Deshpande, Abhishek

Abstract Background: Clostridioides difficile infection (CDI) requiring colectomy carries substantial mortality risk, with optimal timing of surgery remaining poorly defined. We examined temporal trends in colectomy among inpatients with CDI, identified predictors of surgical intervention and postoperative mortality, and evaluated the association between surgical timing and patient outcomes. Methods: A retrospective cohort study was conducted using the National Inpatient Sample database from 2018 to 2022. We compared patients undergoing colectomy with those managed medically. To minimize confounding by hospital-onset cases, the analysis of surgical timing and mortality was restricted to patients undergoing colectomy within 8 days of admission. Predictors were identified using survey-weighted logistic regression and LASSO regression models. Results: Among 240,564 CDI hospitalizations (representing 1,207,995 weighted nationally), 717 patients underwent colectomy (3,585 weighted). CDI prevalence declined from 0.99% (2018) to 0.76% (2022), while colectomy rates increased from 0.28% to 0.34%. Peritonitis (OR 5.42; 95% CI, 4.46–6.59), coagulopathy (OR 4.96; 95% CI, 3.76–6.55), and sepsis/septic shock (OR 3.89; 95% CI, 3.39–4.47) were the strongest predictors of colectomy. Among patients undergoing colectomy within 8 days (2,830 weighted), in-hospital mortality was 26.5% overall, increasing from 21.0% (2018) to 30.7% (2022). Sepsis/septic shock (OR 8.20; 95% CI 2.92–23.07) and coagulopathy (OR 7.27; 95% CI 3.31–15.97) predicted mortality. Each additional day from admission to colectomy was associated with a 16% (OR 1.16; 95% CI 1.04–1.28) increased mortality risk. Conclusions: In this nationally representative cohort, surgical timing was an independent and modifiable determinant of survival in patients with CDI requiring colectomy. Our findings underscore the importance of early surgical consultation for CDI patients with peritonitis, sepsis, and coagulopathy.

Abstract Background Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter “VOS,” formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI. Methods Adults with rCDI were randomized to receive VOS or placebo (4 capsules daily for 3 days) following standard-of-care antibiotics. In this post hoc analysis, the rate of rCDI through week 8 was assessed in VOS-treated participants compared with placebo for subgroups including (i) Charlson comorbidity index (CCI) score category (0, 1–2, 3–4, ≥5); (ii) baseline creatinine clearance (<30, 30–50, >50 to 80, or >80 mL/minute); (iii) number of CDI episodes, inclusive of the qualifying episode (3 and ≥4); (iv) exposure to non-CDI-targeted antibiotics after dosing; and (v) acid-suppressing medication use at baseline. Results Of 281 participants screened, 182 were randomized (59.9% female; mean age, 65.5 years). Comorbidities were common with a mean overall baseline age-adjusted CCI score of 4.1 (4.1 in the VOS arm and 4.2 in the placebo arm). Across all subgroups analyzed, VOS-treated participants had a lower relative risk of recurrence compared with placebo. Conclusions In this post hoc analysis, VOS reduced the risk of rCDI compared with placebo, regardless of baseline characteristics, concomitant medications, or comorbidities.

INTRODUCTION: The use of proton-pump inhibitors (PPIs) has been associated with various adverse effects including increased risk of major adverse cardiovascular events, community acquired clostridium difficile infection, chronic kidney disease and dementia. Some studies over the past decade have suggested an association between PPIs use and ischemic stroke. METHODS: We pooled the data after comprehensive literature search from the PubMed, Embase, Cochrane Library and Scopus databases using ‘proton pump inhibitors’ AND ‘stroke’ as the keywords. RevMan was used for the entry and analysis of data. A random effects model was created given the significant heterogeneity of the included studies and a funnel plot was made to assess the publication bias. Our primary objective was to study whether all-comers patients on PPIs are at an increased risk of stroke. Sub-group analysis was also done to investigate the association between patients on dual anti-platelet therapy [DAPT] (aspirin and clopidogrel) with or without PPIs and stroke. RESULTS: After searching 774 titles, 25 titles were selected to be included in the systematic review and 15 articles for the meta-analysis. Our pooled analysis of 155,406 patients (46,652 patients on PPI and 101,892 patients without PPI found a positive association between the use of PPI and stroke (odds ratio = 1.28, 95% confidence interval = 1.12, 1.48, P = 0.001) [Figure 1]. Given the significant heterogeneity of the studies (I2= 60%) a sub-group analysis was done which also suggested an increased risk of stroke associated with PPI use among patients on dual antiplatelet therapy (OR: 1.43, 95% CI: 1.26, 1.66, p< 0.001, I2= 11%) [Figure 2]. Analysis of the included randomized controlled trials revealed an OR: 1.47, 95% CI: 0.66, 3.25 but the results were not statistically significant (p< 0.81) [Figure 3]. CONCLUSION: In a pooled analysis of over 155,000 patients we found a positive association between the use of PPIs and stroke. Our results are limited by significant heterogeneity and retrospective study design of the observational studies. Rigorous clinical trials are needed to establish the safety of PPIs in relation to stroke, especially among patients on DAPT. Until definitive data emerges, patients on DAPT are probably best served by being off PPIs or being on alternative acid suppression regimen, unless there is a compelling indication for PPI use.