David Gordon

Background and Purpose While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. Methods We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer’s exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. Results During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. Conclusion We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) has helped many patients achieve functional independence. The effect of time‐to‐treatment based in specific epochs and as related to Alberta Stroke Program Early CT Score (ASPECTS) has not been established. The goal of the study was to evaluate the association between last known normal (LKN)‐to‐puncture time and good functional outcome.METHODS: We conducted a retrospective cohort study of prospectively collected acute ischemic stroke patients undergoing MT for large vessel occlusion. We used binary logistic regression models adjusted for age, Modified Treatment in Cerebral Ischemia score, initial National Institutes of Health Stroke Scale, and noncontrast CT ASPECTS to assess the association between LKN‐to‐puncture time and favorable outcome defined as Modified Rankin Score 0‐2 on discharge.RESULTS: Among 421 patients, 328 were included in analysis. Increased LKN‐to‐puncture time was associated with decreased probability of good functional outcome (adjusted odds ratio [aOR] ratio per 15‐minute delay = .98; 95% confidence interval [CI], .97‐.99; P = .001). This was especially true when LKN‐puncture time was 0‐6 hours (aOR per 15‐minute delay = .94; 95% CI, .89‐.99; P = .05) or ASPECTS 8‐10 (aOR = .98; 95% CI, .97‐.99; P = .002) as opposed to when LKN‐puncture time was 6‐24 hours (aOR per 15‐minute delay = .99; 95% CI, .97‐1.00; P = .16) and ASPECTS P = .37).CONCLUSION: Decreased LKN‐groin puncture time improves outcome particularly in those with good ASPECTS presenting within 6 hours. Strategies to decrease reperfusion times should be investigated, particularly in those in the early time window and with good ASPECTS.

Background: There is limited data on predictors of sICH in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. Methods: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke center over a 30-month period. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH to identify independent predictors of sICH with p<0.1. We then derived an sICH prediction score and validated it using the Blood Pressure After Endovascular Treatment (BEST) multicenter prospective registry. Results: We identified 578 patients with acute ischemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: Thrombolysis in cerebral ischemia score, Alberta stroke program early computed tomography score (ASPECTS), and Glucose level, and using these predictors, we derived the weighted TAG score which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48-2.66, AUC=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22-1.79, AUC=0.69) cohorts. Conclusion: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

Background: There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation.Methods: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke centre over a 30-month period. Clinical and radiographic data on these patients were obtained from the prospective quality improvement database. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH using χ² and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry.Results: We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts.Conclusion: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.

Introduction Belimumab, an anti-B-lymphocyte-stimulator antibody, is approved for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE). Rituximab, a B cell-depleting anti-CD20 antibody, remains in the SLE treatment armamentarium despite failed trials in lupus nephritis and extrarenal lupus. These biologics, which operate through complementary mechanisms, might result in an enhanced depletion of circulating and tissue-resident autoreactive B lymphocytes when administered together. Thus, belimumab and rituximab combination may be a highly effective treatment of SLE. This study aims to evaluate and compare the efficacy, safety and tolerability of subcutaneous (SC) belimumab and a single cycle of rituximab in patients with SLE with belimumab alone. Methods and analysis BLISS-BELIEVE is a three-arm, randomised, double-blind, placebo-controlled, 104-week superiority study. Two hundred adults with SLE will be randomised 1:2:1 to arm A, belimumab SC 200 mg/week for 52 weeks plus placebo at weeks 4 and 6; arm B, belimumab SC 200 mg/week for 52 weeks plus rituximab 1000 mg at weeks 4 and 6; arm C, belimumab SC 200 mg/week plus standard of care for 104 weeks. The 52-week treatment period (arms A and B) is followed by a 52-week observational phase. The primary efficacy endpoint is the proportion of patients with disease control (SLE Disease Activity Index (SLEDAI)−2K≤2, without immunosuppressants and with a prednisone-equivalent dose of ≤5 mg/day) at week 52. Major secondary efficacy endpoints are the proportion of patients in clinical remission (defined as SLEDAI-2K=0, without immunosuppressants and corticosteroids) at week 64, and the proportion of patients with disease control at week 104. Safety endpoints include the incidence of adverse events (AEs), serious AEs and AEs of special interest. Ethics and dissemination Within 6 months of the study’s primary manuscript publication, anonymised individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. Trial registration number NCT03312907; Pre-results.

Objective The Systemic Lupus Erythematosus (SLE) Responder Index (SRI), developed as a primary outcome measure for use in clinical trials, captures improvement in SLE disease activity without concomitant worsening in disease manifestations. This study investigated the relationships between the SRI and clinical/laboratory correlates of SRI response in patients with SLE. Methods This was a post-hoc analysis of the phase III, double-blind, placebo-controlled study of subcutaneous BeLimumab in Subjects with Systemic lupus erythematosus - SubCutaneous (BLISS-SC). Patients were randomised to weekly belimumab 200 mg subcutaneously or placebo, plus standard SLE therapy. Changes from baseline to week 52 in clinical and laboratory parameters were compared among SRI responders and non-responders, irrespective of the treatment received. Results SRI responders (n=475) had significantly better (pConclusion SRI response is associated with improvements in clinical and laboratory measures, strengthening its value as a clinically meaningful primary endpoint in clinical trials.