis has attempted to bring together different types of evidence. The aim of the present work was to update it. METHODS: Evidence for associations between OFC and dietary folate, supplement use, folic acid fortification, biomarkers of folate status, and variants of MTHFR (C677T and A1298C) were included. Potentially eligible articles were systematically identified from PubMed, Medline, Embase, and Web of Science (2007-2020) and combined using random-effects meta-analysis when appropriate. Quality assessments were conducted using the Newcastle-Ottawa scale and Cochrane's risk of bias tool. RESULTS: Sixty-four studies published since the previous knowledge synthesis were identified, with eight of these identified through a supplementary search from October, 2018 to August, 2020. There was an inverse association between folic acid-containing supplement use before or during pregnancy and cleft lip with or without cleft palate (CL/P) (OR 0.60, 95% CI 0.51-0.69), with considerable between-study heterogeneity. The prevalence of CL/P showed a small decline post-folic acid fortification in seven studies (OR 0.94, 95% CI 0.86-1.02). No association was found between OFC and genetic markers of folate status. The coronavirus-19 pandemic has threatened food availability globally and therefore there is a need to maintain and even enhance surveillance concerning maternal intake of folate and related vitamins. CONCLUSIONS: The risk of non-syndromic OFC was reduced among pregnant women with folic acid-containing supplements during the etiologically relevant period. However, high heterogeneity between included studies, incomplete reporting of population characteristics and variation in timing of exposure and supplement types mean that conclusions should be drawn with caution.

Inhibition of HBsAg secretion by nucleic acid polymers in HepG2.2.15 cells.

More than 290 million people have chronic HBV infection and are at risk of developing cirrhosis and hepatocellular carcinoma. HBV subviral particles are produced in large excess over virions in infected patients and are the primary source of HBsAg, which is postulated to be important in allowing HBV to chronically persist by interfering with immune function. Nucleic acid polymers (NAPs) have been shown to result in clearance of HBsAg from the blood in pre-clinical and clinical studies. In this study, we show for the first time the recapitulation of NAP- induced inhibition of secretion of HBsAg in vitro using the human HepG2.2.15 cell line. With the restoration of endosomal release of NAPs in vitro using the UNC7938 compound, NAPs were observed to selectively impair the secretion of HBsAg without any intracellular HBsAg accumulation. Additionally, the structure-activity relationship of NAPs for this antiviral activity is similar to that previously reported in other infectious diseases and identifies an exposed hydrophobic protein domain as the target interface for this antiviral effect. The presented in vitro model, the first one to be based on a human derived cell line that constitutively expresses HBV, is a very promising tool for the identification of the host proteins(s) targeted by NAPs.