Yale University

Left ventricular (LV) dysfunction is a potential cardioembolic source of ischemic stroke, but its role in recurrent stroke risk and treatment response remains unclear. We explore whether LV injury associates with the risk of recurrent stroke and modifies the association between anticoagulation and stroke recurrence using real-world data. We performed a multicenter, retrospective study of Cardiac Abnormalities in Stroke Prevention and Recurrence cohort across 27 US sites. Patients with LV ejection fraction ≥20% were included. LV injury, defined as LV ejection fraction 20% to 40% and wall motion abnormality, was the primary exposure and treatment effect modifier. The treatment of interest was anticoagulant versus antiplatelet therapy. The composite outcome included recurrent stroke, major bleeding, or death. Outcomes were evaluated using unadjusted and inverse probability weighting adjusted Cox proportional hazards models, with treatment effect modification tested by LV injury status. Among 2685 patients enrolled, 2328 with complete data were analyzed (median age, 65 years; 49.8% female; median follow-up, 1.6 years). LV injury was present in 310 patients (13.3%). Overall, 535 events occurred: 258 recurrent ischemic strokes, 28 hemorrhagic strokes, 67 major hemorrhages, and 256 deaths. LV injury was associated with a higher unadjusted risk of the primary outcome (hazard ratio [HR], 1.51 [95% CI, 1.21-1.87]), though nonsignificant after inverse probability weighting adjustment (adjusted HR, 1.29 [95% CI, 0.97-1.70]). In the LV injury subgroup, anticoagulation versus antiplatelet therapy was associated with a lower risk of the primary outcome (adjusted HR, 0.24 [95% CI, 0.10-0.59]), relative to the non-LV injury subgroup (adjusted HR, 1.28 [95% CI, 0.83-1.95]; p[LV-interaction], 0.001). Similar interactions were seen for EF 20% to 40% (versus >40%; adjusted HR, 0.19 [95% CI, 0.04-0.86]; p[LV-interaction], 0.001) and wall motion abnormality (versus no wall motion abnormality; adjusted HR, 0.33 [95% CI, 0.15-0.73]). After cryptogenic stroke, anticoagulation in those with LV injury was associated with lower rates of recurrent stroke, major bleeding, and death. These findings warrant confirmation in a dedicated randomized controlled trial. URL: https://www.clinicaltrials.gov; Unique identifier: NCT06398366.

Postictal deficits are a well-recognized phenomenon, yet their mechanisms and predictors remain poorly understood. Distinguishing postictal deficits from recurring nonconvulsive seizures (NCSz) or nonconvulsive status epilepticus (NCSE), their main differential diagnosis, can be challenging. This study aimed to identify clinical and electrographic features predictive of ongoing or recurrent ictal activity and to explore biomarkers associated with the duration and severity of postictal deficits. We conducted a retrospective case-control study of patients with prolonged (>1 h) postictal deficits at a tertiary medical center between 2017 and 2022. Based on electroencephalographic (EEG) findings, patients were classified as having uncomplicated Todd's palsy or recurring NCSz. Clinical, imaging, and electrographic characteristics were compared between groups, and factors associated with postictal duration were analyzed. Among 112 patients, 86 (77%) had uncomplicated Todd's palsy and 26 (23%) had recurring NCSz. Patients with NCSz were younger (63 vs. 76 years, p = .022) and had longer deficits (2.5 vs. 1.5 days, p = .024). Sporadic epileptiform discharges (73% vs. 22%, p < .001) and rhythmic or periodic discharges on the ictal-interictal continuum (50% vs. 16%, p = .001) were significantly more frequent in the NCSE group, even when limited to short EEGs or the first 30 min of continuous EEG (96% vs. 40%, p < .001). Consequently, 2HELPS2B scores were higher in NCSE patients (2 vs. 1, p = .0065). In the uncomplicated Todd's palsy group, a preceding focal to bilateral tonic-clonic seizure (1.5 vs. 1.0 days, p = .04) and any rhythmic or periodic discharges on EEG (3.0 vs. 1.5 days, p = .003) were associated with longer deficit duration. A notable minority of patients with prolonged postictal deficits have recurring NCSz. In the absence of reliable clinical or imaging predictors, patients with prolonged deficits may benefit from a 30-min EEG followed-when 2HELPS2B score > 1-by extended continuous EEG monitoring.

The study goal was to evaluate the outcomes associated with albumin use in children with sepsis and shock compared with those without shock, using causal inference analysis in a multicenter cohort. This was a secondary analysis of electronic health record data collected from 13 U.S. PICUs between 2012 and 2018, consisting of children younger than 18 years who met Phoenix sepsis criteria within the first 24 hours of PICU admission. Covariate-balancing propensity score weighting was applied to adjust for indication bias in the albumin use. Patients receiving at least 0.5 g/kg albumin within 24 hours of PICU admission were assigned to the albumin group; others to the control. Only 24-hour survivors were included to address immortal time bias. Overall, 17,307 children with sepsis survived at least 24 hours. Of these, 1,344 patients (7.8%) who received albumin within the first 24 hours, and 9,678 (55.9%) met the criteria for septic shock. A significant interaction between albumin use and shock status was observed (interaction: -0.353, p = 0.007), with albumin administration in pediatric septic shock patients associated with lower in-hospital mortality: odds ratio equals to 0.698 (95% CI, 0.629-0.774), risk ratio equals to 0.746 (95% CI, 0.625-0.891), and hazard ratio equals to 0.688 (95% CI, 0.558-0.848). In contrast, there was no difference in outcomes between the albumin and control groups in the non-shock group. Early albumin administration was associated with improved outcomes in children with septic shock, but not in those without shock. These results highlight the importance of considering clinical heterogeneity, such as the presence of shock, in identifying treatment-responsive subgroups and enabling more targeted interventions in pediatric sepsis. Further prospective validation is warranted.