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Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020. https://doi.org/10.1007/s10620-020-06185-7 ) present the clinical outcomes for different FMT methodologies. However, to understand, compare, and contextualize outcomes, this heterogeneity in methods and reporting must be understood. We performed a literature review of randomized controlled trials (RCTs) of FMT for rCDI to evaluate heterogeneity among trials. A methodical search between January 2010 and May 2019 of Medline, Embase, and Cochrane was conducted for studies investigating FMT in adults with rCDI. RCTs were evaluated for a variety of methodological and reporting criteria. Eight RCTs were identified, wherein 14 different FMT preparations were considered (each with distinct protocols for processing, storage, administration, and dosing). Sample sizes were generally small, with only two studies performing FMT in more than 100 patients. Three studies used non-FMT controls (vancomycin), while the remaining compared FMT with differing routes of administration or formulations. Across the identified studies, there was no standardized manner for reporting the timing of the FMT procedure. All studies tracked adverse events; however, follow-up periods were limited. Considerable variability exists among RCTs, with marked differences in study design, control groups, and outcome assessment. Lack of a standard-of-care control in many trials may impact reproducibility of FMT trial outcomes in patients with rCDI. Widespread use of FMT for rCDI is still investigational; therefore, these foundational studies provide opportunities to optimize future trials.

Background Although the incidence, severity and mortality of Clostridioides (Clostridium) difficile infection (CDI) have been increasing, patients’ quality of life changes resulting from CDI have not been studied thoroughly. This study aimed at exploring the consequences of CDI on quality of life through patients’ perspective. Methods An observational, cross-sectional study involving 350 participants with a self-reported CDI diagnosis was conducted through an online self-administered survey. Participants were grouped into those who had active disease (“Current CDI”) and those who had a history of CDI (“Past CDI”). Results One hundred fifteen participants (33%) reported Current CDI and 235 (67%) reported Past CDI. A large majority of participants admitted that their daily activities were impacted by the infection (93.9% and 64.7% of Current and Past CDI respondents respectively, p p = 0.08; psychological consequences p = 0.21). After the infection, 56.6% of respondents noted that post-CDI symptoms remained; 40.9% believed they would never get rid of them. Conclusions While the societal burden of CDI is well described in the literature, our study is one of the first aimed at understanding the major burden of CDI on quality of life. Our results highlight the long-lasting nature of CDI and further reinforce the need for enhanced therapeutics in the prevention and treatment of this devastating infection.

Summary Background Faecal microbiota transplantation (FMT) has shown promise in alleviating the symptoms of irritable bowel syndrome (IBS); however, controlled data on this technique are scarce. The aim of this clinical trial was to assess the efficacy of FMT in alleviating diarrhoea-predominant IBS (IBS-D). Methods We did a double-blind, randomised, placebo-controlled crossover trial in patients aged 18–65 years with moderate-to-severe IBS-D defined by an IBS-Symptom Severity Score (IBS-SSS) of more than 175, recruited from three US centres. Patients were randomly assigned (1:1) in blocks of four with a computer-generated randomisation sequence to receive FMT capsules followed by identical-appearing placebo capsules, or placebo capsules followed by FMT capsules. All participants and study team members were masked to randomisation. An independent staff member assigned the treatments according to consecutive numbers. Patients received either 75 FMT capsules (each capsule contained approximately 0·38 g of minimally processed donor stool) or 75 placebo capsules over 3 days (25 capsules per day). All patients crossed over to the alternate treatment at 12 weeks. The primary outcome was difference in IBS-SSS between the groups at 12 weeks. Intention-to-treat analyses were done and all patients who received study drug were included in an adverse events analysis. The trial was terminated during recruitment because results from an interim analysis revealed futility. The study is registered with ClinicalTrials.gov , number NCT02328547 . Findings From May 28, 2015, to April 21, 2017, 48 patients were randomly assigned to receive FMT first (n=25) or placebo first (n=23). Three participants were lost to follow-up in the FMT group. IBS-SSS did not differ between FMT recipients (mean 221 [SD 105]) and placebo recipients (236 [95]) at 12 weeks (p=0·65), after adjustment for baseline scores. The most common drug-related adverse events included abdominal pain (five [10%] of the 48 participants while receiving FMT capsules vs four [8%] while receiving placebo), nausea (four [8%] vs two [4%]), and exacerbation of diarrhoea (three [6%] vs eight [17%]). One serious adverse event that was unrelated to study drug (acute cholecystitis) was reported in a patient while receiving placebo capsules. Interpretation FMT was safe, but did not induce symptom relief at 12 weeks compared with placebo. Additional studies are needed to determine the efficacy of FMT for IBS-D. Funding National Institutes of Health.

Background & aimsFecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers.MethodsPatients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes.ResultsOf the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n= 5 [2%]) and abdominal pain (n= 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%).ConclusionsThis prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.

Mesenteric ischemia (MI), both acute (AMI) and chronic (CMI), is a challenging diagnosis to make, and early diagnosis and treatment are vital to improve outcomes. This manuscript summarizes the most up to date information on diagnosis and treatment of these disorders. There have been several significant advancements in the computed tomography (CT) diagnostic imaging as well as medical and endovascular management of AMI and CMI. In appropriate populations, endovascular interventions appear superior to open surgical management with lower mortality, morbidity, and cost of care. Efficient clinical identification and targeted testing are essential to diagnose AMI and CMI. Aggressive resuscitation and early endovascular (or in select cases, surgical) intervention improve outcomes in those with AMI. In those with CMI, considering this on the differential diagnosis and imaging appropriately can identify those that might benefit from intervention and halt progression to acute episodes.

AIM To determine the pathological features of colonic ischaemia (CI) and their relationship to symptom duration, disease distribution and clinical outcome in a real-world, clinical setting. METHOD A retrospective, multicentre chart review was performed in patients diagnosed with CI at Montefiore Medical Center (January 2005 to July 2015), and Yale-New Haven Hospital (January 2005 to June 2010). Patients were included if clinical presentation, colonoscopic findings and colonic pathology were all consistent with CI. RESULTS Six hundred and sixteen patients with pathologically proven CI were included. Common pathological findings included inflammation (51.1%), ulceration (38.2%), fibrosis (26.0%) and necrosis (20.4%). Infarction and ghost cells were seen in 1.6% and 0.2% of cases, respectively. There was a significant relationship between symptom duration and hyalinization of the lamina propria (P = 0.05) and cryptitis/crypt abscesses (P = 0.01). Patients with isolated right CI (IRCI) were more likely than patients with isolated left CI (ILCI) to exhibit necrosis (P < 0.01), cryptitis/crypt abscess (P < 0.01) and inflammation (P = 0.03). Patients with poor outcomes were more likely to exhibit necrosis (P < 0.01) and capillary fibrin thrombi (P < 0.01) and less likely to exhibit fibrosis (P < 0.01) and epithelial changes (P < 0.01). CONCLUSION CI is accompanied by a broad spectrum of pathological findings. The traditional pathognomonic findings of CI are rare and cannot be relied upon to exclude the diagnosis. Patients with IRCI and/or poor outcomes were more likely to have pathological findings of necrosis than patients who had ILCI and/or nonpoor outcomes.

Sclerosing mesenteritis includes a spectrum of inflammatory disorders involving the adipose tissue of the bowel mesentery. To perform a systematic review of previously reported cases of sclerosing mesenteritis (SM) to determine the epidemiology, risk factors, methods of diagnosis, treatment patterns and outcomes for this disease. Medline, PubMed, Google Scholar and Cochrane database were searched using keywords mesenteric panniculitis, retractile mesenteritis, mesenteric lipodystrophy and sclerosing mesenteritis. Data was collated into a single excel database, transferred into SPSS (Version 21.0) and analyzed. Patients diagnosed with SM were between ages of 3 and 88 with a mean age of 55 ± 19.2 years. SM was more common in Caucasians (n = 28, 60.8% of those reporting ethnicity) and men (n = 133, 69.3%) with a male to female ratio of 2.3:1. 28.6% (n = 55) of patients reported a prior abdominal surgery or abdominal trauma, 8.9% (n = 17) had a history of malignancy, and 5.7% (n = 11) of autoimmune disease. 85.4% (n = 164) underwent surgical abdominal exploration (open or laparoscopic); 41.7% (n = 80) had surgery with resection of the involved bowel and mesentery. 34.9% (n = 67) of patients received medical treatment with the majority of them receiving steroids (n = 56, 83.5%). Symptom duration of more than a month (66.7% vs 40.4%, p

Rifaximin is an antimicrobial which is used for prophylaxis of hepatic encephalopathy in patients with cirrhosis and has known anti-Clostridioides difficile activity. The aim of this study is to assess whether the rate of C. difficile infection (CDI) is decreased in patients with cirrhosis on chronic rifaximin compared with those who are not. We retrospectively identified consecutive patients admitted to Montefiore Medical Center from 2010 to 2014 with cirrhosis and diarrhea who were tested for CDI. Demographics, comorbidities, medication exposure, baseline laboratory data, and outcomes were recorded. Patients with cirrhosis and diarrhea on chronic rifaximin were compared with those not on rifaximin. The chronic rifaximin group was then isolated, and those with and without CDI were compared. Of 701 patients with cirrhosis and diarrhea, 149 were on chronic rifaximin and 552 were not. 12.8% of patients on chronic rifaximin had CDI compared with 29.7% of those not on rifaximin (P

BACKGROUND Colon ischaemia is a common disease which has been associated with various medications and comorbidities. AIM To test the hypothesis that there are differences in the frequencies of these associations in older compared with younger patients. METHODS A retrospective cohort study was performed of patients hospitalized with colon ischaemia at two major medical centres from 2005-2017. Clinical, colonoscopic and pathologic criteria were used to identify patients admitted with colon ischaemia; patients with other types of colitis were excluded. Demographic and medical data were extracted. Two cohorts were created: patients aged 18-64 years and patients > 65 years. These were compared using SAS 14.3. RESULTS A total of 788 patients were included, of which 271 (34.4%) were of ages 18-64 years, and 517 (66.6%) were 65 years old or older. In the older cohort, constipation-inducing medications (83.8% vs 64.1%; P =

Objective: Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection. Methods: A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI). Results: In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group. Conclusions: Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

Clostridioides difficile infection (CDI) has been an epidemic for many years. Our biggest challenge in treating CDI is preventing recurrence, which is seen in approximately 25% of patients with initial infection and in 40–60% of those with subsequent episodes. Given the major disease burden of this infection, appropriate data-driven treatment remains essential. Clinical treatment guidelines provide an unbiased critical analysis of the literature, integrating the quality of the available data to make recommendations. As CDI has been evolving and more research has become available, the frequency of guideline issue from various global societies has increased, as has the detail of the recommendations to fit more relevant clinical scenarios. In this review, we will discuss clinical guideline recommendations over three time periods: The Initial Guidelines 1995–1997, The Second Wave 2009–2013, and The Modern Era 2014–present. We see the changing recommendations from metronidazole or vancomycin for initial infection during earlier times to preferential treatment with fidaxomicin within the Infectious Diseases Society of America (IDSA) and Society of Healthcare Epidemiology of America (SHEA) joint guidelines provisional update in late 2020. The recommended treatments for first recurrence were initially with the same antimicrobial as the first episode but have since changed to having multiple options for one or more recurrences. We have also seen the addition of immune boosting treatments, including fecal microbiota transplantation (FMT)/microbiota restoration therapy (MRT) and bezlotoxumab in the more modern recommendations. As the guidelines are evolving with the times, it remains important to understand the differences among them so we can apply this information clinically and optimize patient outcomes.

Background & Aims Patients with ischemia isolated to the right side of the colon (IRCI) frequently have poor outcomes. IRCI and acute mesenteric ischemia (AMI) are caused by reductions in blood supply from the superior mesenteric artery and its branches. We investigated a group of patients with IRCI associated with AMI that developed initially or shortly thereafter, and compared outcomes of patients with IRCI and AMI vs those with only IRCI. Methods We performed a retrospective study of data collected from 313 consecutive patients with colonic ischemia who were hospitalized at Montefiore Medical Center in New York from 1998 through 2009. Based on colonoscopy, biopsy analyses, and surgery reports, we identified patients with IRCI with concurrent or proximately developing AMI (IRCI+AMI) and those with only IRCI. Demographics, evaluation, disease distribution, and outcome data were compared between groups. Results Of 313 patients with colonic ischemia, 20.8% had IRCI; of these, 84.6% had only IRCI and 15.4% had IRCI+AMI. Chronic obstructive pulmonary disease was found more frequently in patients with IRCI+AMI (40.0%) than in patients with IRCI alone (12.7%; P P 3 /μL; P P = .001), and 30-day mortality was higher among patients with IRCI+AMI (70.0% vs 14.5% for patients with only IRCI; P Conclusions Based on an analysis of 313 patients with colonic ischemia, patients with IRCI+AMI have even more severe disease than those with IRCI alone. Chronic obstructive pulmonary disease was observed more frequently in patients with IRCI+AMI. Patients with IRCI+AMI had increased levels of blood urea nitrogen and/or white blood cell counts. Patients with IRCI should undergo vascular imaging analyses immediately to detect AMI; patients without AMI should be monitored closely for its subsequent development.

BACKGROUND Clostridium difficile infection (CDI) is the most common nosocomial infection in the US and cirrhotic patients with CDI have increased risk for poor outcome. AIM The aim of this study is to evaluate the impact of CDI on short-term mortality in patients with cirrhosis and identify predictors of mortality in these patients. METHODS We retrospectively identified patients at Montefiore Medical Center from 2010 to 2014 with cirrhosis, diarrhea and a C. difficile toxin assay. Demographics, co-morbidities, medications, laboratory data and outcomes were recorded. RESULTS Of 701 patients with cirrhosis who had a CDI assay, 183 were CDI+ and 518 CDI-. Patients with CDI were older, had more frequent CKD on hemodialysis and heart failure, were less frequently on rifaximin and lactulose and had increased glucocorticoid exposure. 30-day mortality was higher in patients with CDI (23.0% vs 16.6%, p

Background Colon ischaemia is the most common ischaemic disorder of the gastrointestinal system, can affect any segment of the colon, and may present with a range of symptoms. Diagnosis can be challenging due to symptom overlap with other conditions, varied aetiology, and often rapid and self-resolving course. Aim To review comprehensively the literature regarding the pharmacological aetiologies of colonic ischaemia to enhance the understanding of the various mechanisms of disease, presentations, distribution, and outcomes. Methods A PubMed search for "colon ischaemia" and "ischaemic colitis" alone as well as in combination with various known pharmacologic causes was performed. Only the highest quality and relevant literature was included in this review. The quality of the literature for each association was rated by the authors and a consensus was made when discrepancies were encountered. Only associations that were deemed "moderate" or "strong" were included. Results The literature considering pharmacologically associated colonic ischaemia is diverse, lacks codification and is characterised by numerous case reports and case series. Constipation-inducing drugs, digoxin, hormonal therapies, illicit drugs, immunomodulators, laxatives, and NSAIDs were strongly associated with colonic ischaemia. Antimicrobials, appetite suppressants, chemotherapies, decongestants, diuretics, ergot alkaloids, serotonin agents, statins, and vasopressor agents were moderately associated. Conclusions Patients presenting with abdominal pain, diarrhoea, or bloody stool need to be evaluated for the possibility of this condition and treated accordingly. Timely diagnosis is necessary to improve patient outcomes. This review aims to increase awareness among clinicians regarding the presentation of pharmacologically induced colonic ischaemia.

ACG Clinical Guideline: Epidemiology, Risk Factors, Patterns of Presentation, Diagnosis, and Management of Colon Ischemia (CI)

Glucocorticoids are commonly used to treat various illnesses in patients at risk for Clostridium difficile-associated disease (CDAD), but the effect of such immunosuppression on outcome has not been studied. We hypothesized that glucocorticoid use increases the risk of 30-day mortality in patients with CDAD.We identified consecutive inpatients from 1 January 2004 to 30 September 2008, who had a positive Clostridium difficile toxin assay and recorded their demography, glucocorticoid usage before CDAD diagnosis, 30-day mortality, Charlson comorbidity score, and pertinent laboratory data. Three cohorts were created: Group 1: CDAD (+) without glucocorticoid use, Group 2: CDAD (+) with glucocorticoid use, and Group 3: CDAD (-) with symptomatic diarrhea and receiving glucocorticoids.Groups 1, 2, and 3 consisted of 841, 285, and 898 patients, respectively. Significant multivariate predictors of short-term mortality were age in Group 1 (P0.001); age (P=0.007), Charlson score (P=0.004), and an endocrine indication for glucocorticoid use (P0.01) in Group 2; and age (P0.001), sex, (P=0.02), Charlson score (P0.001), weight-adjusted glucocorticoid dose (1.10+/-0.03), and prednisone use (P0.01) in Group 3. When considering all patients with CDAD (Groups 1 and 2), the use of any glucocorticoid resulted in an increased mortality with a hazard ratio of 2.1+/-0.19 (P0.001). Mortality rates were 9.6%, 19.3%, and 9.7% for Groups 1, 2, and 3 (P0.001 for Groups 1 and 3 vs. Group 2), respectively. Through Kaplan-Meier survival analysis, comparing the three groups revealed that patients with CDAD who received glucocorticoids were at significantly increased risk of short-term mortality compared with the control groups (Groups 1 and 3, P0.001).Mortality of patients with CDAD on glucocorticoids, regardless of the severity of CDAD, was significantly higher than the mortality of patients with CDAD not on glucocorticoids and those on glucocorticoids with symptomatic diarrhea and without C. difficile infection.

Ischemic colitis is the most common manifestation of ischemic injury to the gastrointestinal tract, and the variety of defined causes is increasing. Local hypoperfusion and reperfusion injury are both thought to contribute to the disease process, which manifests with a wide spectrum of injury including reversible colopathy (subepithelial hemorrhage and edema), transient colitis, chronic colitis, stricture, gangrene, and fulminant universal colitis. The distribution is typically segmental. Older studies showed that any portion of the colon can be involved; recently, it was established that the site of involvement and prognosis can be correlated. In particular, isolated involvement of the right side of the colon was shown to have a different presentation and worse outcome than ischemic colitis involving other segments. Diagnosis is usually made clinically and supported by radiologic imaging and colonoscopic evaluation. Most patients respond to conservative supportive therapy, although some with severe disease require surgical intervention.