Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native ...South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations. A total of 1,011 individuals, representing 50 tribal populations from 81 settlements, were genotyped for up to 17 short tandem repeat (STR) markers and 16 single nucleotide polymorphisms (Y-SNPs), the latter resolving phylogenetic lineages Q and C. Virtually no structure became apparent for the extant Y-chromosomal genetic variation of South American males that could sensibly be related to their inter-tribal geographic and linguistic relationships. This continent-wide decoupling is consistent with a rapid peopling of the continent followed by long periods of isolation in small groups. Furthermore, for the first time, we identified a distinct geographical cluster of Y-SNP lineages C-M217 (C3*) in South America. Such haplotypes are virtually absent from North and Central America, but occur at high frequency in Asia. Together with the locally confined Y-STR autocorrelation observed in our study as a whole, the available data therefore suggest a late introduction of C3* into South America no more than 6,000 years ago, perhaps via coastal or trans-Pacific routes. Extensive simulations revealed that the observed lack of haplogroup C3* among extant North and Central American natives is only compatible with low levels of migration between the ancestor populations of C3* carriers and non-carriers. In summary, our data highlight the fact that a pronounced correlation between genetic and geographic/cultural structure can only be expected under very specific conditions, most of which are likely not to have been met by the ancestors of native South Americans.
Purpose
The aim of this study was to analyze sex differences in outcome after thrombectomy for acute ischemic stroke in clinical practice in a large prospective multicenter registry.
Methods
Data of ...consecutive stroke patients treated with thrombectomy (June 2015–April 2018) derived from an industry-independent registry (German Stroke Registry–Endovascular Treatment) were prospectively analyzed. Multivariable binary logistic regression analyses were applied to determine whether sex is a predictor of functional independence outcome (defined as a modified Rankin scale mRS 0–2) 90 days after stroke.
Results
In total, 2316 patients were included in the analysis, 1170 (50.5%) were female and 1146 (49.5%) were male. Women were older (median age 78 vs. 72 years;
p
< 0.001) and more frequently had a prestroke functional impairment defined by mRS >1 (24.8% vs. 14.1%;
p
< 0.001). In unadjusted analyses, independent outcome at 90 days was less frequent in women (33.2%) than men (40.6%;
p
< 0.001). Likewise, mortality was higher in women than in men (30.7% vs. 26.4%;
p
= 0.024). In adjusted regression analyses, however, sex was not associated with outcome. Lower age, a lower baseline National Institutes of Health Stroke Scale score, a higher Alberta Stroke Program Early CT score, prestroke functional independence, successful reperfusion, and concomitant intravenous thrombolysis therapy predicted independent outcome.
Conclusion
Women showed a worse functional outcome after thrombectomy for acute ischemic stroke in clinical practice; however, after adjustment for crucial confounders sex was not a predictor of outcome. The difference in outcome thus appears to result from differences in confounding factors such as age and prestroke functional status.
Public education campaigns are recommended to increase awareness for stroke. The effect of a public advertising and education campaign in an urban region in Germany was assessed and compared with a ...control region. We hypothesized that such a campaign would increase the number of patients being admitted by emergency medical services (EMS). A multimedia campaign and targeted education of health care professionals and the public was employed in Berlin during six consecutive months to disseminate knowledge about stroke symptoms and appropriate actions to take. Data on time to hospital admission and details on transport were retrieved from registries for the episode before, during, and after the campaign. To test the effect of the campaign, it was compared with another urban region in Germany (Ruhr-Area), where no campaign had been conducted. Between January 2010 and February 2011, 9,166 patients with stroke or transient ischemic attack (TIA) were documented in Berlin and 9,994 in the Ruhr-Area. In both regions, following the campaign period, patients were more often admitted to hospital within the first 2 hr after onset (Berlin: odds ratio OR = 1.16, 95% confidence interval CI = 1.02, 1.32; Ruhr-Area: OR = 1.18, 95% CI = 1.05, 1.34). Patients were more likely being admitted via EMS after the campaign (Berlin: OR = 1.71, 95% CI = 1.50, 1.94; Ruhr-Area: OR = 1.34, 95% CI = 1.17, 1.53). The results suggest that an increased uptake of EMS triggered shorter time to hospital admission. A reduction in delay to hospitalization and an increased uptake of EMS were observed over the study period for both regions. No effect of the campaign was identified.
Abstract Background Endovascular treatment (ET) options for acute stroke due to distal middle cerebral artery occlusions are rapidly evolving, but data on outcome and safety are sparse. We therefore ...performed an analysis of patients undergoing ET for primary M3 occlusions in routine clinical practice in a nationwide registry. Methods Patients enrolled between 01/20 and 12/21 in the prospective, multicenter German Stroke Registry-Endovascular Treatment (GSR-ET) were screened for mechanical thrombectomy performed for primary M3 occlusion. We analyzed neurological deficit as measured by the National Institute of Health Stroke Scale (NIHSS), symptomatic intracranial hemorrhage (sICH), thrombectomy technique, successful reperfusion (modified Thrombolysis in Cerebral Infarction mTICI score of 2b-3) and functional outcome as measured by the modified Rankin Scale (mRS) at discharge and 90 days. Results Out of 5574 patients, 11 patients (0.2%, median age 80 years, 54.5% female) underwent ET for primary M3 occlusion. All patients had pre-admission mRS ≤ 1, median NIHSS on admission was 8, and successful reperfusion was achieved in 6/11 patients (54.5%). While no vasospasm, dissection or perforation was reported, symptomatic intracranial hemorrhage occurred in 2 patients (18.2%). Favorable outcome (mRS ≤ 2) was achieved in 6/11 patients (54.5%) at 90-day follow-up. Conclusions ET for primary M3 occlusions is rarely performed. While technically feasible, the procedure’s potential benefits must be carefully weighed against its associated risks, including clinically relevant complications. Caution and further research is needed to optimize patient selection for this intervention. Trial Registration GSR-ET; ClinicalTrials.gov Identifier: NCT03356392; Trial Registration Date: 11/29/2017.
The Coronavirus Disease 2019 (COVID-19) pandemic may have altered emergency workflows established to optimize the outcome of patients with large-vessel occlusion (LVO) stroke.
We here analyzed ...workflow time intervals and functional outcomes of LVO patients treated with endovascular thrombectomy (ET) during the COVID-19 pandemic in Germany.
We compared the frequency, pre- and intrahospital workflow time intervals, rates of reperfusion, and functional outcome of patients admitted from March 1st to May 31st 2020 with patients admitted during the same time interval in 2019 to 12 university and municipal hospitals across Germany (
= 795).
The number of LVO patients treated with ET between March to May 2020 was similar when compared to the same interval in 2019. Direct-to-center patients and patients admitted through interhospital transfer in 2020 showed similar pre- and intrahospital workflow time intervals compared to patients admitted in 2019, except for a longer door-to-groin time in patients admitted through interhospital transfer in 2020 (47 min vs 38 min,
= 0.005). Rates of reperfusion were not significantly different between 2020 and 2019. Functional outcome at discharge of LVO patients treated in 2020 was not significantly different compared to patients treated in 2019.
Pre- and intrahospital workflows, ET efficacy, and functional outcome of LVO patients treated with ET were not affected during the COVID-19 pandemic in our large cohort from centers across Germany.
Abstract Studying the Y chromosomes of indigenous tribes of Ecuador revealed a lack of strategic SNP assays to examine the substructure of South American native populations. In most studies dealing ...with South American samples so far only the most common Y-SNP M3 of haplogroup Q was analyzed, because this is known to define a founder group in South America. Studies of SNPs ancestral to Q-M3 (Q1a3a) to confirm the results or the typing of Q subclades have often been neglected. For this reason we developed a SNaPshot assay, which allows first for a hierarchical testing of all main haplogroups occurring in South American populations and second for a detailed analysis of haplogroups Q and C thought having ancient Asian descent. We selected 16 SNPs from the YCC haplogroup tree and established two multiplexes. The first multiplex (“SA Major”) includes 12 Y-SNPs defining the most frequent haplogroups occurring in South America (M42, M207, M242, M168, M3, M145, M174, M213, RPS4Y711, M45, P170, and M9). The second multiplex (“SA SpecQ”) contains Y-SNPs of haplogroup Q, especially of the subclade Q-M3 (M19, M194, P292, M3, and M199). Within our Ecuadorian sample, haplogroup Q-M3 (xM19, M194, P292, and M199) was predominant, but we also found haplogroup E and R, which can be attributed to recent admixture. Moreover, we found four out of 65 samples, which were tested to be haplogroup C3* (C-M217) the modal haplogroup in Mongolians and widespread in indigenous populations of the Russian Far East as well as in Eastern Asia. This haplogroup is not known to be the result of recent admixture and has been found only one time before in South America. Since haplogroup C occurs in Asia and in North America (C3b or C-P39), we assume that these C-lineages are ancient as well. Therefore, we established a third multiplex (“SA SpecC”), which allows the further subtyping of haplogroup C, mainly of subclade C3 defined by the Y-SNP M217 (M407, M48, P53.1, M217, P62, RPS4Y711, M93, M86, and P39). Altogether, these three multiplexes cover the most frequent haplogroups in South America and allow for a maximal resolution of the Y-chromosomal SNP diversity in Amerindian population samples.
BACKGROUND AND PURPOSE—Endovascular treatment for large vessel occlusion in ischemic stroke has proven to be effective in large clinical trials. We aimed to provide real-world estimates of ...endovascular treatment reperfusion rates and functional outcome on a countrywide scale.
METHODS—Two thousand seven hundred ninety-four patients with large vessel occlusion were included into an investigator-initiated, industry-independent, prospective registry in 25 sites in Germany between June 2015 and April 2018. The primary outcome was the score on the modified Rankin Scale ranging from zero (no symptoms) to 6 (death) at 3 months. Secondary analyses included the prediction of a good outcome (modified Rankin Scale, 0–2). Dichotomized analyses of predictors were performed using logistic regression adjusted for potential confounders.
RESULTS—Median age was 75 years (interquartile range, 64–82); median National Institutes of Health Stroke Scale score was 15 (interquartile range, 10–19). Vessel occlusion was in the anterior circulation in 2265 patients (88%) and in the posterior circulation in 303 patients (12%). Intravenous alteplase before endovascular treatment was given in 1457 patients (56%). Successful reperfusion was achieved in 2143 subjects (83%). At 3 months, 854 patients (37%) showed a good outcome; mortality was 29%. There was no difference between anterior and posterior circulation occlusions (P=0.27). Significant predictors for a good outcome were younger age (odds ratio OR, 1.06; 95% CI, 1.05–1.07), no interhospital transfer (OR, 1.39; 95% CI, 1.03–1.88), lower stroke severity (OR, 1.10; 95% CI, 1.08–1.13), smaller infarct size (OR, 1.26; 95% CI, 1.15–1.39), alteplase use (OR, 1.49; 95% CI, 1.08–2.06), and reperfusion success (OR, 1.69; 95% CI, 1.45–1.96).
CONCLUSIONS—High rates of favorable outcome can be achieved on a countrywide scale by endovascular treatment. Mortality appears to be greater in the daily routine than otherwise reported by authors of large randomized trials. There were no outcome differences between the anterior and posterior circulation.
CLINICAL TRIAL REGISTRATION—URLhttps://www.clinicaltrials.gov. Unique identifierNCT03356392.
IMPORTANCE: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. OBJECTIVE: To determine the ...association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH. DESIGN, SETTING, AND PARTICIPANTS: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015). EXPOSURE: Surgical hematoma evacuation vs conservative treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH. RESULTS: Among 578 patients with cerebellar ICH, propensity score–matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio AOR, 0.94 95% CI, 0.81 to 1.09, P = .43; adjusted risk difference ARD, −3.7% 95% CI, −8.7% to 1.2%) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 95% CI, 1.07 to 1.45, P = .005; ARD, 18.5% 95% CI, 13.8% to 23.2%) and at 12 months (71.7% vs 57.2%; AOR, 1.21 95% CI, 1.03 to 1.42, P = .02; ARD, 17.0% 95% CI, 11.5% to 22.6%). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% P = .003; ARD, −34.7% −38.8% to −30.6%; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% P < .001; ARD, 28.2% 95% CI, 24.6% to 31.8%; P value for interaction, .02). CONCLUSIONS AND RELEVANCE: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.
Endovascular therapy is the standard of care in the treatment of acute ischemic stroke due to large-vessel occlusion. Often, more than one retrieval attempt is needed to achieve reperfusion. We aimed ...to quantify the influence of endovascular therapy on clinical outcome depending on the number of retrievals needed for successful reperfusion in a large multi-center cohort.
For this observational cohort study, 2611 patients from the prospective German Stroke Registry included between June 2015 and April 2018 were analyzed. Patients who received endovascular therapy for acute anterior circulation stroke with known admission National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score, final Thrombolysis in Cerebral Infarction score, and number of retrievals were included. Successful reperfusion was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. The primary outcome was defined as functional independence (modified Rankin Scale score of 0-2) at day 90. Multivariate mixed-effects models were used to adjust for cluster effects of the participating centers and confounders.
The inclusion criteria were met by 1225 patients. The odds of good clinical outcome decreased with every retrieval attempt required for successful reperfusion: the first retrieval had the highest odds of good clinical outcome (adjusted odds ratio, 6.45 95% CI, 4.0-10.4), followed by the second attempt (adjusted odds ratio, 4.56 95% CI, 2.7-7.7), and finally the third (adjusted odds ratio, 3.16 95% CI, 1.8-5.6).
Successful reperfusion within the first 3 retrieval attempts is associated with improved clinical outcome compared with patients without reperfusion. We conclude that at least 3 retrieval attempts should be performed in endovascular therapy of anterior circulation strokes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03356392.
Objective
To investigate parameters associated with hematoma enlargement in non–vitamin K antagonist oral anticoagulant (NOAC)‐related intracerebral hemorrhage (ICH).
Methods
This retrospective ...cohort study includes individual patient data for 190 patients with NOAC‐associated ICH over a 5‐year period (2011–2015) at 19 departments of neurology across Germany. Primary outcome was the association of prothrombin complex concentrate (PCC) administration with hematoma enlargement. Subanalyses were calculated for blood pressure management and its association with the primary outcome. Secondary outcomes include associations with in‐hospital mortality and functional outcome at 3 months assessed using the modified Rankin Scale.
Results
The study population for analysis of primary and secondary outcomes consisted of 146 NOAC‐ICH patients with available follow‐up imaging. Hematoma enlargement occurred in 49/146 (33.6%) patients with NOAC‐related ICH. Parameters associated with hematoma enlargement were blood pressure ≥ 160mmHg within 4 hours and—in the case of factor Xa inhibitor ICH—anti‐Xa levels on admission. PCC administration prior to follow‐up imaging was not significantly associated with a reduced rate of hematoma enlargement either in overall NOAC‐related ICH or in patients with factor Xa inhibitor intake (NOAC: risk ratio RR = 1.150, 95% confidence interval CI = 0.632–2.090; factor Xa inhibitor: RR = 1.057, 95% CI = 0.565–1.977), regardless of PCC dosage given or time interval until imaging or treatment. Systolic blood pressure levels < 160mmHg within 4 hours after admission were significantly associated with a reduction in the proportion of patients with hematoma enlargement (RR = 0.598, 95% CI = 0.365–0.978). PCC administration had no effect on mortality and functional outcome either at discharge or at 3 months.
Interpretation
In contrast to blood pressure control, PCC administration was not associated with a reduced rate of hematoma enlargement in NOAC‐related ICH. Our findings support the need of further investigations exploring new hemostatic reversal strategies for patients with factor Xa inhibitor–related ICH. Ann Neurol 2018;83:186–196
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