Publications by Year: 2026

BACKGROUND: Pleural mesothelioma (PM) represents an uncommon and exceptionally lethal malignancy. The sarcomatoid subtype constitutes the rarest histological variant, traditionally linked to the worst prognosis, while the advantages of operative intervention remain inadequately established. In this study, we present findings from a cohort of 34 sequential cases with sarcomatoid mesothelioma managed at a specialized high-volume center employing pleurectomy decortication (PD) within a comprehensive therapeutic strategy. We aim to identify patients in this cohort who may benefit from a multimodality approach.

METHODS: All patients diagnosed with sarcomatoid mesothelioma between 2007 and 2019 who received PD at our facility were enrolled, and relevant medical, histopathological, and operative data collected. Survival curves generated through Kaplan-Meier methodology alongside log-rank testing enabled comparison of longevity outcomes, while Cox proportional hazards modeling facilitated examination of predictive variables.

RESULTS: The cohort included 31 male subjects (91.2%), 24 procedures performed on the right side (70.6%), with a median patient age of 71.5 years (range, 51-85 years). Preoperative treatment was administered to 8 individuals (24.2%), while 23 participants (67.7%) underwent intraoperative heated chemotherapy (IOHC). Macroscopic complete resection (MCR) was accomplished in 22 cases (64.7%). Mortality at 30 and 90 days post-surgery stood at 2.9% and 14.7%, respectively. The median overall survival for the entire cohort reached 7.4 months, extending to 20.1 months among those with forced expiratory volume in 1 second (FEV1) at or above 80% predicted. In multivariate analysis, preoperative FEV1 ≥80% was associated with prolonged overall survival [P=0.01; hazard ratio (HR) =0.54].

CONCLUSIONS: As expected, the median survival for most patients with sarcomatoid histology who undergo surgery is under one year. However, a small subset of patients with FEV1 ≥80% do quite well using the multimodality approach.

COVID-19 has affected millions of individuals worldwide, yet the neuro-ophthalmic consequences among survivors remain incompletely characterized. In this case report, we describe a case of unilateral optic neuritis identified in the emergency department using ultrasound in a previously healthy young woman shortly after confirmed SARS-CoV-2 infection. This case highlights the importance of recognizing neuro-ophthalmic sequelae of COVID-19, outlines the diagnostic evaluation, and demonstrates clinical improvement with corticosteroid therapy.

Background and objective Large language models (LLMs) are increasingly being explored as adjuncts to medical education; however, comparative data on the performance and error patterns of newer models on standardized licensing-style questions remain limited. This study evaluated two advanced large language models (LLMs) - Gemini-Pro and GPT-4 Turbo - on the National Board of Medical Examiners (NBME) Step 1-style multiple-choice questions to assess accuracy, reasoning quality, and common failure modes relevant to exam preparation and clinical reasoning training. Methods A total of 112 NBME Step 1 questions were collected; seven image- or table-dependent items were excluded, yielding 105 text-only questions. Prompts were standardized to include the clinical stem, query, and answer choices and were submitted via Python API to Gemini-Pro and GPT-4 Turbo. Outputs were independently adjudicated by two third-year medical students and one board-certified physician using binary accuracy scoring and structured evaluation of reasoning features (logical reasoning, internal information use, and external knowledge application). Incorrect responses were categorized as logical, informational, or statistical errors. Comparative analyses included raw accuracy calculations and chi-square testing of reasoning-feature distributions. Results GPT-4 Turbo achieved 90.99% accuracy on the January 2024 NBME Step 1 question set, substantially outperforming Gemini-Pro (54.46%). GPT-4 Turbo demonstrated fewer errors overall, with lower logical (16%), informational (4%), and statistical (4%) error rates compared with older baselines reported in the study (e.g., GPT-3.5 logical errors 42%). GPT-4 Turbo incorporated external information in 76% of correct responses versus 25% for Gemini-Pro, and differences in performance metrics between GPT-4 Turbo and Gemini-Pro were statistically significant (p < 0.05). Conclusions GPT-4 Turbo markedly outperformed Gemini-Pro on text-based NBME Step 1 questions, showing higher accuracy, stronger reasoning consistency, and fewer logical/informational failures. These findings support GPT-4 Turbo's potential role as a high-yield supplementary tool for Step 1-style learning and feedback, while underscoring the need for continued refinement and cautious, supervised integration of LLMs into medical education, given persistent (though reduced) error rates.

INTRODUCTION: Treatment-refractory obsessive-compulsive disorder (trOCD) is a complex network disorder that may require personalized treatment strategies due to disease heterogeneity. A multi-site, multi-stage, double-blinded, randomized crossover clinical trial is underway, using stereo-electroencephalography (sEEG) to guide selection of multi-nodal targets for deep brain stimulation (DBS) for trOCD.

OBJECTIVES: To describe the clinical trial design, emphasizing personalized surgical targeting strategies that ensure the feasibility and precision of sEEG electrode placement, and enable adequate sampling of relevant targets in trOCD for network evaluation and modulation.

METHODS: Adults with severe trOCD (Yale-Brown Obsessive Compulsive Scale ≥28) who meet eligibility criteria are enrolled in this three-stage clinical trial (NCT05623306). Stage 1 involves sEEG electrode implantation in trOCD implicated regions and inpatient evaluation. Individualized probabilistic tractography-guided target refinement is performed for surgical planning. Multimodal recordings are taken while participants stay in the psychiatric monitoring unit for 12 days. In stage 2, up to four permanent DBS electrodes are implanted followed by stimulation optimization. Stage 3 is the randomized, double-blinded crossover phase.

EXPECTED OUTCOMES: Safety, feasibility and preliminary efficacy will be assessed in this ongoing study. We anticipate that the use of sEEG to guide selection of multi-nodal targets for DBS will be safe, feasible and result in clinically meaningful improvements in symptom severity and functional impairment in trOCD.

DISCUSSION: We present the clinical protocol of sEEG-guided investigation of brain networks involved in trOCD and describe our tractography-guided surgical targeting strategy designed to optimize individualized network engagement and neuromodulation.

BACKGROUND: Spironolactone and oral minoxidil are effective female alopecia monotherapies. Combination therapy is commonly used, though safety and tolerability data are limited.

OBJECTIVE: To assess safety and tolerability by adverse effect incidence.

METHODS: Retrospective cohort study conducted in females aged ≥18 taking combination therapy for hair loss.

RESULTS: A total of 432 patients were included. Average spironolactone and low-dose oral minoxidil doses at time of adverse drug effects were 87.6 ± 51.4 mg and 1.8 ± 1.1 mg, respectively. Adverse effect incidence was 37.7% (n = 163). Hypertrichosis was most common (n = 53, 12.3%) followed by dizziness/lightheadedness/orthostasis (n = 52, 12.0%). Simultaneous initiation was observed to reduce hypertrichosis risk by 64.8% (odds ratio: 0.35; 95% confidence interval 0.13-0.94; P = .037). Concurrent use of ≥1 additional blood pressure-altering medications increased orthostatic effects risk (odds ratio: 3.29; 95% confidence interval: 1.65-6.58; P = .001). Dosage and treatment initiation pattern did not significantly increase risk of blood pressure effects. In 46.0% of cases, the therapeutic regimen was unmodified. When adjustments were made, they largely occurred in the outpatient setting (94.3%).

LIMITATIONS: Retrospective descriptive study lacking a control group.

CONCLUSION: Adverse effects from combination therapy are generally mild and managed outpatient. Concomitant use of ≥1 blood pressure-altering drugs increases risk of hypotension-related symptoms. Simultaneous initiation may reduce risk of hypertrichosis without increasing risk of hypotension-related effects.

BACKGROUND & AIMS: Disruption of the intestinal barrier facilitates microbial translocation to the liver and contributes to chronic liver disease. We aimed to study the role of the fecal proteome for disease progression in patients with alcohol-associated hepatitis.

METHODS: We used fecal proteomics data from a multicenter cohort of patients with alcohol-associated hepatitis (n=80), alcohol use disorder (n=20), and controls (n=19) (InTeam), and a cathepsin B activity assay in an independent multicenter cohort of patients with alcohol-associated hepatitis (n=80), alcohol use disorder (n=20), and controls (n=18) (AlcHepNet). Mice lacking cathepsin B in myeloid cells and transgenic mice overexpressing occludin in intestinal epithelial cells, were subjected to the chronic-plus-binge ethanol feeding model (NIAAA).

RESULTS: Fecal proteomics and activity analysis revealed that the protease cathepsin B progressively increased with alcohol use disorder and alcohol-associated hepatitis compared to controls, and is associated with higher short-term mortality in patients with alcohol-associated hepatitis. Cathepsin B is predominantly expressed in intestinal macrophages and is upregulated by ethanol. Cathepsin B deficiency in myeloid cells or oral treatment with the gut-restricted cathepsin B inhibitor CA074 stabilized gut barrier by preserving the tight junction protein occludin, lowered serum LPS levels, and attenuated ethanol-induced steatohepatitis. Transgenic overexpression of occludin in intestinal epithelial cells sufficed to reduce steatohepatitis and blunted the effects of CA074 in ethanol-fed mice. Cathepsin B proteolytically cleaves occludin in enzymatic assays, and its inhibition prevented occludin degradation and barrier disruption in intestinal organoids and epithelial monolayers. Molecular modeling and peptide profiling reveal specific cathepsin B-induced cleavage sites in the extracellular region of occludin.

CONCLUSIONS: Intestinal cathepsin B is an essential mediator of gut barrier dysfunction and therapeutic target in alcohol-associated liver disease.

IMPACT AND IMPLICATIONS: Intestinal barrier disruption facilitates the microbial translocation to the liver, contributing to the progression of alcohol-associated hepatitis, however the molecular mechanisms driving barrier dysfunction remain incompletely understood. Our study identified the protease cathepsin B as a key contributor to the progression of alcohol-associated liver disease by degrading the extracellular region of tight junction protein occludin in the intestine, which in turn leads to barrier disruption. This work advances the field by addressing causality, uncovering the molecular target, and proposing cathepsin B as a promising therapeutic target in alcohol-associated hepatitis, a condition for which liver transplantation remains the only effective treatment in a limited subset of patients.

OBJECTIVE: Placenta Accreta Spectrum (PAS) occurs in approximately 0.17% pregnancies in the general obstetric population. We aimed to estimate the prevalence of PAS following myomectomy surgery and evaluate differences in the risks by myomectomy surgical approach.

DATA SOURCES: PubMed, Embase, Scopus, and Web of Science were searched on prespecified dates (inception-March 2025).

STUDY ELIGIBILITY CRITERIA: Studies were eligible if they reported pregnancy outcomes in patients with a documented history of myomectomy in which the surgical approach was specified.

STUDY APPRAISAL AND SYNTHESIS METHODS: This systematic review and meta-analysis was conducted per PRISMA guidelines and registered on PROSPERO (CRD42024513596). Pooled prevalence estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. Planned subgroup analyses were conducted for myomectomy surgical approach and PAS-accompanying morbidities of postpartum hemorrhage, placenta previa, placental abruption, and uterine rupture, and heterogeneity was assessed using I2 statistics.

RESULTS: Seventy-six studies comprising 11065 pregnancies across 24 countries were included. The pooled prevalence of PAS following myomectomy was 1% (95% CI, 1-2%). Prespecified subgroup analyses demonstrated that PAS prevalence was highest after open myomectomy (2%; 95% CI, 1-4%; 111/4474) compared to laparoscopic (1%; 95% CI, 0-3%; 36/1172), robotic (1%; 95% CI, 0-4%; 4/262), and hysteroscopic approaches (<1%; 95% CI, 0-1%; 3/271), although differences between surgical groups were not statistically significant (P = 0.67). Secondary outcomes-including postpartum hemorrhage (2%), placenta previa (1%), placental abruption (1%), and uterine rupture (<1%)-showed similar prevalence patterns across surgical approaches.

CONCLUSIONS: In this meta-analysis of over 11,000 patients, the overall prevalence of PAS following myomectomy was approximately 1-2% and did not significantly differ by surgical approach. Likewise, major obstetric complications, including postpartum hemorrhage, placenta previa, and uterine rupture, showed no significant variations among open, laparoscopic, hysteroscopic, and robotic myomectomies. Therefore, the choice of surgical approach for myomectomy can be individualized based on patient characteristics, myoma features, and surgical expertise.