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Objective To assess whether eculizumab, a terminal complement inhibitor, improves patient‐ and physician‐reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods Patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open‐label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open‐label extension were analyzed. Results Of the 125 patients who participated in REGAIN, 117 enrolled in the open‐label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open‐label extension. Interpretation Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis.

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Evaluation of stroke etiology is an important aspect of stroke care affecting secondary prevention measures. Despite recent advances in diagnostic testing, determining the stroke etiology can remain a challenging task particularly for less common causes of stroke such as mitral annular calcification. This case will review the benefit of histopathological clot evaluation after thrombectomy to identify uncommon causes of embolic stroke which may change management.

Introduction: Patients with large vessel occlusion stroke (LVO) benefit from thrombolysis before thrombectomy. Previous meta-analysis suggested superiority of tenecteplase over alteplase in achieving good clinical outcome at 3 months. Aim: We aimed to compare clinical outcomes after tenecteplase 0.25 mg/kg versus alteplase in patients with LVO. Methods: An experienced librarian searched PubMed and Scopus databases through July 13, 2022 for randomized controlled trials comparing tenecteplase with alteplase in patients with LVO. We included trials using 0.25 mg/kg tenecteplase dose, reporting blindly assessed pre-specified clinical outcomes at 3-4 months among patients with LVO. Two authors independently reviewed eligibility and extracted the data. We used RevMan 5.4 and random effect models with inverse variance weights to calculate odds ratios (OR) and 95% confidence intervals (CI). This systematic review is registered (CRD42022349414). Results: From 585 retrieved abstracts, 3 trials and 1 pooled secondary analysis involving 704 unique patients met the inclusion criteria. Among patients with LVO, tenecteplase 0.25mg/kg is not superior to alteplase in achieving good clinical outcome (defined as modified Rankin Scale [mRS] 0-2, OR 1.82 (95% CI 0.91-3.65, panel A); nor all-cause mortality, OR 0.75 (95% CI 0.49-1.13, panel B); while tenecteplase increases the odds of excellent outcome (mRS 0-1), OR 1.52 (95% CI 1.11-2.09, panel C), and odds of functional improvement (defined as a shift on the ordinal mRS), OR 1.54 (95% CI 1.07-2.20, panel D). High heterogeneity was present (I2 =70%) for the good clinical outcome. Conclusion: Tenecteplase is not superior over alteplase in achieving good clinical outcome. Tenecteplase, as compared to alteplase, increases the odds of functional improvement and excellent outcome. These findings support bridging tenecteplase in patients with LVO.

Background: Mobile stroke units (MSU) have reduced time to thrombolysis, improved outcomes in ischemic stroke, but their sustainability and external costs have not been thoroughly evaluated. Fossil fuel combustion produces carbon dioxide (CO 2 ) and air pollution, which contribute to global climate crisis and excess mortality. Aim: To estimate the mortality cost of MSU due to increment of CO 2 and air pollution from fuel burned by MSU. Methods: Fuel cost of annual operation of MSU, obtained through correspondence, was used to obtain annual volume of gasoline burned by MSU. Estimate of excess global mortality between 2020 and 2100 from CO 2 -related climate change per increment of CO 2 was obtain from literature on the Mortality Cost of Carbon. Assuming the annual city-wide fuel consumption by road vehicles (publicly available) is directly proportional to excess mortality attributable to local traffic-related fine particulate matter (PM 2.5 ) air pollution (obtained from the literature), I estimated the increment of excess mortality related to air pollution produced by MSU operations. Results: Annual operation of one MSU burned 14.552 EUR of fuel, or 10.3 ton of gasoline, producing 24.7 ton of CO 2 . Such an increment of CO 2 in 2020 is expected to cause 0.0056 excess deaths (95% CI -0.0042, 0.0168) globally between 2020 and 2100 by contribution to climate crisis. In Berlin, mobile sources burn about 1.250.000 tons of liquid fossil fuel annually; and ~744 of annual deaths are attributable to traffic-related air pollution [2.17% (95% CI 1.55%, 2.79%) of total mortality]. Assuming the emission factor of MSU is the same as the local vehicle average, MSU-related air pollution leads to 0.0061 excess deaths (95% CI: 0.0044, 0.0079) per MSU-year. Conclusion: Fossil fuel combustion related to MSU operation is estimated to cause 0.0117 excess annual deaths (95% CI 0.0002, 0.0247) due to contribution to local air pollution and global climate crisis.

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Introduction: We aimed to quantify and trend excess cerebrovascular deaths among middle-aged adults that could be attributed to Black-white and rural-urban disparity in the US. Methods: Annual age-adjusted mortality rates (AAMR) for ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) among middle aged adults (ages 35-64) were obtained from Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research database from 1999 to 2019. AAMR difference between African-Americans and whites (Black-white disparity), as well as residents of Non-Metro and Large Metro counties (Rural-Urban disparity) was used to estimate excess event- and gender- specific annual deaths attributable to each disparity. Linear AAMR epochs and parallelism were assessed with Joinpoint. Results: Lives lost to Black-white disparity decreased from 3850 in 1999 to 2750 in 2013 and stagnated since. The finding was driven by decline in SAH and ICH mortality between 1999 and 2019, and recent increase in excess deaths due to IS (105 in 2014, 240 in 2019). Lives lost to Rural-urban disparity increased from 360 in 1999 to 740 in 2019, driven by excess deaths due to ICH (-30 in 1999, 100 in 2019) and recently IS (50 in 2013, 130 in 2019). Conclusion: Black-white disparity accounting for ~2750 excess deaths among blacks per year remains the leading inequity in cerebrovascular mortality. This is 3.7 times more deaths than Rural-Urban disparity in 2019.