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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: Acute Eosinophilic pneumonia (AEP) is an eosinophilic pulmonary condition defined by symptoms of less than or equal to 1 month's duration, pulmonary infiltrates on imaging, pulmonary eosinophilia of 25% or greater on bronchoalveolar lavage (BAL) cell count or eosinophilic pneumonia on lung biopsy, and absence of other eosinophilic pulmonary diseases. It can be associated with a multitude of exposures, including medications, inhalants as well as systemic conditions. We report a case of AEP associated with intramuscular (IM) progesterone administration. Case: A 36-year-old female presented to the emergency department with dyspnea on exertion, cough productive of yellow sputum, and subjective fever of two days’ duration. She had undergone in vitro fertilization using IM Progesterone as luteal phase support and experienced a miscarriage one week prior. She had a heart rate of 132 and required oxygen at 2 Liters per minute via nasal cannula to maintain her saturation at 92%. Her complete blood count showed an absolute eosinophil count of 1800 cells/uL. She underwent a computed tomography angiography scan of the chest, which was negative for a pulmonary embolism but showed diffuse bilateral peripheral ground-glass opacities as well as consolidations in both lung bases. She was empirically started on prednisone 40 mg per day. She later underwent a flexible bronchoscopy with BAL of the right middle lobe as well as transbronchial cryobiopsies of the right lung. The BAL cell differential showed 63% eosinophils confirming the diagnosis of AEP. Pathology revealed patchy organizing pneumonia with scattered eosinophils. Autoimmune workup was negative, including antineutrophil antibodies, Anti-myeloperoxidase, and anti-proteinase-3 antibodies. Infectious workup, including blood, sputum, and BAL cultures, was also negative. The patient dramatically improved with steroid administration. Her symptoms resolved, and she was discharged on room air with a 4-week prednisone taper. A follow-up chest x-ray revealed resolution of the infiltrates. Discussion: AEP is a rare condition. One epidemiological study estimated the incidence of AEP at 9.1/100,000 person-years in a population of United States military personnel. Given the lack of other inciting medications and negative autoimmune and infectious workup, IM progesterone administration was deemed the likely etiology of her presentation. There are four case reports of IM progesterone as a cause of AEP. This case represents a classic presentation of AEP with the secondary to progesterone administration and with symptoms resolving promptly with steroid administration.

Abstract Introduction Medullary thyroid cancer (MTC) is an uncommon malignancy arising from the C-cells of the thyroid gland. It makes up 2% of all thyroid cancers, with both familial and sporadic patterns noted. It is most commonly diagnosed in the fourth to sixth decade of life, with the lungs being a common site of metastasis. We present a case of metastatic MTC with a rare pulmonary presentation. Case Description The patient presented at the age of 28 after having a chronic complaint of stomach pain and diarrhea. Imaging of the abdomen revealed small nodules in the lower pulmonary fields. Dedicated imaging of the chest was subsequently ordered. This study was notable for an enlarged left lobe of the thyroid extending into the mediastinum with two large mediastinal lymph nodes. A fine-needle aspiration of the left neck lymph node was consistent with MTC and there were hematologic findings of elevated calcitonin and CEA. Testing for the RET proto-oncogene was negative. Pathology on total thyroidectomy confirmed the diagnosis, with further sampling identifying metastasis in the thoracic spine (T12). Initial therapy with pazopanib was commenced. After some time on stable therapy, the patient was noted to have waxing and waning pulmonary micro-nodularity associated with increase in his calcitonin levels. There was a finding of a miliary pattern of disease on chest imaging. The pulmonary service was consulted due to these findings in conjunction with sub-acute cough. Pulmonary biopsy was performed, with findings of nodular amyloidosis; Congo red stain highlighted amyloid deposition. Immunohistochemical studies were performed, revealing rare cell groups that were positive for calcitonin, CEA, CAM5.2, TTF-1, chromogranin, and synaptophysin. After further discussion with the Pathology service, the patient was given formal diagnosis of amyloid deposition of the Acal subtype due to metastatic medullary thyroid cancer. Discussion This case highlights a patient diagnosed with sporadic MTC, later found to have metastatic related pulmonary amyloid deposition. While local amyloid deposition can be seen in MTC, it is unusual to have diffuse parenchymal disease due todiffuse parenchymal disease due to distant deposition. There are only four other instances in the literature of a similar presentation. Amyloid deposition is associated with worse outcomes, but the patient had a good outcome with treatment by a tyrosine-kinase inhibitor.

ABSTRACT Background Diffuse intrinsic pontine glioma (DIPG) carries a poor prognosis with a median survival of less than 12 months. Key molecular features include histone H3 mutation (K27M) and AKT pathway dysregulation. There is currently no curative treatment. Methods This is a Phase I study of vorinostat and temsirolimus in newly diagnosed (Stratum 1) and progressive (Stratum 2) DIPG (NCT02420613). The primary aims are to determine the safety, maximum tolerated dose (MTD), and toxicities. A modified 3 + 3 design was used to establish the MTD, where the first three patients were assigned the first dose level regardless of stratum. Stratum 1 received radiotherapy with vorinostat, followed by up to 10 cycles of vorinostat and temsirolimus. Stratum 2 received up to 12 cycles of vorinostat and temsirolimus. Vorinostat was administered at a fixed dose of 230 mg/m 2 daily on Days 1–8, and temsirolimus was administered on Days 1 and 8 at 25 mg/m 2 (Dose level 1) or 35 mg/m 2 (Dose level 2). Results Six patients were enrolled, three in each stratum. No dose‐limiting toxicity was observed, and most adverse effects were limited to Grades 1 or 2, including fatigue, myelosuppression, hyperlipidemia, hyperglycemia, elevated creatinine, nausea, vomiting, and headache. One patient experienced Grade 3 leukopenia. In the study, the MTD with acceptable toxicity was vorinostat 230 mg/m 2 and temsirolimus 35 mg/m 2 . Conclusions Overall, the combination of temsirolimus and vorinostat is well‐tolerated and safe, prompting the need for larger studies to investigate its efficacy.

Objective: Pulmonary involvement is commonly observed in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presenting with manifestations such as diffuse alveolar hemorrhage, inflammatory infiltrates, pulmonary nodules, and tracheobronchial disease. We aimed to identify distinct subgroups of tracheobronchial disease patterns in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using latent class analysis (LCA), and to evaluate their clinical characteristics and outcomes. Methods: We conducted a retrospective cohort study using electronic medical records of patients aged >18 years diagnosed with AAV and tracheobronchial disease between 1 January 2002 and 6 September 2022. Patients with follow-up <6 months were excluded. LCA was employed to identify disease subtypes based on 10 pre-defined indicators. Maximum likelihood estimation with 10 repetitions per model ensured robustness in model selection, guided by the Akaike information criterion (AIC). Patient and disease characteristics were summarized and compared across predicted classes. Statistical analyses included Kruskal–Wallis and Fisher’s exact tests for continuous and categorical variables, respectively. The primary outcome was time to relapse of the tracheobronchial inflammation after starting immunosuppressive medication, analyzed using the Kaplan–Meier method and log-rank tests. Secondary outcomes included severity of pulmonary disease on pulmonary function tests, endoscopic interventions, tracheostomy, or mortality during follow-up. Results: Among 136 identified AAV patients assessed for tracheobronchial involvement, 111 (81.6%) were included after excluding 25 without tracheal or bronchial disease. Predominant findings included subglottic stenosis (91.0%), lower tracheal stenosis (16.2%), and bronchial stenosis (17.1%). LCA identified a three-class model as optimal: tracheal predominant (n = 94), tracheobronchial (n = 12), and bronchial predominant (n = 5). Tracheal predominant patients showed reduced risk of ear, eye, and lower respiratory manifestations, with milder obstruction on pulmonary function testing (PFT). Tracheobronchial-class patients were prone to saddle nose deformity (50%), extensive lower respiratory involvement (91.7%), and renal disease (66.7%). Bronchial predominant patients exhibited severe obstructive disease (median forced expiratory volume in 1 s (FEV1)% predicted: 58, IQR 34–66; FEV1/forced vital capacity (FVC) ratio: 56.9, interquartile range (IQR) 43–63.3) but lacked systemic AAV manifestations. LCA classes did not predict outcomes such as endoscopic intervention, tracheostomy, recurrent tracheobronchial narrowing, or mortality. Conclusion: LCA shows promise in subtype stratification of AAV patients, yet its utility in predicting outcomes and guiding treatment remains limited based on our analysis. Future studies with enhanced phenotypic data and larger cohorts are warranted to improve predictive accuracy.

Background/Objectives: Peri-intubation hypotension is a known complication of endotracheal intubation. In the hospital setting, peri-intubation hypotension has been shown to increase hospital mortality and length of stay. The use of prophylactic vasopressors at the time of sedation induction to prevent peri-intubation hypotension has been raised. This systematic review and meta-analysis aims to review the safety and efficacy of this practice. Methods: The study was fully registered with PROSPERO on 13 October 2022, and screening for eligibility was initiated on 20 September 2024. Randomized controlled trials, along with retrospective or prospective cohort studies, were included in the search. The terms “peri-intubation hypotension”, “vasopressors”, “intubation”, and “anesthesia induced hypotension” were used to search the title/summary in PubMed, Cochrane Library, and Google Scholar databases. An assessment of bias for each study was conducted using the Newcastle-Ottawa Quality Assessment Scale. The primary outcome was the rate of hypotension peri-intubation. Any complications secondary to hypotension or vasopressors were the secondary outcome. Results: We identified 13 studies, which were all randomized controlled studies, to include in the final analysis. The risk ratio for preventing peri-intubation hypotension was 1.6 (95% CI, 1.2–2.14) with the use of prophylactic phenylephrine while giving propofol versus no prophylactic vasopressors and 1.28 (95% CI 1.03–1.60) with the use of ephedrine. Conclusions: These findings suggest that in patients undergoing intubation in the operating room with propofol, prophylactic vasopressors given with induction for intubation decrease the odds of hypotension.

SummaryGlobal obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus‐based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two‐round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence‐based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.

Background and Objectives: The epidemiological data regarding mortality rates of adults with sarcoidosis and non-ischemic cardiovascular disease (CVD) are limited. A retrospective observational analysis was conducted to identify trends and disparities related to sarcoidosis and non-ischemic cardiovascular disease mortality among the adult US population from 1999 to 2022. Methods: We used the Centers for Disease Control and Prevention (CDC) WONDER database to extract death certificate data for the adult US population (≥25 years). The age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and annual percent changes (APCs) were determined using Joinpoint. Results: Between 1999 and 2022, 23,642 deaths were identified related to non-ischemic CVD + sarcoidosis. The overall AAMR increased from 0.2 (95% CI, 0.2 to 0.3) in 1999 to 0.5 (95% CI, 0.5 to 0.6) in 2022. Females had a higher AAMR than males (0.6 vs. 0.5). Non-Hispanic (NH) blacks had the highest AAMR, followed by NH whites and Hispanic or Latinos. The southern region had the highest AAMR (0.7: 95% CI, 0.6–0.7), followed by the Midwest (0.6, 95% CI, 0.54–0.669), the Northeast (0.5, 95% CI, 0.5 to 0.6), and the West (0.4; 95% CI, 0.3–0.4). Urban and rural areas had comparable mortality rates (0.5 vs. 0.6). People aged 65+ had the highest AAMRs. Conclusions: The overall mortality rates for non-ischemic CVD and sarcoidosis have increased in the US from 1999 to 2022. Females and NH blacks had higher AAMRs, while a minimal variation was observed based on geographical regions. Early diagnosis and prompt management are the keys to reducing the mortality burden of non-ischemic CVD plus sarcoidosis.

Background/Objective: To investigate the effect of mycophenolate mofetil (MMF) and rituximab (RTX) on pulmonary function test (PFT) results in a mixed cohort of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), longitudinally followed up for 1 year in a single academic center. Methods: Patients with CTD-ILD were identified in electronic medical records from 1 January 2009 to 30 April 2019. Prescribed MMF and RTX doses, dosage changes, and therapy plans were analyzed individually with improvement in PFT outcomes determined using multivariable linear regression models during 12-month follow-up. Results: Forty-seven patients with CTD-ILD, treated with MMF, RTX, or both, were included. Patients on combined MMF and RTX had worse PFT outcomes at baseline compared with patients on monotherapy. Substantial improvement was observed among all PFT outcomes from baseline to 12 months, regardless of medication dosage or therapy plans. The diffusing capacity of the lungs for carbon monoxide (DLCO) worsened by an average of 7.21 mL/(min*mmHg) (95% CI, 4.08–10.33; p < 0.001) among patients on RTX compared to combined therapy. Patients on higher doses of MMF at baseline experienced an average increase of 0.93 (95% CI, 0.04–1.82) units in DLCO from baseline to 6 months (p = 0.04) and a 2.79% (95% CI, 0.61–4.97%) increase in DLCO from 6 to 12 months (p = 0.02) within patients on concurrent RTX at 6-month follow-up. Conclusions: The treatment of CTD-ILD with MMF and/or RTX was associated with overall improvement in PFT outcomes. Combined therapy resulted in significant improvements in DLCO compared with monotherapy. Higher doses of MMF also provided greater improvements in DLCO.

Abstract OBJECTIVES Safety, efficacy and durability are important considerations when selecting a bioprosthesis for aortic valve replacement (AVR). This study assessed 7-year clinical outcomes and haemodynamic performance of the Avalus bioprosthesis. METHODS Patients indicated for surgical AVR were enrolled in this prospective, nonrandomized trial, conducted across 39 sites globally. The primary end-point of this analysis was freedom from surgical explant or percutaneous valve-in-valve reintervention due to structural valve deterioration (SVD) at 7 years of follow-up, determined using Kaplan–Meier (KM) analysis. We also evaluated a composite end-point of SVD and/or severe haemodynamic dysfunction requiring reintervention. Survival, valve-related safety events and haemodynamic performance were assessed. Deaths and safety events were adjudicated by an independent clinical events committee. RESULTS A total of 1132 patients underwent surgical AVR. Mean age was 70 years; 854 patients (75%) were men. The mean STS risk of mortality was 2.0 ± 1.4%, and 659 patients (58%) had a New York Heart Association classification of I/II. One or more concomitant procedures were performed in 577 patients (51%). At 7 years, the Kaplan–Meier rate of freedom from SVD/severe haemodynamic dysfunction requiring reintervention was 1.2% (0.5–2.5%) with no cases adjudicated as SVD. The survival rate was 82.6% (79.5–85.0%). The KM event rate was 5.7% (4.3–7.7%) for reintervention, 6.3% (4.9–8.3%) for endocarditis and 0.4% (0.1–1.1%) for valve thrombosis. Mean aortic gradient, dimensionless velocity index and effective orifice area were 13.8 ± 5.9 mmHg, 0.42 ± 0.09 and 1.99 ± 0.53 cm2, respectively. CONCLUSIONS This analysis demonstrated excellent durability of the Avalus valve with good clinical outcomes and stable haemodynamic performance through 7 years of follow-up.