Citations

Abstract In this study, we quantified differences in iris stiffness between female and male subjects in healthy and postlaser peripheral iridotomy (post-LPI) groups using an image-based inverse modeling approach. We analyzed anterior segment optical coherence tomography (AS-OCT) images from 25 participants across four groups. Finite element models were created using **solidworks, **abaqus, and a custom C program, modeling the iris as a neo-Hookean material. We found that post-LPI females had significantly higher normalized elastic modulus (E′=3.81±1.74) than healthy females (E′=0.92±0.31,p=0.004), while no significant difference was observed in males. Post-LPI females also showed significantly higher stiffness than post-LPI males (p=0.003). Here, p denotes the probability value, with p<0.05 considered statistically significant. Our findings suggest that sex-based differences in iris biomechanics may contribute to the higher susceptibility of females to primary angle-closure disease. Despite the small sample size, this preliminary study highlights the need for larger, sex-stratified investigations into glaucoma pathophysiology.

ImportanceMidlife vascular risk factors are associated with an elevated risk of dementia. However, the total contribution of vascular risk factors in midlife and late life with incident dementia is uncertain.ObjectiveTo quantify the proportion of incident dementia attributable to modifiable vascular risk factors measured in midlife and late life and to examine differences by apolipoprotein ε4 genotype, self-reported race, and sex.Design, Setting, and ParticipantsThis was a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study using 33 years of follow-up (1987-2020). The setting included ARIC field centers (Jackson, Mississippi; Forsyth County, North Carolina; Minneapolis suburbs, Minnesota; Washington County, Maryland). Study baseline in Black and White participants with complete exposure and covariate data was set by age at risk factor measurement (45-54 years, 55-64 years, and 65-74 years). Data were analyzed from August 2023 to December 2024.ExposuresHypertension (systolic blood pressure [BP] ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of medication for BP), diabetes (fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, self-reported physician’s diagnosis, or use of any diabetes medication), and current smoking (self-reported).Main Outcomes and MeasuresIncident dementia. Population attributable fractions were estimated by age 80 years, and separately after 80 years, from having at least 1 vascular risk factor by age at risk factor measurement.ResultsA total of 7731 participants were included in analysis of risk factors measured at age 45 to 54 years (4494 female [58%]; 2207 Black [29%]; 5524 White [71%]), 12 274 contributed to analysis of risk factors measured at age 55 to 64 years (6698 female [55%]; 2886 Black [24%]; 9388 White [76%]), and 6787 contributed to analysis of risk factors measured at age 65 to 74 years (3764 female [56%], 1375 Black [20%]; 5412 White [80%]). There were 801, 995, and 422 dementia cases by 80 years, respectively. The fraction of dementia by 80 years attributable to at least 1 vascular factor at age 45 to 54 years was 21.8% (95% CI, 14.3%-29.3%), at 55 to 64 years was 26.4% (95% CI, 19.1%-33.6%), and at 65 to 74 years was 44.0% (95% CI, 30.9%-57.2%). Attributable fractions for these factors were higher in apolipoprotein ε4 noncarriers at age 55 years and older (range, 33.3%-61.4%), Black individuals at age 45 years and older (range, 25.5%-52.9%), and female individuals at age 55 years and older (range, 29.2%-51.3%). Only 2% to 8% of dementia cases after 80 years were attributable to these factors.Conclusions and RelevanceResults of this cohort study suggest that between 22% and 44% of incident dementia cases by 80 years in the ARIC study were attributed to midlife and late-life vascular risk factors. Assuming causal relationships, maintaining optimal vascular health across the life course could mitigate a sizeable proportion of dementia risk by 80 years.

This case series describes a distinctive inspiratory noise observed during sleep in patients with IgLON5-antibody disease.

The prevalence of comorbid metabolic dysfunction–associated steatotic liver disease (MASLD) and obesity has increased exponentially over the last several years, with current estimates demonstrating that up to 40% of adults in the United States have MASLD. Metabolic dysfunction–associated steatohepatitis is now a leading indication for liver transplantation, and rates of obesity and MASLD pre-transplant and post-transplant are on the rise. Our understanding of the physiology of obesity and metabolic disease and the availability of effective obesity treatments have evolved over the same time frame. With the availability of new anti-obesity medications, there has been a debate over the role of pharmacotherapy versus interventional approaches in the treatment of obesity and MASLD in the liver transplantation population. In October 2024, the American Society of Transplantation (AST) Liver and Intestinal Community of Practice held a virtual Controversies Conference on obesity and liver transplantation. Experts in the field presented the available data, and smaller working groups had interactive breakout sessions that identified knowledge gaps and developed recommendations. This perspective prepared on behalf of the participants of the AST Controversies Conference on obesity and liver transplant aims to summarize the available evidence for surgical and pharmaceutical treatment in the liver transplantation population.

Background: Supracondylar humerus fractures (SCH) are the most common type of elbow fracture in children, with many cases requiring surgery. Treatment of postoperative pain for SCH has high variability, but can often be treated effectively with minimal or no opioids. Furthermore, there is significant morbidity related to pediatric opioid consumption. The goal of this study was to characterize prescription patterns in the United States following closed reduction and percutaneous pinning (CRPP) of SCH. Methods: All patients aged 10 or younger years who underwent CRPP of SCH from January 2010 to December 2021 were identified in the PearlDiver Mariner Claims Database. The primary outcome was postoperative pain medication prescriptions in the 30 days following SCH CRPP. Patient demographics, prescription duration, and morphine milligram equivalents (MME) were analyzed. Multivariable-log-binomial mixed regression models were constructed to assess factors associated with increased opioid prescription. Results: In total, 43,611 SCH CRPP cases in patients aged 10 or younger were identified from 2010 to 2021. Throughout the study period, 48.6% of patients (21,191/43,611) received and filled a narcotic pain prescription. The percentage of patients receiving opioid medication decreased from 54.7% in 2010 to 27.4% in 2021. Opioid prescriptions totaled a mean of 6.1±2.1 days of narcotics with a mean of 79.2 MME prescribed per patient. Increased patient age, increased Elixhauser comorbidity index, and Medicaid insurance were all associated with increased opioid prescription (P<0.001). Living in the Northeast, increased family income, and commercial insurance were associated with decreased opioid prescriptions (P<0.001). Conclusions: Nearly half of the patients over the past decade treated with CRPP for SCH received a narcotic prescription. However, there has been a steady decline in the proportion of patients being prescribed opioids, with only 27.4% receiving opioids in 2021. Further, patients with increased comorbidities or those insured by Medicaid with lower mean family income may be at risk for increased opioid prescription. While efforts have been made to reduce opioid overprescribing, there continues to be room for further reduction in opioid utilization after CRPP for SCH moving forward.

ABSTRACT Background Kidney disease significantly increases the risk of dementia, including among kidney transplant (KTx) recipients. To date, the cost implications of dementia after KTx are not well described. Methods We performed a retrospective cohort study of US Renal Data System (USRDS) data (2006–2020) to estimate cost of care for ≥65‐year‐old Medicare insured KTx recipients (2006–2020) with newly diagnosed dementia ( n = 3285), compared to propensity‐matched controls without dementia ( n = 6570). KTx recipients age 65+ years with post‐KTx dementia were identified by diagnosis codes, and costs were computed based on payments on Medicare claims. Average costs per month, marginal costs per month, and cumulative costs were compared after dementia diagnosis versus after the equivalent time post‐KTx in controls. Results Dementia was diagnosed at a mean of 5.1 ± 3.4 years post‐KTx. Patients' characteristics were well matched in cases versus controls, including age (mean: 70.1 vs. 69.9 years), sex (38.4% vs. 37.9% women), race (23.7% vs. 22.2% African American), and cause of ESKD (45.4% vs. 43.7% diabetes). Over 4 years post‐KTx, dementia was associated with reduced survival (27% vs. 68%) along with $66 145 (95% CI $51 560‐$78 489) higher Medicare spending. Average monthly costs in dementia patients reached a maximum of $12 713 and exceeded the cost of unaffected patients by up to $9789 per month. Conclusions Post‐KTx dementia dramatically increased resource utilization and reduced post‐KTx surivival. These findings highlight the need for care pathways that better integrate cognitive health assessment and management into the care of KTx candidates and recipients.

(1) Burn injuries demand multidisciplinary, evidence-based care, yet the extensive literature complicates timely decision making. Retrieval-augmented generation (RAG) synthesizes research while addressing inaccuracies in pretrained models. However, citation bias in sourcing for RAG often prioritizes highly cited studies, overlooking less-cited but valuable research. This study examines RAG’s performance in burn management, comparing citation levels to enhance evidence synthesis, reduce selection bias, and guide decisions. (2) Two burn management datasets were assembled: 30 highly cited (mean: 303) and 30 less-cited (mean: 21). The Gemini-1.0-Pro-002 RAG model addressed 30 questions, ranging from foundational principles to advanced surgical approaches. Responses were evaluated for accuracy (5-point scale), readability (Flesch–Kincaid metrics), and response time with Wilcoxon rank sum tests (p < 0.05). (3) RAG achieved comparable accuracy (4.6 vs. 4.2, p = 0.49), readability (Flesch Reading Ease: 42.8 vs. 46.5, p = 0.26; Grade Level: 9.9 vs. 9.5, p = 0.29), and response time (2.8 vs. 2.5 s, p = 0.39) for the highly and less-cited datasets. (4) Less-cited research performed similarly to highly cited sources. This equivalence broadens clinicians’ access to novel, diverse insights without sacrificing quality. As plastic surgery evolves, RAG’s inclusive approach fosters innovation, improves patient care, and reduces cognitive burden by integrating underutilized studies. Embracing RAG could propel the field toward dynamic, forward-thinking care.

Abstract Normal pressure hydrocephalus is typically defined by the triad of gait disturbance, cognitive impairment, and urinary incontinence, and is characterized on MRI by disproportionately enlarged subarachnoid-space. Gait disturbance is also a commonly reported symptom in Parkinsonian disorders, especially progressive supranuclear palsy, although the frequency, clinical significance and mechanisms of hydrocephalus in these disorders are unclear. We aimed to assess the prevalence of hydrocephalic MRI parameters in a large cohort of Parkinsonian disorders and evaluate associations with clinical features and abnormalities on MRI and PET. Two hundred and thirty-eight participants with a Parkinsonian disorder, including 181 progressive supranuclear palsy, 36 corticobasal syndrome and 21 Parkinson’s disease, were enrolled from Mayo Clinic by the Neurodegenerative Research Group between September 2009 to October 2023. Automated detection of disproportionately enlarged subarachnoid-space hydrocephalus (D) was applied and using Evans’ index (E) cut-off point &gt;0.3, participants were classified based on both measures as imaging-suggestive of hydrocephalus (D+E+), enlarged subarachnoid-space only (D+E−), large Evans’ index only (D−E+) and no imaging evidence of hydrocephalus (D−E−). Demographic, clinical and imaging features, including magnetic resonance parkinsonism index, cortical and subcortical volumes, white matter hyperintensities, diffusion tractography metrics, and metabolism on PET, were compared across groups. Among the 238 participants, 24 had borderline subarachnoid space scores and were excluded. The remaining 214 participants were classified as: D+E+ (n = 20, 9%); D+E− (n = 8, 4%); D−E+ (n = 71, 33%) and D−E− (n = 115, 54%). Among the progressive supranuclear palsy participants, 11% were D+E+, 4% D+E−, 34% D−E+ and 51% D−E−. Most cases (n = 18) in the imaging-suggestive of hydrocephalus D+E+ group had progressive supranuclear palsy. The D+E+ participants were older, had more disorientation, more downgaze palsy, greater midbrain and cortical atrophy, lower striatal metabolism, greater degeneration of long-range white matter tracts, larger cistern areas and more periventricular and deep white matter hyperintensities compared to the D−E− participants without imaging evidence of hydrocephalus. The D+E− participants had the highest metabolism in the paracentral lobule and superior parietal gyrus. The D−E+ participants showed worse disease severity and greater midbrain and cortical atrophy compared to the D−E− participants. These findings demonstrate that disproportionately enlarged subarachnoid-space hydrocephalus occurs in ∼15% of progressive supranuclear palsy participants, and is associated with worse clinical and imaging outcomes, as well as white matter hyperintensities. We hypothesize that disproportionately enlarged subarachnoid-space may be a mechanistic byproduct of degeneration and subsequent cerebrospinal fluid flow re-distribution in progressive supranuclear palsy.

Background: High-grade gliomas (HGGs), particularly glioblastoma (GBM), are associated with exceptionally high mortality and inevitable recurrence. In considering novel treatment options for these devastating diseases, immunotherapies represent promising candidates. Immunotherapies have demonstrated efficacy for several advanced tumors outside the central nervous system, highlighting a potential role for these agents in treating HGGs. However, multiple challenges to immunotherapy efficacy have tempered therapeutic benefit in practice, including local and systemic immunosuppression, intratumoral heterogeneity, and various mechanisms of intrinsic and acquired resistance. In the past 30 years, diverse immunotherapeutic subclasses have been assessed for benefit against HGGs. Methods: We performed a PubMed search for randomized clinical trials performed within the last 30 years evaluating the following immunotherapy agents for high-grade gliomas: immune checkpoint inhibitors, vaccines, oncologic viruses, cytokines, and CAR T-cells. The present review offers a critical analysis of key pre-clinical and clinical trials that have shaped the immunotherapy landscape for high-grade gliomas over the past two decades. Results/Conclusions: Across the different immunotherapeutic methods and modalities explored thus far, a recurring theme emerges: while therapeutic strategies with a compelling conceptual basis are continually under development and even demonstrate a benefit in preclinical and early-phase trials, larger and later-phase trials consistently fail to produce concordantly significant outcomes. To date, no large-scale clinical trial has demonstrated a benefit of sufficient consequence to change practice. Continued critical appraisal of the strengths and pitfalls of prior investigative work, optimization of treatment development and delivery, and innovative approaches to combination therapy design will collectively be integral to future therapeutic advancement.

ABSTRACT Background Mitral transcatheter edge‐to‐edge repair (TEER) is approved for patients with severe functional mitral regurgitation (FMR) beyond optimal medical therapy (OMT). Aims We aimed to assess TEER's efficacy beyond OMT in patients with severe FMR. Methods A systematic review and meta‐analysis were conducted, including randomized controlled trials from PubMed, Cochrane, Scopus, and EMBASE up to September 2024. Primary outcome: heart failure hospitalization (HFH); secondary outcomes: cardiovascular (CV) mortality, all‐cause mortality, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Time‐to‐event data from Kaplan−Meier curves were reconstructed for individual patient data. Results Three studies (1423 patients) were included. TEER significantly reduced HFH (RR 0.73, 95% CI 0.58−0.92, p < 0.01) and CV mortality (RR 0.79, 95% CI 0.66−0.95, p = 0.01), and improved KCCQ scores (mean difference 14.32, 95% CI 10.85−17.80, p < 0.01) compared to OMT. No significant difference was found for all‐cause mortality (RR 0.80, 95% CI 0.63−1.02, p = 0.07). Prognostic meta‐analysis showed a 34% reduced risk of HFH (HR 0.66, 95% CI 0.45−0.96, p = 0.03), but no effect on all‐cause or CV mortality. Reconstructed Kaplan−Meier analysis confirmed a 34% reduced risk of HFH (HR 0.65, p < 0.001), with effect attenuation after 15 months in landmark analysis (HR 0.64, p = 0.07). RMST analysis showed a 2.9‐month longer HFH‐free survival with TEER ( p < 0.01). Conclusion In patients with FMR, TEER significantly reduces HFH, improves functional status, and lowers CV mortality at 24 months but does not significantly affect all‐cause mortality. The device group experienced a modest, but significant, 2.9‐month longer HFH‐free survival compared to the control group. However, the reduction in HFH showed attenuation beyond 15 months.