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Importance Bilateral vocal cord paralysis is a challenging problem to manage in adults, and a known complication of thyroid surgery which is more common in resource-limited settings. Posterior graft laryngotracheal reconstruction is a management option that has not been studied in this population or setting. Objective To report the surgical outcomes of posterior graft laryngotracheal reconstruction for bilateral vocal cord paralysis in a resource-limited setting, and to evaluate the efficacy of a hybrid system for teaching this technique in Kenya. Design Retrospective cohort study. Setting Tertiary public referral hospital, Eldoret, Kenya Participants Adults >18 years with tracheostomy dependence secondary to bilateral vocal cord paralysis after thyroid surgery or other iatrogenesis. The hybrid training program included Kenyan surgeons and surgical trainees. Intervention or Exposures Posterior graft laryngotracheal reconstruction and hybrid training system included didactic lectures, simulation-based training, case discussion and planning, and live cases. Main Outcomes Measures One-year airway outcomes measured by achievement of tracheostomy decannulation, and self-reported surgeon knowledge and skill acquisition. Results Ten patients met criteria and were included in the analysis, with mean age 42 years (range 30-62 years) and had been tracheostomy dependent for an average of 6 years (range 1-12 years). Seven (70%) had open reconstruction, and 3 (30%) had endoscopic reconstruction. All were decannulated and remained tracheostomy-free at 1 year. Three surgeons and 7 trainees participated in the hybrid teaching methods. All reported increased comfort in laryngotracheal reconstruction, with all 3 surgeons reporting comfort performing the surgeries independently. Conclusion Posterior graft laryngotracheal reconstruction shows promise as a potential method of treating bilateral vocal cord paralysis and achieving decannulation in a resource-limited setting. Relevance The methods reported in this study lend themselves to replication and expansion to other similar settings. The authors plan to replicate this work in other centers in East Africa.

ABSTRACT Background Over the years, prognostic indexes have been developed to help clinicians stratify patients with biliary tract cancers (BTC) into risk groups. This study aims to identify a new prognostic index for patients with BTC treated with cisplatin, gemcitabine and durvalumab (CGD) in the first‐line setting. Patients and Methods The study population consisted of patients with BTC from 11 Eastern and Western Countries. Using multivariate analysis for overall survival (OS), we identified 5 baseline statistically significant variables: stage, carcinoembryonic antigen (CEA) levels, albumin levels, gamma glutamyl transferase (GGT) levels, neutrophil‐to‐lymphocyte ratio (NLR). Metastatic disease is a prognostic factor with a superior weight considering the HR of 3.62, while all the others can be considered prognostic factors with equivalent weight as the HRs are quite similar (HRs between 1.55 and 1.92). Based on these reasons, we developed a prognostic model called the MAGIC‐D index by assigning a score of 2 for metastatic disease, and a score of 1 for CEA increased levels, albumin decreased levels, GGT increased levels, NLR ≥ 3. Patients were stratified into three risk groups as follows: low‐risk group (Score from 0 to 2), intermediate‐risk group (Score from 3 to 4) and high‐risk group (Score from 5 to 6). At the first data cutoff (April 2024), these data were available for 319 patients that composed the training cohort used for the analysis. At the second data cutoff (May 2025), 79 patients were further enrolled and composed the validation cohort. Results Median progression‐free survival was 11.7 months in low‐risk group (20.7%), 8.7 months in intermediate‐risk group (46.4%) and 5.4 months in high‐risk group (32.9%) [low‐risk hazard ratio (HR): 0.27, intermediate‐risk HR: 0.55, high‐risk HR: 1, p < 0.0001]. Median OS was 18.4 months in low‐risk group,15.9 months in intermediate‐risk group and 7.8 months in high‐risk group (low‐risk HR: 0.17, intermediate‐risk HR: 0.43, high‐risk HR: 1, p < 0.0001). There was no difference in overall response rate (low‐risk: 31.8%, intermediate‐risk: 36.5% and high‐risk: 25.7%; p = 0.0718), while disease control rate was significantly different across the three risk groups (low‐risk: 83.3%, intermediate‐risk: 70.9% and high‐risk: 60.9%; p < 0.0001) as well as the rate of patients receiving a second‐line therapy (low‐risk: 54.5%, intermediate‐risk: 48.6% and high‐risk: 25.7%; p = 0.0061). Finally, the prognostic role in terms of OS and PFS of the MAGIC‐D index was confirmed in a validation cohort of 79 patients. Conclusion The MAGIC‐D index is an easy‐to‐use tool able to stratify patients with BTC with different prognoses undergoing first‐line therapy with CGD.

Background: Levetiracetam administration via intravenous push (IVP) may improve outcomes in status epilepticus (SE) by decreasing time to administration. However, there is a paucity of literature describing the safety of IVP administration of higher loading doses used for early management of SE. Objective: The purpose of this evaluation was to investigate the safety of high-dose IVP levetiracetam. Methods: This was a retrospective, single-arm cohort study conducted at an academic medical center. Patients were included if they received IVP levetiracetam ≥3000 mg. The primary outcome was a composite of clinically significant adverse events (AEs) within 1-hour post-administration of levetiracetam: hypotension, hypertension, bradycardia, tachycardia, arrhythmia, and/or injection site reaction. Results: A total of 140 patients met inclusion criteria, receiving a median levetiracetam dose of 4000 mg (interquartile range [IQR] = 3000, 4500). Seventeen (12.1%) patients experienced a clinically significant AE. The most common clinically significant AE was hypotension (9.2% [10/109]), followed by tachycardia (3.6% [4/112]), arrhythmia (1.8% [2/112]), hypertension (0.9% [1/109]), and injection site reaction (0.7% [1/140]). Eighty percent [8/10] of patients who experienced clinically significant hypotension were on at least 1 medication with potential confounding hemodynamic effects. Conclusion and Relevance: In this retrospective, single-arm analysis, high-dose (≥3000 mg) IVP levetiracetam was relatively well-tolerated but associated with a higher rate of clinically significant hypotension than has been reported in the previous literature, although several confounding factors may have contributed to this outcome. Our findings support the continued use of high-dose IVP levetiracetam with appropriate hemodynamic monitoring; hemodynamic effects should be further explored in future studies.

Abstract Rationale A subset of patients with group 1 pulmonary hypertension (PH) have superimposed left heart abnormalities with unclear metabolic implications. Objectives To compare serum/transpulmonary metabolome between group 1 PH stratified by heart failure with preserved ejection fraction (HFpEF) probability. Methods Patients with group 1 PH were stratified into low (&lt;25%) and high (⩾75%) HFpEF-ABA (age, body mass index, and atrial fibrillation) probability, with healthy control subjects and subjects with clinical HFpEF used for comparison of venous and transpulmonary metabolomics. Measurements and Main Results Group 1 PH + high HFpEF probability (n = 131) was associated with a significant increase in 207 metabolites (false discovery rate [FDR] P &lt; 0.05 and fold change &gt;1) (n = 193, t test) and a significant decrease in 231 metabolites (FDR P &lt; 0.05 and fold change &lt;1) (n = 193, t test) compared with group 1 PH + low HFpEF probability (n = 62). Group 1 PH + high HFpEF probability was associated with enhanced tryptophan metabolism with higher downstream kynurenine metabolite concentrations and lower serotonin concentrations (FDR P &lt; 0.002 for all, n = 193, t test). Linoleate (precursor to arachidonic acid and prostaglandins) and arginine and homoarginine (precursors to nitric oxide) were all lower in group 1 PH + high HFpEF probability (FDR P &lt; 0.03 for all, n = 193, t test). Metabolome changes in group 1 PH + high HFpEF probability overlapped with clinical HFpEF (n = 240) but were abnormal relative to control subjects (n = 85) (P &lt; 0.0001 for all, n = 456, t test). There was no evidence of differential transpulmonary uptake/release of most metabolites, suggesting probable nonpulmonary origin (except for serotonin, interaction P = 0.04; and kynurenine, interaction P = 0.03; n = 433, mixed model). Conclusions Patients with group 1 PH + high HFpEF probability have a unique metabolome characterized by enhanced tryptophan-kynurenine pathway breakdown, deficiency of amino acids (such as glycine and serine), lower serotonin, and decreased prostaglandin and nitric oxide precursors. Despite fulfilling clinical criteria for group 1 PH, these metabolome changes were comparable with clinical HFpEF, supporting biological overlap between these two forms of PH.

ABSTRACTObjectivesTo achieve consensus among expert laser surgeons on standards for the prevention and management of adverse events from fully ablative laser resurfacing of the face.Materials and MethodsDelphi study with two rounds of ratings and revisions until consensus was achieved. The draft set of statements was developed by a steering committee based on expert clinical experience. This was followed by two rounds of rating and revisions completed by an expert panel, then a virtual consensus meeting. In both rounds, respondents rated the draft statements on a 9‐point Likert scale (1 = strongly disagree; 9 = strongly agree) and optionally provided comments. The consensus meeting was supplemented by the results of a systematic review of the literature (from 2000 to 2023).ResultsTwo rounds of Delphi survey were completed by 34 participants across four countries. Represented specialties were dermatology, facial plastic surgery, plastic surgery, and oculoplastic surgery. The initial 105 statements from round 1 expanded to 112 in round 2, with 96 statements achieving consensus. These included possible adverse events (11 statements); absolute and relative contraindications to treatment (5 statements); preoperative care and antimicrobial prophylaxis precautions (16 statements); intraoperative precautions (17 statements); postoperative care (21 statements); monitoring for and management of infection (16 statements); management of pigmentation changes (6 statements); and management of scarring and incipient scarring (4 statements).ConclusionAn international consensus statement was developed for the prevention and management of complications associated with fully ablative laser resurfacing of the face. While expert practices vary, key factors for optimizing outcomes include careful patient selection, counseling, and meticulous pre‐ and postoperative care. Further research will improve our understanding of this treatment technique.

BACKGROUND: Patients with lung disease, sleep apnea, and chronic thromboemboli can develop pulmonary hypertension, currently classified as group 3 or 4. Many of these patients also have risk factors for heart failure with preserved ejection fraction (HFpEF), but the optimal approach to identify the disease overlap remains unclear. METHODS: Pretest probability for HFpEF was determined using the HFpEF-ABA (age, body mass index, atrial fibrillation) algorithm among adjudicated group 3 or 4 patients at risk for pulmonary hypertension in the PVDOMICS study (Redefining Pulmonary Hypertension Through Pulmonary Vascular Disease Phenomics). Patients were stratified by current resting right heart catheterization criteria, and in a separate analysis, stratified only by HFpEF-ABA probability into low (<25%), intermediate, and high (≥75%) HFpEF probability groups. RESULTS: Among 598 patients with group 3 disease, 27% (n=161) had elevated pulmonary capillary wedge pressure (PCWP) with postcapillary pulmonary hypertension even at rest, which was associated with the highest exercise PCWP. However, regardless of this resting PCWP-based classification, a larger subset had intermediate-to-high HFpEF-ABA probabilities (32% [n=197] high and 57% [n=358] intermediate HFpEF probability). High HFpEF probability in group 3 disease was associated with higher resting and dynamic PCWP response to NO, fluid, and exercise ( P <0.0001 for all). These changes were comparable with more traditionally defined HFpEF without pulmonary vascular disease (n=61) but less severe than those with combined precapillary and postcapillary pulmonary hypertension HFpEF (n=31; interaction P =0.006). Increasing HFpEF probability in group 3 disease was associated with worse left heart remodeling, quality of life, 6-minute walk distance, and peak VO 2 ( P <0.0001 for all). Findings were replicated in group 4 disease (n=102). CONCLUSIONS: Quantifying pretest probability for HFpEF in patients with sleep apnea, lung disease, or chronic thromboemboli identifies a progressive gradient for dynamic PCWP abnormalities with worse functional status and quality of life. These subclinical left heart abnormalities are not universally detectable by resting right heart catheterization alone and call for further study of whether strategies to prevent or treat HFpEF might improve functional status in these patients with high risk of occult HFpEF.

Abstract Cortico‐cortical evoked potentials (CCEPs) are an active electrophysiological technique used during intracranial electroencephalography to evaluate the effective connectivity and influence of therapeutic stimulation between distinct cortical regions and pinpoint epileptogenic zones (EZs) in patients with epilepsy. Various methodologies have been implemented to analyze CCEPs and characterize the epileptogenic networks for EZ localization. Despite its promise, their interpretation remains challenging due to the large volumes of spatially and temporally complex data generated. Early studies focused largely on qualitative descriptors and predefined, semi‐quantitative features such as waveform morphology and peak latencies. However, these methods are limited by the significant heterogeneity in CCEP waveform conformations across patients and cortical regions. The specific technique used for extraction of features, such as the spectral band power and root mean squared values, remains open to empirical refinement, as does choice of appropriate latency windows, with no consensus reached regarding the optimal approach. Graph theoretical metrics such as degree centrality, betweenness centrality, and clustering coefficients can provide a rich representation of epileptogenic network connectivity. However, these metrics are often abstract and difficult to interpret in a clinical setting or to the non‐expert, and their neuroscientific substrates remains poorly understood. The lack of standardization in stimulation protocol and data‐processing pipelines has further contributed to inconsistency in reported findings. Emerging machine learning approaches have been increasingly applied to CCEP data, offering a more data‐driven and potentially generalizable way to identify electrophysiological biomarkers of the epileptogenic effective connectivity. In this article, we discuss qualitative, quantitative, and spectral features; network‐analytical metrics; and more recently, data driven methodologies aimed at improving the interpretability and clinical utility of CCEP data.

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.

Background Right ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood. Methods We performed global untargeted metabolomics on plasma from 55 patients who underwent gold‐standard RV‐PA coupling measurements using multibeat pressure volume loop assessment in a single‐center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex‐adjusted linear regression was performed to identify associations between metabolites and coupling metrics. Additionally, we performed a metabolic flux analysis using gene expression data from RV tissue in an independent cohort of 32 patients. Partial least squares–discriminant analysis was used to identify metabolites and reactions characteristic of the decompensated RV. Results RV‐PA coupling was negatively associated with tricarboxylic acid (TCA) cycle intermediate levels. Specifically, plasma α‐ketoglutarate and fumarate were significantly associated with all coupling metrics in both cohorts. Metabolic flux analysis indicated that decompensated RVs exhibited aberrant TCA cycle activity, including reduced acetyl coenzyme A entry and increased lactate elimination, suggesting a shift from the TCA cycle toward glycolysis at the RV tissue level. Conclusions We identify an association between circulating TCA cycle intermediate levels and RV‐PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV‐targeted therapies.