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Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a patient for therapeutic purposes. Current guidelines recommend FMT for the prevention of multiply recurrent Clostridioides difficile infection (CDI) after two recurrences, with cure rates approaching 90%. Emerging evidence also supports the use of FMT in the management of severe and fulminant CDI, resulting in decreased mortality and colectomy rates compared with standard of care approach. FMT shows promise as salvage therapy for critically-ill, refractory CDI patients who are poor surgical candidates. FMT should be considered early in the clinical course of severe CDI, preferably within 48 hours of failing to respond to antibiotic therapy and volume resuscitation. Besides CDI, ulcerative colitis was more recently identified as a potential treatment target for FMT. Several live biotherapeutics for microbiome restoration are on the horizon.

Despite regular need for colonoscopy in patients with Crohn's disease (CD), the efficacy and tolerability of bowel preparation (BP) agents is rarely assessed in this population. Assessing BP quality with existing scales may be challenging in CD due to presence of inflammation, bowel resection, and strictures.To provide recommendations for assessing BP quality in clinical trials for CD using a modified Research and Development/University of California, Los Angeles appropriateness process.Based on systematic reviews and a literature search, 110 statements relating to BP quality assessment in CD were developed. A panel of 15 gastroenterologists rated the statements as appropriate, uncertain, or inappropriate using a 9-point Likert scale.Panelists considered it appropriate that central readers, either alone or with local assessment, score BP quality in clinical trials. Central readers should be trained on scoring BP quality and local endoscopists on performing high-quality video recording. Both endoscope insertion and withdrawal phases should be reviewed to score BP quality in each colonic segment and segments should align with endoscopic disease activity indices. The Harefield Cleansing Scale and the Boston Bowel Preparation Scale were considered appropriate. The final score should be calculated as the average of all visualized segments. Both total and worst segment scores should also be assessed.We developed a framework for assessing BP quality in patients with CD based on expert feedback. This framework could support the development or refinement of BP quality scales and the integration of BP quality assessment in future CD studies.

Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Using a novel electronic reporting tool, we aimed to prospectively describe the onset of tofacitinib efficacy during induction therapy in a real-world study. Methods Patient-reported outcome data (PROs) including the simple clinical colitis activity index (SCCAI), PRO Measurement Identification Systems (PROMIS) measures, and adverse events were collected daily for the first 14 days and at day 28 and 56. Paired t tests and P for trend were utilized to compare changes in SCCAI over time. Bivariate analyses and logistic regression models were performed to describe response (SCCAI Results Of all included patients (n = 96), 67% had failed ≥2 biologics, and 61.5% were on concomitant steroids. Starting at day 3, PROs showed significant and persistent decline of the mean SCCAI (−1.1, P < 000.1) including significantly lower SCCAI subscores for stool frequency (−0.3; P < .003), bleeding (−0.3; P < .0002) and urgency (−0.2; P < .001). Steroid-free remission at day 14, 28, and 56 was achieved in 25%, 30.2%, and 29.2% of patients, respectively. Neither prior biologics nor endoscopic severity were independently predictive of response or remission in multivariate models. Numeric improvements in all PROMIS measures (anxiety, depression, social satisfaction) were seen through day 56. Rates of discontinuation due to adverse events were low. Conclusions In this prospective real-world study, tofacitinib resulted in a rapid and persistent improvement in UC disease activity PROs. The safety findings were consistent with the established safety profile of tofacitinib.

Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. Results: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4–41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7–54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6–55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3–18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. Conclusion: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226

Background & Aims We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. Methods A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist–naive and –exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. Results A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist–naive and −exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist−treated patients. However, in TNF-antagonist−naive patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Conclusions Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist−naive patients.

Background Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. Methods We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. Results Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. Conclusion The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis.We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT.Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P.001), had Child-Pugh scores of B or C (100% vs 37.7%; P.001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death.In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.

Background Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results Two hundred and forty patients from 10 studies (8 case series, 1 case–control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.

INTRODUCTION Celiac disease (CeD) and inflammatory bowel disease (IBD) are autoimmune diseases of the bowel with similar clinical symptoms. This study aims to characterize the clinical course of both diseases in subjects with overlap of CeD and IBD (CeD+IBD) on a gluten free diet (GFD) and IBD medications. METHODS We conducted a retrospective study of demographic and serological characteristics in subjects with CeD+ IBD at a large academic center using appropriate International Classification of Disease (ICD)-10 codes from 2017 to June 2022. RESULTS 36 subjects had IBD +CeD. 96% of subjects were Caucasian and 67% were female. The diagnosis of CeD post-dated the diagnosis of IBD by 3.6 years. Ulcerative colitis (UC) and Crohn’s disease (CD) occurred equally in IBD +CeD. About 75% of subjects had L2+L3, B1 phenotype per Montreal classification. 44% of UC +CeD subjects had pancolitis with 72% of them being classified as S0 (never severe) per Paris classification. 83% of subjects initiated a self-taught GFD. Only 17% of subjects sough advice from a celiac dietician. Mean duration at which GFD was initiated was 0.7 yrs from the initial diagnosis of CeD. Only 1/36 subjects followed a strict GFD during 6.5 years of follow up. The second and third assessment of GFD happened after a mean of 3.7 yrs and 5.2 yrs from the time of initiation of a GFD with only 1/36 subjects adhering to a strict GFD at these time points. Serum tTG IgA levels were tested on average at 4, 91, 154, 186 and 192 weeks from the diagnosis of CeD, with a consistent drop in mean tTG IgA titers to 45, 33, 19, 25 and 4 respectively. Only 1 subject got tTG IgA measurements over the next 250 weeks of follow up. Over a 10.1 year follow up since the diagnosis of IBD, descending proportions of subjects needing IBD medications were as follows: topical 5-ASA (aminosalicyates) (19/36)>oral steroids (18/36)> anti-TNF (tumor necrosis factor) (18/36)> anti-integrins (12/36)> azathioprine (10/36)> anti-IL12/23 (8/36)> topical 5-ASA (4/36)> MTX (methotrexate) (5/36)> topical steroids at 2/36. Mean time to initiation of IBD medications (in weeks) after GFD initiation as a reference point were in an order of oral 5-ASA (-67) < anti-TNF (-39) < AZA (-14) CONCLUSIONS Majority of subjects depended on a self-educated GFD. A small proportion of CeD +IBD subjects were assessed per clinical guidelines with respect to adherence to a GFD, serology. At least 50% of subjects with CeD+IBD needed escalation of IBD treatment to biologics and/or steroid rescue over 10 years despite initiation of GFD (albeit suboptimal). We need to further substantiate these findings with exclusive IBD and celiac control groups. We suggest establishing CeD centers at tertiary hospitals for adequate clinical guideline adherence.

Hematotoxicity after chimeric antigen receptor (CAR) T-cell therapy is associated with infection and death but management remains unclear. We report results of 31 patients receiving hematopoietic stem cell boost (HSCB; 30 autologous, 1 allogeneic) for either sustained severe neutropenia of grade 4 (38 days before HSCB (44%; P = .029). In conclusion, early or prophylactic HSCB showed quick response and improved outcomes for sustained moderate to severe neutropenia after CAR-T.

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.

Fecal microbiota transplantation (FMT) emerged as rescue treatment for multiply recurrent Clostridioides difficile infections (rCDIs) nonresponsive to standard therapy. However, estimation of FMT efficacy varies among different protocols and formulations, while placebo-controlled clinical trials have excluded most rCDI patients because of medical comorbidities. This study aimed to determine the safety and effectiveness of capsule FMT (cap-FMT) and colonoscopy FMT (colo-FMT) for rCDI using standardized products in a large, multicenter, prospective, real-world cohort.Clinical outcomes and adverse events after FMT performed for rCDI at 6 sites were captured in a prospective registry. FMT was performed using 1 of 2 standardized formulations of microbiota manufactured by the University of Minnesota Microbiota Therapeutics Program, freeze-dried/encapsulated or frozen-thawed/liquid. The FMT administration route was determined by the treating physician. The rCDI cure rate was assessed at 1 and 2 months. Safety data were collected within the first 72 hours and at 1 and 2 months. Logistic regression was used to investigate factors associated with FMT failure.A total of 301 FMTs were performed in 269 unique patients. Two-thirds were cap-FMT. CDI cure rates were 86% (95% CI, 82%-90%) at 1 month and 81% (95% CI, 75%-86%) at 2 months. There was no difference in the 1-month or 2-month cure rate between cap-FMT and colo-FMT. Cap-FMT recipients were older and less likely to be immunosuppressed or have inflammatory bowel disease. Patient factors of older age and hemodialysis were associated with FMT failure by 2 months on multivariate logistic regression. In addition, post-FMT antibiotic use was associated with FMT failure at 2 months. One serious adverse event was related to colonoscopy (aspiration pneumonia), otherwise no new safety signals were identified.Cap-FMT using freeze-dried capsules has a similar safety and effectiveness profile compared with colo-FMT, without the procedural risks of colonoscopy. Although highly effective overall, patient selection is a key factor to optimizing FMT success.

Background Antidepressants are recommended for the treatment of chronic musculoskeletal pain; however, target serum concentrations based on therapeutic drug monitoring (TDM) have not been established. Therefore, the authors analyzed routine care TDM data of antidepressants in patients with chronic pain with and without depression in terms of treatment outcomes in an interdisciplinary multimodal pain treatment (IMPT) program. Methods Patients with chronic musculoskeletal pain and TDM for amitriptyline (n = 45) or duloxetine (n = 30) were retrospectively included. The German pain questionnaire for pain intensity and the Depression Anxiety Stress scale were applied at T0 and at the end of the IMPT program (T1). A relief of pain intensity score ≥2 was considered as a positive outcome. Comorbid depression was diagnosed based on ICD-10 criteria. Serum concentrations of antidepressants were measured for routine clinical care TDM. Results After IMPT, stress improved in all subgroups, and depressive symptoms improved only in the duloxetine group. Overall, 40% and 27% of patients in the amitriptyline and duloxetine subgroup, respectively, were responders in terms of maximum pain score relief. Responders with comorbid depression were treated with a dose that led to a 1.7-fold higher serum concentration of the active moiety of amitriptyline (amitriptyline + nortriptyline) compared with nonresponders. Similarly, a 2.3-fold higher serum concentration was observed in depressed responders than in nondepressed responders (at minimum 131.5 ng/mL). Conclusions Dosing of antidepressants for chronic pain relief should specifically take comorbid depression into account. TDM may provide better outcomes of pain relief in an IMPT setting in patients with comorbid depression.

"Patients with inflammatory bowel disease, including ulcerative colitis (UC) and Crohn disease, have altered gut microbiomes. The success of fecal microbiota transplantation (FMT) in the treatment of Clostridioides difficile infection, a disease that is also marked by dysbiosis, has spurred research in applying FMT to UC. So far, 3 randomized controlled trials have demonstrated benefit in mild to moderate UC disease course after FMT. However, important questions regarding optimal stool preparation, route, and frequency of administration, as well as characteristics of the stool donor and recipient still remain."

Background Indiana State opioid prescription legislation has been shown to decrease overall opioid prescriptions. However, this effect has not been studied in specific diseases associated with chronic pain such as inflammatory bowel disease (IBD). We aimed to determine the effect of state opioid prescription legislation on opioid prescribing patterns in IBD. Methods A retrospective cohort analysis using an interrupted time-series from December 15, 2010 to July 1, 2018, with 2 time periods separated by Title 844 of the Indiana Administrative Code, in a statewide health care system capturing the majority of the state’s population including all adult patients with IBD. The primary outcome was opioid prescription rate per person-year. Results In total, 9436 patients met inclusion criteria. After legislation, the total number of opioid orders per patient-year continued to increase (0.543, 95% CI, 0.528-0.558, to 0.663, 95% CI, 0.654-0.672), with fewer scripts from the emergency department (0.113, 95% CI, 0.106-0.120, to 0.092, 95% CI, 0.088-0.095) and more from outpatient providers (0.303, 95% CI, 0.292-0.314 to 0.432, 95% CI, 0.424-0.439). There were increases in biologic (0.206, 95% CI, 0.197-0.215 to 0.517, 95% CI, 0.509-0.525) and steroid (0.182, 95% CI, 0.173-0.190 to 0.237, 95% CI, 0.232-0.243) prescriptions per person-year following legislation. Factors associated with heavy opioid use included chronic steroids (odds ratio, 5.030; 95% CI, 4.176-6.054), history of IBD-related surgery (odds ratio, 2.807; 95% CI, 2.367-3.323) and current smoking (odds ratio, 2.650; 95% CI, 2.223-3.158). Conclusions Despite legislation and the increased use of disease-modifying drugs, statewide opioid prescriptions continued to increase. The increase in opiate use, high steroid use, and significant health care utilization suggests poor underlying disease control.

Purpose of review With the growing popularity and commercialization of probiotics, it is important to understand the implications of existing randomized controlled trials and their applicability in the clinical setting to treat luminal gastrointestinal diseases. Recent findings Probiotics may be useful in the prevention of antibiotic-associated diarrhea, prevention of Clostridioides difficile infection and eradication of Helicobacter pylori. Some evidence supports the use of probiotics in the treatment of ulcerative colitis, prevention and treatment of pouchitis and irritable bowel syndrome. Caution has to be exercised in immunocompromised and critically ill individuals. New society guidelines do not encourage probiotic use in gastrointestinal disorders with the exception of premature infants to prevent necrotizing enterocolitis. Summary Despite burgeoning body of literature and wide acceptance by the public, a thorough understanding of efficacy and safety of probiotics is lacking. Uniform dosage, standardized clinical end points, personalization based on host microbial profile and longer duration of follow-up on the research front may help in the future in appropriate positioning of probiotics in health and disease.

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI); however, a small percentage of patients fail to achieve cure even after two FMTs. This high-risk cohort remains poorly understood. We performed a multicenter, multinational retrospective review of patients that underwent at least one FMT for a CDI indication at four academic FMT referrals. Patients’ data including CDI, FMT, and FMT variables were assessed. The primary outcome was FMT failure after a second FMT defined as persistent diarrhea and positive laboratory test for C. difficile (PCR or toxin) despite a second FMT within 8 weeks of the first FMT. A multivariable logistic regression model was performed to determine predictors of second FMT failure. A total of 540 patients received at least one FMT during the study period, of which 432 patients had success following the first FMT, 108 had documented failure (25%). Among those who failed the first FMT, 63 patients received a second FMT, of which 36 achieved cure, and 24 had documented failure after the second FMT. Patients that failed the first FMT but did not receive a second FMT and those lost to follow-up were excluded leaving 492 patients included in the analysis. The second FMT failure rate was 4.8% (24/492). Risk factors for second FMT failure identified by multivariable logistic regression included: inpatient status (OR 7.01, 95% CI: 2.37–20.78), the presence of pseudomembranes (OR 3.53, 95% CI: 1.1–11.33), and immunocompromised state (OR 3.56, 95% CI: 1.45–8.72) at the time of first FMT. This study identifies clinically relevant risk factors predictive of failing a second FMT. Clinicians can use these variables to help identify high-risk patients and provide a better-informed consent regarding the possibility of needing multiple FMTs.

Fecal microbiota transplantation (FMT) is the process of transplanting stool from a healthy donor into the gut of a diseased individual for therapeutic purposes. It has a clearly defined role in the treatment of recurrent Clostridium difficile (reclassified as “Clostridioides difficile”) infection (CDI), with cure rates over 90% and decreased rates of subsequent recurrence compared with anti-CDI antibiotics. There is emerging evidence that FMT is also effective in the treatment of severe and fulminant CDI, with associated decreases in mortality and colectomy rates compared with standard antibiotic therapy. FMT shows promise as salvage therapy for critically-ill CDI patients refractory to maximum medical therapy and not deemed to be surgical candidates. FMT should be considered early in the course of severe CDI and should be delivered immediately in patients with signs of refractory CDI. Expansion of FMT's use along the spectrum of CDI severity has potential to decrease associated rates of mortality and colectomy.

Introduction: Up to 15% of hospitalized patients with Clostridioides difficile infection (CDI) develop severe CDI (SCDI) or Fulminant CDI (FCDI). Due to high rates of mortality in medically-refractory CDI cases, 30% of patients with severe infection historically require surgical intervention. However, colectomy itself is an imperfect solution because it is difficult to predict who will fail medical therapy, patients with SCDI are more likely to have underlying medical conditions that make them poor surgical candidates, and post-surgical mortality still approaches 30-50%.Areas covered: This review will serve as a clinically-based review of severe and fulminant CDI management including discussion of models to predict severe infection, emerging treatments, novel targets for therapy, and innovations in surgical management.Expert opinion: Among the most promising studies to emerge in the last decade have involved fecal microbiota transplantation (FMT), which is already recommended by multiple society guidelines for recurrent CDI (RCDI). In the case of SCDI/FCDI, multiple studies have safely and successfully utilized FMT to produce rates of cure in the 70-90% range. Additionally, patients who have FCDI refractory to medical therapy and are poor candidates for colectomy may benefit from FMT as salvage therapy.

Background and Aims Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring-fitted cap (EndoRings; EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. Methods This was a single-center, randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate, insertion times, withdrawal times, and ease of passage through the sigmoid colon. Results EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, P = .025), but there were no statistically significant differences in ADR or sessile serrated polyp detection rate. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with Endo-Rings and contributed substantially to the overall results. Conclusions EndoRings can increase adenoma detection without a significant increase in procedure time, but the effect varies between operators. The use of EndoRings slows colonoscope insertion. (Clinical trial registration number: NCT03418662.)

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients.UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Mucosal exposure devices including distal attachments such as the cuff and cap have shown variable results in improving adenoma detection rate (ADR) compared with high-definition white light colonoscopy (HDWLE).We performed a prospective, multicenter randomized controlled trial in patients undergoing screening or surveillance colonoscopy comparing HDWLE to 2 different types of distal attachments: cuff (CF) (Endocuff Vision) or cap (CP) (Reveal). The primary outcome was ADR. Secondary outcomes included adenomas per colonoscopy, advanced adenoma and sessile serrated lesion detection rate, right-sided ADR, withdrawal time, and adverse events. Continuous variables were compared using Student's t test and categorical variables were compared using chi-square or Fisher's exact test using statistical software Stata version16. A P value.05 was considered significant.A total of 1203 subjects were randomized to either HDWLE (n = 384; mean 62 years of age; 81.3% males), CF (n = 379; mean 62.7 years of age; 79.9% males) or CP (n = 379; mean age 62.1 years of age; 80.5% males). No significant differences were found among 3 groups for ADR (57.3%, 59.1%, and 55.7%; P = .6), adenomas per colonoscopy (1.4 ± 1.9, 1.6 ± 2.4, and 1.4 ± 2; P = .3), advanced adenoma (7.6%, 9.2%, and 8.2%; P = .7), sessile serrated lesion (6.8%, 6.3%, and 5.5%; P = .8), or right ADR (48.2%, 49.3%, and 46.2%; P = .7). The number of polyps per colonoscopy were significantly higher in the CF group compared with HDWLE and CP group (2.7 ± 3.4, 2.3 ± 2.5, and 2.2 ± 2.3; P = .013). In a multivariable model, after adjusting for age, sex, body mass index, withdrawal time, and Boston Bowel Preparation Scale score, there was no impact of device type on the primary outcome of ADR (P = .77). In screening patients, CF resulted in more neoplasms per colonoscopy (CF: 1.7 ± 2.6, HDWLE: 1.3 ± 1.7, and CP: 1.2 ± 1.8; P = .047) with a shorter withdrawal time.Results from this multicenter randomized controlled trial do not show any significant benefit of using either distal attachment devices (CF or CP) over HDWLE, at least in high-detector endoscopists. The Endocuff may have an advantage in the screening population. (ClinicalTrials.gov, Number: NCT03952611).

There has been an increase in the burden of Clostridioides difficile infection (CDI),1 especially in high-risk populations such as patients with inflammatory bowel disease (IBD).2 The prevalence of CDI in the IBD population is up to 8-fold higher than comparable controls, with increased rates of recurrence and CDI-associated mortality.3 In addition, CDI may induce an IBD flare, and worsen disease severity and clinical course.4 Fecal microbiota transplantation (FMT) is a guideline recommended therapy for recurrent CDI5; however, supportive randomized trials excluded patients with IBD. In retrospective trials of patients with IBD, FMT failure rates had been reported to be approximately 25% to 30%.6 In addition, Khoruts and colleagues reported that patients with IBD and CDI were more likely to fail FMT,7 leading to further uncertainty regarding the safety and efficacy of FMT in IBD patients with concurrent CDI. Accordingly, we conducted the first prospective study examining the efficacy of FMT among patients with IBD and CDI. Methods We conducted an open-label, prospective, single-arm, multicenter cohort study at 4 tertiary care FMT referral centers (Brigham and Women’s Hospital, Indiana University, Brown University, and Mount Sinai Hospital; NCT03106844). Patients with a confirmed diagnosis of IBD and 2 or more confirmed CDI episodes within 12 months, including the most recent episode occurring within 3 months, were enrolled. In keeping with CDI clinical guidelines,5 polymerase chain reaction or glutamate dehydrogenase with toxin enzyme immunoassay were permitted for the qualifying CDI episode. Patients with a total or subtotal colectomy, isolated ileal or small bowel Crohn’s disease, those pregnant or breastfeeding, those treated with vancomycin or metronidazole for more than 60 days, or those who had undergone a prior FMT within 12 months were excluded. Baseline IBD and CDI data were collected. All patients underwent a single FMT via colonoscopy. Four robustly screened healthy donors were used (OpenBiome, Cambridge, MA).8 Stool testing, including glutamate dehydrogenase, toxin enzyme immunoassay ,and polymerase chain reaction, was performed 1, 8, and 12 weeks post-FMT regardless of symptoms to assess for CDI and C. difficile colonization rates. All stool testing was performed at a central laboratory. The primary outcome was FMT failure through week 8, defined as diarrhea (3 or more loose stools daily for 3 or more days) and stool testing positive for C. difficile via 2-step testing using glutamate dehydrogenase and toxin enzyme immunoassay. Patients who met the criteria for failure underwent a second FMT. Secondary outcomes included C. difficile colonization defined as patients without diarrhea whose stool remained positive via polymerase chain reaction post-FMT. Results Fifty participants were enrolled (August 2017 to October 2019) among whom 15 had Crohn’s disease and 35 had ulcerative colitis (Table 1). The mean age of participants was 43 years (range 21–91) and the cohort was primarily female (58%). A total of 49 patients received treatment. One patient withdrew before treatment and was not replaced. Among the 49 participants, 1 patient was lost to follow-up after the week 1 visit and was treated as an FMT failure. Baseline CDI characteristics: 48% had 2 CDI episodes before entry, among whom 87.5% (21/24) were diagnosed via polymerase chain reaction at the qualifying episode; 38% had 3 confirmed episodes, among whom 78.9% (15/19) were diagnosed via polymerase chain reaction; and 14% had 4 prior CDI episodes among whom 71% were diagnosed via polymerase chain reaction (5/7).

Fecal microbiota transplantation (FMT) is a recommended therapy to prevent recurrent Clostridioides difficile infection (CDI).1,2 Stool banks have emerged to enable safe widespread access by provid...

Purpose of review This article will review current management strategies for severe and fulminant Clostridioides difficile infection (CDI). Recent findings Clostridioides difficile is the most common nosocomial cause of infectious diarrhea. With the rise of hypervirulent strains of CDI, almost 8% of patients hospitalized with CDI are afflicted with severe CDI (SCDI) or fulminant CDI (FCDI). A significant proportion of these patients do not respond to recommended anti-CDI antibiotic therapy such as oral vancomycin and fidaxomicin. Current recommendations suggest that patients with refractory CDI should proceed to colectomy or diverting loop ileostomy with colonic lavage. However, both of these surgical interventions result in high rates of post-surgical mortality approaching 30%. Fecal microbiota transplantation (FMT) is a promising therapy that is recommended in recurrent CDI. Recent studies have found that FMT can safely produce cure rates between 70 and 90% in patients with SCDI and FCDI, while significantly decreasing rates of CDI-related mortality and colectomy. A patient population likely to benefit the most from FMT is elderly patients due to their increased risk for CDI, treatment failure, and high comorbidity burden that may preclude surgical intervention. FMT should be considered in patients with SCDI or FCDI particularly when traditional anti-CDI antibiotics are ineffective.

Introduction: Fecal microbiota transplantation (FMT) is a procedure involving transfer of stool from a healthy donor into the intestinal tract of a diseased recipient to restore intestinal microbia...

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

Background Vedolizumab effectiveness estimates immediately after Food and Drug Administration (FDA) approval for ulcerative colitis (UC) and Crohn’s disease (CD) are limited by use in refractory populations. We aimed to compare treatment patterns and outcomes of vedolizumab in 2 time frames after FDA approval. Methods We used 2 data sets for time trend analysis, an academic multicenter vedolizumab consortium (VICTORY) and the Truven MarketScan database, and 2 time periods, May 2014–June 2015 (Era 1) and July 2015–June 2017 (Era 2). VICTORY cumulative 12-month clinical remission, corticosteroid-free remission, and mucosal healing rates, and Truven 12-month hospitalization and surgery rates, were compared between Eras 1 and 2 using time-to-event analyses. Results A total of 3661 vedolizumab-treated patients were included (n = 1087 VICTORY, n = 2574 Truven). In both cohorts, CD and UC patients treated during Era 2 were more likely to be biologic naïve. Compared with Era 1, Era 2 CD patients in the VICTORY consortium had higher rates of clinical remission (31% vs 40%, P = 0.03) and mucosal healing (42% vs 58%, P < 0.01). These trends were not observed for UC. In the Truven database, UC patients treated during Era 2 had lower rates of inflammatory bowel disease–related hospitalization (22.4% vs 9.6%, P < 0.001) and surgery (17.2% vs 9.4%, P = 0.008), which was not observed for CD. Conclusion Since FDA approval, remission and mucosal healing rates have increased for vedolizumab-treated CD patients, and vedolizumab-treated UC patients have had fewer hospitalizations and surgeries. This is likely due to differences between patient populations treated immediately after drug approval and those treated later., There has been a shift in utilization of vedolizumab in both Crohn’s disease and ulcerative colitis toward earlier use in the treatment sequencing algorithm. This shift in utilization is associated with improvements in response and disease outcomes.

The risk of a new Clostridium difficile infection (CDI) after FMT is unknown if non-CDI antibiotics are required. It is uncertain if anti-CDI prophylaxis or probiotics would reduce risk. We therefore aimed to compare the risk of CDI with and without antibiotic exposure and the benefit of concomitant anti-CDI antibiotic or probiotic prophylaxis. This is a multicenter retrospective study carried out at three large FMT referral centers of patients who underwent FMT for recurrent CDI. Patients were assessed for antibiotic use, as well as concomitant use of prophylactic anti-CDI antibiotics or probiotics. Time to CDI recurrence after FMT was evaluated using the Kaplan–Meier method. A total of 404 patients were included: 63% were females, with a mean age of 61.3 ± 18.8 years. Mean length of post-FMT follow-up was 18.1 ± 11.9 months (range 2.2–45.2). Among the entire cohort 8.1% (n = 33) experienced a CDI recurrence. Overall, 111 patients (27.4%) used a non-CDI antibiotic, of which 16.2% (n = 18) experienced a CDI recurrence. Patients who used non-CDI antibiotics were more likely to develop CDI (HR 8.44, 95% CI 4.21–16.93, p

The gastrointestinal microbiome is intrinsically linked to the spread of antibiotic resistance. Antibiotic treatment puts patients at risk for colonization by opportunistic pathogens like vancomycin resistant Enterococcus and Clostridioides difficile by destroying the colonization resistance provided by the commensal microbiota. Once colonized, the host is at a much higher risk for infection by that pathogen. Furthermore, we know that microbiome community differences are associated with disease states, but we do not have a good understanding of how we can use these changes to classify different patient populations. To that end, we have performed a multicenter retrospective analysis on patients who received fecal microbiota transplants to treat recurrent Clostridioides difficile infection. We performed 16S rRNA gene sequencing on fecal samples collected as part of this study and used these data to develop a microbiome disruption index. Our microbiome disruption index is a simple index that is predictive across cohorts, indications, and batch effects. We are able to classify pre-fecal transplant vs post-fecal transplant samples in patients with recurrent C. difficile infection, and we are able to predict, using previously-published data from a cohort of patients receiving hematopoietic stem cell transplants, which patients would go on to develop bloodstream infections. Finally, we also identified patients in this cohort that were initially colonized with vancomycin resistant Enterococcus and that 92% (11/12) were decolonized after the transplant, but the microbiome disruption index was unable to predict such decolonization. We, however, were able to compare the relative abundance of different taxa between the two groups, and we found that increased abundance of Enterobacteriaceae predicts whether patients were colonized with vancomycin resistant Enterococcus. This work is an early step towards a better understanding of how microbiome predictors can be used to help improve patient care and patient outcomes.

Clostridium difficile infection (CDI) has become the leading cause of nosocomial infection in the United States with significant risk of both morbidity and mortality. While antimicrobial therapy forms the basis of treatment, there are several clinical scenarios in which antimicrobial therapy alone is insufficient. Evidence continues to show the safety and efficacy fecal microbiota transplantation (FMT) in recurrent and severe CDI. This review will outline FMT efficacy, safety, and indications and present practical advice for clinicians interested in best practices around delivery of FMT.

Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.

Background Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results Two hundred and forty patients from 10 studies (8 case series, 1 case–control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.

Background & Aims This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. Methods Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC 50% among those with baseline FC >250 μg/g) and C-reactive protein (CRP) response (high-sensitivity CRP 50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). Results The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). Conclusions The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679