BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS 2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Background The importance and specific role(s) of eosinophils in modulating the immune/inflammatory phenotype of allergic pulmonary disease remain to be defined. Established animals models assessing the role(s) of eosinophils as contributors and/or causative agents of disease have relied on congenitally deficient mice where the developmental consequences of eosinophil depletion are unknown. Methods We developed a novel conditional eosinophil-deficient strain of mice (iPHIL) through a gene knock-in strategy inserting the human diphtheria toxin (DT) receptor (DTR) into the endogenous eosinophil peroxidase genomic locus. Results Expression of DTR rendered resistant mouse eosinophil progenitors sensitive to DT without affecting any other cell types. The presence of eosinophils was shown to be unnecessary during the sensitization phase of either ovalbumin (OVA) or house dust mite (HDM) acute asthma models. However, eosinophil ablation during airway challenge led to a predominantly neutrophilic phenotype (>15% neutrophils) accompanied by allergen-induced histopathologies and airway hyperresponsiveness in response to methacholine indistinguishable from eosinophilic wild type mice. Moreover, the iPHIL neutrophilic airway phenotype was shown to be a steroid-resistant allergic respiratory variant that was reversible upon restoration of peripheral eosinophils. Conclusions Eosinophil contributions to allergic immune/inflammatory responses appear to be limited to the airway challenge and not the sensitization phase of allergen provocation models. The reversible steroid-resistant character of the iPHIL neutrophilic airway variant suggests underappreciated mechanisms by which eosinophils shape the character of allergic respiratory responses.

Supratentorial stroke presenting as contralateral hemiparesis is predominantly related to contralateral projection of the corticospinal tract. While most corticospinal fibers decussate at the level of the medulla, some tracts continue descending as ipsilateral ventral corticospinal fibers. In this systematic review of the literature and 2 case reports specifically seen in our institute, we describe the presence of ipsilateral hemiparesis in ischemic and hemorrhagic stroke patients. We compiled available information about the existence of uncrossed corticospinal tracts and/or the presence of bilateral operating motor cortical networks. There was an association in patients with congenital uncrossed corticospinal tracts and posterior fossa malformations. There was also a high correlation of ipsilateral hemiparesis in patients with remote infarction. A previous stroke was seen in 50% of the patients, all except for 1 case were ischemic in nature. Patients with previous infarcts do demonstrate an adaptive compensation for damaged or disconnected regions of an injured area. This emphasizes the need to consider the investigation for previous infarctions or underlying genetic structural defects by using certain imaging modality.

Patients diagnosed with acute pulmonary embolism (PE) are at an elevated risk for short-term mortality. An accurate prognostic model is important in guiding appropriate management. We aimed to use machine learning (ML) to predict 30-day all-cause mortality in patients diagnosed with acute PE. METHODS: 439 patients (48% men, 61AE15 years) diagnosed with acute PE at our institution were retrospectively analyzed. We included 101 variables from a range of domains including demographics, clinical, laboratory, echocardiographic, and CT imaging as candidate predictors. Machine learning algorithms including extreme gradient boosting (XGBoost), gradient boosting machine (GBM), random forest (RF), deep neural networks (DNN), and generalized linear models (GML) were evaluated on their classification performance and validated with 5-fold cross-validation. The PE severity index (PESI) and its simplified version (sPESI) were used as reference models. RESULTS: XGBoost was the best performing model in predicting 30-day all-cause mortality (AUC, 0.922 (95% confidence interval [

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