Citations

Importance Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure. Objective To estimate the worldwide burden of SAH. Design, Setting, and Participants Based on the repeated cross-sectional Global Burden of Disease (GBD) 2021 study, the global burden of SAH in 1990 to 2021 was estimated. Moreover, the SAH burden was compared with other diseases, and its associations with 14 individual risk factors were investigated with available data in the GBD 2021 study. The GBD study included the burden estimates of nontraumatic SAH among all ages in 204 countries and territories between 1990 and 2021. Exposures SAH and 14 modifiable risk factors. Main Outcomes and Measures Absolute numbers and age-standardized rates with 95% uncertainty intervals (UIs) of SAH incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) as well as risk factor–specific population attributable fractions (PAFs). Results In 2021, the global age-standardized SAH incidence was 8.3 (95% UI, 7.3-9.5), prevalence was 92.2 (95% UI, 84.1-100.6), mortality was 4.2 (95% UI, 3.7-4.8), and DALY rate was 125.2 (95% UI, 110.5-142.6) per 100 000 people. The highest burden estimates were found in Latin America, the Caribbean, Oceania, and high-income Asia Pacific. Although the absolute number of SAH cases increased, especially in regions with a low sociodemographic index, all age-standardized burden rates decreased between 1990 and 2021: the incidence by 28.8% (95% UI, 25.7%-31.6%), prevalence by 16.1% (95% UI, 14.8%-17.7%), mortality by 56.1% (95% UI, 40.7%-64.3%), and DALY rate by 54.6% (95% UI, 42.8%-61.9%). Of 300 diseases, SAH ranked as the 36th most common cause of death and 59th most common cause of DALY in the world. Of all worldwide SAH-related DALYs, 71.6% (95% UI, 63.8%-78.6%) were associated with the 14 modeled risk factors of which high systolic blood pressure (population attributable fraction [PAF] = 51.6%; 95% UI, 38.0%-62.6%) and smoking (PAF = 14.4%; 95% UI, 12.4%-16.5%) had the highest attribution. Conclusions and Relevance Although the global age-standardized burden rates of SAH more than halved over the last 3 decades, SAH remained one of the most common cardiovascular and neurological causes of death and disabilities in the world, with increasing absolute case numbers. These findings suggest evidence for the potential health benefits of proactive public health planning and resource allocation toward the prevention of SAH.

Abstract Introduction Rapid eye movement (REM) sleep behavior disorder (RBD) is the single strongest predictor of Parkinson’s disease (PD) risk. Given neurotrauma and psychiatric morbidity, the aging post-9/11 Veteran cohort is a target population for understanding probable RBD frequency and neuroprotection opportunities. We previously reported over 50% of post-9/11 Veterans screened positive for probable RBD. We aimed to examine frequencies of prodromal PD markers and polysomnography (PSG)-confirmed RBD in post-9/11 Veterans. Methods Veterans with probable RBD based on the single-question RBD screen (n=12) were recruited from the Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS) Houston cohort. Participants were assessed for subthreshold parkinsonism (Unified Parkinson’s Disease Rating Scale-III Motor score >3, excluding action tremor), olfactory loss (12-item Sniffin’ Sticks), TBI exposures, autonomic symptoms, orthostasis, excessive daytime sleepiness, post-traumatic stress disorder (PTSD), and psychiatric comorbidities. PSG studies were conducted per American Academy of Sleep Medicine guidelines. A board-certified sleep physician confirmed the presence of REM sleep without atonia. We compared the frequency of prodromal marker positivity between participants with and without subthreshold parkinsonism. Results All 12 participants were male (6 [50%] Black, 3 [25%] Hispanic) with a mean (SD) age of 44.4 ± 6.7 years. PSG data (n=10) revealed REM sleep without atonia in 5 (50%), moderate obstructive sleep apnea (OSA) in 2 (20%), and severe OSA in 2 (20%) participants. Five (41.6%) participants had mild motor dysfunction suggestive of subthreshold parkinsonism on the UPDRS-III (M±SD score of 8.6 ± 5.9), while 7 participants had normal or low UPDRS-III ratings (2.3 ± 1.3; p=0.02). Veterans with subthreshold parkinsonism had lower Sniffin’ Sticks scores than those without (M±SD 9.4 ± 2.07 vs. 11.29 ± 0.76; 95% CI: 0.01–3.76, p=0.049). Conclusion This pilot study suggests that motor and olfactory prodromal PD markers are frequent in post-9/11 Veterans with probable RBD. Larger prospective cohort studies are required to further quantify REM sleep without atonia and assess synuclein-specific biomarkers in this population. Support (if any) Center for Alzheimer’s and Neurodegenerative Diseases at Baylor College of Medicine [MJ]; VA CSR&D (#IK2CX002363-01A1) [MJ]; VA RR&D (B9268-X) [RJ]; NIH/NIA/NINDS (U19-AG071754 & R34-AG056639) [ES]; and AASM [ES].

AbstractStandard of care first‐line systemic treatment for advanced biliary tract cancer includes chemo‐immunotherapy with gemcitabine, cisplatin, and durvalumab, followed by maintenance durvalumab monotherapy. The present work aims to investigate the differences in baseline clinical and molecular characteristics between patients with early progression during chemo‐immunotherapy and those who reach durvalumab maintenance therapy. The study population included patients with unresectable, locally advanced, or metastatic BTC who received treatment at 38 clinical Institutions in 12 countries from July 2021 to December 2023. The primary objective of the study was to investigate whether baseline clinical and molecular characteristics differed between patients with early progression during chemo‐immunotherapy versus those reaching durvalumab maintenance therapy. Four hundred forty‐eight patients were included in this study. Two hundred twenty‐seven patients (50.7%) received maintenance with durvalumab monotherapy, whereas 221 (49.3%) did not receive maintenance therapy due to PD during first‐line chemo‐immunotherapy before completing 8 cycles. Results show that patients who received maintenance were more likely to be older (≥70 years), have an ECOG = 0, locally advanced disease, and a neutrophil‐to‐lymphocyte ratio (NLR) <3. A higher proportion of patients with BAP1 mutations received maintenance, while TP53 mutations were more common in those who progressed early. According to the present analysis, a substantial proportion of patients (50.7%) with advanced BTC who were treated with chemotherapy plus durvalumab proceeded to receive maintenance therapy with durvalumab monotherapy, with a median treatment duration of 4.4 cycles. Patients ≥70 years, with ECOG PS 0, with locally advanced disease, and with NLR <3 had a higher likelihood of receiving maintenance therapy.

Abstract Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observed comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identified distinct NSCLC-like (KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles. Serial sampling revealed stable mutational but shifting transcriptomic landscapes over time. NSCLC-like LCNECs showed elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression, while SCLC-like subtypes expressed higher levels of DLL3. Immunofluorescence confirmed FGL-1 in NSCLC-like LCNECs, and H&E slide analyses indicated fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers. These findings highlight LCNEC’s distinct immunogenomic profile, supporting future investigations into LAG-3, SPINK1, and DLL3-targeted therapies.

Background/Objectives: Facial analysis is critical for preoperative planning in facial plastic surgery, but traditional methods can be time consuming and subjective. This study investigated the potential of Artificial Intelligence (AI) for objective and efficient facial analysis in plastic surgery, with a specific focus on Multimodal Large Language Models (MLLMs). We evaluated their ability to analyze facial skin quality, volume, symmetry, and adherence to aesthetic standards such as neoclassical facial canons and the golden ratio. Methods: We evaluated four MLLMs—ChatGPT-4o, ChatGPT-4, Gemini 1.5 Pro, and Claude 3.5 Sonnet—using two evaluation forms and 15 diverse facial images generated by a Generative Adversarial Network (GAN). The general analysis form evaluated qualitative skin features (texture, type, thickness, wrinkling, photoaging, and overall symmetry). The facial ratios form assessed quantitative structural proportions, including division into equal fifths, adherence to the rule of thirds, and compatibility with the golden ratio. MLLM assessments were compared with evaluations from a plastic surgeon and manual measurements of facial ratios. Results: The MLLMs showed promise in analyzing qualitative features, but they struggled with precise quantitative measurements of facial ratios. Mean accuracy for general analysis were ChatGPT-4o (0.61 ± 0.49), Gemini 1.5 Pro (0.60 ± 0.49), ChatGPT-4 (0.57 ± 0.50), and Claude 3.5 Sonnet (0.52 ± 0.50). In facial ratio assessments, scores were lower, with Gemini 1.5 Pro achieving the highest mean accuracy (0.39 ± 0.49). Inter-rater reliability, based on Cohen’s Kappa values, ranged from poor to high for qualitative assessments (κ > 0.7 for some questions) but was generally poor (near or below zero) for quantitative assessments. Conclusions: Current general purpose MLLMs are not yet ready to replace manual clinical assessments but may assist in general facial feature analysis. These findings are based on testing models not specifically trained for facial analysis and serve to raise awareness among clinicians regarding the current capabilities and inherent limitations of readily available MLLMs in this specialized domain. This limitation may stem from challenges with spatial reasoning and fine-grained detail extraction, which are inherent limitations of current MLLMs. Future research should focus on enhancing the numerical accuracy and reliability of MLLMs for broader application in plastic surgery, potentially through improved training methods and integration with other AI technologies such as specialized computer vision algorithms for precise landmark detection and measurement.

ABSTRACT Background and hypothesis Podocytopathy associated with likely pathogenic/pathogenic variants of Transient receptor potential cation channel subfamily C member 6 (TRPC6) (TRPC6-AP) has been recognized for about 20 years. As a result of its rarity however, the spectrum of clinical phenotypes and genotype–phenotype correlation of TRPC6-AP remains poorly understood. Here, we characterized clinical, histological and genetic correlates of familial and sporadic patients with TRPC6-AP. Methods In this multicentre observational study, an online questionnaire followed by a systematic literature review was performed to create a cohort with comprehensive data on genetic and clinical outcomes [age of onset, clinical presentation, treatment response, kidney biopsy findings and progression to kidney failure (KF)]. Logistic regression, Cox proportional hazards model and Kaplan–Meier analyses investigated the associations between genetic variants and disease progression. Results Among 87 families (96 familial and 45 sporadic cases), 31 distinct missense TRPC6 variants (including 2 novel) were identified, with c.2683C&gt;T p.(Arg895Cys) and c.523C&gt;T p.(Arg175Trp) the commonest variants. Proteinuric kidney disease/nephrotic syndrome was the most common clinical presentation (83.7%), while focal segmental glomerulosclerosis was the most common histological finding (89.4%). By 33 (interquartile range 17–40) years, 48.9% (69/141) of patients had progressed to KF. Sporadic TRPC6-AP demonstrated an earlier progression to KF than familial cases (P = .001) and were more likely to present with nephrotic syndrome [odds ratio 4.34 (1.85–10.15); P = .001]. Gain-of-function TRPC6 variants were more frequent in familial than sporadic TRPC6-AP (70.8% vs 44.4%; P = .004). Compared with patients with other TRPC6 variants, patients with TRPC6 p.R175W and p.R895C variants progressed to KF earlier [median kidney survival of 21 years, hazard ratio 2.985 (95% confidence interval 1.40–5.79); and 38 years, hazard ratio 1.65 (95% confidence interval 1.01–2.81), respectively, log-rank P = .005]. Conclusion Our study shows unique clinical and genetic correlations of TRPC6-AP, which may enable personalized care and promising novel therapies.

Background: Revisional bariatric surgery for recurrent weight gain is becoming more common, though it carries higher risks and may be less effective than primary bariatric surgery. This study compares clinical outcomes between primary and revisional duodenal switch (DS) in patients with a body mass index (BMI) > 55 kg/m2. Methods: A retrospective cohort study was conducted on 20 patients who underwent either primary or revisional duodenal switch (DS) surgeries, including biliopancreatic diversion with duodenal switch (BPDDS) and Single-Anastomosis Duodeno-Ileal Bypass with Sleeve Gastrectomy (SADI-s), between January 2015 and December 2023. Revisional DS was defined as the conversion from Sleeve Gastrectomy (SG) to either BPDDS (C-BPDDS) or SADI-S (C-SADI-S). Perioperative and postoperative variables were analyzed. A statistical analysis was performed using chi-square and McNemar tests for categorical variables and Student’s t-test for continuous variables. A p-value of <0.05 was considered significant. Results: Eleven primary DS patients (six BPDDS, five SADI-s) and nine revisional DS patients (five C-BPDDS, four C-SADI-s) were included. The revisional group had a slightly higher preoperative BMI (57.56 ± 5.92 kg/m2 vs. 55.93 kg/m2 ± 6.91 kg/m2). Although operative times were shorter in the revisional group (153.20 ± 53.26 vs. 193.27 ± 46.79 min), the length of stay was longer (2.70 ± 1.25 vs. 2.18 ± 1.16 days). Primary DS patients experienced three minor late complications (dehydration, nephrolithiasis), whereas the revisional group had one major complication (internal hernia requiring reoperation). At the 12-month follow-up, both groups demonstrated similar outcomes in terms of percentage of total weight loss (%TWL) (primary DS: 25.25% ± 12.38 vs. revisional DS: 30.31% ± 10.79) and percentage of excess weight loss (%EWL) (primary DS: 48.41% ± 22.93 vs. revisional DS: 53.24% ± 14.48). Conclusions: Revisional DS was associated with shorter operation times and similar weight loss to primary DS. Additionally, it was accomplished safely and led to adequate and sustained weight loss in patients with a BMI greater than 55 kg/m2.

Abstract Goals/Purpose This study aims to examine the sentiment and polarization of social media content regarding transgender care. We seek to quantitatively analyze social media posts related to transgender care using sentiment analysis, assessing the extent of positive or negative bias in online discussions about transgender healthcare. By establishing a baseline understanding of how online misinformation may impact public perceptions of transgender care, we highlight the importance of addressing online extremism in healthcare as a public health concern. This research represents the first large-scale natural language processing (NLP) analysis of online sentiment towards transgender care, utilizing sentiment analysis to minimize bias and provide quantitative insights into the impact of online rhetoric on public perception and patient care. Methods/Technique The lead author mined X for posts that mentioned transgender surgery (TG) and gender affirming surgery (GAS) from January 2018 to December 2023. Two different NLP models then analyzed the posts. The first was a binary model that characterized each post as positive or negative. The latter was an emotion-based model that scored each post about seven emotions – fear, sadness, anger, disgust, neutral, surprise, and joy. Posts were then classified by their highest-scoring emotion. An exponential regression analysis within the Python language was performed to study the trend in annual X post volume related to gender surgery. To determine whether there were statistically significant differences in sentiment between transgender (TG) and gender-affirming surgery (GAS) topics, independent two-sample t-tests were conducted for both positive and negative sentiments for each year within the study period. Results/Complications In total, there were 81,264 posts related to gender surgery included in our analysis. In 2018 there were 2,093 posts, compared to 2023 where there were 40,258 posts – a roughly 20-fold increase in annual post volume. In our exponential regression model, annual post volume demonstrated a strong positive trend R2 = 0.939, p = 0.001, Figure 1). Most of the posts were classified as ‘negative’ (63,192 posts, 78%). Mean scores for both GAS and TG posts trended towards more negative and less positive sentiments over the study period (Figure 2). When comparing annual TG to GAS posts, those that mentioned TG were significantly more negative and less positive in every year studied (p &lt; 0.05). Conclusion Our analysis of social media posts related to gender-affirming surgery (GAS) and transgender (TG) care reveals a significant increase in online discourse over the past five years. The volume of posts grew exponentially from 2,093 in 2018 to 40,258 in 2023, representing a 20-fold increase. This rise in online discussion reflects the growing public interest and controversy surrounding transgender healthcare.The sentiment analysis revealed a trend toward increasingly negative rhetoric. A substantial majority (78%) of the posts were classified as negative, indicating a prevalence of critical or hostile attitudes towards GAS and TG care on social media platforms. The mean sentiment scores for both GAS and TG-related posts showed a consistent shift toward more negative and less positive sentiments over time. Notably, posts specifically mentioning transgender individuals or issues consistently displayed more negative and less positive sentiments compared to general GAS-related posts across all years studied. This finding suggests that transgender-specific topics are subject to particularly intense scrutiny and criticism online.These results highlight the urgent need for strategies to address misinformation and negative rhetoric surrounding transgender healthcare on social media platforms. The increasing volume and negativity of online discussions may contribute to a hostile environment for transgender individuals seeking care and for healthcare providers offering these services. Future research should focus on developing effective interventions to counter this trend and promote more balanced, informed discussions of transgender healthcare issues online.