PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection.

OBJECTIVE: To evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA) - the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the United States (US) Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment. DESIGN: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72h of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively. RESULTS: Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups. CONCLUSIONS: RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date and findings support use of RBL to prevent rCDI in a broad patient population. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (NCT03931941).

Crohn's pericarditis identified with point-of-care ultrasonography: A case report.

We report the case of a 71-year-old male with Crohn's disease, shortness of breath, and chest pain that highlights cardiac involvement in inflammatory bowel disease and the role of point-of-care ultrasonography using an alternate cardiac ultrasound window in making the diagnosis of Crohn's pericarditis. The role of ultrasonography in diagnosis and management of inflammatory bowel disease focuses primarily on intestinal pathology. Cardiac involvement is a rare but clinically impactful extraintestinal manifestation, the diagnosis of which benefits from ultrasonography if the clinician performing and interpreting the exam is aware of the possibility and understands the potential value of whole-body ultrasonography as part of a physical exam.

The digital rectal examination: a multicenter survey of physicians' and students' perceptions and practice patterns.

OBJECTIVES: The digital rectal examination (DRE) may be underutilized. We assessed the frequency of DREs among a variety of providers and explored factors affecting its performance and utilization. METHODS: A total of 652 faculty, fellows, medical residents, and final-year medical students completed a questionnaire about their use of DREs. RESULTS: On average, 41 DREs per year were performed. The yearly number of examinations was associated with years of experience and specialty type. Patient refusal rates were lowest among gastroenterology (GI) faculty and highest among primary-care doctors. Refusal rates were negatively correlated with comfort level of the physician in performing a DRE. More gastroenterologists used sophisticated methods to detect anorectal conditions, and gastroenterologists were more confident in diagnosing them. Confidence in making a diagnosis with a DRE was strongly associated with the number of DREs performed annually. CONCLUSIONS: The higher frequencies of performing a DRE, lower refusal rate, degree of comfort, diagnostic confidence, and training adequacy were directly related to level of experience with the examination. Training in DRE technique has diminished and may be lost. The DRE's role in medical school and advanced training curricula needs to be re-established.

Efficacy and safety of EMR to completely remove Barrett's esophagus: experience in 41 patients.

BACKGROUND: EMR is typically used to remove focal abnormalities of the esophageal mucosa. However, larger areas of Barrett's esophagus (BE) can be resected through side-by-side resections. OBJECTIVE: To assess the efficacy and safety of EMR to completely remove BE. DESIGN: Retrospective, single-center study. SETTING: University of Iowa Hospitals and Clinics. PATIENTS: Between January 2006 and December 2010, 46 patients underwent EMR for complete removal of BE. Three were lost to follow-up, one died of unrelated causes before completion, and one was still undergoing EMR treatment at the conclusion of the study. The remaining 41 patients were included for analysis. The worst histologic grade was low-grade dysplasia in 4 patients, high-grade dysplasia without cancer in 26 patients, and high-grade dysplasia with superficial adenocarcinoma in 11 patients. BE was circumferential in 65.9% of cases, and the mean (± SD) length was 3.3 ± 2.3 cm. INTERVENTION: EMR was performed by using a cap (n = 4), a multiband ligator device (n = 31), or both (n = 6), with a mean (± SD) of 2.4 ± 1.2 sessions per patient. MAIN OUTCOME MEASUREMENTS: Remission rates and complications. RESULTS: Remission of high-grade dysplasia and cancer, all dysplasia, and all BE was achieved in 94.6%, 85.4%, and 78.0%, respectively. Complications included minor bleeding (31.7%), perforations (4.9%), and strictures (43.9%). All complications were managed conservatively. LIMITATIONS: Retrospective design. CONCLUSION: Complete removal of BE with EMR is effective but associated with a high complication rate, which is mainly related to stricture formation. This needs to be considered when choosing between available treatment modalities.

Sleep deprivation is hyperalgesic in patients with gastroesophageal reflux disease.

BACKGROUND & AIMS: Studies have demonstrated that gastroesophageal reflux disease (GERD) can cause sleep deprivation because of nighttime heartburn or short, amnestic arousals during sleep. Sleep deprivation has been associated with reports of increased GERD severity. Our aim was to determine whether sleep deprivation enhances perception of intraesophageal acid in patients with GERD vs healthy controls. METHODS: Ten healthy controls and 10 patients with erosive esophagitis (grades B-D) were included in the study. All subjects were randomized to either sleep deprivation (1 night with /=7 hours sleep/night). Patients crossed over to the other arm after a washout period of 1 week. To ensure proper sleep time, we objectively monitored subjects with an actigraph. The morning after sufficient sleep or sleep deprivation, patients underwent stimulus response functions to esophageal acid perfusion. RESULTS: Ten healthy controls and 10 GERD patients completed all stages of the study. GERD patients demonstrated a significant decrease in lag time to symptom report (91 +/- 21.6 vs 282.7 +/- 67 sec, respectively, P = .02), increase in intensity rating (9.3 +/- 1.4 vs 4.4 +/- 0.9 cm, respectively, P = .02), and increase in acid perfusion sensitivity score (48.3 +/- 8.5 vs 22.7 +/- 4.5 sec x cm/100, respectively, P = .02) after sleep deprivation as compared with nights of good sleep. Normal subjects did not demonstrate any differences in stimulus response functions to acid between sufficient sleep and sleep deprivation (578 +/- 164 vs 493.8 +/- 60.3 sec, 0.3 +/- 0.2 vs 0.45 +/- 0.2 cm, and 0.4 +/- 0.3 vs 2.4 +/- 1.4 sec x cm/100, respectively, all P = NS). CONCLUSIONS: Sleep deprivation is hyperalgesic in patients with GERD and provides a potential mechanism for increase in GERD symptom severity in sleep-deprived patients.

The pathophysiology of non-cardiac chest pain.

Various underlying mechanisms have been described in patients with non-cardiac chest pain (NCCP). By far, gastroesophageal reflux disease (GERD) is the most common cause and thus requires initial attention when patients with NCCP are managed. Esophageal dysmotility can be demonstrated in 30% of the NCCP patients, but appears to play a very limited role in symptom generation. A significant number of patients with NCCP lack any evidence of GERD and have been consistently shown to have reduced perception thresholds for pain. Peripheral and/or central sensitization have been suggested to be responsible for visceral hypersensivity in NCCP patients. Further understanding of the underlying mechanisms for pain in patients with NCCP will likely improve our current therapeutic approach.