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Background and Aims: High rates of technical and clinical success were reported for lumen-apposing metal stent (LAMS) placement for peripancreatic fluid collection (PFC) drainage. However, data on the adverse event (AE) rates are heterogeneous. The aim of this study was to evaluate the incidence, severity, management, and risk factors of AEs related to the use of LAMSs for drainage of PFCs in a large cohort of patients., Methods: This is a multicenter, international, retrospective review from 15 centers of all patients who underwent placement of LAMSs for the management of PFCs. A nested case-control study was conducted in patients with (case) or without (control) AEs., Results: Three hundred thirty-three procedures in 328 patients were performed (5 patients treated with 2 LAMSs). Technical success was achieved in 321 patients (97.9%). Three hundred four patients were finally included in the study (7 excluded for lost to follow-up information; 10 excluded for deaths unrelated to LAMSs). The rate of clinical success was 89.5%. Seventy-nine LAMS-related AEs occurred in 74 of 304 patients (24.3%), after a mean time of 25.3 days (median, 18 days; interquartile range, 6-30) classified as 20 (25.3%) mild, 54 (68.4%) moderate, or 5 (6.3%) severe. On multivariable analysis compared with control subjects, cases were more likely to have walled-off necrosis (WON) versus pancreatic pseudocysts (odds ratio, 2.18; 95% confidence interval, 1.09-4.46; P = .028), whereas cases were less likely to have undergone tract (balloon) dilation (yes vs no; odds ratio, .47; 95% confidence interval, .22-.93; P = .034)., Conclusions: Data from this large international retrospective study confirm that the use of LAMSs for management of PFCs has excellent technical and good clinical success rates. The rate of AEs, however, is not negligible and should be carefully considered before using these stents for drainage of PFCs and in particular for WON. Further prospective studies are needed to confirm these findings. (Clinical trial registration number: NCT03544008.)., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. All rights reserved.)

This corrects the article DOI: 10.1038/ni.3690.

Inflammatory bowel diseases involve the dynamic interaction of host genetics, the microbiome and inflammatory responses. Here we found lower expression of NLRP12 (which encodes a negative regulator of innate immunity) in human ulcerative colitis, by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12 deficiency in mice caused increased basal colonic inflammation, which led to a less-diverse microbiome and loss of protective gut commensal strains (of the family Lachnospiraceae) and a greater abundance of colitogenic strains (of the family Erysipelotrichaceae). Dysbiosis and susceptibility to colitis associated with Nlrp12 deficency were reversed equally by treatment with antibodies targeting inflammatory cytokines and by the administration of beneficial commensal Lachnospiraceae isolates. Fecal transplants from mice reared in specific-pathogen-free conditions into germ-free Nlrp12-deficient mice showed that NLRP12 and the microbiome each contributed to immunological signaling that culminated in colon inflammation. These findings reveal a feed-forward loop in which NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12 deficiency can reverse dysbiosis.

Opinion Statement: Performing endoscopic procedures in the elderly carries known enhanced risk compared to the general population. Weighing the benefits against the risks is easy when a patient is in immediate danger, but a gray area arises in screening protocols in an elderly patient of average risk. In this review, we compare national and international guidelines in average risk screening procedures (colonoscopic colorectal screening, Barrett's surveillance) to find consensus for screening practice in the elderly. With minor differences between societal guidelines, it is widely agreed that 75 years is the appropriate age to begin to weigh risks and benefits according to a patient's state of health and comorbidities. For colorectal screening, most guidelines advocate complete cessation of screening after the age of 85 years. Such consensus must take into account an aging population where patients are living healthier for longer and thus may be appropriate candidates for screening procedures even if beyond designated ages of screening cessation.

Background: In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined., Methods: We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies., Results: Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting., Conclusions: Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.

Gnotobiotic rodents provide an important technique to study the functional roles of commensal bacteria in host physiology and pathophysiology. To ensure sterility, these animals must be screened frequently for contamination. The traditional screening approaches of culturing and Gram staining feces have inherent limitations, as many bacteria are uncultivable and fecal Gram stains are difficult to interpret. Thus, we developed and validated molecular methods to definitively detect and identify contamination in germ-free (GF) and selectively colonized animals. Fresh fecal pellets were collected from rodents housed in GF isolators, spontaneously contaminated ex-GF isolators, selectively colonized isolators and specific pathogen-free (SPF) conditions. DNA isolated from mouse and rat fecal samples was amplified by polymerase chain reaction (PCR) and subjected to quantitative PCR (qPCR) using universal primers that amplify the 16S rRNA gene from all bacterial groups. PCR products were sequenced to identify contaminating bacterial species. Random amplification of polymorphic DNA (RAPD) PCR profiles verified bacterial inoculation of selectively colonized animals. These PCR techniques more accurately detected and identified GF isolator contamination than current standard approaches. These molecular techniques can be utilized to more definitively screen GF and selectively colonized animals for bacterial contamination when Gram stain and/or culture results are un-interpretable or inconsistent.

Inflammatory bowel diseases (IBD) result from dysregulated immune responses toward microbial and perhaps other luminal antigens in a genetically susceptible host, and are associated with altered composition and diversity of the intestinal microbiota. The interleukin 10-deficient (IL-10 (-/-) ) mouse has been widely used to model human IBD; however the specific alterations that occur in the intestinal microbiota of this mouse model during the onset of colonic inflammation have not yet been defined. The aim of our study was to define the changes in diversity and composition that occur in the intestinal microbiota of IL-10 (-/-) mice during the onset and progression of colonic inflammation. We used high throughput sequencing of the 16S rRNA gene to characterize the diversity and composition of formerly germ-free, wild-type and IL-10 (-/-) mice associated with the same intestinal microbiota over time. Following two weeks of colonization with a specific pathogen-free (SPF) microbiota we observed a significant increase in the diversity and richness of the intestinal microbiota of wild-type mice. In contrast, a progressive decrease in diversity and richness was observed at three and four weeks in IL-10 (-/-) mice. This decrease in diversity and richness was mirrored by an increase in Proteobacteria and Escherichia coli in IL-10 (-/-) mice. An increase in E. coli was also observed in conventionally raised IL-10 (-/-) mice at the point of colonic inflammation. Our data reports the sequential changes in diversity and composition of the intestinal microbiota in an immune-mediated mouse model that may help provide insights into the primary vs. secondary role of dysbiosis in human IBD patients.

Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS (n = 16) and healthy controls (n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls (P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated.

Enteric microbiota can contribute to Crohn's disease and ulcerative colitis in several ways. Pathogenic or functionally altered commensal bacteria with increased mucosal adherence, invasion and intracellular persistence can activate pathogenic T cells and chronic intestinal inflammation. Compositional changes in intestinal microbiota can lead to decreased protective and increased aggressive species. Genetic polymorphisms resulting in increased mucosal permeability, decreased microbial killing, ineffective clearance of bacteria, biased TH1 and TH17 immune responses and loss of immunological tolerance are probably key contributors to IBD. Future therapies for these heterogeneous diseases should be individualized based on the patient-specific subset.