Delivery of Fecal Material to Terminal Ileum Is Associated with Long-Term Success of Fecal Microbiota Transplantation.

BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (CDI). However, 10-20% of patients still fail to recover following FMT. There is a need to understand why these failures occur and if there are modifiable factors that can be addressed by clinicians performing FMT. AIMS: We sought to identify factors related to the FMT procedure itself which could impact FMT outcomes. We also aimed to identify patient demographics which might be associated with FMT outcomes and whether any factors were associated with early FMT failure compared to late CDI recurrence. METHODS: We performed a retrospective multicenter cohort analysis of FMT procedures between October 2005 and November 2020. We collected data on patient demographics, details of the FMT procedure, and procedure outcomes. Using univariate and multivariate regression, we evaluated whether these factors were associated with long-term FMT success, early FMT failure (less than 60 days following procedure), or late CDI recurrence (more than 60 days following procedure). RESULTS: Long-term success of FMT was strongly correlated with any delivery of stool to the terminal ileum (Odds Ratio [OR] 4.83, 95% confidence interval [CI] 1.359-17.167) and underlying neurologic disease (OR 8.012, 95% CI 1.041-61.684). Lower bowel prep quality was significantly associated with both early FMT failure (p = 0.034) and late CDI recurrence (p = 0.050). CONCLUSIONS: Delivery of stool to the terminal ileum is significantly associated with long-term success following FMT. This is a relatively safe practice which could easily be incorporated into the standard of care for colonoscopic FMT.

Lost microbes of COVID-19: Bifidobacterium, Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity.

OBJECTIVE: The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls. DESIGN: Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels. RESULTS: Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria. CONCLUSION: We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention. TRIAL REGISTRATION NUMBER: NCT04031469 (PCR-) and 04359836 (PCR+).

ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.

ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides difficile Infections.

Clostridioides difficile infection occurs when the bacterium produces toxin that causes diarrhea and inflammation of the colon. These guidelines indicate the preferred approach to the management of adults with C. difficile infection and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation process. In instances where the evidence was not appropriate for Grading of Recommendations Assessment, Development, and Evaluation but there was consensus of significant clinical merit, key concept statements were developed using expert consensus. These guidelines are meant to be broadly applicable and should be viewed as the preferred, but not the only, approach to clinical scenarios.

Diverticular Disease in the Elderly.

PURPOSE OF REVIEW: While few diseases are limited solely to the elderly, diverticular disease is clearly more prevalent with increasing age and therefore the aim of this review is to focus on the clinical implications of diverticular disease in the elderly. RECENT FINDINGS: Diverticulitis in the elderly is best managed with an individualized treatment approach including considerations for selective antibiotic usage even in uncomplicated disease. Furthermore, due to the increased prevalence of ischemic colitis in the elderly and the similarities in presentation with diverticular hemorrhage, there needs to be a high index of suspicion and appropriate evaluation for ischemic colitis in patients with hematochezia, particularly if they have abdominal pain. The elderly are a vulnerable population where the index of suspicion for complications of diverticular disease should be high.

International Consensus on Diverticulosis and Diverticular Disease. Statements from the 3rd International Symposium on Diverticular Disease.

The statements produced by the Chairmen and Speakers of the 3rd International Symposium on Diverticular Disease, held in Madrid on April 11th-13th 2019, are reported. Topics such as current and evolving concepts on the pathogenesis, the course of the disease, the news in diagnosing, hot topics in medical and surgical treatments, and finally, critical issues on the disease were reviewed by the Chairmen who proposed 39 statements graded according to level of evidence and strength of recommendation. Each topic was explored focusing on the more relevant clinical questions. The vote was conducted on a 6-point scale and consensus was defined a priori as 67% agreement of the participants. The voting group consisted of 124 physicians from 18 countries, and agreement with all statements was provided. Comments were added explaining some controversial areas.

Critical Issues on Diverticular Disease.

In this session diverse critical issues in diverticular disease were considered, including "In or outpatient management of uncomplicated diverticulitis?", "Segmental colitis associated with diverticulosis: what is it?"and "Diverticular inflammation is a risk factor for colorectal cancer?". The conclusions drawn are outlined in the statements but in summary, outpatient management is safe in selected patients, as long as correct diagnosis and stage are assured, and this can allow a cost effective treatment. Non-antibiotic management is also safe but should be confined as an outpatient treatment in carefully selected patients.  Segmental colitis associated with diverticulosis (SCAD) is a defined pathological entity (only diagnosed on biopsy) characterized by an inflammatory bowel disease-like pathology, occurring principally in the sigmoid colon, with rectal and right colon sparing.  The pathogenesis is unclear but may include a genetic predisposition, microbiome alteration and ischaemia. Treatment can last months, and depends on severity, options include antibiotics, 5 ASA and probiotics for mild cases. Severe disease needs systemic steroids or even anti TNFα treatment.  Whether diverticular inflammation is a risk factor for colorectal cancer was debated and the conclusion that within the first eighteen months of diagnosis of diverticular disease associations with cancer are found, likely due to similar symptoms and misclassification of disease. After that time, diverticular disease does not increase the risk of colorectal cancer. Therefore, this is recommended to exclude cancer with imaging and colonoscopy after healing of the first episode of diverticulitis.

The DICA Endoscopic Classification for Diverticular Disease of the Colon Shows a Significant Interobserver Agreement among Community Endoscopists: an International Study.

BACKGROUND AND AIMS: The Diverticular Inflammation and Complication Assessment (DICA) endoscopic classification of diverticulosis and diverticular disease (DD) is currently available. It scores severity of the disease as DICA 1, DICA 2 and DICA 3. Our aim was to assess the agreement on this classification in an international endoscopists community setting. METHODS: A total of 96 doctors (82.9% endoscopists) independently scored a set of DD endoscopic videos. The percentages of overall agreement on DICA score and a free-marginal multirater kappa (κ) coefficient were reported as statistical measures of interrater agreement. RESULTS: Overall agreement in using DICA was 91.8% with a free-marginal kappa of 88% (95% CI 80-95). The overall agreement levels were: DICA 1, 85.2%; DICA 2, 96.5%; DICA 3, 99.5%. The free marginal κ was: DICA 1 = 0.753, DICA 2 = 0.958, DICA 3 = 0.919. The agreement about the main endoscopic items was 83.4% (k 67%) for diverticular extension, 62.6% (k 65%) for number of diverticula for each district, 86.8% (k 82%) for presence of inflammation, and 98.5 (k 98%) for presence of complications. CONCLUSIONS: The overall interrater agreement in this study ranges from good to very good. DICA score is a simple and reproducible endoscopic scoring system for diverticulosis and DD.

Course of the Diverticular Disease: What is changing?

In this session several critical issues in diverticular disease were considered, including "It is Symptomatic Diverticular Disease or Irritable Bowel Syndrome?", "What do determine evolution to diverticulitis, bowel habits alteration or inflammation?", and "Prevention of acute diverticulitis: Is it at all possible?". The first talking compared symptoms and laboratory findings between Symptomatic Uncomplicated Diverticular Disease  (SUDD) and Irritable Bowel Syndrome (IBS). Although both disease share some symptoms, and although IBS can occur in patients having diverticulosis,  SUDD and IBS can be differentiate using a combination of symptoms and laboratory tools. The second talking debated what are the most important risk factors for the evolution towards acute diverticulitis. Current data seem to exclude a significant role of bowel habits alteration, while inflammation seems to have a stronger role, especially in causing acute diverticulitis recurrence. The third talking analyzed about the acute diverticulitis prevention. Primary prevention seem to be little better when using mesalazine, while no definite conclusion can be drawn about the use of fiber and rifaximin. About the secondary prevention, no drugs can be currently advised due to lacking of definite results. At the same time, surgery should be advised on case-by-case basis.

Antibiotics in Uncomplicated Acute Diverticulitis: To Give or Not to Give?

Acute uncomplicated diverticulitis (AUD) is generally felt to be caused by obstruction and inflammation of a colonic diverticulum and occurs in about 4-5% of patients with diverticulosis. The cornerstone of AUD treatment has conventionally been antibiotic therapy, but with a paradigm shift in the underlying pathogenesis of the disease from bacterial infection to more of an inflammatory process, as well as concerns about antibiotic overuse, this dogma has recently been questioned. We will review emerging data that supports more selective antibiotic use in this population, as well as newer guidelines that advocate this position as well. While there are no discrete algorithms to guide us, we will attempt to suggest clinical scenarios where antibiotics may reasonably be withheld.

Diverticular Disease: An Update on Pathogenesis and Management.

Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review.