Faculty Bibliography

INTRODUCTION/BACKGROUND:Papillary thyroid cancer (PTC) often follows an indolent course with a favorable prognosis. This has led to evolving guideline-based, low-intensity treatment options for low-risk patients. Recently, the purported benefit of total thyroidectomy (TT) over unilateral lobectomy for PTC with clinical lateral neck nodal metastasis (cN1b) has come into question. MATERIALS AND METHODS/METHODS:A retrospective analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results database was performed to study patients with PTC with ipsilateral cN1b disease from 1975 to 2020. Kaplan-Meier curves and log-rank tests were used to compare disease-specific survival (DSS) difference between lobectomy and TT at 10 y. Multivariable Cox proportional hazards analysis was performed to determine the independent association of lobectomy versus TT with DSS, correcting for age and lymph node ratio, defined as the ratio of pathologically positive lymph nodes to total number examined. RESULTS:Among 2943 patients (median [interquartile range] age, 45 [26] y), 42 underwent lobectomy and 2901 underwent TT. Unadjusted DSS at 10 y in the lobectomy and TT groups were 51.0% (95% confidence interval, 31.4%-82.8%) and 86.8% (95% confidence interval, 84.8%-88.9%), respectively. On multivariable analysis of all patients, older age (hazard ratio [HR], 1.08; P < 0.001) and male gender (HR, 1.74; P < 0.001) were associated with lower adjusted DSS, whereas treatment with TT (HR, 0.387; P = 0.005) and receipt of radioactive iodine (RAI) (HR, 0.604; P < 0.001) were associated with improved adjusted DSS. In addition, we observed that the magnitude of survival benefit conferred by RAI and TT were reduced with decreasing age (P < 0.001). CONCLUSIONS:This longitudinal cohort study suggests that, while TT is associated with a DSS benefit in most patients with PTC and ipsilateral cN1b disease, this association may not exist in a smaller cohort of younger patients. These findings raise the possibility that unilateral surgical clearance without RAI could offer adequate oncologic outcomes in selected younger individuals; however, further investigation is warranted to confirm these observations and inform clinical decision-making.

BACKGROUND:Fixed-dose combination (FDC) antihypertensives combine two or more agents. Compared with non-FDC antihypertensives of multiple classes (multi-pill therapy), combination-pill therapy using FDC antihypertensives may improve hypertension control. However, combination-pill therapy remains low. OBJECTIVES/OBJECTIVE:This study aims to assess: 1) the association between combination-pill therapy and medication adherence, health care utilization, and costs; and 2) the potential to mitigate racial and ethnic differences in medication adherence. METHODS:A retrospective cohort analysis was conducted using the 2017-2021 Merative MarketScan Medicaid database. The study sample included adults aged 18 to 64 years with hypertension, continuously enrolled 1 year before and after a random index date of prescription. The propensity score overlap weighting method was used to balance characteristics between individuals using combination- and multi-pill therapy. Logistic models were used for medication adherence (defined as medication possession ratio [MPR] ≥80%), linear models for continuous MPRs, negative binomial models for health care utilization, and generalized linear models for costs. RESULTS:Compared with multi-pill therapy, combination-pill therapy was associated with higher medication adherence (3.17 in MPR; 95% CI: 2.79-3.55), fewer hypertension-related emergency department visits (220 per 1,000 individuals; 95% CI: -235 to -204), fewer hospitalizations (153 per 1,000 individuals, 95% CI: -160 to -146), and lower costs ($2,862 per person, 95% CI: -$3,035 to -$2,689). However, differences in medication adherence persisted, with non-Hispanic Black adults demonstrating lower adherence than non-Hispanic White adults. CONCLUSIONS:Combination-pill therapy could improve hypertension management and save costs for the Medicaid program and beneficiaries. However, persistent racial and ethnic differences in adherence highlight the need for tailored interventions.

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: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.

IMPORTANCE/UNASSIGNED:Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased risk of diabetic retinopathy (DR) and nonarteritic anterior ischemic optic neuropathy (NAION). The risk of sight-threatening complications associated with GLP-1 RAs is underexamined. OBJECTIVE/UNASSIGNED:To investigate whether the use of GLP-1 RAs in patients with T2D is associated with the development of DR, NAION, or DR complications. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study of adults (aged ≥18 years) with T2D and a recent hemoglobin A1c level of 6.5% or higher was conducted between January 1, 2015, and September 30, 2022, using the TriNetX database. The cohort was divided into 2 groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals received prescriptions for a GLP-1 RA. The statistical analysis was conducted on October 10, 2024. EXPOSURES/UNASSIGNED:At least 2 prescriptions of a GLP-1 RA given 6 months apart. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Cox proportional hazard regression models were used to evaluate the primary outcome: association between GLP-1 RAs and the risk of incident DR, NAION, or sight-threatening complications over a 2-year follow-up period. RESULTS/UNASSIGNED:After PSM, 185 066 individuals (mean [SD] age, 59.0 [12.5] years; 93 389 females [50.5%]) were prescribed GLP-1 receptor agonists. Use of GLP-1 RAs was associated with an increased incidence of DR (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11), while no statistically significant difference was observed in the risk of NAION (HR, 1.26; 95% CI, 0.94-1.70). In a subgroup analysis of 32 695 patients with preexisting DR, GLP-1 RAs were not associated with progression to proliferative DR (HR, 1.06; 95% CI, 0.97-1.15) or diabetic macular edema (HR, 0.98; 95% CI, 0.95-1.01) but were associated with a lower occurrence of vitreous hemorrhages (HR, 0.74; 95% CI, 0.68-0.80), neovascular glaucoma (HR, 0.78; 95% CI, 0.68-0.88), or blindness (HR, 0.77; 95% CI, 0.73-0.82). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of individuals with T2D, GLP-1 RA use was associated with a modestly increased risk of incident DR; however, fewer patients experienced sight-threatening DR complications, including blindness, even among those with preexisting DR. These findings suggest that all patients with T2D treated with GLP-1 RAs, regardless of preexisting DR, should be regularly screened and monitored for potential complications of T2D.

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.