Citations

AbstractSkeletal muscle atrophy was a characteristic of type 1 diabetes (T1DM) prior to insulin discovery and replacement. Indirect calorimetry during the post‐absorptive state demonstrated that increased fuel oxidation during transient insulin deprivation in T1DM caused depletion of energy stores. Further, insulin has a critical role in preserving muscle mitochondrial content and function by enhancing mitochondrial biogenesis and proteostasis. Insulin deficiency not only inhibits mitochondrial biogenesis but also accelerates the degradation of mitochondrial proteins, causing a decline in mitochondrial content and efficiency. Inefficient mitochondrial respiration, reflected by the uncoupling of oxidative phosphorylation and consequent decline in ATP production, adversely affects many cellular functions and causes high oxidative stress. Oxidative stress adversely affects cardiovascular functions and damages many skeletal muscle proteins, accelerating their degradation and explaining muscle atrophy. Increased degradation of muscle proteins increases amino acid efflux that stimulates the liver to synthesize many non‐insulin‐dependent proteins, potentially contributing to macrovascular complications. This phenomenon explains a paradoxical increase in whole‐body protein synthesis during insulin deficiency. Further, the mitochondrial biology of brain regions rich in insulin receptors concurrent with accelerated transport of ketones and lactate across the blood–brain barrier during insulin deficiency seems to protect the brain from oxidative stress. In contrast, insulin resistance associated with less ketone and lactate production renders the brain susceptible to protein oxidative damage. Oxidative damage and reduced ATP production potentially explain the higher prevalence of dementia in insulin‐resistant people. Enhancement of insulin sensitivity by aerobic exercise and metformin in pre‐clinical studies prevents mitochondrial dysfunction and oxidative damage to the brain.

Breast-conserving surgery (BCS) is a standard treatment for breast cancer, but achieving clear negative margins to avoid re-excision remains a challenge. Current intraoperative margin assessment techniques, such as frozen section analysis and imprint cytology, are limited by resource demands and workflow integration challenges. This study explores the physical design considerations for a handheld intraoperative imaging probe to assess tumor cavity margins during BCS. Data were collected through 9 surgical observations, 11 semi-structured interviews with breast surgeons, and interdisciplinary team meetings. Inductive thematic analysis identified key design priorities, including ergonomic handling, flexible probe tips, consistent tissue contact, and compatibility with both direct and tunneled access. Surgeons emphasized the need for quick scanning times and binary margin outputs, with interest in supplementary real-time imaging. These findings offer foundational insights for the iterative development of a clinically viable margin assessment tool aimed at reducing re-excisions and improving surgical outcomes in breast cancer care.

Background: The American opioid use disorder (OUD) and overdose epidemic require physicians and advanced care providers to be prepared to care for patients with this life-threatening condition. Learning to identify, engage, and treat patients with OUD with medications is an essential skill for providers, as is developing requisite confidence and therapeutic attitudes regarding the care of patients with OUD (CP-OUD). To address the need for improved OUD treatment education, our team built and implemented a 12-module asynchronous course entitled, “Care of Patients with Opioid Use Disorder”, in 3 Doctor of Medicine (MD) programs and a Graduate School of Nursing (GSN) program. Methods: Students self-reported their attitudes and confidence regarding the CP-OUD before and after each module. Twelve questions assessed confidence, and 12 questions assessed attitude. Students’ change in confidence and attitudes before and after training was calculated. Results: Responses were collected between January 2021 and November 2024. The number of students completing each module ranged from 552 to 967 MD students and 81 to 149 GSN students. Students reported improved confidence after completing each of the 12 modules (<0.0001). Students reported improved attitudes after completing 10 of the 12 modules (<0.0001). Differences ranging from small to medium size were observed between MD and GSN student’s baseline confidence for 4 modules, and baseline attitudes for 6 modules. Conclusions: Asynchronous learning modules can be effectively implemented in medical and nursing education to improve confidence and attitudes regarding the CP-OUD. The use of asynchronous training modules allows for flexible deployment, as evidenced by their use in 3 MD programs and a GSN program. Future research should investigate whether improved confidence and attitudes during medical and nursing education result in more graduates caring for patients with OUD post-training.

ABSTRACTIntroductionRituximab is used off‐label for treating cold agglutinin disease (CAD) in the United States; however, real‐world data on its use are limited.MethodsThis study examined (1) treatment patterns, (2) prespecified safety outcomes, and (3) changes in hemolytic markers post rituximab infusion (threshold change from baseline: hemoglobin [Hb]: ≥2 g/dL increase; bilirubin or lactate dehydrogenase [LDH]: ≥50% decrease). Of 611 patients with CAD (Cohort 1) identified using Optum's de‐identified Market Clarity database (2007‐2021), 94 who received rituximab (Cohort 2) were included.ResultsRituximab was predominantly used as monotherapy; the median (interquartile range; IQR) number of rituximab courses per patient was 1.0 (1.0–2.0); 24 (25.5%) patients had ≥1 incomplete course and 37 (39.4%) required blood transfusion. The incidence rate (IR) of serious infections per 1000 patient‐years (95% CI) post rituximab initiation was three times higher than before rituximab initiation (637.1 [242.2–1032.0] vs. 245.4 [125.1–365.6]). Cohort 2 had a similar IR of thromboembolic events and slightly higher hospitalization rates and deaths than Cohort 1. After the first course of rituximab, 69.5% (41/59), 59.6% (28/47), and 31.3% (10/32) of patients reached thresholds for Hb, bilirubin, and LDH, respectively. The median (IQR) duration of improvement was 44 (13.3–90.8), 98 (29.0–257.0), and 93 (21.3–161.8) days for Hb, bilirubin, and LDH, respectively. Reversal from threshold occurred in 68.3% (28/41), 53.6% (15/28), and 80.0% (8/10) of patients for Hb, bilirubin, and LDH, respectively.ConclusionRituximab showed a limited durability of response and an increased risk of infection, suggesting the need for more effective and safer treatment options.Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

The advent of continuous glucose monitoring (CGM) in non-insulin-treated individuals raises the possibility of quantifying disposition index (DI), a key metric of β-cell function usually assessed in research settings, in outpatients. A method for DI estimation from postprandial glucose data only (DI G ) was developed and validated against a reference. DI G can be used to assess therapy effectiveness and degree of glucose tolerance in non-insulin-treated individuals, paving the way for its quantification in real-life conditions from CGM devices.

Abstract Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela. However, evidence from in vivo patient data and long-term follow-up is limited, and the degree of progression remains elusive. In this multicentre study, clinical and brain MRI data were collected from 127 patients across 12 countries to investigate the relationships between clinical presentations and the development of distinct brain atrophy patterns. Our data show that most patients develop a complex multisystem phenotype as the disease progresses; however, neuromuscular manifestations rarely emerge at later disease stages. By comparison to healthy controls, this disease presents with severe substructure-specific atrophy, especially affecting the hypothalamus, brainstem, accumbens and basal ganglia, which, in age-independent analyses, show significant ventricular enlargement and also suggest progression of brainstem atrophy over the disease course. Moreover, the focality of atrophy was functionally linked to specific symptoms, with more severe involvement of the basal ganglia in patients with movement disorders, and greater atrophy in the hippocampus and thalamus in patients with cognitive impairment. Taken together, our results provide evidence of distinct atrophy patterns in anti-IgLON5 disease, which closely mirror sites of pathophysiologic processes, including autoantibody binding and tau deposition. Our data emphasize the brainstem as the pathophysiological hub of the disease and provide normative data for the incorporation of atrophy measurements into routine clinical assessments and future treatment studies to monitor disease trajectory and evaluate future treatment strategies.

Abstract Objective To assess the localization and lateralization values of ictal emotional features and ictal defensive behaviors in pediatric and young adult patients with frontal lobe epilepsy (FLE). Methods Children and young adults with FLE were identified from a single institution's epilepsy surgery database. Two epileptologists determined by consensus the presence of ictal emotional features (positive‐ smile, laughter, humming, singing; negative‐ fear, crying, anger, disgust, contempt, sadness) and ictal defensive behaviors (freezing with a fearful facial expression, shielding the face with hands, burying the face in a pillow, or exhibiting hyperkinetic motor behaviors like attempting to escape from bed or resisting restraint) in each patient's first video EEG (vEEG). Historic seizure semiology and vEEG reports were compared with the consensus vEEG analysis. Longitudinal changes in ictal emotional features were defined by the emergence or resolution of ictal emotional features between historic seizure semiology and re‐review of presurgical vEEG analysis. Subgroup analyses were conducted according to the seizure lateralization (left vs. right) and sublobar localization (precentral, medial, lateral, extensive) based on surgical extent. Results Twenty‐three FLE patients were included (female 39%; mean age at vEEG analysis: 11.28 years, range 1.75–20.17). The inter‐rater reliability was very good for both ictal emotional features ( κ = 0.81, 95% CI: 0.59–1) and ictal defensive behaviors ( κ = 0.91, 95% CI: 0.79–1). Ictal emotional features were observed in 10 patients (43.4%), with negative emotions present in 70% (7/10) of these cases. vEEG reports lacked documentation of ictal emotional features in two patients. Although ictal emotional features showed no statistical correlation by sublobar regions, ictal defensive behaviors were consistently seen in medial compared to lateral FLE (100% vs. 16.6%; p = 0.004). Longitudinal changes in ictal emotional features were observed in 8 (34.7%) patients. Significance Ictal emotional features were common in pediatric and young adult FLE patients and were mainly negative. Ictal defensive behaviors were more likely associated with medial FLE. Longitudinal changes in ictal emotional features occurred in about a third of pediatric and young adult patients with FLE. Plain Language Summary This study examined emotional features and defensive behaviors during seizures in children and young adults with FLE. Negative emotions were commonly seen during seizures. Ictal defensive behaviors were more frequently observed in patients with medial FLE, and recognizing these signs could help clinicians localize the seizures. Changes in emotional features were seen over time in about one‐third of children and young adult patients.

ABSTRACTObjectivesThyroglossal duct cyst (TGDC) associated carcinoma is rare, accounting for less than 2% of TGDC cases. The majority of cases are classified as papillary thyroid carcinoma (PTC). Standard treatment for TGDC‐PTC involves a Sistrunk procedure and prophylactic total thyroidectomy (TT). However, the necessity of these extensive surgical interventions remains debated. This report aims to explore whether individualized surgical approaches may reduce morbidity while maintaining favorable oncological outcomes.MethodsRetrospective case series of three patients with TGDC‐PTC.ResultsThe age range at presentation for our patients with TGDC‐PTC was 26 to 50. Case 1 involved a 38‐year‐old patient with a cystic mass near the hyoid bone and submental lymphadenopathy who underwent cyst excision with level Ia lymph node clearance. Case 2 is of a 50‐year‐old patient with a history of TGDC‐PTC who presented with a recurrent neck mass 9 years after the initial surgery and underwent a revision Sistrunk procedure. Case 3 presents a 26‐year‐old patient with a large TGDC and a benign thyroid nodule who underwent a Sistrunk procedure. All three patients had PTC confirmed by final pathology. All had no evidence of recurrent disease at follow‐up evaluations ranging from 1 to 12 years.ConclusionThis case series demonstrates the feasibility and safety of individualized surgical management for TGDC‐PTC. Risk stratification allowed for tailored interventions and avoided overly aggressive approaches. Further studies are needed to establish definitive guidelines for managing TGDC‐PTC, particularly in low‐risk patients.Level of Evidence4.

ABSTRACT Objectives Multicenter research of geriatric emergency department (GED) care remains limited. Our objectives were to: 1. Prospectively collect data prioritized by the Geriatric Emergency care Applied Research (GEAR) network, a transdisciplinary taskforce for GED care, and create a multicenter GED research repository of prospective and electronic health record (EHR) data, 2. Assess concordance between prospective and EHR data. Methods The GEAR Standardization Study (GEARSS) is a multicenter, prospective study of older emergency department (ED) patients (65+) focusing on the 4Ms of age‐friendly care (mobility, medication safety, mentation, what matters) and elder mistreatment. Demographic and clinical data were collected via interviews by trained research assistants (RA) on Days 0, 4, 30, and 90 and linked to EHR. Prevalence of chronic comorbidities and incident delirium were measured and reported using descriptive statistics. Prospective and EHR data concordance was assessed with Cohen's Kappa. Results 999 participants were recruited from 5 EDs (3/25/2021–6/30/2022) across 3 institutions: Grady Health System, Northwestern Memorial Hospital, and Yale New Haven Health. The cohort was 57.0% female, 55.2% White, 39.1% Black, and 3.4% Hispanic, and the mean age was 75.1 years. For rheumatologic disease, peptic ulcer disease, diabetes, renal disease, and cancer, prevalence differed between prospective and EHR data by > 10%. About two‐thirds of participants were at risk for falls. Concordance between prospective and EHR data was good for ethnicity ( K = 0.73); excellent for sex ( K = 1.00), age ( K = 1.00), and race ( K = 0.98); fair for disposition ( K = 0.53); slight for ED observation status ( K = 0.33) and dementia diagnosis ( K = 0.24); poor for delirium presence ( K = 0.07). Conclusion In GEARSS, demographic variables aligned strongly between prospective and EHR data, while diagnosis, disposition, and mentation factors did not. This multicenter data source provides preliminary findings for common geriatric syndromes and conditions. Choice of measures using these data should be driven by GED research questions.