The benefit of mechanical thrombectomy (MT) in patients with stroke presenting with mild deficits (National Institutes of Health Stroke Scale [NIHSS] score <6) owing to emergency large-vessel occlusion (ELVO) remains uncertain. OBJECTIVE To assess the outcomes of patients with mild-deficits ELVO (mELVO) treated with MT vs best medical management (bMM). DATA SOURCES We retrospectively pooled patients with mELVO during a 5-year period from 16 centers. A meta-analysis of studies reporting efficacy and safety outcomes with MT or bMM among patients with mELVO was also conducted. Data were analyzed between 2013 and 2017. STUDY SELECTION We identified studies that enrolled patients with stroke (within 24 hours of symptom onset) with mELVO treated with MT or bMM. MAIN OUTCOMES AND MEASURES Efficacy outcomes included 3-month favorable functional outcome and 3-month functional independence that were defined as modified Rankin Scale scores of 0 to 1 and 0 to 2, respectively. Safety outcomes included 3-month mortality and symptomatic and asymptomatic intracranial hemorrhage (ICH). RESULTS We evaluated a total of 251 patients with mELVO who were treated with MT (n = 138; 65 women; mean age, 65.2 years; median NIHSS score, 4; interquartile range [IQR], 3-5) or bMM (n = 113; 51 women; mean age, 64.8; median NIHSS score, 3; interquartile range [IQR], 2-4). The rate of asymptomatic ICH was lower in bMM (4.6% vs 17.5%; P = .002), while the rate of 3-month FI (after imputation of missing follow-up evaluations) was lower in MT (77.4% vs 88.5%; P = .02). The 2 groups did not differ in any other efficacy or safety outcomes. In multivariable analyses, MT was associated with higher odds of asymptomatic ICH (odds ratio [OR], 11.07; 95% CI, 1.31-93.53; P = .03). In the meta-analysis of 4 studies (843 patients), MT was associated with higher odds of symptomatic ICH in unadjusted analyses (OR, 5.52; 95% CI, 1.91-15.49; P = .002; I 2 = 0%). This association did not retain its significance in adjusted analyses including 2 studies (OR, 2.06; 95% CI, 0.49-8.63; P = .32; I 2 = 0%). The meta-analysis did not document any other independent associations between treatment groups and safety or efficacy outcomes. CONCLUSIONS AND RELEVANCE Our multicenter study coupled with the meta-analysis suggests similar outcomes of MT and bMM in patients with stroke with mELVO, but no conclusions about treatment effect can be made. The clinical equipoise can further be resolved by a randomized clinical trial.
Background and purpose: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischaemic stroke (AIS) patients with large vessel or distal occlusions and mild neurological deficits, defined as National Institutes of Health Stroke Scale scores < 6 points. Methods: The primary efficacy outcome was 3-month functional independence (FI) [modified Rankin Scale (mRS) scores 0-2] that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included 3-month favorable functional outcome (mRS scores 0-1) and mRS score distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. Results: We evaluated 336 AIS patients with large vessel or distal occlusions and mild stroke severity (mean age 63 AE 15 years, 45% women). Patients treated with IVT (n = 162) had higher FI (85.6% vs. 74.8%, P = 0.027) with lower mRS scores at hospital discharge (P = 0.034) compared with the remaining patients. No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality. IVT was associated with higher likelihood of 3-month FI [odds ratio (OR), 2.19; 95% confidence intervals (CI), 1.09-4.42], 3-month favorable functional outcome (OR, 1.99; 95% CI, 1.10-3.57), functional improvement at discharge [common OR (per 1-point decrease in mRS score), 2.94; 95% CI, 1.67-5.26)] and at 3 months (common OR, 1.72; 95% CI, 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders, including mechanical thrombectomy. Conclusions: Intravenous thrombolysis is independently associated with higher odds of improved discharge and 3-month functional outcomes in AIS patients with large vessel or distal occlusions and mild stroke severity. IVT appears not to increase the risk of systemic or symptomatic intracranial bleeding.
Length-dependent activation of calcium-dependent myocardial force generation provides the basis for the Frank-Starling mechanism. To directly compare the effects of mutations associated with hypertrophic cardiomyopathy and dilated cardiomyopathy, the native troponin complex in skinned trabecular fibers of guinea pigs was exchanged with recombinant heterotrimeric, human, cardiac troponin complexes containing different human cardiac troponin T subunits (hcTnT): hypertrophic cardiomyopathyassociated hcTnT R130C , dilated cardiomyopathy-associated hcTnT K210 or the wild type hcTnT (hcTnT WT) serving as control. Force-calcium relations of exchanged fibers were explored at short fiber length defined as 110% of slack length (L 0) and long fiber length defined as 125% of L 0 (1.25 L 0). At short fiber length (1.1 L 0), calcium sensitivity of force generation expressed by −log [Ca 2+ ] required for half-maximum force generation (pCa 50) was highest for the hypertrophic cardiomyopathy-associated mutation R130C (5.657 ± 0.019), intermediate for the wild type control (5.580 ± 0.028) and lowest for the dilated cardiomyopathy-associated mutation K210 (5.325 ± 0.038). Lengthening fibers from 1.1 L 0 to 1.25 L 0 increased calcium sensitivity in fibers containing hcTnT R130C (delta-pCa 50 = +0.030 ± 0.010), did not alter calcium sensitivity in the wild type control (delta-pCa 50 = −0.001 ± 0.010), and decreased calcium sensitivity in fibers containing hcTnT K210 (delta-pCa 50 = −0.034 ± 0.013). Length-dependent activation indicated by the delta-pCa 50 was highly significantly (P < 0.001) different between the two mutations. We hypothesize that primary effects of mutations on length-dependent activation contribute to the development of the diverging phenotypes in hypertrophic and dilated cardiomyopathy.
Introduction: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) and mild neurological deficits defined as National Institutes of Health Stroke Scale scores <6 points (mELVO). Methods: The primary efficacy outcome was three-month functional independence (FI; mRS-scores of 0-2) that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included three-month favorable functional outcome (FFO; mRS-scores of 0-1) and mRS-scores distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. Results: We evaluated 336 AIS patients with mELVO (mean age: 63±15 years, 45% women). Patients treated with IVT (n=162) had higher FI (85.6% vs. 74.8%, p=0.027) with lower mRS scores at hospital discharge (p=0.034) compared to the rest. Three-month mRS-scores tended to be lower in the IVT group (p=0.069). No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality (p>0.1). IVT was associated with higher likelihood of 3-month FI (OR=2.19, 95%CI: 1.09-4.42), 3-month FFO (OR=1.99, 95%CI: 1.10-3.57) and functional improvement at discharge [cOR (per 1-point decrease in mRS-score)=2.94, 95%CI: 1.67-5.26] and at 3 months (cOR=1.72, 95%CI: 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders including mechanical thrombectomy. Conclusion: IVT is independently associated with higher odds of improved discharge and three-month functional outcomes in AIS patients with mELVO. IVT does not increase the risk of systemic or intracranial bleeding.
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