BACKGROUND: Recent evidence suggests a correlation between modified Rankin Scale-based measures, an outcome measure commonly used in acute stroke trials, and mortality-based measures used by health agencies in the evaluation of hospital performance. We aimed to examine whether the 2 types of measures are interchangeable in relation to evaluation of hospital performance in acute ischemic stroke. METHODS: Five outcome measures, unfavorable functional outcome (3-month modified Rankin Scale score ≥2), death or dependency (3-month modified Rankin Scale score ≥3), 1-month mortality, 3-month mortality, and 1-year mortality, were collected for 8292 individuals who were hospitalized for acute ischemic stroke between January 2014 and May 2015 in 14 hospitals participating in the Clinical Research Collaboration for Stroke in Korea – National Institute of Health registry. Hierarchical regression models were used to calculate per-hospital risk-adjusted outcome rates for each measure. Hospitals were ranked and grouped based on the risk-adjusted outcome rates, and the correlations between the modified Rankin Scale-based and mortality-based ranking and their intermeasure reliability in categorizing hospital performance were analyzed. RESULTS: The comparison between the ranking based on the unfavorable functional outcome and that based on 1-year mortality resulted in a Spearman correlation coefficient of −0.29 and Kendall rank coefficient of −0.23, and the comparison of grouping based on these 2 types of ranks resulted in a weighted kappa of 0.123 for the grouping in the top 33%/middle 33%/bottom 33% and 0.25 for the grouping in the top 20%/middle 60%/bottom 20%, respectively. No significant correlation or similarity in grouping capacities were found between the rankings based on the functional outcome measures and those based on the mortality measures. CONCLUSIONS: This study shows that regardless of clinical correlation at an individual patient level, functional outcome-based measures and mortality-based measures are not interchangeable in the evaluation of hospital performance in acute ischemic stroke.

Obesity hypoventilation syndrome (OHS) is defined as the combination of daytime hypercapnia (awake PaCO2 ≥45 mm Hg) and obesity (body mass index ≥30 kg/m2). Untreated OHS is associated with comorbidities, including cardiovascular diseases, heart failure, pulmonary hypertension, and metabolic syndrome. Continuous positive airway pressure (PAP) therapy with non-invasive ventilation is the gold standard for treating OHS. PAP therapy is highly effective; however, some adverse effects can affect long-term compliance. Air leakage through the mouth or around a mask is a common adverse effect of PAP therapy. Air leakage through the nasolacrimal duct or due to unsealed circuits has also been reported as a complication of PAP therapy; however, it is relatively rare. Considering the negative association between the level of air leakage and adherence to PAP therapy, clarifying the cause of air leakage during PAP therapy and minimizing it are key to successful outcomes. We report a case of air leakage through the nasolacrimal duct that was improved by inserting a gel foam patch inside the lacrimal sac of a patient with OHS with a history of reconstructive surgery for nasolacrimal duct obstruction.

Background Aneurysmal subarachnoid hemorrhage (aSAH) causes systemic changes that contribute to delayed cerebral ischemia (DCI) and morbidity. Circulating metabolites reflecting underlying pathophysiological mechanisms warrant investigation as biomarker candidates. Methods Blood samples, prospectively collected within 24 hours (T1) of admission and 7-days (T2) post ictus, from patients with acute aSAH from two tertiary care centers were retrospectively analyzed. Samples from healthy subjects and patients with non-neurologic critical illness served as controls. A validated external analysis platform was used to perform untargeted metabolomics. Bioinformatics analyses were conducted to identify metabolomic profiles defining each group and delineate metabolic pathways altered in each group. Machine learning (ML) models were developed incorporating key metabolites to improve DCI prediction. Results Among 70 aSAH, 30 healthy control, and 17 sick control subjects, a total of 1,117 metabolites were detected. Groups were matched among key clinical variables. DCI occurred in 36% of aSAH subjects, and poor functional outcome was observed in 70% at discharge. Metabolomic profiles readily discriminated the groups. aSAH subjects demonstrated a robust mobilization of lipid metabolites, with increased levels of free fatty acids (FFAs), mono- and diacylglycerols (MAG, DAG) compared with both control groups. aSAH subjects also had decreased circulating amino acid derived metabolites, consistent with increased catabolism. DCI was associated with increased sphingolipids (sphingosine and sphinganine) and decreased acylcarnitines and S- adenosylhomocysteine at T1. Decreased lysophospholipids and acylcarnitines were associated with poor outcomes. Incorporating metabolites into ML models improved prediction of DCI compared with clinical variables alone. Conclusions Profound metabolic shifts occur after aSAH with characteristic increases in lipid and decreases in amino acid metabolites. Key lipid metabolites associated with outcomes (sphingolipids, lysophospholipids, and acylcarnitines) provide insight into systemic changes driving secondary complications. These metabolites may also prove to be useful biomarkers to improve prognostication and personalize aSAH care.

Mutation of KRAS in endothelial cells (KRAS-ECs) leads to intracerebral hemorrhage (ICH) in brain arteriovenous malformation (bAVM), resulting in severe disabilities or even death. However, it is unclear what causes this hemorrhagic conversion of bAVMs. Here, using a locally established, clinically relevant sporadic bAVM mouse model, created by overexpressing mutant KRAS (KRAS ^G12V ) in brain ECs, we demonstrate that KRAS-ECs act as trigger for activation of microglia (MG) and infiltration of macrophages (Mϕ). Using a 3-dimensional immunostaining approach with cleared human and mouse bAVM tissues, we demonstrate an abundance of MG/Mϕ around the bAVM nidus. The presence of MG/Mϕ was correlated to the blood-brain barrier leakage in bAVM areas. Time-lapsed intravital imaging in Cx3cr1-gfp;Ccr2-rfp reporter mice demonstrated the dynamic activation of MG and infiltration of Mϕ toward mutant KRAS ^G12V –modified dysplastic vessels. Importantly, a time-course analysis showed that these activated MG and infiltrated Mϕ are present around the bAVMs prior to hemorrhagic conversion, and controlled depletion of MG/Mϕ reduced ICH incidence in bAVMs. Inhibition of MG/Mϕ with long-term minocycline treatment attenuated the incidence of ICHs around bAVMs. Our study indicates that MG/Mϕ are involved in destabilization of KRAS ^G12V -induced bAVM, leading to hemorrhagic conversion/ICH. Thus, modulation of MG/Mϕ may reduce ICH risk in patients with bAVM.

Obstructive sleep apnea (OSA) and atrial fibrillation (AF) are associated with increased morbidity and mortality. OSA and AF share multiple risk factors, including hypertension, cardiovascular disorders, congestive heart failure, and metabolic syndrome. Although the two conditions are likely to have a bidirectional association, recent studies have suggested that OSA contributes to the development of AF through direct mechanical effects on cardiac remodeling. We report a patient with severe OSA showing immediate conversion of AF to normal sinus rhythm with optimal continuous positive airway pressure (CPAP) therapy. This supports that OSA may lead to AF, which can be effectively reversed with CPAP therapy.

Introduction Delayed cerebral ischemia (DCI) is a potentially preventable complication from an aneurysmal subarachnoid hemorrhage (SAH). The micro-RNAs (miR) 34 family has shown its ability to disrupt the blood-brain barrier and redox metabolism and might contribute to the complex pathophysiology of DCI. This study aimsto evaluate the association between the serum levels of miR-34c and the occurrence of DCI. Methods This retrospective observational study is based on 72 subjects with acute aneurysmal SAH who were admitted to a single tertiary center between December 2017 and July 2021. Subjects were prospectively adjudicated for clinical outcomes, including delayed cerebral ischemia.Levels of miR-34c were measured in plasma collected within 48 hours of ictus. Patients were median-dichotomized into having a higher or lower plasma level of miR-34c. miR34c levels were compared between DCI and no DCI groups using the Wilcoxon rank sum tests. A multivariable logistic regression model and the Cox proportional hazard model were used to evaluate the effect of higher miR-34c levels. Results The median age was 54 years, 76% were females, and 21% developed DCI. Early miR-34c levels were significantly higher in SAH subjects who progressed to have DCI with Cohen’s d of 0.75 (p<0.05). Even after adjusting for age, sex, histories of diabetes, hypertension, Hunt-Hess grade, and modified Graeb scores, a higher miR-34c level was associated with 5.7-fold increased odds of DCI (p<0.05; 95% CI: 1.35-32.22). Survival analysis adjusting for the known predictors also revealeda 5.4-fold higher hazard of DCI for the patients with a higher miR-34c level (p < 0.05; 95% CI 1.22-25.43). Conclusion The present study demonstrates the potential importance of circulating miR-34c in predicting DCI in SAH patients. Given the known importance of the miR-34 family in vascular physiology, it may be an important target for future studies.