Faculty Bibliography

Animals need daily intakes of three macronutrients: sugar, protein, and fat. Under fasted conditions, however, animals prioritize sugar as a primary source of energy. They must detect ingested sugar-specifically D-glucose-and quickly report its presence to the brain. Hypothalamic neurons that can respond to the caloric content in the gut regardless of the identity of macronutrient have been identified, but until now, the existence of neurons that can encode the specific macronutrients remained unknown. We found that a subset of corticotropin-releasing factor (CRF)-expressing neurons in the hypothalamic paraventricular nucleus (CRF^PVN) respond specifically to D-glucose in the gut, separately from other macronutrients or sugars. CRF^PVN neuronal activity is essential for fasted mice to develop a preference for D-glucose. These responses of CRF^PVN neurons to intestinal D-glucose require a specific spinal gut-brain pathway including the dorsal lateral parabrachial nuclei. These findings reveal the neural circuit that encodes the identity of D-glucose.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry. Prim Care Companion CNS Disord 2025;27(4):25f03975. Author affiliations are listed at the end of this article.

Thoracic outlet syndrome (TOS) comprises a range of conditions characterized by compression of the brachial plexus, subclavian artery, or subclavian vein as these structures traverse the thoracic outlet. Although TOS was first documented in 1860 by Willshire, it remains a diagnostic and therapeutic challenge-particularly for cardiologists evaluating upper-extremity ischemia, suspected arm emboli, or unexplained swelling. This article provides a cardiology-focused overview of TOS, emphasizing the condition's subtypes (neurogenic, venous, and arterial), key diagnostic approaches, comparative surgical outcomes, and considerations relevant to cardiovascular specialists. Literature pertaining to TOS pathophysiology, clinical diagnosis, imaging, and surgical management was reviewed. Where available, quantitative outcome data and success rates are highlighted to guide evidence-based decision-making. TOS is commonly categorized into neurogenic, venous, and arterial forms. Each subtype necessitates a distinct approach. Developments in imaging (magnetic resonance imaging, computed tomography angiography, and dynamic ultrasound) and refined surgical techniques have improved diagnostic accuracy and therapeutic success: yet questions remain regarding long-term efficacy and optimal procedural approaches. Prompt differentiation between TOS and intrinsic cardiac or major vascular etiologies is essential for preventing severe complications such as limb ischemia and permanent nerve damage. A multidisciplinary model integrating cardiologists, vascular surgeons, neurologists, and physical therapists offers the best outcomes. Further studies, particularly large-scale comparative trials, are needed to standardize diagnostic protocols and evaluate emerging surgical approaches.

There is a growing amount of literature on the benefits of using open-ended questions (OEQs) to assess knowledge in medical education. However, it is unknown how many US medical schools include OEQs in their assessment toolkits and how they are being used. The purpose of this study was to determine if OEQ assessments are an emerging trend in US medical education. We distributed an online survey to assessment leadership at all 156 US accredited allopathic medical schools between September 2022 and April 2024. Questions focused on the use or future interest of OEQs to assess medical knowledge in the pre-clerkship and clerkship curriculum. We calculated descriptive statistics for prevalence and use rates, and completed a conventional content analysis for open-ended comments. Seventy-eight US medical schools completed the survey (50% response rate). Forty schools (51%) reported using OEQs for medical knowledge assessment. OEQs were used during the pre-clerkship (28 schools), clerkship (two schools) or both parts of the curriculum (10 schools). On average, OEQs accounted for 20% of the pre-clerkship and 11% of the clerkship assessments at each school. Schools used OEQs to assess students' understanding, assess certain types of knowledge, and develop students' deeper learning. Representatives at schools not currently using OEQs reported considering using them in the future but expressed concerns about the amount of time needed to implement them. Numerous schools are using OEQs to assess medical knowledge, suggesting that this assessment format is feasible. Institutions can be innovative in their assessments by extending beyond multiple-choice questions and incorporating other question formats, such as OEQs, to fit their educational needs. This study provides a foundation for future research to explore the utility of OEQs and how to overcome the challenges of implementing OEQ assessments.

IMPORTANCE/UNASSIGNED:Hospital course (HC) summarization represents an increasingly onerous discharge summary component for physicians. Literature supports large language models (LLMs) for HC summarization, but whether physicians can effectively partner with electronic health record-embedded LLMs to draft HCs is unknown. OBJECTIVES/UNASSIGNED:To compare the editing effort required by time-constrained resident physicians to improve LLM- vs physician-generated HCs toward a novel 4Cs (complete, concise, cohesive, and confabulation-free) HC. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Quality improvement study using a convenience sample of 10 internal medicine resident editors, 8 hospitalist evaluators, and randomly selected general medicine admissions in December 2023 lasting 4 to 8 days at New York University Langone Health. EXPOSURES/UNASSIGNED:Residents and hospitalists reviewed randomly assigned patient medical records for 10 minutes. Residents blinded to author type who edited each HC pair (physician and LLM) for quality in 3 minutes, followed by comparative ratings by attending hospitalists. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Editing effort was quantified by analyzing the edits that occurred on the HC pairs after controlling for length (percentage edited) and the degree to which the original HCs' meaning was altered (semantic change). Hospitalists compared edited HC pairs with A/B testing on the 4Cs (5-point Likert scales converted to 10-point bidirectional scales). RESULTS/UNASSIGNED:Among 100 admissions, compared with physician HCs, residents edited a smaller percentage of LLM HCs (LLM mean [SD], 31.5% [16.6%] vs physicians, 44.8% [20.0%]; P < .001). Additionally, LLM HCs required less semantic change (LLM mean [SD], 2.4% [1.6%] vs physicians, 4.9% [3.5%]; P < .001). Attending physicians deemed LLM HCs to be more complete (mean [SD] difference LLM vs physicians on 10-point bidirectional scale, 3.00 [5.28]; P < .001), similarly concise (mean [SD], -1.02 [6.08]; P = .20), and cohesive (mean [SD], 0.70 [6.14]; P = .60), but with more confabulations (mean [SD], -0.98 [3.53]; P = .002). The composite scores were similar (mean [SD] difference LLM vs physician on 40-point bidirectional scale, 1.70 [14.24]; P = .46). CONCLUSIONS AND RELEVANCE/UNASSIGNED:Electronic health record-embedded LLM HCs required less editing than physician-generated HCs to approach a quality standard, resulting in HCs that were comparably or more complete, concise, and cohesive, but contained more confabulations. Despite the potential influence of artificial time constraints, this study supports the feasibility of a physician-LLM partnership for writing HCs and provides a basis for monitoring LLM HCs in clinical practice.

Patients with diabetes are prone to developing cerebrovascular disease (CVD) due to a multitude of factors. Particularly, the hyperglycemic environment is a key contributor to the progression of diabetes-associated complications. However, there is a dearth of knowledge regarding glucose transporter 1 (GLUT1, also known as SLC2A1)-dependent mechanisms responsible for these adverse effects. Here, we revealed the importance of glucose transporter 1 in preserving brain endothelial cell homeostasis beyond regulating glucose uptake. To elucidate the GLUT1-mediated protective mechanism, we used bulk RNA sequencing (RNA-Seq) to analyze the transcriptomic alterations under hyperglycemia and GLUT1-deficient conditions and validated the critical gene changes in cultured human brain endothelial cells and diabetic mouse models. We found that GLUT1 downregulation is linked to increased expression levels of podocalyxin (PODXL) and decreased thioredoxin-interacting protein (TXNIP) within healthy brain endothelial cells incubated with high glucose, demonstrating an antistress response mechanism. Interestingly, brain endothelial cells isolated from diabetic mice no longer showed a similar protection mechanism. Instead, the diabetic endothelial cells are characterized by considerably enriched GLUT1 and TXNIP expression under a hyperglycemic state. GLUT1 overexpression recaptures the diabetic features, such as elevated expression of TXNIP and NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, along with increased IL-1β production and permeability. Our findings of a GLUT1-dependent regulatory mechanism for the endothelium provide a potentially deeper insight into mechanistic shifts that occur due to the diabetic disease state and the pathogenesis of diabetes-associated vascular complications.NEW & NOTEWORTHY Glucose transporter-1 is known for regulating glucose uptake in brain endothelial cells. This study used global transcriptome analysis and diabetic mouse models to reveal the novel role of glucose transporter 1 in regulating brain endothelial cell homeostasis by reducing the inflammation response and increasing the protection mechanism. Importantly, the glucose transporter 1-dependent protection mechanism is compromised in diabetic conditions, which explains why patients with diabetes have a high risk of cerebrovascular diseases.

IMPORTANCE/UNASSIGNED:Fluorescence-guided surgery aims to improve intraoperative identification of vital structures. Rizedisben is a myelin-binding fluorophore that fluoresces in the blue light (370-425 nm) spectrum to improve intraoperative nerve identification. OBJECTIVE/UNASSIGNED:To determine the optimal safe and clinically effective dose of rizedisben for sustained intraoperative fluorescence of nerve structures. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A single-arm, open-label, phase 1 study was conducted in patients undergoing robot-assisted laparoscopic radical prostatectomy (RALP) at an urban academic cancer center in New York City between January 2023 and October 2024. Using a dose escalation design, increasing doses of rizedisben were administered after safety was assessed at each level until a clinically effective dose was determined. The obturator nerve served as the reference nerve for measuring fluorescence intensity. Eligible patients were 18 years old and older, diagnosed with prostate cancer, and scheduled for RALP. Patients were recruited in preoperative clinic visits once deemed eligible for the study. Those with prior pelvic surgery or radiation, known central or peripheral nervous system disease, current use of neurotoxic medications, recent exposure to phototoxic drugs, or serious kidney or liver dysfunction were excluded. INTERVENTIONS/UNASSIGNED:Rizedisben was intravenously administered intraoperatively 30 minutes prior to visualization of the obturator nerve. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Safety was assessed through 45 postoperative days. Fluorescence was measured via subjective intraoperative scoring and by post hoc objective image analysis. Clinically effective dose was defined as achieving sustained fluorescence of the obturator nerve in 3 or more of 5 patients in 2 consecutive cohorts, provided fewer than 20% of patients experienced grade 2 or greater toxicity. Sustained fluorescence was defined as moderate or better fluorescence for 90 minutes or longer. At the clinically effective dose, fluorescence assessments of the neurovascular bundles were included. RESULTS/UNASSIGNED:Thirty-eight patients (median [IQR] age, 61.5 [57.8-66.3] years) enrolled in and completed the trial. Dosing was escalated from 0.25 to 3.0 mg/kg. There was 1 grade 2 adverse event (rash) possibly attributable to rizedisben. Sustained fluorescence of the obturator nerve was achieved in all patients at 3.0 mg/kg. Prostate neurovascular bundles demonstrated evidence of fluorescence in 8 of 9 (89%) patients at 3.0 mg/kg. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this phase 1 trial of rizedisben, the 3.0-mg/kg dose was shown to be generally well tolerated and clinically effective. At this dose, there was excellent sustained fluorescence of the obturator nerves, and the neurovascular bundles were visualized in 8 of 9 patients. Based on these data, we are designing phase 2 studies with rizedisben for additional indications. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04983862.