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Background: Recurrent Clostridioides difficile infection (rCDI) occurs in up to 35% of patients with CDI, and further recurrence is common. Fecal microbiota, live-jslm (RBL) is safe and effective for preventing rCDI in adults following antibiotic treatment for rCDI when administered rectally. There is clinical interest in alternative routes of administration. Objectives: CDI-SCOPE assessed the safety and clinical effectiveness of RBL when administered via colonoscopy to adults with rCDI. Design: Single-arm, exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received one administration of RBL consisting of one 150-mL dose of RBL, delivered via colonoscopy to the right side of the colon. The primary endpoint assessed RBL-related treatment-emergent adverse events (TEAEs) within 8 weeks of RBL administration or until confirmed treatment failure. Secondary endpoints included treatment success (absence of CDI recurrence for 8 weeks following RBL administration), physician experience administering RBL via colonoscopy, and physician perception of participant benefit. Results: Of 54 participants screened, 41 were enrolled and received RBL via colonoscopy; 39 participants completed the 8-week visit. Five TEAEs in four participants (9.8%) were assessed as related to RBL, all of which were gastrointestinal and mild in severity. Overall, 18 participants (43.9%) experienced 33 TEAEs within 8 weeks, most of which were of mild (25/33; 75.8%) or moderate (5/33; 15.2%) severity. No TEAEs led to intensive care unit admission or death. Overall, 39 participants (95.1%) experienced treatment success; 2 participants (4.9%) withdrew consent and had an indeterminate outcome. Among physicians, 90.2% of investigators indicated a “positive” or “very positive” experience administering RBL by colonoscopy. All physicians assessed participant benefit as “much” or “very much” improved. Conclusion: This single-arm study suggests RBL administered via colonoscopy is practical, safe, and effective for preventing CDI recurrence following antibiotic treatment in adults. Trial registration: ClinicalTrials.gov: NCT05831189. Plain language summary Safety and prevention of Clostridioides difficile reinfection by fecal microbiota, live-jslm (RBL) when given during a colonoscopy Some patients who have had Clostridioides difficile infection (CDI) keep being reinfected. Fecal microbiota, live-jslm (REBYOTA®, abbreviated here as RBL) is a microbiome-based product that prevents another CDI reinfection after antibiotic treatment. RBL is given via the rectum but can also be given during a colonoscopy. The CDI-SCOPE trial looked at how safe RBL was and how well it prevented more CDI reinfections. Forty-one adults who had CDI more than once were given one dose of RBL during a colonoscopy. Investigators then monitored participants for side effects or CDI reinfections. After 8 weeks, four people (9.8%) had mild gastrointestinal side effects considered related to RBL, and none had confirmed CDI reinfections. The trial showed that RBL is safe and effective at preventing CDI reinfection in adults when given during colonoscopy.

Background: Fecal microbiota, live-jslm (RBL) is a microbiota-based product for the prevention of recurrent Clostridioides difficile infection (rCDI) in adults following antibiotic treatment. The safety and clinical effectiveness of RBL administered via colonoscopy in adults with rCDI were evaluated in CDI-SCOPE. An 8-week analysis showed 9.8% of participants had RBL-related treatment-emergent adverse events (TEAEs; primary endpoint) and 95.1% experienced treatment success (no CDI recurrence). Objectives: To evaluate long-term safety and clinical effectiveness of RBL through 6 months of follow-up in CDI-SCOPE. Design: Single-arm exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received a single 150-mL dose of RBL to the right colon via colonoscopy. The primary endpoint was RBL-related TEAEs through 8 weeks after RBL administration or confirmed treatment failure. Secondary endpoints included safety up to 6 months after RBL administration. Exploratory analyses included assessment of further CDI episodes. Results: Of the 41 participants enrolled, 39 completed trial assessments through 6 months. From 8 weeks through 6 months after RBL administration, 36 TEAEs in 15 participants (36.6%) were reported, one of which (irritable bowel syndrome) was RBL-related; most TEAEs (97.2%) were of mild or moderate severity. Over the 6-month trial period, 23 participants (56.1%) experienced 69 TEAEs; 94.2% were of mild or moderate severity. Serious TEAEs occurred in three participants (7.3%), none of which were related to RBL or its administration, and no TEAEs led to discontinuation or death. Overall, 38 participants (92.7%) did not experience further CDI episodes, 1 (2.4%) did between 8 weeks and 6 months, and 2 (4.9%) had an indeterminate outcome due to trial withdrawal before 8 weeks. Conclusion: RBL administered via colonoscopy was safe and effective for preventing CDI recurrence in adults with rCDI in CDI-SCOPE. Trial registration: ClinicalTrials.gov: NCT05831189. Infographic

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. A total of 652 faculty, fellows, medical residents, and final-year medical students completed a questionnaire about their use of DREs. 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. 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.

Background: Fecal microbiota, live-jslm (RBL) is a microbiota-based product for the prevention of recurrent Clostridioides difficile infection (rCDI) in adults following antibiotic treatment. The safety and clinical effectiveness of RBL administered via colonoscopy in adults with rCDI were evaluated in CDI-SCOPE. An 8-week analysis showed 9.8% of participants had RBL-related treatment-emergent adverse events (TEAEs; primary endpoint) and 95.1% experienced treatment success (no CDI recurrence). Objectives: To evaluate long-term safety and clinical effectiveness of RBL through 6 months of follow-up in CDI-SCOPE. Design: Single-arm exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received a single 150-mL dose of RBL to the right colon via colonoscopy. The primary endpoint was RBL-related TEAEs through 8 weeks after RBL administration or confirmed treatment failure. Secondary endpoints included safety up to 6 months after RBL administration. Exploratory analyses included assessment of further CDI episodes. Results: Of the 41 participants enrolled, 39 completed trial assessments through 6 months. From 8 weeks through 6 months after RBL administration, 36 TEAEs in 15 participants (36.6%) were reported, one of which (irritable bowel syndrome) was RBL-related; most TEAEs (97.2%) were of mild or moderate severity. Over the 6-month trial period, 23 participants (56.1%) experienced 69 TEAEs; 94.2% were of mild or moderate severity. Serious TEAEs occurred in three participants (7.3%), none of which were related to RBL or its administration, and no TEAEs led to discontinuation or death. Overall, 38 participants (92.7%) did not experience further CDI episodes, 1 (2.4%) did between 8 weeks and 6 months, and 2 (4.9%) had an indeterminate outcome due to trial withdrawal before 8 weeks. Conclusion: RBL administered via colonoscopy was safe and effective for preventing CDI recurrence in adults with rCDI in CDI-SCOPE. Trial registration: ClinicalTrials.gov: NCT05831189.

Background: Recurrent Clostridioides difficile infection (rCDI) occurs in up to 35% of patients with CDI, and further recurrence is common. Fecal microbiota, live-jslm (RBL) is safe and effective for preventing rCDI in adults following antibiotic treatment for rCDI when administered rectally. There is clinical interest in alternative routes of administration. Objectives: CDI-SCOPE assessed the safety and clinical effectiveness of RBL when administered via colonoscopy to adults with rCDI. Design: Single-arm, exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received one administration of RBL consisting of one 150-mL dose of RBL, delivered via colonoscopy to the right side of the colon. The primary endpoint assessed RBL-related treatment-emergent adverse events (TEAEs) within 8 weeks of RBL administration or until confirmed treatment failure. Secondary endpoints included treatment success (absence of CDI recurrence for 8 weeks following RBL administration), physician experience administering RBL via colonoscopy, and physician perception of participant benefit. Results: Of 54 participants screened, 41 were enrolled and received RBL via colonoscopy; 39 participants completed the 8-week visit. Five TEAEs in four participants (9.8%) were assessed as related to RBL, all of which were gastrointestinal and mild in severity. Overall, 18 participants (43.9%) experienced 33 TEAEs within 8 weeks, most of which were of mild (25/33; 75.8%) or moderate (5/33; 15.2%) severity. No TEAEs led to intensive care unit admission or death. Overall, 39 participants (95.1%) experienced treatment success; 2 participants (4.9%) withdrew consent and had an indeterminate outcome. Among physicians, 90.2% of investigators indicated a “positive” or “very positive” experience administering RBL by colonoscopy. All physicians assessed participant benefit as “much” or “very much” improved. Conclusion: This single-arm study suggests RBL administered via colonoscopy is practical, safe, and effective for preventing CDI recurrence following antibiotic treatment in adults. Trial registration: ClinicalTrials.gov: NCT05831189.

Some older baby boomers with hepatitis C got it from a blood transfusion before 1992, when widespread screening of the blood supply began in the United States.

Years of important research has revealed that cells heavily invest in regulating their size. Nevertheless, it has remained unclear why accurate size control is so important. Our recent study using hematopoietic stem cells (HSCs) in vivo indicates that cellular enlargement is causally associated with aging. Here, we present an overview of these findings and their implications. Furthermore, we performed a broad literature analysis to evaluate the potential of cellular enlargement as a new aging hallmark and to examine its connection to previously described aging hallmarks. Finally, we highlight interesting work presenting a correlation between cell size and age-related diseases. Taken together, we found mounting evidence linking cellular enlargement to aging and age-related diseases. Therefore, we encourage researchers from seemingly unrelated areas to take a fresh look at their data from the perspective of cell size.

The sudden appearance of a large cluster of animals with gross abnormalities may signal a significant change in an ecosystem. We describe an unusual concentration of beak deformities that appear to have arisen rapidly within Alaska and now extend southward along the Pacific Coast. In Alaska we have documented 2,160 Black-capped Chickadees (Poecile atricapillus) and 435 individuals of 29 other species of birds, primarily during the past decade, with grossly overgrown and often crossed beaks. The annual prevalence of beak abnormalities among adult Black-capped Chickadees in south-central Alaska varied from 3.6% to 9.7% and averaged 6.5 ± 0.5% between 1999 and 2008. Only 0.05 ± 0.05% of nestlings and 0.3 ± 0.2% of juveniles <6 months old had abnormal beaks, which suggests that this is either a latent developmental or an acquired condition. We documented 80 cases in which a Black-capped Chickadee captured with an apparently normal beak was subsequently recaptured with a beak abnormality and 8 cases in which a beak deformity was no longer detectable upon recapture. Necropsy and histopathology of a sample of affected individuals provided no conclusive evidence of the etiology of this condition. Deformities appear to affect primarily the keratin layer of the beak and may result from abnormally rapid growth of the rhamphotheca. Some affected birds also exhibited lesions in other keratinized tissues of the skin, legs, feet, claws, and feathers, which may represent a systemic disorder or secondary conditions. Additional studies are currently underway to determine diagnostic signs and the underlying cause of this avian keratin disorder.

ObjectiveWhile greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with high BMI.MethodsGARFIELD-AF is a prospective registry of 52 057 newly diagnosed AF patients. The study population comprised 40 482 participants: 703 underweight (BMI <18.5 kg/m2), 13 095 normal (BMI=18.5–24.9 kg/m2), 15 043 overweight (BMI=25.0–29.9 kg/m2), 7560 obese (BMI=30.0–34.9 kg/m2) and 4081 extremely obese (BMI ≥35.0 kg/m2). Restricted cubic splines quantified the association of BMI with outcomes. Comparative effectiveness of NOACs and vitamin K antagonists (VKAs) by BMI was performed using propensity score overlap-weighted Cox models.ResultsThe median age of participants was 71.0 years (Q1; Q3 62.0; 78.0), and 55.6% were male. Those with high BMI were younger, more often had vascular disease, hypertension and diabetes. Within 2-year follow-up, a U-shaped relationship between BMI and all-cause mortality was observed, with BMI of ~30 kg/m2 associated with the lowest risk. The association with new/worsening heart failure was similar. Only low BMI was associated with major bleeding and no association emerged for non-haemorrhagic stroke. BMI was similarly associated with outcomes in men and women. BMI did not impact the lower rate of all-cause mortality of NOACs compared with VKAs.ConclusionsIn the GARFIELD-AF registry, underweight and extremely obese AF patients have increased risk of mortality and new/worsening heart failure compared with normal or obese patients.

The derivation of authentic embryonic stem cells (ESCs) from diverse mammalian species offers valuable opportunities for advancing regenerative medicine, studying developmental biology, and enabling species conservation. Here, we report the development of a robust, serum-free culture system, termed 6iL/E4 that enables the derivation and long-term self-renewal of ESCs from multiple mammalian species, including mouse, rat, bovine, rabbit, and human. Using systematic signaling pathway analysis, we identified key regulators-including GSK3α, STAT3, PDGFR, BRAF, and LATS-critical for ESC maintenance across species. Additionally, inducible expression of KLF2 and NANOG enhances the naive pluripotency and chimeric potential of bovine ESCs. The E4 medium also supports stable ESC growth while minimizing lineage bias. These findings reveal conserved principles underlying ESC self-renewal across divergent mammalian species and provide a universal platform for cross-species stem cell research, disease modeling, and biotechnology applications.