Faculty Bibliography

PURPOSE/UNASSIGNED:Eosinophil-related cutaneous adverse events (ercAE) are common after systemic cancer therapies and often affect health-related quality of life (HRQoL). In this study, we investigate the efficacy and safety of benralizumab for ercAE following systemic cancer therapies. PATIENTS AND METHODS/UNASSIGNED:This single-arm, single-center, open-label, phase II trial (NCT04552288) in patients with cancer and systemic therapy-associated ercAE was performed from September 2020 to October 2023. Benralizumab 30 mg was administered subcutaneously according to the approved dosing schedule, with 3 doses given every 4 weeks followed by 3 doses given every 8 weeks. The primary endpoint was clinical response (reduction in ercAE to Common Terminology Criteria for Adverse Events grade ≤ 1 by week 4). Secondary endpoints included HRQoL, rash body surface area (rash-BSA), eosinophil levels, and AE. RESULTS/UNASSIGNED:At baseline (N = 47), ercAE were attributed to phosphoinositide 3-kinase inhibitors in 47%, checkpoint inhibitors in 21%, tyrosine kinase inhibitors in 9%, and antibody-drug conjugates in 9%; ercAE were grade 2 and 3 in 49% and 51% of patients, respectively. Of the 42 patients evaluable for the primary endpoint, 76% of patients (n = 32/42) responded to treatment by week 4; median ercAE grade decreased from 2 to 1 (P < 0.0001). Patients exhibited improved HRQoL, reduced mean rash-BSA, and decreased peripheral eosinophils. All patients with ercAE following alpelisib (n = 18) or enfortumab vedotin (n = 4) responded by week 4 (both P < 0.05). Most AE were mild to moderate and likely unrelated to benralizumab. CONCLUSIONS/UNASSIGNED:Benralizumab demonstrated favorable efficacy and safety against grade 2/3 ercAE related to novel cancer therapies. Further investigation in larger placebo-controlled trials is warranted.

Acute cholecystitis affects ∼200,000 individuals annually in the United States, with laparoscopic cholecystectomy as the gold standard treatment. However, in high-risk surgical candidates, alternative drainage methods are necessary. Percutaneous transhepatic gallbladder drainage (PT-GBD) has traditionally served as the primary alternative intervention, offering rapid decompression, but is limited by a negative impact on the patient's quality of life, the risk of long-term or even permanent tube placement, adverse events, and high recurrence rates. Endoscopic approaches, such as endoscopic transpapillary gallbladder drainage (ET-GBD) and, more recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), have emerged as viable alternatives to PT-GBD. EUS-GBD, first introduced in 2007, offers technical and clinical outcomes comparable to PT-GBD with fewer adverse events, shorter hospital stays, and lower rates of recurrence. The introduction of lumen-apposing metal stents (LAMS) has revolutionized EUS-GBD, simplifying deployment and enabling subsequent internal gallbladder access, which allows additional interventions such as cholecystoscopy and stone removal. EUS-GBD is now supported by international guidelines, and 1 device has achieved FDA approval for the management of acute cholecystitis in nonsurgical candidates. Proper patient selection is essential, guided by multidisciplinary evaluation, with EUS-GBD contraindicated in specific scenarios such as gallbladder perforation, coagulopathy, and large-volume ascites. Technical considerations include choice of access site (transgastric versus transduodenal), stent type, and procedural route [direct (freehand) or wire-guided]. Postprocedural care and stent management remain variable and nonstandardized. Emerging data suggest that interval cholecystectomy can still be performed safely after EUS-GBD. As adoption of EUS-GBD with LAMS expands, structured training and standardization of practice are crucial to optimizing outcomes.

BACKGROUND/UNASSIGNED:The conventional view holds that left ventricular (LV) apical ballooning in stress cardiomyopathy is caused by a hyperadrenergic state related to emotional or physical stress. However, some suggest ballooning also occurs in obstructive hypertrophic cardiomyopathy (HCM) when obstruction becomes severe. Nearly all cases of apical ballooning in HCM were reported in patients with LV outflow tract obstruction. Herein, we present a case due to mid-ventricular obstruction. CASE SUMMARY/UNASSIGNED:A 52-year-old woman presented with dyspnoea and chest pain. She denied any recent emotional or physical stress. Physical examination was notable for a Grade 2/6 systolic murmur along the left sternal border. The peak high-sensitivity troponin level was 315 ng/L (normal < 6 ng/L). Coronary angiography was unremarkable. Echocardiography revealed LV apical ballooning with severely reduced LV ejection fraction. In addition, there was severe septal hypertrophy with mid-cavity obstruction. Continuous-wave Doppler interrogation across the obstruction revealed a bifid ('lobster claw') configuration with a characteristic abrupt early systolic drop in flow velocity. The patient was treated with beta-blockers. Follow-up examination revealed resolution of apical ballooning. DISCUSSION/UNASSIGNED:We believe apical ballooning in our patient with HCM resulted from severe afterload mismatch (produced by mid-cavity obstruction) and supply-demand ischaemia, as well as the limited contractile reserve that characterizes myopathic muscle. This is supported by the rapid decline in early systolic flow velocity seen with Doppler interrogation (lobster claw configuration) across the obstruction.

BACKGROUND:Parastomal hernia repair is technically complex and associated with substantial morbidity, yet disparities in outcomes among racial groups have not been evaluated. Identifying inequalities in this population may inform strategies to improve access and perioperative care. METHODS:The ACS-NSQIP database from 2013 to 2023 was queried for adults undergoing parastomal hernia repair. Demographics, comorbidities, and operative details were compared among White patients, Black patients, and Hispanic patients. Primary outcomes included 30-day morbidity, infectious complications, and length of stay (LOS). Multivariable logistic and linear regression models were performed using a two step forward selection model adjusting for comorbidities and surgical details. RESULTS:A total of 3,513 patients were included (White 85, Black 8, Hispanic 7%). Black patients had higher unadjusted rates of morbidity (38 vs 30 White, 32% Hispanic; p = 0.023), serious complications (20 vs 13% white vs 13% Hispanic, p = 0.008), infectious complications (20 vs 13 White, 15% Hispanic; p = 0.004), and longer median LOS (6 vs 5 days White, 6 days Hispanic; p = 0.005). On multivariable analysis, Black race remained independently associated with increased odds of overall morbidity (aOR 1.31, 95% CI 1.01-1.70; p = 0.043), serious complications (aOR 1.65; CI 1.15-2.34, p = 0.006), and infectious complications (OR 1.44, 95% CI 1.04-1.98, p = 0.026) compared to white patients. CONCLUSION/CONCLUSIONS:This is the first national study to characterize racial disparities in parastomal hernia repair. Black patients experienced higher morbidity, infectious complications, and length of stay compared to White patients, while Hispanic patients did not differ from White patients. Disparities were emphasized in emergent cases, suggesting that barriers to timely elective repair possible drive imbalances in parastomal hernia repair, warranting interventions for underserved populations, with early referral, equal access, and tailored perioperative support.

Large language models (LLMs) have shown increasing promise in the mental health field. LLMs are especially well suited to play a role in the labor-intensive, costly process of clinical assessment, as they can interact with a patient or participant directly to conduct a mental health assessment. We conducted a preregistered scoping review to (a) describe the unique capabilities of LLMs for clinical assessment, (b) determine the current state of the field in applying LLMs to directly assess patient/participant mental health (including screening, diagnosis, and monitoring of symptoms), and (c) highlight future research to facilitate the application of LLMs. We included work published in both Chinese and English. Only 10 studies met criteria for direct LLM-based mental health assessment. The evidence base was recent and heterogeneous: Four studies focused primarily on diagnostic interviewing or classification, five on symptom or severity assessment, and one on task-based multimodal depression assessment. Studies varied across text, voice, and multimodal formats, and depression was the dominant target. Across studies, stronger performance tended to be reported in tools that used structured interviewing logic, domain-specific adaptation, and clinically anchored reference standards. However, the evidence base remains small, with many studies employing limited validation procedures, and heavily weighted toward early-stage or nonjournal publications. The limited pace of academic validation means that, at present, LLMs are best understood as emerging assessment-support tools rather than replacements for clinical evaluation. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Lupus nephritis (LN) and diabetic nephropathy (DN) are leading causes of kidney failure, characterized by distinct yet overlapping patterns of glomerular injury. While histopathology remains central to diagnosis, it provides limited insight into the underlying molecular remodeling. Here, we applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to define the spatial N-glycan landscape across human kidney biopsies from healthy controls (HCs) and patients with DN or LN. Whole-biopsy analyses demonstrated that identical N-glycan species adopt distinct spatial distributions depending on the disease context. Healthy kidneys were enriched in bisected N-glycans, DN in biantennary and sialylated species, and LN in fucosylated and paucimannose N-glycans, reflecting divergent enzymatic and pathogenic pathways. Glomerulus-resolved analyses substantially enhanced discrimination among disease groups, revealing previously undetected differences and highlighting disease-specific molecular phenotypes that were masked at the whole biopsy level. Notably, glomeruli classified as histologically normal exhibited distinct N-glycan signatures across disease states, indicating that molecular remodeling occurs independently of the overt structural changes. Within biopsies, N-glycan class composition shifted systematically with glomerular injury, with DN displaying more uniform remodeling and LN demonstrating greater phenotypic heterogeneity. Mixed-effect modeling confirmed significant morphology-dependent differences while accounting for biopsy-level clustering. MALDI-IHC analysis further supported phenotype-specific molecular differences across the glomerular subtypes. Collectively, these findings establish glomerular N-glycan architecture as a major driver of glycomic divergence across kidney diseases and position spatial N-glycomics as a translational approach for defining disease-specific molecular signatures within intact renal tissues.

INTRODUCTION/BACKGROUND:Craniopharyngioma is histologically benign yet locally aggressive, with frequent recurrence. Long-term multicenter outcomes after stereotactic radiosurgery (SRS) remain incompletely defined. METHODS:We performed a retrospective multi-institutional cohort study through the International Radiosurgery Research Foundation including 296 patients from 13 centers. Median age at first SRS was 33.6 years. Median tumor volume was 1.32 cm³ and median margin dose was 12.0 Gy. The primary endpoint was local control (LC); secondary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier methods estimated outcomes, and Cox proportional hazards models evaluated predictors of LC. RESULTS:Actuarial 1-, 5-, and 10-year LC was 93.5%, 76.2%, and 70.1%. Actuarial 1-, 5-, and 10-year OS was 98.2%, 93.6%, and 85.2%, and PFS was 92.4%, 73.6%, and 64.8%. Mixed solid-cystic phenotype had worse LC than non-mixed tumors (log-rank p = 0.025); non-mixed phenotype remained independently associated with improved LC (HR 0.53, p = 0.026). Visual fields improved in 10%, were unchanged in 86%, and deteriorated in 4%; visual acuity improved in 6%, was unchanged in 91%, and worsened in 3%. Ten-year freedom from endocrine deterioration was 96.7%. Diabetes insipidus improved in 6.3%, worsened in 0.5% and other pituitary dysfunction was noted in 2.6%, CONCLUSION: In this international multi-institutional experience, SRS achieved durable long-term control with favorable survival and low incidence of visual and endocrinologic dysfunction. Mixed phenotype was an important determinant of LC. CLINICAL TRIAL NUMBER/BACKGROUND:Not applicable.

In mesial temporal lobe epilepsy, resection or ablation-typically of anterior temporal structures-is highly successful in achieving seizure freedom. However, in a substantial proportion of patients, seizures recur for unclear reasons. Invasive hippocampal recordings suggest that, in some patients, hippocampal seizures are highly focal, often restricted to the anterior or posterior hippocampus. This led us to hypothesize that resection or ablation limited to the hippocampal subregion(s) involved at seizure onset is more likely to control seizures than surgery that does not address the specific onset locations. We present a case in which seizures were successfully controlled after posterior hippocampal ablation, as well as a retrospective case series of 18 patients in which 10 cases demonstrated focal onsets within the anterior or posterior hippocampus. Better outcomes occurred when surgery was concordant with the onset region(s) versus discordant (n = 7 concordant vs. 11 discordant patients, P = 0.046, Barnard Exact test). These data suggest that mesial temporal lobe epilepsy can be subdivided according to whether the hippocampal onset pattern is focal or nonfocal, and that targeting localized seizure onset zones within the hippocampus can be effective for seizure control, while limiting surgical morbidity and potentially the risk of adverse cognitive outcomes.