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  • 1
    In: Molecular Syndromology, S. Karger AG, Vol. 6, No. 5 ( 2015), p. 210-221
    Abstract: We present 2 cases with multiple de novo supernumerary marker chromosomes (sSMCs), each derived from a different chromosome. In a prenatal case, we found mosaicism for an sSMC(4), sSMC(6), sSMC(9), sSMC(14) and sSMC(22), while a postnatal case had an sSMC(4), sSMC(8) and an sSMC(11). SNP-marker segregation indicated that the sSMC(4) resulted from a maternal meiosis II error in the prenatal case. Segregation of short tandem repeat markers on the sSMC(8) was consistent with a maternal meiosis I error in the postnatal case. In the latter, a boy with developmental/psychomotor delay, autism, hyperactivity, speech delay, and hypotonia, the sSMC(8) was present at the highest frequency in blood. By comparison to other patients with a corresponding duplication, a minimal region of overlap for the phenotype was identified, with 〈 i 〉 CHRNB3 〈 /i 〉 and 〈 i 〉 CHRNA6 〈 /i 〉 as dosage-sensitive candidate genes. These genes encode subunits of nicotinic acetylcholine receptors (nAChRs). We propose that overproduction of these subunits leads to perturbed component stoichiometries with dominant negative effects on the function of nAChRs, as was shown by others in vitro. With the limitation that in each case only one sSMC could be studied, our findings demonstrate that different meiotic errors lead to multiple sSMCs. We relate our findings to age-related aneuploidy in female meiosis and propose that predivision sister-chromatid separation during meiosis I or II, or both, may generate multiple sSMCs.
    Type of Medium: Online Resource
    ISSN: 1661-8769 , 1661-8777
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2015
    detail.hit.zdb_id: 2546218-0
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  • 2
    In: Clinical Neuroradiology, Springer Science and Business Media LLC, Vol. 31, No. 3 ( 2021-09), p. 799-810
    Abstract: To provide real-world data on outcome and procedural factors of late thrombectomy patients. Methods We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS  ≤  2). Results Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n  = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients ( p  = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. Conclusion In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.
    Type of Medium: Online Resource
    ISSN: 1869-1439 , 1869-1447
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2232347-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 8 ( 2022-08), p. 2528-2537
    Abstract: Strokes in the working-age population represent a relevant share of ischemic strokes and re-employment is a major factor for well-being in these patients. Income differences by sex have been suspected a barrier for women in returning to paid work following ischemic stroke. We aim to identify predictors of (not) returning to paid work in patients with large vessel occlusion treated with mechanical thrombectomy (MT) to identify potential areas of targeted vocational rehabilitation. Methods: From 6635 patients enrolled in the German Stroke Registry Endovascular Treatment between 2015 and 2019, data of 606 patients of the working population who survived large vessel occlusion at least 90 days past MT were compared based on employment status at day 90 follow-up. Univariate analysis, multiple logistic regression and analyses of area under the curve were performed to identify predictors of re-employment. Results: We report 35.6% of patients being re-employed 3 months following MT (median age 54.0 years; 36.1% of men, 34.5% of women [ P =0.722]). We identified independent negative predictors against re-employment being female sex (odds ratio [OR] , 0.427 [95% CI, 0.229–0.794]; P =0.007), higher National Institutes of Health Stroke Scale (NIHSS) score 24 hours after MT (OR, 0.775 [95% CI, 0.705–0.852]; P 〈 0.001), large vessel occlusion due to large-artery atherosclerosis (OR, 0.558 [95% CI, 0.312–0.997]; P =0.049) and longer hospital stay (OR, 0.930 [95% CI, 0.868–0.998]; P =0.043). Positive predictors favoring re-employment were excellent functional outcome (modified Rankin Scale score of 0–1) at 90 day follow-up (OR, 11.335 [95% CI, 4.864–26.415] ; P 〈 0.001) and combined treatment with intravenous thrombolysis (OR, 1.904 [95% CI, 1.046–3.466]; P =0.035). Multiple regression modeling increased predictive power of re-employment status significantly over prediction by best single functional outcome parameter (National Institutes of Health Stroke Scale 24 hours after MT ≤5; R 2 : 0.582 versus 0.432; area under the receiver operating characteristic curve: 0.887 versus 0.835, P 〈 0.001). Conclusions: There is more to re-employment after MT than functional outcome alone. In particular, attention should be paid to possible systemic barriers deterring women from resuming paid work. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03356392.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 4 ( 2021-04), p. 1265-1275
    Abstract: Tandem lesions in the anterior circulation account for up to 30% of all large vessel occlusion strokes. The optimal periprocedural approach in these lesions is still a matter of debate. Methods: Data from the German Stroke Registry—Endovascular Treatment between June 2015 and December 2019 were analyzed. The German Stroke Registry—Endovascular Treatment is an academic, independent, prospective, multicenter, observational registry study with 25 participating stroke centers from all over Germany enrolling consecutive mechanical thrombectomy patients. Tandem lesions were defined as a combination of a relevant extracranial internal carotid artery (ICA) pathology (ipsilateral stenosis 〉 70% or occlusion) and concomitant intracranial large vessel occlusion. Successful reperfusion was defined as modified Thrombolysis in Cerebral Infarction score of 2b-3. The modified Rankin Scale score of 0 to 2 at 3 months indicated good outcome. The aim of this study was to investigate the safety and efficacy of different technical strategies in tandem lesions. Results: Out of 6635 patients, 874 (13.2%) presented with tandem lesions. Of these, 607 (69.5%) underwent acute treatment of the extracranial ICA. Acute treatment of the extracranial ICA lesion led to a higher probability of successful reperfusion (odds ratio, 40.63 [95% CI, 30.03–70.06]) compared with patients who did not undergo acute treatment of the extracranial ICA lesion and was associated with good clinical outcome (39.5% versus 29.3%, P 〈 0.001) and a lower rate of mortality (17.1% versus 27.1%, P 〈 0.001) at 3 months. Further significant predictors of successful reperfusion were age (odds ratio, 0.98 [95% CI, 0.96–0.99]; P =0.035) and intravenous thrombolysis (odds ratio, 10.58 [95% CI, 10.04–20.4]; P =0.033). Intracranial-first approach (n=227) compared with extracranial-first approach (n=267) resulted in a shorter time to flow restoration (53.5 versus 72.0 minutes, P 〈 0.001) and a higher nonsignificant probability of good outcome (45.8% versus 33.0%, P =0.24) without differences in periprocedural complications. Conclusions: In tandem lesions in the anterior circulation, acute treatment of the extracranial ICA lesion is associated with better clinical outcome and lower mortality. The intracranial-first approach might provide advantages.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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