Citations

Abstract Introduction 0.05% Chlorhexidine Gluconate (CHG) has gained popularity as an irrigant and dip for inflatable penile prosthesis (IPP) surgery. Prior in vitro data is conflicting on the impact of CHG use with hydrophilic coated devices. Objective We sought to identify possible associations between CHG use and hydrophilic IPP infection rate. Methods We conducted a retrospective cohort study of 2,933 patients undergoing IPP implantation across 14 referral centers. Data collection spanned from January 1, 2017 to March 1, 2024. Each surgeon contributed patients who underwent IPP implantation with CHG used as an irrigant and/or dip as well as an equal number of consecutive control patients without CHG use. The primary outcome was IPP explant for postoperative infection. Univariable analysis was used to compare patient demographics, and logistic regression analysis was performed to assess factors associated with infection. Results Hydrophilic devices were implanted in 2,150 patients. Median follow-up for non-CHG patients was 13 months (IQR 18) and four months (IQR 9) for CHG patients. The incidence of infection with intraoperative CHG use was significantly higher compared to those without CHG use (4.6%, 46/1,001 vs. 2.1%, 24/1,148, p<0.001). On multivariable logistic regression analysis, intraoperative CHG use was associated with infection (OR 2.07, 95% CI 1.24-3.47, p=0.01). Additional variables associated with infection included immunosuppression, prior IPP infection, prior priapism, and revision surgery (p<0.01, Table). On subgroup analyses, the increased infection risk of CHG was most clear when CHG was used as both irrigation and dip (OR 2.03, 95% CI 1.19-3.46, p=0.01) and when CHG was used during revision surgery (OR 3.36, 95% CI 1.15-9.82, p=0.03). Conclusions In a large multi-institutional cohort, intraoperative CHG use was associated with an elevated incidence of hydrophilic IPP infection. Providers may take these findings into consideration when performing IPP surgery with hydrophilic devices, especially during revision surgery. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Intuitive Surgical, Fidelis, Urofill, Boston Scientific, Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, Acerus Pharma; Endo Pharma

Objectives: Consensus clinical criteria for refractory septic shock were recently developed, but the incidence and outcomes with these criteria are unknown. There were two aims: 1) to describe the incidence of refractory septic shock and 2) to assess outcomes of patients with septic shock meeting refractory septic shock criteria compared with those who did not. Design: Multicohort, retrospective study. For aim 1, a descriptive epidemiologic study was designed to ascertain the cumulative incidence of refractory septic shock in patients with septic shock. For aim 2, a cohort study was conducted to compare hospital mortality between patients meeting refractory septic shock clinical criteria compared with those who did not. Setting: Large U.S. health system from 2012 to 2024. Patients: Adults (age ≥ 18 yr) meeting both Centers for Disease Control and Prevention Adult Sepsis Event and Sepsis-3 clinical criteria for septic shock. Patients with missing hospital discharge disposition and incomplete vasopressor dosage information were excluded. Interventions: None. Measurements and Main Results: Clinical criteria for refractory septic shock were operationalized as concomitant occurrence of norepinephrine (base) equivalent greater than 0.5 µg/kg/min and lactate greater than 2 mmol/L. Risk-adjusted hospital mortality was assessed with a generalized linear mixed-effects model with a random effect for hospital and fixed effects for age, sex, Elixhauser Comorbidity Index, and Sequential Organ Failure Assessment (original description, without cardiovascular component). Of 35,914 patients assessed, 15,732 patients with septic shock were included. Refractory septic shock occurred in 3423 patients (21.8%), with a cumulative incidence of 218 cases (95% CI, 211–224) per 1000 patients with septic shock. Hospital mortality with refractory septic shock was 64.4%, and risk-adjusted hospital mortality odds were 4.87-fold higher (95% CI, 4.46–5.31) compared with patients without refractory septic shock. Conclusions: Clinical criteria for refractory septic shock were fulfilled in about one in five patients with septic shock and associated with substantially higher mortality.

The recent approval of encorafenib, cetuximab, and FOLFOX based on the phase III BREAKWATER trial has introduced a new standard of care for the first-line treatment of BRAF V600E–mutated metastatic colorectal cancer (mCRC). However, its safety and efficacy in patients with significant liver dysfunction remains unclear and, as such, patients are often excluded from pivotal clinical trials. This report presents a case of BRAF V600E–mutated mCRC presenting with extensive hepatic involvement and liver dysfunction. Despite the absence of guidelines, the patient was initiated on full-dose encorafenib, cetuximab, and FOLFOX. He experienced a rapid clinical and biochemical response, with near-normalization of liver enzymes after cycle 1, and complete functional recovery by cycle 3. Treatment was well tolerated, with no significant adverse events throughout 9 cycles. He subsequently transitioned to maintenance 5-FU, cetuximab, and encorafenib. Posttreatment blood-based next-generation sequencing revealed no residual actionable mutations. The patient then successfully underwent complete surgical resection of his primary tumor and metastatic disease with negative margins. This case highlights the importance of considering encorafenib-based therapy in select patients with BRAF V600E–mutated mCRC in the setting of compromised liver function.

A 46-year-old female was admitted to the hospital for confusion, cognitive decline, and hallucinations with alcohol withdrawal. Her history was notable for Alcohol use disorder (AUD) and family history of Alzheimer's disease (AD). Comprehensive workup was unrevealing for metabolic encephalopathy, infection, or nutritional deficiencies. Phosphatidyl ethanol level was 1181, indicating severe alcohol misuse. Phospho-Tau 217 testing raised suspicion of AD and FDG-PET scan confirmed patterns consistent with early onset AD. AUD can precipitate earlier or more severe onset of AD. Phospho-Tau 217 can be a useful screening marker to identify people at risk of AD to prompt intensive treatment.

Objectives: The electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD) trial is a multisite study evaluating the effectiveness of ECT for severe agitation in individuals with advanced dementia. Given that participants lack decisional capacity because of advanced cognitive impairment, the trial required a structured and ethically sound approach to obtaining informed consent and assent across jurisdictions with differing legal requirements, including Massachusetts, New York, Georgia, Minnesota, and Michigan. This paper describes the approach used in the study. Methods: We describe the consent framework developed for the ECT-AD trial, including procedures for identifying legally authorized representatives, complying with state-specific laws for ECT consent, obtaining surrogate consent for research participation, and assessing patient assent and dissent using a standardized tool. Conclusions: The approach used in this study may serve as a practical model for future research involving individuals without decision-making capacity and legally complex interventions such as ECT.

Background: While surgeon burnout is extensively documented, the medical community has limited corresponding data regarding what it might mean to thrive in the profession as captured by robust measures of “flourishing.” Study Design: We conducted a cross-sectional survey measuring flourishing in a sample of 1,000 practicing US surgeons from the American Medical Association Masterfile between September and December 2025, including the Harvard Flourish Index (FI) and Secure Flourish Index (SFI). We used multivariable regression to assess personal and professional correlates of flourishing. Results Of 959 eligible surgeons in our sample, 283 (30%) responded. Mean flourishing (SFI) score was 7.98 (± 1.21) on a 0-10 scale (higher score=higher flourishing). Surgeons reported the highest flourishing in "Financial and Material Stability" (8.57 ± 2.11) and "Meaning and Purpose" (8.50 ± 1.39), while "Close Social Relationships" (7.41 ± 2.08) was the lowest-ranked domain. In multivariate linear regression, working fewer hours (adjusted β (each additional hour), -0.02; p<0.001), having children (adjusted β, 0.43; p=0.05) and viewing surgery as a calling (adjusted β, 0.28; p=0.006) were associated with higher flourishing. A majority (88%) of surgeons view the profession as a calling. Conclusion: Practicing surgeons report high levels of flourishing, with scores surpassing several historical medical and non-medical cohorts. Most surgeons reported comparatively high scores in meaning and purpose concurrent with deficits in social connectivity. Burnout and well-being conversations in the surgical professions may benefit from a flourishing framework. Naming meaning and purpose exemplars while being able to identify key deficits like social connectivity may be crucial for helping surgeons thrive.

Interlobular septal thickening (ILST) is a feature on chest computed tomography (CT) that is characterized by abnormal widening of the interlobular septa, which are thin connective tissues that separate secondary pulmonary lobules within the lung parenchyma. They contain pulmonary venules and lymphatic vessels. On CT, these septa are normally not visible in healthy patients. However, various pulmonary pathologic conditions can lead to ILST. If present, ILST can be categorized into 3 different patterns based on its morphologic appearance: smooth, nodular, and irregular/fibrotic. Each pattern occurs from different disease processes with little overlap. In this pictorial essay, we review common and rare etiologies for each type of ILST. For each disease, we discuss relevant pathophysiology, epidemiology, risk factors, symptoms, physical exam findings, labs, and management. Subsequently, we present the ILST features along with the distribution (eg, unilateral, bilateral, central, peripheral) and ancillary imaging findings that can support the diagnosis. Finally, characteristic and high-resolution figures are presented.

Purpose: Neuroendocrine neoplasms (NENs) are increasingly recognized to have a hereditary predilection, yet the prevalence and clinical relevance of pathogenic germline variants (PGVs) in unselected patients with NEN remain poorly defined. This prospective, multicenter study aimed to evaluate the prevalence and clinical utility of PGVs through universal multigene panel testing in a diverse cohort of patients with NENs. Patients and Methods: Between 2018 and 2024, we enrolled unselected patients with NENs from 3 Mayo Clinic Cancer Centers. Germline genetic testing was performed using a next-generation sequencing panel of up to 84 cancer predisposition genes. Patients were not selected based on age, disease stage, ethnicity, or family history. Variants were classified as PGVs, variants of uncertain significance (VUS), or negative. Clinical and demographic data were analyzed descriptively. Results: Among 88 patients, PGVs were identified in 15.9% (n=14), most frequently in high- or moderate-penetrance genes including MEN1 , CHEK2 , MITF , and MUTYH . PGVs were most commonly found in pancreatic NENs [n=12/55 (21.8%)], followed by small bowel NENs [n=2/20 (10%)], with no PGVs detected in lung NENs. Mismatch repair (MMR) gene alterations were identified in 5.7% of patients, including 1 MLH1 PGV and 4 MSH2/MSH6 VUS, 2 of which demonstrated MMR deficiency by protein testing. VUS were reported in 34.1% of patients. Notably, 35.7% of PGV-positive patients did not meet current NCCN or ACMG testing criteria, and 53.9% had PGVs in genes outside of cancer-specific guideline recommendations. Conclusions: Universal germline testing in unselected patients with NEN identified clinically relevant PGVs in over 15% of cases. These findings support broader genetic testing approaches to guide treatment, enhance familial risk assessment, and inform cascade testing—regardless of traditional clinical selection criteria.

Importance Stool metabolites influencing gut motility and sensation may contribute to fecal incontinence (FI). Objective The objective of this study was to test whether FI is associated with higher levels of butyrate and Clostridiales taxa in stool. Study Design Stool metabolites and microbiota were compared between 96 women with FI and 42 controls. FI frequency and subtype (urgency vs insensible) were measured using a 14-day bowel diary, St. Mark’s score, and the Accidental Bowel Leakage questionnaire. Metabolite analysis included targeted analysis (8 short-chain fatty acids including butyrate, 17 bile acids, and 8 tryptophan derivatives) and untargeted analysis. Stool microbiota were characterized using 16S rRNA gene sequencing. Multivariable and exploratory multiomics factor analysis were performed with statistical significance defined as false discovery rate (FDR) ≤0.10. Results The FI group had a higher proportion of Bristol stool types 2 and 6 than controls ( P = 0.005). The mean number of leaks for the FI group was 1.7 ± 1.7 per day, 38% had urgency FI, and 39% had insensible FI. There was no significant difference between groups in butyrate levels and Clostridiales taxa. Multiomics analysis identified glycerolipids (monoacylglycerols and diacylglycerols) associated with FI (FDR = 0.08). In addition, insensible FI was associated with glycerolipids, long-chain saturated and monounsaturated fatty acids, phospholipids, and dipeptides (FDR = 0.08–0.09). The top weighted microbiota associated with these metabolites were Lachnospiraceae and Ruminococcaceae; however, these taxa were not directly associated with FI. Conclusion Butyrate and Clostridiales were not associated with FI. Novel stool metabolite signatures were identified, suggesting new biological pathways and potential therapeutic targets for FI.