Publications by authors named "Timo Siepmann"

103 Publications

Strength of clinical evidence leading to approval of novel cancer medicines in Europe: A systematic review and data synthesis.

Pharmacol Res Perspect 2021 Aug;9(4):e00816

Division of Healthcare Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany.

We aimed to evaluate the quality of clinical evidence that substantiated approval of cancer medicines by the European Medicines Agency (EMA) in the last decade. We performed a systematic review and data synthesis of EMA documents in agreement with PRISMA guidelines. We included the European Public Assessment Reports, Summaries of Product Characteristics, and published randomized controlled trials (RCTs) on anti-cancer drugs approved by EMA from 2010 to 2019, and excluded drugs not indicated for targeting solid or hematological tumors and non-innovative treatments. We synthesized frequencies of approvals differentiating between unblinded and blinded RCTs with and without overall survival (OS) as a predefined primary outcome measure. We assessed the frequency of post-approval RCTs for indications without at least one RCT at the time of approval. Of 199 approvals, 159 (80%) were supported by at least one RCT, 63 (32%) by at least one RCT having OS as the primary or co-primary endpoint, 74 (37%) by at least one blinded RCT, and 30 (15%) by at least one blinded RCT having OS as the primary or co-primary endpoint. Whereas 40 approvals (20%) were not supported by any RCT and, of those, 9 (22%) were followed by a post-approval RCT. While the majority of approvals of cancer medicines approved by EMA was supported by at least one RCT, we noted substantial methodological heterogeneity of the studies. Clinical trial registration: PROSPERO registration number CRD42020206669.
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http://dx.doi.org/10.1002/prp2.816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262606PMC
August 2021

Case Report: Eighteen Month Relapse- Free Survival Following Radical Multidisciplinary Oncological Treatment in a 68-Year-Old Male Patient With Histiocytic Sarcoma.

Front Oncol 2021 7;11:633215. Epub 2021 Jun 7.

Department of General and Visceral Surgery, Klinikum Chemnitz gemeinnützige Gesellschaft mit beschränkter Haftung (gGmbH), Chemnitz, Germany.

Introduction: Histiocytic Sarcoma (HS) is a rare and aggressive malignancy, and patients can present with rapid tumor growth and invasion. The optimal diagnostic and therapeutic management is unknown since only a few cases have been published. Here we report a patient with histiocytic sarcoma of the right groin.

Case: A 68 year-old male patient presented to our hospital with suspicion of a superinfected atheroma of the right groin. Computed tomography showed an abdominal tumor of unknown entity. Detailed assessment including immunohistochemically evaluation of biopsy material confirmed HS. The patient underwent radical tumor resection including compartment-resection of the right thigh. During five additional cycles of chemotherapy over a period of 1.5 years he remained relapse-free.

Summary: Diagnostic work up and treatment of HS is challenging, as there is a paucity of clinical reports and lack of standard guidelines for care. In the present case report, aggressive multidisciplinary treatment resulted in good clinical outcome, however, further studies evaluating this approach in similar patients are needed.
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http://dx.doi.org/10.3389/fonc.2021.633215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215356PMC
June 2021

Randomized Sham-Controlled Pilot Study of Neurocardiac Function in Patients With Acute Ischaemic Stroke Undergoing Heart Rate Variability Biofeedback.

Front Neurol 2021 26;12:669843. Epub 2021 May 26.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Neurocardiac dysfunction worsens clinical outcome and increases mortality in stroke survivors. We hypothesized that heart rate variability (HRV) biofeedback improves neurocardiac function by modulating autonomic nervous system activity after acute ischaemic stroke (AIS). We randomly allocated (1:1) 48 acute ischaemic stroke patients to receive nine sessions of HRV- or sham biofeedback over 3 days in addition to comprehensive stroke unit care. Before and after the intervention patients were evaluated for HRV standard deviation of normal-to-normal intervals (SDNN, primary outcome), root mean square of successive differences between normal heartbeats (RMSSD), a predominantly parasympathetic measure, and for sympathetic vasomotor and sudomotor function. Severity of autonomic symptoms was assessed survey of autonomic symptom scale total impact score (TIS) at baseline and after 3 months. We included 48 patients with acute ischaemic stroke [19 females, ages 65 (4.4), median (interquartile range)]. Treatment with HRV biofeedback increased HRV post intervention [SDNN: 43.5 (79.0) ms vs. 34.1 (45.0) ms baseline, = 0.015; RMSSD: 46.0 (140.6) ms vs. 29.1 (52.2) ms baseline, = 0.015] and alleviated autonomic symptoms after 3 months [TIS 3.5 (8.0) vs. 7.5 (7.0) baseline, = 0.029], which was not seen after sham biofeedback (SDNN: = 0.63, RMSSD: = 0.65, TIS: 0.06). There were no changes in sympathetic vasomotor and sudomotor function ( = ns). Adding HRV biofeedback to standard stroke unit care led to improved neurocardiac function and sustained alleviation of autonomic symptoms after acute ischaemic stroke, which was likely mediated by a predominantly parasympathetic mechanism. www.ClinicalTrials.gov, identifier: NCT03865225.
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http://dx.doi.org/10.3389/fneur.2021.669843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187903PMC
May 2021

Diagnostic accuracy of narrow-band imaging endoscopy with targeted biopsies compared with standard endoscopy with random biopsies in patients with Barrett's esophagus: A systematic review and meta-analysis.

J Gastroenterol Hepatol 2021 Jun 13. Epub 2021 Jun 13.

Department of Gastroenterology, The Lyell McEwin Hospital, Adelaide, South Australia, Australia.

Background And Aim: Endoscopic surveillance for dysplasia in Barrett's esophagus (BE) with random biopsies is the primary diagnostic tool for monitoring clinical progression into esophageal adenocarcinoma. As an alternative, narrow-band imaging (NBI) endoscopy offers targeted biopsies that can improve dysplasia detection. This study aimed to evaluate NBI-guided targeted biopsies' diagnostic accuracy for detecting dysplasia in patients undergoing endoscopic BE surveillance compared with the widely used Seattle protocol.

Methods: Cochrane DTA Register, MEDLINE/PubMed, EMBASE, OpenGrey, and bibliographies of identified papers were searched until 2018. Two independent investigators resolved discrepancies by consensus, study selection, data extraction, and quality assessment. Data on sensitivity, specificity, and predictive values were pooled and analyzed using a random-effects model.

Results: Of 9528 identified articles, six studies comprising 493 participants were eligible for quantitative synthesis. NBI-targeted biopsy showed high diagnostic accuracy in detection of dysplasia in BE with a sensitivity of 76% (95% confidence interval [CI]: 0.61-0.91), specificity of 99% (95% CI: 0.99-1.00), positive predictive value of 97% (95% CI: 0.96-0.99), and negative predictive value of 84% (95% CI: 0.69-0.99) for detection of all grades of dysplasia. The receiver-operating characteristic curve for NBI model performance was 0.8550 for detecting all dysplasia.

Conclusion: Narrow-band imaging-guided biopsy demonstrated high diagnostic accuracy and might constitute a valid substitute for random biopsies during endoscopic surveillance for dysplasia in BE.
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http://dx.doi.org/10.1111/jgh.15577DOI Listing
June 2021

Mapping of predictors of the disengagement of the descending inhibitory pain modulation system in fibromyalgia: an exploratory study.

Br J Pain 2021 May 30;15(2):221-233. Epub 2020 May 30.

Graduate Program in Medical Science, School of Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

Background: The main symptoms of fibromyalgia comprise diffuse pain, disability, depressive symptoms, catastrophizing, sleep disruption and fatigue, associated with dysfunction of the descending pain-modulating system (DPMS).

Objectives: We aimed to identify patterns of main symptoms of fibromyalgia and neuroplasticity biomarkers (i.e. brain-derived neurotrophic factor (BDNF) and S100B protein) in non-responders to the conditioned pain modulation task (CPM-task) induced by immersion of hand in cold water (0-1°C). Furthermore, we evaluated if these patterns predict responsiveness to CPM-task.

Methods: This cross-sectional study included 117 women with fibromyalgia (( = 60) non-responders and ( = 57) responders), with age ranging from 30 to 65 years old. We analysed changes in numerical pain scale (NPS-10) during the CPM-task using a standardized protocol.

Results: A hierarchical multivariate logistic regression analysis was used to construct a propensity score-adjusted index to identify non-responders compared to responders to CPM-task. The following variables were retained in the models: analgesic use four or more times per week, heat pain threshold (HPT), poor sleep quality, pain catastrophizing, serum levels of BDNF, number of psychiatric diagnoses and the impact of symptoms of fibromyalgia on quality of life. Receiver operator characteristics (ROC) analysis showed non-responders can be discriminated from responders by a composite index of more frequent symptoms of fibromyalgia and neuroplasticity markers (area under the curve (AUC) = 0.83, sensitivity = 100% and specificity = 98%).

Conclusion: Patterns of fibromyalgia symptoms and neuroplasticity markers may be helpful to predict responsiveness to the CPM-task which might help personalize treatment and thereby contribute to the care of patients with fibromyalgia.
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http://dx.doi.org/10.1177/2049463720920760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138619PMC
May 2021

[Association of COVID-19 and Stroke: Pathophysiology and Clinical Relevance].

Fortschr Neurol Psychiatr 2021 Jun 21;89(6):289-295. Epub 2021 May 21.

Klinik und Poliklinik für Neurologie, Universitätsklinik Carl Gustav Carus, Technische Universität Dresden.

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http://dx.doi.org/10.1055/a-1484-0224DOI Listing
June 2021

Quality of life after hospitalization predicts one-year readmission risk in a large Swiss cohort of medical in-patients.

Qual Life Res 2021 Jul 18;30(7):1863-1871. Epub 2021 May 18.

Division of Health Care Sciences, Dresden International University, Dresden, Germany.

Purpose: Estimating the probability of readmission following hospitalization using prediction scores can be complex. Quality of life (QoL) may provide an easy and effective alternative.

Methods: Secondary analysis of the prospective "TRIAGE" cohort. All medical in-patients admitted to a Swiss tertiary care institution (2016-2019) ≥18 years with a length of stay of ≥2 days (23,309 patients) were included. EQ-5D VAS, EQ-5D index, and Barthel index were assessed at a single telephone interview 30-day after admission. Patients lost to follow-up were excluded. Readmission was defined as a non-elective hospital stay at our institution >24 h within 1 year after discharge and assessed using area under the curve (AUC) analysis with adjustment for confounders.

Results: 12,842 patients (43% females, median age 68, IQR 55-78) were included. Unadjusted discrimination was modest at 0.59 (95% CI 0.56-0.62) for EQ-5D VAS. Partially adjusted discrimination (for gender) was identical. Additional adjustment for insurance, Charlson comorbidity index, length of stay, and native language increased the AUC to 0.66 (95% CI 0.63-0.69). Results were robust irrespective of time to event (12, 6 or 3 months). A cut-off in the unadjusted model of EQ-5D VAS of 55 could separate cases with a specificity of 80% and a sensitivity of 30%.

Conclusion: QoL at day 30 after admission can predict one-year readmission risk with similar precision as more intricate tools. It might help for identification of high-risk patients and the design of tailored prevention strategies.
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http://dx.doi.org/10.1007/s11136-021-02867-5DOI Listing
July 2021

Inadvertent hypothermia after endovascular therapy is not associated with improved outcome in stroke due to anterior circulation large vessel occlusion.

Eur J Neurol 2021 Aug 4;28(8):2479-2487. Epub 2021 Jun 4.

Department of Neurology, Dresden Neurovascular Center, Technische Universität Dresden, Dresden, Germany.

Background And Purpose: Hypothermia may be neuroprotective in acute ischemic stroke. Patients with anterior circulation large vessel occlusion (acLVO) are frequently hypothermic after endovascular therapy (EVT). We sought to determine whether this inadvertent hypothermia is associated with improved outcome.

Methods: We extracted data of consecutive patients (January 2016 to May 2019) who received EVT for acLVO from our prospective EVT register of all patients screened for EVT at our tertiary stroke center. We assessed functional outcome at 3 months and performed multivariate analysis to calculate adjusted risk ratios (aRRs) for favorable outcome (modified Rankin Scale scores = 0-2) and mortality across patients who were hypothermic (<36°C) and patients who were normothermic (≥36°C to <37.6°C) after EVT. Moreover, we compared the frequency of complications between these groups.

Results: Among 837 patients screened, 416 patients received EVT for acLVO and fulfilled inclusion criteria (200 [48.1%] male, mean age = 76 ± 16 years, median National Institutes of Health Stroke Scale score = 16, interquartile range [IQR] = 12-20). Of these, 209 patients (50.2%) were hypothermic (median temperature = 35.2°C, IQR = 34.7-35.7) and 207 patients were normothermic (median temperature = 36.4°C, IQR = 36.1-36.7) after EVT. In multivariate analysis, hypothermia was not associated with favorable outcome (aRR = 0.99, 95% confidence interval [CI] = 0.75-1.31) and mortality (aRR = 1.18, 95% CI = 0.84-1.66). More hypothermic patients suffered from pneumonia (36.4% vs. 25.6%, p = 0.02) and bradyarrhythmia (52.6% vs. 16.4%, p < 0.001), whereas thromboembolic events were distributed evenly (5.7% vs. 6.8%, not significant).

Conclusions: Inadvertent hypothermia after EVT for acLVO is not associated with improved functional outcome or reduced mortality but is associated with an increased rate of pneumonia and bradyarrhythmia in patients with acute ischemic stroke.
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http://dx.doi.org/10.1111/ene.14906DOI Listing
August 2021

Ultrasonography Grading of Internal Carotid Artery Disease: Multiparametric German Society of Ultrasound in Medicine (DEGUM) versus Society of Radiologists in Ultrasound (SRU) Consensus Criteria.

Ultraschall Med 2021 May 5. Epub 2021 May 5.

Department of Neurology, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.

Purpose:  We sought to determine the diagnostic agreement between the revised ultrasonography approach by the German Society of Ultrasound in Medicine (DEGUM) and the established Society of Radiologists in Ultrasound (SRU) consensus criteria for the grading of carotid artery disease.

Materials And Methods:  Post-hoc analysis of a prospective multicenter study, in which patients underwent ultrasonography and digital subtraction angiography (DSA) of carotid arteries for validation of the DEGUM approach. According to DEGUM and SRU ultrasonography criteria, carotid arteries were independently categorized into clinically relevant NASCET strata (normal, mild [1-49 %], moderate [50-69 %], severe [70-99 %], occlusion). On DSA, carotid artery findings according to NASCET were considered the reference standard.

Results:  We analyzed 158 ultrasonography and DSA carotid artery pairs. There was substantial agreement between both ultrasonography approaches for severe (κw 0.76, CI95 %: 0.66-0.86), but only fair agreement for moderate (κw 0.38, CI95 %: 0.19-0.58) disease categories. Compared with DSA, both ultrasonography approaches were of equal sensitivity (79.7 % versus 79.7 %; p = 1.0) regarding the identification of severe stenosis, yet the DEGUM approach was more specific than the SRU approach (70.2 % versus 56.4 %, p = 0.0002). There was equality of accuracy parameters (p > 0.05) among both ultrasonography approaches for the other ranges of carotid artery disease.

Conclusion:  While the sensitivity was equivalent, false-positive identification of severe carotid artery stenosis appears to be more frequent when using the SRU ultrasonography approach than the revised multiparametric DEGUM approach.
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http://dx.doi.org/10.1055/a-1487-5941DOI Listing
May 2021

Autotitrating Bilevel Positive Airway Pressure in Large Vessel Steno-Occlusive Stroke Patients With Suspected Sleep Apnea: A Multicenter Randomized Controlled Study.

Front Neurol 2021 13;12:667494. Epub 2021 Apr 13.

Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, United States.

We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke. In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0-2], stroke recurrence, and mortality at 90 days were assessed. Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, = 14; control, = 10): median baseline NIHSS 13 (5.5-18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients ( = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: -2.0, IQR = 7 points vs. -0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, = 0.67), stroke recurrence (0 vs. 20%, = 0.16), and death (14 vs. 20%, = 1.0). No safety concerns were identified. In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted. ClinicalTrials.gov, identifier: NCT01812993.
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http://dx.doi.org/10.3389/fneur.2021.667494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076592PMC
April 2021

Acute kidney injury in patients with malignant middle cerebral artery infarction undergoing hyperosmolar therapy with mannitol.

J Crit Care 2021 Aug 26;64:22-28. Epub 2021 Feb 26.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Electronic address:

Purpose: To assess the kidney safety profile of mannitol in patients with malignant middle cerebral artery (MCA) infarction.

Material And Methods: We studied consecutive patients with malignant MCA infarction (01/2008-01/2018). Malignant MCA infarction was defined according to DESTINY criteria. We compared clinical endpoints including acute kidney injury (AKI; according to Kidney Disease: Improving Global Outcomes [KDIGO]) and dialysis between patients with and without mannitol. Multivariable model was built to explore predictor variables of AKI and in-hospital death.

Results: Overall, 219 patients with malignant MCA infarction were included. Mannitol was administered in 93/219 (42.5%) patients with an average dosage of 650 g (250-950 g). Patients treated with mannitol more frequently suffered from AKI (39.8% vs. 11.9%; p < 0.001) and required hemodialysis (7.5% vs. 0.8%; p = 0.01) than patients without mannitol. At discharge, more patients in the mannitol group had persistent AKI than control patients (23.7% vs. 6.4%, p < 0.001). In multivariable model, mannitol emerged as independent predictor of AKI (OR 5.02, 95%CI 2.36-10.69; p < 0.001).

Conclusions: Acute kidney injury appears to be a frequent complication of hyperosmolar therapy with mannitol in patients with malignant MCA infarction. Given the lack of evidence supporting effectiveness of mannitol in these patients, its routine use should be carefully considered.
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http://dx.doi.org/10.1016/j.jcrc.2021.02.007DOI Listing
August 2021

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Neurology 2021 06 25;96(23):e2824-e2838. Epub 2021 Mar 25.

Department of Neurology (R.G.N., M.H.M., M.Frankel, D.C.H.), Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine, Atlanta; Department of Radiology (M.M.Q., M.A., T.N.N., A.K.) and Radiation Oncology (M.M.Q.), Boston Medical Center, Boston University School of Medicine, Massachusetts; Department of Neurology (S.O.M.), Federal University of Rio Grande do Sul, Porto Alegre; Hospital de Clínicas de Porto Alegre (S.O.M.), Brazil; Department of Stroke Neurology (H. Yamagami), National Hospital Organization, Osaka National Hospital, Japan; Department of Neurology (Z.Q.), Xinqiao Hospital of the Army Medical University, Chongqing, China; Department of Neurology (O.Y.M.), Stroke and Neurointervention Division, Alexandria University Hospital, Alexandria University, Egypt; Boston University School of Medicine (A.S.), Massachusetts; 2nd Department of Neurology (A.C.), Institute of Psychiatry and Neurology, Warsaw, Poland; Department of Neurology (G.T., L.P.), National & Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece; Faculdade de Medicina (D.A.d.S.), Universidade de Lisboa, Lisbon, Portugal; Department of Neurology (J.D., R.L.), Leuven University Hospital, Belgium; International Clinical Research Center and Department of Neurology (R.M.), St. Anne´s University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Neurology (P.V.), Groeninge Hospital, Kortrijk; Department of Neurology (P.V.), University Hospitals Antwerp; Department of Translational Neuroscience (P.V.), University of Antwerp, Belgium; Department of Neurology (J.E.S., T.G.J.), Cooper Neurological Institute, Cooper University Hospital, Camden, New Jersey; Department of Neurology and Neurosurgery (J. Kõrv), University of Tartu, Estonia; Department of Neurology (J.B., R.V.,S.R.), Loyola University Chicago Stritch School of Medicine, Illinois; Department of Neurosurgery (C.W.L.), Kaiser Permanente Fontana Medical Center; Department of Neurology (N.S.S.), Kaiser Permanente Los Angeles Medical Center; Department of Neurology (A.M.Z., S.A.S.), UT Health McGovern Medical School, Houston, Texas; Department of Neurology (A.L.Z.), Medical University of South Carolina, Charleston; Department of Internal Medicine (G.N.), School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, Pennsylvania; Department of Neurology (A.L.), Ohio Health Riverside Methodist Hospital Columbus; Department of Medicine and Neurology (A.R.), University of Otago and Wellington Hospital, New Zealand; Department of Neurology (E.A.M.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Neurology (A.W.A., D. Alsbrook), University of Tennessee Health Center, Memphis; Department of Neurology (D.Y.H.), University of North Carolina at Chapel Hill; Departments of Neurology (S.Y.) and Radiology (E.R.), New York University Grossman School of Medicine; Douala Gynaeco-Obstetric and Pediatric Hospital (E.G.B.L.), University of Douala, Faculty of Medicine and Pharmaceutical Science, Cameroon; Ain Shams University Specialized Hospital (H.M.A., H.M.S., A.E., T.R.); Cairo University Affiliated MOH Network (F.H.); Department of Neurology (TM.), Nasser Institute for Research and Treatment, Cairo; Mansoura University Affiliated Private Hospitals Network (W.M.), Egypt; Kwame Nkrumah University of Science and Technology (F.S.S.), Kumasi, Ghana; Stroke Unit (T.O.A., K.W.), University of Ilorin Teaching Hospital; Neurology Unit (B.A.), Department of Medicine, Lagos State University Teaching Hospital; Department of Medicine (E.O.N.), Federal Medical Centre Owerri, Imo State, Nigeria; Neurology Unit (T.A.S.), Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria; University College Hospital (J.Y.), Ibadan, Nigeria; The National Ribat University Affiliated Hospitals (H.H.M.), Khartoum, Sudan; Neurology Section (P.B.A.), Department of Internal Medicine, Aga-Khan University, Medical College East Africa, Dar es Salaam, Tanzania; Tunis El Manar University (A.D.R.), Military Hospital of Tunis; Department of Neurology (S.B.S.), Mongi Ben Hmida National Institute of Neurology, Faculty of Medicine of Tunis, University Tunis El Manar, Tunisia; Department of Physiology (L.G.), Parirenyatwa Hospital, and Departments of Physiology and Medicine (G.W.N.), University of Zimbabwe, Harare; Department of Cerebrovascular/Endovascular Neurosurgery Division (D.S.), Erebouni Medical Center, Yerevan, Armenia; Department of Neurology (A.R.), Sir Salimulah College, Dhaka, Bangladesh; Department of Neurology (Z.A.), Taihe Hospital of Shiyan City, Hubei; Department of Neurology (F.B.), Nanyang Central Hospital, Henan; Department of Neurology (Z.D.), Wuhan No. 1 Hospital, Hubei, China; Department of Neurology (Y. Hao.), Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Neurology (W.H.), Traditional Chinese Medicine Hospital of Maoming, Guangdong; Department of Neurology (G.Li.), Affiliated Hospital of Qingdao University, Shandong; Department of Neurology (W.L), The First Affiliated Hospital of Hainan Medical College; Department of Neurology (G.Liu.), Wuhan Central Hospital, Hubei; Department of Neurology (J.L.), Mianyang 404th Hospital, Sichuan; Department of Neurology (X.S.), Yijishan Hospital of Wannan Medical College, Anhui; Department of Neurology and Neuroscience (Y.S.), Shenyang Brain Institute, Shenyang First People's Hospital, Shenyang Medical College Affiliated Brain Hospital; Department of Neurology (L.T.), Affiliated Yantai Yuhuangding Hospital of Qingdao University, Shandong; Department of Neurology (H.W.), Xiangyang Central Hospital, Hubei; Department of Neurology (B.W., Y.Yan), West China Hospital, Sichuan University, Chengdu; Department of Neurology (Z.Y.), Affiliated Hospital of Southwest Medical University, Sichuan; Department of Neurology (H.Z.), Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine; Department of Neurology (J.Z.), The First Affiliated Hospital of Shandong First Medical University; Department of Neurology (W.Z.), First Affiliated Hospital of Fujian Medical University, China; Acute Stroke Unit (T.W.L.), The Prince of Wales Hospital, Kwok Tak Seng Centre for Stroke Research and Intervention, The Chinese University of Hong Kong; Interventional Neurology (C.C.), MAX Superspecialty Hospital, Saket, New Delhi; NH Institute of Neurosciences (V.H.), NH Mazumdar Shaw Medical Center, Bangalore; Department of Neurology (B.M.), Apollo Speciality Hospitals Nellore; Department of Neurology (J.D.P.), Christian Medical College, Ludhiana, Punjab; Sree Chitra Tirunal Institute for Medical Sciences and Technology (P.N.S.), Kerala, India; Stroke Unit (F.S.U.), Pelni Hospital, Jakarta, Indonesia; Neurosciences Research Center (M. Farhoudi, E.S.H.), Tabriz University of Medical Sciences, Tabriz, Iran; Beer Sheva Hospital (A.H.); Department of Interventional Neuroradiology, Rambam Healthcare Campus, Haifa, Israel (A.R., R.S.H.); Departments of Neurology (N.O.) and Neurosurgery (N.S.), Kobe City Medical Center General Hospital, Kobe; Department of Stroke and Neurovascular Surgery (D.W.), IMS Tokyo-Katsushika General Hospital; Yokohama Brain and Spine Center (R.Y.); Iwate Prefectural Central (R.D.); Department of Neurology and Stroke Treatment (N.T.), Japanese Red Cross Kyoto Daiichi Hospital; Department of Neurology (T.Y.), Kyoto Second Red Cross Hospital; Department of Neurology (T.T.), Japanese Red Cross Kumamoto Hospital; Department of Stroke Neurology (Y. Yazawa), Kohnan Hospital, Sendai; Department of Cerebrovascular Medicine (T.U.), Saga-Ken Medical Centre; Department of Neurology (T.D.), Saitama Medical Center, Kawagoe; Department of Neurology (H.S.), Nara City Hospital; Department of Neurology (Y.S.), Toyonaka Municipal Hospital, Osaka; Department of Neurology (F. Miyashita), Kagoshima City Hospital; Department of Neurology (H.F.), Japanese Red Cross Matsue Hospital, Shimane; Department of Neurology (K.M.), Shiroyama Hospital, Osaka; Department of Cerebrovascular Medicine (J.E.S.), Niigata City General Hospital; Department of Neurology (Y.S.), Sugimura Hospital, Kumamoto; Stroke Medicine (Y. Yagita), Kawasaki Medical School, Okayama; Department of Neurology (Y.T.), Osaka Red Cross Hospital; Department of Stroke Prevention and Treatment (Y.M.), Department of Neurosurgery, University of Tsukuba, Ibaraki; Department of Neurology (S.Y.), Stroke Center and Neuroendovascular Therapy, Saiseikai Central Hospital, Tokyo; Department of Neurology (R.K.), Kin-ikyo Chuo Hospital, Hokkaido; Department of Cerebrovascular Medicine (T.K.), NTT Medical Center Tokyo; Department of Neurology and Neuroendovascular Treatment (H. Yamazaki), Yokohama Shintoshi Neurosurgical Hospital; Department of Neurology (M.S.), Osaka General Medical Center; Department of Neurology (K.T.), Osaka University Hospital; Department of Advanced Brain Research (N.Y.), Tokushima University Hospital Tokushima; Department of Neurology (K.S.), Saiseikai Fukuoka General Hospital, Fukuoka; Department of Neurology (T.Y.), Tane General Hospital, Osaka; Division of Stroke (H.H.), Department of Internal Medicine, Osaka Rosai Hospital; Department of Comprehensive Stroke (I.N.), Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurology (A.K.), Asfendiyarov Kazakh National Medical University; Republican Center for eHealth (K.F.), Ministry of Health of the Republic of Kazakhstan; Department of Medicine (S.K.), Al-Farabi Kazakh National University; Kazakh-Russian Medical University (M.Z.), Kazakhstan; Department of Neurology (J.-H.B.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (Y. Hwang), Kyungpook National University Hospital, School of Medicine, Kyungpook National University; Ajou University Hospital (J.S.L.); Department of Neurology (S.B.L.), Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Department of Neurology (J.M.), National Medical Center, Seoul; Department of Neurology (H.P., S.I.S.), Keimyung University School of Medicine, Dongsan Medical Center, Daegu; Department of Neurology (J.H.S.), Busan Paik Hospital, School of Medicine, Inje University, Busan; Department of Neurology (K.-D.S.), National Health Insurance Service Ilsan Hospital, Goyang; Asan Medical Center (C.J.Y.), Seoul, South Korea; Department of Neurology (R.A.), LAU Medical Center-Rizk Hospital, Beirut, Lebanon; Department of Medicine (W.A.W.Z., N.W.Y.), Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur; Sultanah Nur Zahirah (Z.A.A., K.A.I.), Kuala Terengganu; University Putra Malaysia (H.b.B.); Sarawak General Hospital, Kuching (L.W.C.); Hospital Sultan Abdul Halim (A.B.I.), Sungai Petani Kedah; Hospital Seberang Jaya (I.L.), Pulau Pinang; Thomson Hospital Kota Damansara (W.Y.T.), Malaysia; "Nicolae Testemitanu" State University of Medicine and Pharmacy (S.G., P.L.), and Department of Neurology, Emergency Medicine Institute, Chisinau, Republic of Moldova; Department of Stroke Unit (A.M.A.H.), Royal Hospital Muscat, Oman; Neuroscience Institute (Y.Z.I., N.A.), Hamad Medical Corporation, Doha, Qatar; St. Luke's Medical Center-Institute of Neurosciences (M.C.P.-F., C.O.C.), Quezon City, Philippines; Endovascular Neurosurgery (D.K.), Saint-Petersburg Dzhanelidze Research Institute of Emergency Medicine, St. Petersburg, Russia; Department of Neurology (A.A.), Stroke Unit, King Saud University, College of Medicine, Riyadh; Department of Neurosurgery (H.A.-J.), Interventional Radiology, and Critical Care Medicine, King Fahad Hospital of the University, Imam Abdulrahman bin Faisal University, Saudi Arabia; Singapore National Neuroscience Institute (C.H.T.); Changi General Hospital (M.J.M.), Singapore; Neuroscience Center, Raffles Hospital (N.V.), Singapore; Department of Neurology (C.-H.C., S.-C.T.), National Taiwan University Hospital; Department of Radiology (A.C.), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Dicle University Medical School and Hospital (E.A.), Diyarbakir; Stroke and Neurointervention Unit (O.A., A.O.O.), Eskisehir Osmangazi University; Gaziantep University Faculty of Medicine (S.G.), Turkey; Department of Neurology (S.I.H., S.J.), Neurological Institute at Cleveland Clinic Abu Dhabi, United Arab Emirates; Stroke Center (H.L.V., A.D.C.), Hue Central Hospital, Hue, Vietnam; Stroke Department (H.H.N., T.N.P.), Da Nang Hospital, Da Nang City; 115 People's Hospital (T.H.N., T.Q.N.), Ho Chi Minh City, Vietnam; Department of Neurology (T.G., C.E.), Medical University of Graz; Department of Neurology (M. K.-O.), Research Institute of Neurointervention, University Hospital Salzburg/Paracelsus Medical University, Austria; Department of Neurology (F.B., A.D.), Centre Hospitalier Universitaire de Charleroi, Belgium; Department of Neurology (S.D.B., G.V.), Sint Jan Hospital, Bruges; Department of Neurology (S.D.R.), Brussels University Hospital (UZ Brussel); Department of Neurology (N.L.), ULB Erasme Hospitals Brussels; Department of Neurology (M.P.R.), Europe Hospitals Brussels; Department of Neurology (L.Y.), Antwerp University Hospital, Belgium; Neurology Clinic (F.A., T.S.), St. Anna University Hospital, Sofia, Bulgaria; Department of Neurology (M.R.B.), Sestre Milosrdnice University Hospital, Zagreb; Department of Neurology (H.B.), Sveti Duh University Hospital, Zagreb; Department of Neurology (I.C.), General Hospital Virovitica; Department of Neurology (Z.H.), General Hospital Zabok; Department of Radiology (F. Pfeifer), University Hospital Centre Zagreb, Croatia; Regional Hospital Karlovy Vary (I.K.); Masaryk Hospital Usti nad Labem (D.C.); Military University Hospital Praha (M. Sramek); Oblastní Nemocnice Náchod (M. Skoda); Regional Hospital Pribram (H.H.); Municipal Hospital Ostrava (L.K.); Hospital Mlada Boleslav (M. Koutny); Hospital Vitkovice (D.V.); Hospital Jihlava (O.S.); General University Hospital Praha (J.F.); Hospital Litomysl (K.H.); Hospital České Budejovice (M.N.); Hospital Pisek (R.R.); Hospital Uherske Hradiste (P.P.); Hospital Prostejov (G.K.); Regional Hospital Chomutov (J.N.); Hospital Teplice (M.V.); Mining Hospital Karvina (H.B.); Thomayer Hospital Praha (D.H.); Hospital Blansko (D.T.); University Hospital Brno (R.J.); Regional Hospital Liberec (L.J.); Hospital Ceska Lipa (J.N.); Hospital Sokolov (A.N.); Regional Hospital Kolin (Z.T.); Hospital Trutnov (P. Fibrich); Hospital Trinec (H.S.); Department of Neurology (O.V.), University Hospital Ostrava, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Bispebjerg Hospital (H.K.C.), University of Copenhagen; Stroke Center (H.K.I., T.C.T.), Rigshospitalet, University of Copenhagen; Aarhus University Hospital (C.Z.S.), Aarhus; Neurovascular Center, Zealand University Hospital, University of Copenhagen (T.W.), Roskilde, Denmark; Department of Neurology and Neurosurgery (R.V.), University of Tartu, Estonia; Neurology Clinic (K.G.-P.), West Tallinn Central Hospital; Center of Neurology (T.T.), East Tallinn Central Hospital, School of Natural Sciences and Health, Tallinn University; Internal Medicine Clinic (K.A.), Pärnu Hospital, Estonia; Université Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition (C.C., F.C.); Centre Hospitalier d'Arcachon (M.D.), Gujan-Mestras; Centre Hospitalier d'Agen (J.-M.F.); Neurologie Vasculaire (L.M.) and Neuroradiologie (O.E.), Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Bron; Centre Hospitalier et Universitaire de Bordeaux (E.L., F.R.); Centre Hospitalier de Mont de Marsan (B.O.); Neurologie (R.P.), Fondation Ophtalmologique Adolphe de Rothschild; Versailles Saint-Quentin-en-Yvelines University (F. Pico); Neuroradiologie Interventionelle (M.P.), Fondation Ophtalmologique Adolphe de Rothschild; Neuroradiologie Interventionelle (R.P.), Hôpitaux Universitaires de Strasbourg, France; K. Eristavi National Center of Experimental and Clinical Surgery (T.G.), Tbilisi; Department of Neurosurgery (M. Khinikadze), New Vision University Hospital, Tbilisi; Vivamedi Medical Center (M. Khinikadze), Tbilisi; Pineo Medical Ecosystem (N.L.), Tbilisi; Ivane Javakhishvili Tbilisi State University (A.T.), Tbilisi, Georgia; Department of Neurology (S.N., P.A.R.), University Hospital Heidelberg; Department of Neurology (M. Rosenkranz), Albertinen Krankenhaus, Hamburg; Department of Neurology (H.S.), Elbe Klinken Stade, University Medical Center Göttingen; Department of Neurology (T.S.), University Hospital Carl Gustav Carus, Dresden; Kristina Szabo (K.S.), Department of Neurology, Medical Faculty Mannheim, University Heidelberg, Mannheim; Klinik und Poliklinik für Neurologie (G.T.), Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany; Department of Internal Medicine (D.S.), School of Health Sciences, University of Thessaly, Larissa; Second Department of Neurology (O.K.), Stroke Unit, Metropolitan Hospital, Piraeus, Greece; University of Szeged (P.K.), Szeged; University of Pecs (L.S., G.T.), Hungary; Stroke Center (A.A.), IRCCS Istituto di Ricovero e Cura a Carattere Scientifico, Negrar, Verona; Department of Neurology (F.B.), Ospedale San Paolo, Savona,; Institute of Neurology (P.C., G.F.), Fondazione Policlinico Universitario Agostino Gemelli, Rome; Interventional Neurovascular Unit (L.R.), Careggi University Hospital, Florence; Stroke Unit (D.S.), Azienda Socio Sanitaria Territoriale (ASST) di Lecco, Italy; Maastricht University Medical Center; Department of Neurology (M.U.), Radiology, University Medical Center Groningen; Department of Neurology (I.v.d.W.), Haaglanden Medical Center, the Hague, the Netherlands; Department of Neurology (E.S.K.), Akershus University Hospital, Lørenskog, General Practice, HELSAM, University of Oslo, Norway; Neurological Ward with Stroke Unit (W.B.), Specialist Hospital in Konskie, Gimnazjalna, Poland and Collegium Medicum, Jan Kochanowski University, Kielce, Poland; Neurological Ward with Stroke Unit (M.F.), District Hospital in Skarzysko-Kamienna; Department of Neurology (E.H.L.), Szpitala im T. Marciniaka in Wroclaw; 2nd Department of Neurology (M. Karlinski), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Cerebrovascular Disorders (R.K., P.K.), Poznan University of Medical Sciences; 107th Military Hospital with Polyclinic (M.R.), Walcz; Department of Neurology (R.K.), St. Queen Jadwiga, Clinical Regional Hospital No. 2, Rzeszow; Department of Neurology (P.L.), Medical University of Lublin; 1st Department of Neurology (H.S.-J.), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Stroke Unit (P.S.), Holy Spirit Specialist Hospital in Sandomierz, Collegium Medicum Jan Kochanowski University in Kielce; Copernicus PL (W.F.), Neurology and Stroke Department, Hospital M. Kopernik, Gdansk; Stroke Unit (M.W.), Neurological Department, Stanislaw Staszic University of Applied Sciences, Pila, Poland; Hospital São José (Patricia Ferreira), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Stroke Unit (Paulo Ferreira, V.T.C.), Hospital Pedro Hispano, Matosinhos; Stroke Unit, Internal Medicine Department (L.F.), Neuroradiology Department, Centro Hospitalar Universitário de São João, Porto; Department of Neurology (J.P.M.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal; Department of Neurosciences (T.P.e.M.), Hospital de Santa Maria-CHLN, North Lisbon University Hospital; Hospital São José (A.P.N.), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Department of Neurology (M. Rodrigues), Hospital Garcia de Orta, Portugal; Department of Neurology (C.F.-P.), Transilvania University, Brasov, Romania; Department of Neurology (G.K., M. Mako), Faculty Hospital Trnava, Slovakia; Department of Neurology and Stroke Center (M.A.d.L., E.D.T.), Hospital Universitario La Paz, Madrid; Department of Neurology (J.F.A.), Hospital Clínico Universitario, Universidad de Valladolid; Department of Neurology (O.A.-M.), Complejo Hospitalario Universitario de Albacete; Department of Neurology (A.C.C.), Unidad de Ictus, Hospital Universitario Ramon y Cajal, Madrid; Department of Neurology (S.P.-S), Hospital Universitario Virgen Macarena & Neurovascular Research Laboratory (J.M.), Instituto de Biomedicina de Sevilla-IbiS; Rio Hortega University Hospital (M.A.T.A.), University of Valladolid; Cerebrovascular Diseases (A.R.V.), Hospital Clinic of Barcelona, Spain; Department of Neurology (M. Mazya), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Interventional Neuroradiology (G.B.), University Hospitals of Geneva; Department of Interventional and Diagnostic Neuroradiology (A.B., M.-N.P.), Radiology and Nuclear Medicine, University Hospital Basel; Department of Neurology (U.F.), University of Bern; Department of Neuroradiology (J.G.), University of Bern; Department of Neuroscience (P.L.M., D.S.), Lausanne University Hospital, Switzerland; Department of Stroke Medicine (S.B., J. Kwan), Imperial College Healthcare NHS Trust, Charing Cross Hospital, London; Department of Neurology (K.K.), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, United Kingdom; Department of Neurology (A.B., A. Shuaib), University of Alberta, Edmonton; Department of Neurology (L.C., A. Shoamanesh), McMaster University, Hamilton; Department of Clinical Neurosciences and Hotchkiss Brain Institute (A.M.D., M.D.H.), University of Calgary; Department of Neurology (T.F., S.Y.), University of British Columbia, Vancouver; Mackenzie Health (J.H., C.A.S.) Richmond Hill, Ontario; Department of Neurology (H.K.), Sunnybrook Health Sciences Centre, University of Toronto; Department of Neurology (A. Mackey), Hopital Enfant Jesus, Centre Hospitalier de l'Universite Laval, Quebec City; Department of Neurology (A.P.), University of Toronto; Medicine (G.S.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurosciences (M.A.B.), Hospital Dr. Rafael A. Calderon Guardia, CCSS. San Jose, Costa Rica; Neurovascular Service (J.D.B.), Hospital General San Juan de Dios, Guatemala City; Department of Neurología (L.I.P.R.), Hospital General de Enfermedades, Instituto Guatemalteco de Seguridad Social, Guatemala City, Guatemala; Department of Neurology (F.G.-R.), University Hospital Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon, Mexico; Pacífica Salud-Hospital Punta Pacífica (N.N.-E., A.B., R.K.), Panama; Department of Neurology, Radiology (M.A.), University of Kansas Medical Center; Department of Neurointerventional Neurosurgery (D. Altschul), The Valley Baptist Hospital, Ridgewood, New Jersey; Palmetto General Hospital (A.J.A.-O.), Tenet, Florida; Neurology (I.B., P.K.), University Hospital Newark, New Jersey Medical School, Rutgers, Newark, New Jersey; Community Healthcare System (A.B.), Munster, Indiana; Department of Neurology (N.B., C.B.N.), California Pacific Medical Center, San Francisco; Department of Neurology (C.B.), Mount Sinai South Nassau, New York; University of Toledo (A.C.), Ohio; Department of Neurology (S.C.), University of Maryland School of Medicine, Baltimore, Maryland; Neuroscience (S.A.C.), Inova Fairfax Hospital, Virginia; Department of Neurology (H.C.), Abington Jefferson Hospital, Pennsylvania; Department of Neurology (J.H.C.), Mount Sinai South Nassau, New York; Baptist Health Medical Center (S.D.), Little Rock, Arkansas; Department of Neurology (K.D.), HCA Houston Healthcare Clearlake, Texas; Department of Neurology (T.G.D., R.S.), Erlanger, Tennessee; Wilmington North Carolina (V.T.D.); Department of Vascular and Neurointerventional Services (R.E.), St. Louis University, Missouri; Department of Neurology (M.E.), Massachusetts General Hospital, Boston; Department of Neurology, Neurosurgery, and Radiology (M.F., S.O.-G., N.R.), University of Iowa Hospitals and Clinics, Iowa City; Department of Radiology (D.F.), Swedish Medical Center, Englewood, Colorado; Department of Radiology (D.G.), Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland; Adventist Health Glendale Comprehensive Stroke Center (M.G.), Los Angeles, California; Wellstar Neuroscience Institute (R.G.), Marietta, Georgia; Department of Neurology (A.E.H.), University of Texas Rio Grande Valley-Valley Baptist Medical Center, Texas; Department of Neurology (J.H., B.V.), Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts; Department of Neurology (A.M.K.), Wayne State, Detroit, Michigan; HSHS St. John's Hospital (N.N.K.), Southern Illinois University School of Medicine, Springfield; Virginia Hospital Center (B.S.K.), Arlington; Department of Neurology, University of Michigan, Ann Arbor; Weill-Cornell Medical College (D.O.K.), New York-Presbyterian Queens; Department of Neurology (V.H.L.), Ohio State University, Columbus; Department of Neurology (L.Y.L.), Tufts Medical Center, Boston, Massachusetts; Vascular and Neurointerventional Services (G.L.), St. Louis University, Missouri; Miami Cardiac & Vascular Institute (I.L., A.K.S.), Florida; Department of Neurology (H.L.L.), Oregon Health & Science University, Portland; Department of Emergency Medicine (L.M., M.S.), Steward Holy Family Hospital, Methuen, MA; Vidant Medical Center (S.M.), Greenville, North Carolina; Department of Neurology (A.M.M., D.R.Y.) and Neurosurgery (D.R.Y.), University of Miami Miller School of Medicine, Florida; Department of Neurology (H.M.), SUNY Upstate New York, Syracuse; Memorial Neuroscience Institute (B.P.M.), Pembroke Pines, Florida; Neurosciences (J.M., J.P.T.), Spectrum Health, Michigan State University College of Medicine, Grand Rapids, Michigan; Sutter Health (M.M.), Sacramento, California; Department of Neurology (J.G.M.), Maine Medical Center, Portland; Department of Neurology (S.S.M.), Bayhealth, Dover, Delaware; Department of Neurology and Pediatrics (F.N.), Emory University, Atlanta, Georgia; Department of Neurology (K.N.), University of Arkansas for Medical Sciences, Little Rock; Department of Radiology and Neurology (R.N.-W.), UT Southwestern Medical Center, Dallas, Texas; Ascension St. John Medical Center (R.H.R.), Tulsa, Oklahoma; Riverside Regional Medical Center (P.R.), Newport, Virginia; Department of Neurology (J.R.R., T.N.N.), Boston University School of Medicine, MA; Department of Neurology (A.R.), Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (M.S.), University of Washington School Medicine, Seattle; Department of Neurology (B.S.), University of Massachusetts Medical Center, Worcester; Department of Neurology (A.S.), CHI-Immanuel Neurological Institute, Creighton University, Omaha, Nebraska; Holy Cross Hospital (S.L.S.), Fort Lauderdale, Florida; Department of Neurology (V.S.), Interventional Neuroradiology, University of California in Los Angeles; Banner Desert Medical Center (M.T.), Mesa, Arizona; Hospital de Agudos Dr. Ignacio Privano (O.B., A.L.), Argentina; Institute for Neurological Research, FLENI (V.A.P.L.), Buenos Aires, Argentina; Hospital das Clinicas/São Paulo University (M.S.A., A.C.); Sumare State Hospital (F.B.C., L.V.), São Paulo; Hospital Vera Cruz (L.D.D.S.), Deus Campinas; Irmanandade Santa Casa de Porto Alegre (L.V.G.); Stroke Unit (F.O.L., F. Mont'alverne), Hospital Geral de Fortaleza; Stroke Unit (A.L.L., P.S.C.M.), Hospital Sao Jose, Joinville, Santa Catarina; Stroke Unit (R.T.M.), Neurology, Nossa Senhora da Conceição Hospital, Porto Alegre; Department of Neurology (D.L.M.C.), Hospital Moinhos de Vento, Porto Alegre; Department of Neurology (L.C.R.), Hospital de Base do Distrito Federal; Hospital Ana (V.F.C.), Hospital Juliane, Federal University of Parana, Curitiba, Brazil; Vascular Neurology Unit (P.M.L., V.V.O.), Neurology Service, Department of Neurology and Psychiatry, Clínica Alemana, Universidad del Desarrollo, Santiago; Hospital Padre Hurtado (V.N., J.M.A.T.) Santiago, Chile; Fundación Valle del Lili (P.F.R.A.), Cali; Stroke Center (H.B.), Fundación Santa Fe de Bogotá; Department of Neurology (A.B.C.-Q.), Hospital Departamental Universitario del Quindio San Juan de Dios, Armenia; Clinica Universitaria Colombia (C.E.R.O.), Bogotá; University Hospital of San Vicente Foundation (D.K.M.B.), Medellin; Barranquilla, Colombia (O.L.); Hospital Infantil Universitario de San Jose (M.R.P.), Bogota; Stroke Unit (L.F.D.-E.), Hospital de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Asunción; Neurology Service (D.E.D.M.F., A.C.V.), Hospital Central del Instituto de Prevision Social, Paraguay; Internal Medicine Service (A.J.Z.Z.), Hospital Central de Policia "Rigoberto Caballero", Paraguay; National Institute of Neurological Sciences of Lima Peru (D.M.B.I.); Hospital Edgardo Rebagliati Martins Lima-Peru (L.R.K.); Department of Neurology (B.C.), Royal Melbourne Hospital; Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital and Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth; University of Melbourne (C.H., R.S.), Ballarat Health Service, Australia University of Melbourne; Department of Neurology (T.K.), Royal Adelaide Hospital; Department of Neurosurgery (A. Ma), Royal North Shore Hospital, Sydney; Department of Neurology (R.T.M.), Mater Hospital, Brisbane; Department of Neurology (R.S.), Austin Health, Victoria; Florey Institute of Neuroscience and Mental Health (R.S.), Parkville, Melbourne, Australia; Greymouth Base Hospital (D.S.), New Zealand; Department of Neurology (T.Y.-H.W.), Christchurch Hospital, New Zealand; Department of Neurology (D.L.), University of California in Los Angeles; and Department of Neurology (O.O.Z.), Mercy Health Neurosciences, Toledo, Ohio.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205458PMC
June 2021

Percutaneous edge-to-edge repair of severe mitral regurgitation using the MitraClip XTR versus NTR system.

Clin Cardiol 2021 May 24;44(5):708-714. Epub 2021 Mar 24.

Medizinische Klinik und Poliklinik I, University Hospital Munich Campus Grosshadern, Marchioninistraße, München, Deutschland, Germany.

Background: Transcatheter mitral valve repair (TMVR) has shown to improve symptoms and functional capacity in patients with severe mitral valve regurgitation (MR). Novel device developments provide the technology to treat patients with complex anatomies and large coaptation gaps. Nevertheless, the question of superiority of one device remains unanswered. We aimed to compare the MitraClip XTR and MitraClip NTR system in a real world setting.

Hypothesis: TMVR with the MitraClip XTR system is equally effective, but associated with a higher risk of leaflet injury.

Methods: We retrospectively analyzed peri-procedural and mid-term clinical and echocardiographic outcomes of 113 patients treated for severe MR between March 2018 and August 2019 at the University Hospital of Munich.

Results: Postprocedural MR reduction to ≤2+ was comparable in both groups (XTR: 96.1% vs. NTR: 97.6%, p = .38). There was a significant difference in a composite safety endpoint of periprocedural Major adverse cardiac and cerebrovascular events (MACCE) including leaflet injury between groups (XTR 14.6% vs. NTR 1.7%, 95% CI [2.7, 24.6], p = .012). After a median follow-up of 8.5 (4.4, 14.0) months, durable reduction of MR was confirmed (XTR: in 91.9% vs. NTR: 96.8%, p = .31) and clinical and symptomatic improvement was comparable in both groups accordingly.

Conclusion: While efficacy was comparable in both treatment groups, patients treated with the MitraClip XTR systems showed more events of acute leaflet tear and single leaflet device attachment (SLDA). A detailed echocardiographic assessment should be done to identify risk candidates for acute leaflet injury.
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http://dx.doi.org/10.1002/clc.23599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119798PMC
May 2021

Association of RASSF1A, DCR2, and CASP8 Methylation with Survival in Neuroblastoma: A Pooled Analysis Using Reconstructed Individual Patient Data.

Biomed Res Int 2020 15;2020:7390473. Epub 2020 Dec 15.

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.

Neuroblastoma (NB) is a heterogeneous tumor affecting children. It shows a wide spectrum of clinical outcomes; therefore, development of risk stratification is critical to provide optimum treatment. Since epigenetic alterations such as DNA methylation have emerged as an important feature of both development and progression in NB, in this study, we aimed to quantify the effect of methylation of three distinct genes (RASSF1A, DCR2, and CASP8) on overall survival in NB patients. We performed a systematic review using PubMed, Embase, and Cochrane libraries. Individual patient data was retrieved from extracted Kaplan-Meier curves. Data from studies was then merged, and analysis was done on the full data set. Seven studies met the inclusion criteria. Methylation of the three genes had worse overall survival than the unmethylated arms. Five-year survival for the methylated arm of RASSF1A, DCR2, and CASP8 was 63.19% (95% CI 56.55-70.60), 57.78% (95% CI 47.63-70.08), and 56.39% (95% CI 49.53-64.19), respectively, while for the unmethylated arm, it was 93.10% (95% CI 87.40-99.1), 84.84% (95% CI 80.04-89.92), and 83.68% (95% CI 80.28-87.22), respectively. In conclusion, our results indicate that in NB patients, RASSF1A, DCR2, and CASP8 methylation is associated with poor prognosis. Large prospective studies will be necessary to confirm definitive correlation between methylation of these genes and survival taking into account all other known risk factors. (PROSPERO registration number CRD42017082264).
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755470PMC
June 2021

Role of predictive markers for severe postoperative complications in gynecological cancer surgery: a prospective study (RISC-Gyn Trial).

Int J Gynecol Cancer 2020 12 27;30(12):1975-1982. Epub 2020 Nov 27.

Department of Gynecology with Center for Oncological Surgery, European Competence Center for Ovarian Cancer, Charite Universitatsmedizin Berlin, Berlin, Germany.

Background: Surgery for gynecological cancer involves highly invasive and complex procedures potentially associated with various complications, which can cause extended hospital stays and delay of subsequent therapy, with a detrimental effect on the prognosis. The aim of this study was to explore and define the predictors of severe postoperative complications in patients undergoing surgery for gynecologic cancer.

Methods: Patients undergoing surgery for gynecologic cancers were analyzed prospectively from October 2015 through January 2017. Using validated assessment tools preoperatively, we assessed comorbidities, performance status, quality of life, nutritional and body composition by bioelectrical impedance analysis, and the surgical data of each patient. Surgical complications were graded using the Clavien-Dindo criteria. Using stepwise logistic regression models, we identified predictive markers for postoperative complications.

Results: Of the 226 enrolled patients, 40 (17.7%) experienced a grade ≥IIIb complication according to the Clavien-Dindo criteria. In the regression analysis, overweight/obesity (body mass index >25) (OR 6.41, 95% CI 2.38 to 17.24; p<0.001) and impaired physical functioning defined by a quality of life questionnaire (OR 4.19, 95% CI 1.84 to 9.50; p=0.001) emerged as significant predictors of postoperative complications. Moreover, postoperative complications were predicted by phase angle of bioelectrical impedance analysis <4.75° (OR 3.11, 95% CI 1.35 to 7.16; p=0.008) and Eastern Cooperative Oncology Group (ECOG) performance status >1 (OR 2.51, 95% CI 1.06 to 5.92; p=0.04). Intraoperative factors associated with higher risk of postoperative complications were increased use of norepinephrine (>11 µg/kg/min) (OR 5.59, 95% CI 2.16 to 14.44; p<0.001) and performance of large bowel resection (OR 4.28, 95% CI 1.67 to 10.97; p=0.002).

Conclusion: In patients undergoing surgery for gynecological cancer, preoperative evaluation of performance status according to ECOG, domains of quality of life and nutritional status, as well as intraoperative monitoring of risk factors, might help to identify patients at high risk for severe postoperative complications, and thus reduce surgical morbidity and mortality.
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http://dx.doi.org/10.1136/ijgc-2020-001879DOI Listing
December 2020

Disseminated inflammation of the central nervous system associated with acute hepatitis E: a case report.

BMC Neurol 2020 Oct 27;20(1):391. Epub 2020 Oct 27.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.

Background: Hepatitis E infection affects over 20 million people worldwide. Reports of neurological manifestations are largely limited to the peripheral nervous system. We report a middle-aged genotype 3c male patient with acute hepatitis E virus (HEV) infection and severe neurological deficits with evidence of multiple disseminated inflammatory lesions of the central nervous system.

Case Presentation: A 42-year-old male patient presented to our emergency department with musculoskeletal weakness, bladder and bowel retention, blurred vision and ascending hypoesthesia up to the level of T8. Serology showed elevated liver enzymes and positive IgM-titers of hepatitis E. Analysis of cerebrospinal fluid (CSF) showed mild pleocytosis and normal levels of glucose, lactate and protein. HEV-RNA-copies were detected in the CSF and stool. Within 3 days after admission the patient became paraplegic, had complete visual loss and absent pupillary reflexes. MRI showed inflammatory demyelination of the optic nerve sheaths, multiple subcortical brain regions and the spinal cord. Electrophysiology revealed axonal damage of the peroneal nerve on both sides with absent F-waves. Treatment was performed with methylprednisolone, two cycles of plasma exchange (PLEX), one cycle of intravenous immunoglobulins (IVIG) and ribavirin which was used off-label. Liver enzymes normalized after 1 week and serology was negative for HEV-RNA after 3 weeks. Follow-up MRI showed progressive demyelination and new leptomeningeal enhancement at the thoracic spine and cauda equina 4 weeks after admission. Four months later, after rehabilitation was completed, repeated MRI showed gliotic transformation of the spinal cord without signs of an active inflammation. Treatment with rituximab was initiated. The patient remained paraplegic and hypoesthesia had ascended up to T5. Nevertheless, he regained full vision.

Conclusions: Our case indicates a possible association of acute HEV infection with widespread disseminated central nervous system inflammation. Up to now, no specific drugs have been approved for the treatment of acute HEV infection. We treated our patient off-label with ribavirin and escalated immunomodulatory therapy considering clinical progression and the possibility of an autoimmune response targeting nerve cell structures. While response to treatment was rather limited in our case, detection of HEV in patients with acute neurological deficits might help optimize individual treatment strategies.
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http://dx.doi.org/10.1186/s12883-020-01952-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590485PMC
October 2020

Variability of symptoms in neuralgic amyotrophy following infection with SARS-CoV-2.

Muscle Nerve 2021 01 14;63(1):E8-E9. Epub 2020 Oct 14.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

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http://dx.doi.org/10.1002/mus.27084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536943PMC
January 2021

Risk of Adverse Clinical Outcomes in Hyponatremic Adult Patients Hospitalized for Acute Medical Conditions: A Population-Based Cohort Study.

J Clin Endocrinol Metab 2020 11;105(11)

Endocrinology, Diabetes, and Metabolism, University Hospital Basel, Basel, Switzerland.

Context: Hyponatremia has been associated with excess long-term morbidity and mortality. However, effects during hospitalization are poorly studied.

Objective: The objective of this work is to examine the association of hyponatremia with the risk of in-hospital mortality, 30-day readmission, and other short-term adverse events among medical inpatients.

Design And Setting: A population-based cohort study was conducted using a Swiss claims database of medical inpatients from January 2012 to December 2017.

Patients: Hyponatremic patients were 1:1 propensity-score matched with normonatremic medical inpatients.

Main Outcome Measure: The primary outcome was a composite of all-cause in-hospital mortality and 30-day hospital readmission. Secondary outcomes were intensive care unit (ICU) admission, intubation rate, length-of-hospital stay (LOS), and patient disposition after discharge.

Results: After matching, 94 352 patients were included in the cohort. Among 47 176 patients with hyponatremia, 8383 (17.8%) reached the primary outcome compared with 7994 (17.0%) in the matched control group (odds ratio [OR] 1.06 [95% CI, 1.02-1.10], P = .001). Hyponatremic patients were more likely to be admitted to the ICU (OR 1.43 [95% CI, 1.37-1.50], P < .001), faced a 56% increase in prolonged LOS (95% CI, 1.52-1.60, P < .001), and were admitted more often to a postacute care facility (OR 1.38 [95% CI 1.34-1.42, P < .001). Of note, patients with the syndrome of inappropriate antidiuresis (SIAD) had lower in-hospital mortality (OR 0.67 [95% CI, 0.56-0.80], P < .001) as compared with matched normonatremic controls.

Conclusion: In this study, hyponatremia was associated with increased risk of short-term adverse events, primarily driven by higher readmission rates, which was consistent among all outcomes except for decreased in-hospital mortality in SIAD patients.
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http://dx.doi.org/10.1210/clinem/dgaa547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500475PMC
November 2020

Cost-effectiveness of edoxaban vs low-molecular-weight heparin and warfarin for cancer-associated thrombosis in Brazil.

Thromb Res 2020 12 11;196:4-10. Epub 2020 Aug 11.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Division of Healthcare Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany.

Background: Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. In Brazil, even though low-molecular-weight heparin (LMWH) is the gold standard of care for the management of cancer-associated thrombosis (CAT), its cost limits its use and therefore warfarin is commonly prescribed. Direct oral anticoagulants (DOACs), such as edoxaban, have been introduced as an alternative in this setting.

Objective: The aim of this study was to compare the cost-effectiveness of edoxaban with LMWH (Model 1) and warfarin (Model 2) to support clinicians and hospitals when choosing an anticoagulant to manage CAT.

Materials And Methods: Cost-effectiveness analyses were performed using Markov state-transition models over a timeframe of 5 years, in a hypothetical, 64 years-old patients cancer population with an index VTE event. Transition probabilities, costs, quality-adjusted life years (QALYs) and risk reductions were either derived from the literature, estimated or calculated. A willingness-to-pay limit of 3 Gross Domestic Product (GDP) per head was used. Deterministic and probabilistic sensitivity analyses were performed for robustness. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per QALY gained.

Results: Model 1 base case analysis demonstrated dominance of edoxaban compared to LMWH, with an ICER of $5204.46, representing cost saved per QALY lost. In Model 2, edoxaban was associated with a $736.90 cost increase vs. warfarin, with an ICER of $2541.03. Sensitivity analyses confirmed base-case results.

Conclusion: Edoxaban represents a cost-saving alternative to LMWH for the management of CAT and is cost-effective vs. warfarin.
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http://dx.doi.org/10.1016/j.thromres.2020.08.014DOI Listing
December 2020

Universal laboratory testing for SARS-CoV-2 in hyperacute stroke during the COVID-19 pandemic.

J Stroke Cerebrovasc Dis 2020 Sep 20;29(9):105061. Epub 2020 Jun 20.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, Dresden 01307, Germany. Electronic address:

Objective: Stroke patients are thought to be at increased risk of Coronavirus Disease 2019 (COVID-19). To evaluate yield of universal laboratory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute stroke patients and its impact on hyperacute stroke care.

Methods: Between weeks 14 and 18 in 2020, a protected code stroke protocol including infection control screening and laboratory testing for SARS-CoV-2 was prospectively implemented for all code stroke patients upon arrival to the emergency department. If infection control screen was positive, patients received protective hygienic measures and laboratory test results were available within four hours from testing. In patients with negative screen, laboratory results were available no later than the next working day. Door-to-imaging times of patients treated with thrombolysis or thrombectomy were compared with those of patients treated during the preceding weeks 1 to 13 in 2020.

Results: During the 4-weeks study period, 116 consecutive code stroke patients underwent infection control screen and laboratory testing for SARS-CoV-2. Among 5 (4.3%) patients whose infection control screen was positive, no patient was tested positive for SARS-CoV-2. All patients with negative infection control screens had negative test results. Door-to-imaging times of patients treated with thrombolysis and/or thrombectomy were not different to those treated during the preceding weeks (12 [9-15] min versus 13 [11-17] min, p = 0.24).

Conclusions: Universal laboratory testing for SARS-CoV-2 provided useful information on patients' infection status and its implementation into a protected code stroke protocol did not adversely affect hyperacute stroke care.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7305910PMC
September 2020

Excess Mortality Among Hospitalized Patients With Hypopituitarism-A Population-Based, Matched-Cohort Study.

J Clin Endocrinol Metab 2020 11;105(11)

Division of Endocrinology, Diabetes, and Metabolism, University Hospital Basel, Basel, Switzerland.

Context: Patients with hypopituitarism face excess mortality in the long-term outpatient setting. However, associations of pituitary dysfunction with outcomes in acutely hospitalized patients are lacking.

Objective: The objective of this work is to assess clinical outcomes of hospitalized patients with hypopituitarism with or without diabetes insipidus (DI).

Design, Setting, And Patients: In this population-based, matched-cohort study from 2012 to 2017, hospitalized adult patients with a history of hypopituitarism were 1:1 propensity score-matched with a general medical inpatient cohort.

Main Outcome Measures: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause readmission rates within 30 days and 1 year, intensive care unit (ICU) admission rates, and length of hospital stay.

Results: After matching, 6764 cases were included in the study. In total, 3382 patients had hypopituitarism and of those 807 (24%) suffered from DI. All-cause in-hospital mortality occurred in 198 (5.9%) of patients with hypopituitarism and in 164 (4.9%) of matched controls (odds ratio [OR] 1.32, [95% CI, 1.06-1.65], P = .013). Increased mortality was primarily observed in patients with DI (OR 3.69 [95% CI, 2.44-5.58], P < .001). Patients with hypopituitarism had higher ICU admissions (OR 1.50 [95% CI, 1.30-1.74], P < .001), and faced a 2.4-day prolonged length of hospitalization (95% CI, 1.94-2.95, P < .001) compared to matched controls. Risk of 30-day (OR 1.31 [95% CI, 1.13-1.51], P < .001) and 1-year readmission (OR 1.29 [95% CI, 1.17-1.42], P < .001) was higher among patients with hypopituitarism as compared with medical controls.

Conclusions: Patients with hypopituitarism are highly vulnerable once hospitalized for acute medical conditions with increased risk of mortality and adverse clinical outcomes. This was most pronounced among those with DI.
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http://dx.doi.org/10.1210/clinem/dgaa517DOI Listing
November 2020

Association of history of cerebrovascular disease with severity of COVID-19.

J Neurol 2021 Mar 6;268(3):773-784. Epub 2020 Aug 6.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.

Objective: To determine whether a history of cerebrovascular disease (CVD) increases risk of severe coronavirus disease 2019 (COVID-19).

Methods: In a retrospective multicenter study, we retrieved individual data from in-patients treated March 1 to April 15, 2020 from COVID-19 registries of three hospitals in Saxony, Germany. We also performed a systematic review and meta-analysis following PRISMA recommendations using PubMed, EMBASE, Cochrane Library databases and bibliographies of identified papers (last search on April 11, 2020) and pooled data with those deriving from our multicenter study. Of 3762 records identified, 11 eligible observational studies of laboratory-confirmed COVID-19 patients were included in quantitative data synthesis. Risk ratios (RR) of severe COVID-19 according to history of CVD were pooled using DerSimonian and Laird random effects model. Between-study heterogeneity was assessed using Cochran's Q and I2-statistics. Severity of COVID-19 according to definitions applied in included studies was the main outcome. Sensitivity analyses were conducted for clusters of studies with equal definitions of severity.

Results: Pooled analysis included data from 1906 laboratory-confirmed COVID-19 patients (43.9% females, median age ranging from 39 to 76 years). Patients with previous CVD had higher risk of severe COVID-19 than those without [RR 2.07, 95% confidence interval (CI) 1.52-2.81; p < 0.0001]. This association was also observed in clusters of studies that defined severe manifestation of the disease by clinical parameters (RR 1.44, 95% CI 1.22-1.71; p < 0.0001), necessity of intensive care (RR 2.79, 95% CI 1.83-4.24; p < 0.0001) and in-hospital death (RR 2.18, 95% CI 1.75-2.7; p < 0.0001).

Conclusion: A history of CVD might constitute an important risk factor of unfavorable clinical course of COVID-19  suggesting a need of tailored infection prevention and clinical management strategies for this population at risk.
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http://dx.doi.org/10.1007/s00415-020-10121-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407424PMC
March 2021

Examinations and assessments in patients with a newly acquired spinal cord injury - retrospective chart analysis as part of a quality improvement project.

Swiss Med Wkly 2020 Jul 30;150:w20291. Epub 2020 Jul 30.

Swiss Paraplegic Centre (SPC), Nottwil, Switzerland / Department of Urology, Inselspital, Bern University Hospital, University of Bern, Switzerland.

Aims Of The Study: Examinations and assessments can be used to ensure good quality rehabilitation. Within the framework of a quality improvement project, the aims of the current analysis were: first, to analyse the time points of selected examinations and assessments in the rehabilitation process of patients with a newly acquired spinal cord injury. Second, to identify differences between the subgroups with different aetiologies, levels and completeness of spinal cord injuries. And third, to compare the examinations and assessments performed with the guideline recommendations and to use discrepancies as a starting point for a quality improvement project.

Methods: In this retrospective chart analysis, adult patients with a newly acquired spinal cord injury who were admitted to a single specialised acute care and rehabilitation clinic for their first rehabilitation between December 2013 and December 2014 were included and assessed until discharge. The main objective was to assess the time to examinations or assessments after injury or hospital admission in comparison to the respective recommendations. Analyses were done using time-to-event analysis and represented graphically using Kaplan-Meier plots.

Results: Of the 105 patients included in this study (median age 58 years, 29% female), 61% had a traumatic and 39% a non-traumatic spinal cord injury; 39% were paraplegic and 61% were quadriplegic; and 59% had a motor complete and 41% a sensor-motor incomplete spinal cord injury. The percentage of patients for whom the respective assessment or examination was performed and the percentage of these patients for whom it performed within the recommended time were: 90% and 71% for magnetic resonance imaging; 85% and 90% for computed tomography; 87% and 79% for the manual muscle test; 95% and 59% for the International Standards for Neurological Classification of Spinal Cord (ISNCSCI); 84% and 50% for electrophysiological assessment; 73% and 90% for urodynamic testing; and 49% and 53% for lung function testing.

Conclusions: Our data suggest a relevant gap between recommendations and clinical routine for time to some assessments after spinal cord injury. Within the framework of a quality improvement project, the next steps should be to build a national and international consensus on specific time frames for examinations and assessments in patients with a newly acquired spinal cord injury and thereafter, to develop an institutional implementation strategy.    .
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http://dx.doi.org/10.4414/smw.2020.20291DOI Listing
July 2020

Neuralgic amyotrophy following infection with SARS-CoV-2.

Muscle Nerve 2020 10 10;62(4):E68-E70. Epub 2020 Aug 10.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

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http://dx.doi.org/10.1002/mus.27035DOI Listing
October 2020

Association of Hypertensive Intracerebral Hemorrhage with Left Ventricular Hypertrophy on Transthoracic Echocardiography.

J Clin Med 2020 Jul 8;9(7). Epub 2020 Jul 8.

Dresden Neurovascular Center, Department of Neurology, Dresden University of Technology, 01307 Dresden, Germany.

Introduction: Arterial hypertension is the most frequent cause for spontaneous intracerebral hemorrhage (sICH) and may also cause left ventricular hypertrophy (LVH). We sought to analyze whether hypertensive sICH etiology is associated with LVH.

Methods: We analyzed consecutive patients with sICH who were admitted to our tertiary stroke center during a four-year period and underwent transthoracic echocardiography (TTE) as part of the diagnostic work-up. We defined hypertensive sICH as typical localization of hemorrhage in patients with arterial hypertension and no other identified sICH etiology. We defined an increased end-diastolic interventricular septal wall thickness of ≥11 mm on TTE as a surrogate parameter for LVH.

Results: Among 395 patients with sICH, 260 patients (65.8%) received TTE as part of their diagnostic work-up. The median age was 71 years (interquartile range (IQR) 17), 160 patients (61.5%) were male, the median baseline National Institute of Health Stroke Scale (NIHSS) score was 8 (IQR 13). Of these, 159 (61.2%) patients had a hypertensive sICH and 156 patients (60%) had LVH. In univariable (113/159 (71.1%) vs. 43/101 (42.6%); odds ratio (OR) 3.31; 95% confidence interval (CI) 1.97-5.62); and multivariable (adjusted OR 2.95; CI 1.29-6.74) analysis, hypertensive sICH was associated with LVH.

Conclusions: In patients with sICH, LVH is associated with hypertensive bleeding etiology. Performing TTE is meaningful for diagnosis of comorbidities and clarification of bleeding etiology in these patients. Future studies should include long-term outcome parameters and assess left ventricular mass as main indicator for LVH.
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http://dx.doi.org/10.3390/jcm9072148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408960PMC
July 2020

Randomized controlled three-arm study of NADA acupuncture for alcohol addiction.

Addict Behav 2020 11 31;110:106488. Epub 2020 May 31.

Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. Electronic address:

Introduction: Alcohol addiction compromises cardiovascular health, possibly due to impaired control of the heart and vasculature by the autonomic nervous system. We aimed to assess the effects of National Acupuncture Detoxification Association (NADA) acupuncture on cardiovascular autonomic functions, psychiatric comorbidities and abstinence in patients addicted to alcohol.

Material And Methods: A randomized sham controlled three-arm study was undertaken in 72 patients (nine females, aged 43.7 ± 9.2 years, mean ± SD) undergoing in-patient rehabilitation for alcohol addiction. Patients were randomly allocated (1:1:1) to receive twenty 30-minute NADA or sham acupuncture sessions within six weeks or no intervention. They were evaluated for craving, depression, anxiety and autonomic control of the heart (heart rate variability, HRV), vasculature (laser Doppler flowmetry) and sweat glands (sympathetic skin response). Testing was performed at baseline, immediately post intervention (sham intervention or control period, respectively) and another four weeks later. Abstinence was assessed one year after study completion.

Results: Patients in the NADA arm displayed increased HRV immediately post-intervention compared to baseline (SDNN: 72.8 ms ± 34.2 ms vs. 57.9 ms ± 31.2 ms, p = 0.001). This increase was sustained four weeks later (66.2 ms ± 32.4 ms, p = 0.015). HRV remained unaltered following sham or no acupuncture (p = n.s.). Autonomic function of vasculature and sweat glands, psychiatric comorbidities and one-year abstinence did not differ between study arms.

Conclusions: NADA acupuncture may improve autonomic cardiac function. However, this improvement appears not to translate into alleviation of psychiatric comorbidities or sustained abstinence.
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http://dx.doi.org/10.1016/j.addbeh.2020.106488DOI Listing
November 2020

Myxedema psychosis: A protocol for a systematic review and a pooled analysis.

Medicine (Baltimore) 2020 Jun;99(26):e20778

Internal Medicine Department, Hamad Medical Corporation, Doha, Qatar.

Background: Myxedema psychosis (MP) is a rare presentation of hypothyroidism. Although known for >70 years, a significant lack of systematic literature describing this condition exists. This limits the clinician's ability to identify and manage this entity properly. Hence, we aimed to systematically review the literature and summarize the presentation, diagnosis, management, and outcomes of this rare entity.

Methods: Systematic review following PRISMA guidance. We will perform a comprehensive search of PubMed, Medline, Embase, Google Scholar (first 300 hits), and Cochrane databases for published observational studies, case series, and case reports. We will use descriptive statistics to provide summary estimates of demographics, common presenting features, laboratory test results, imaging findings, treatment administered, and outcomes. Moreover, continuous variables will be compared by the Wilcoxon Mann Whitney test, whereas categorical variables will be assessed by the χ test. Bivariate and multivariate regression will be performed to assess risk factors associated with poor outcome. A scoping review revealed that a meta-analysis might not be feasible owing to the paucity of systematic studies describing the condition.

Results: This is the first systematic review examining this rare entity. Thus, the result of which will be significant. We hope that this review will help in identifying relevant predictive clinical or laboratory characteristics. Additionally, it identifies the best treatment strategies. The findings of this review will help increase our knowledge of this condition so as to recognize this condition promptly. Also, it will assist in differentiating MP from masqueraders, such as Hashimoto encephalopathy (HE). The results of this review will be published in a peer-reviewed journal.

Conclusion: This is the first systematic review exploring MP demographics, diagnosis treatment, and outcomes. The information gathered by this review will be necessary for patients, clinicians, researchers, and guideline makers.

Prospero Registration Number: CRD42020160310.
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http://dx.doi.org/10.1097/MD.0000000000020778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328932PMC
June 2020

Deep Penetrating Nevus and Borderline-Deep Penetrating Nevus: A Literature Review.

Front Oncol 2020 20;10:837. Epub 2020 May 20.

Division of Health Care Sciences, Center for Clinical Research and Management Education, Dresden International University, Dresden, Germany.

Deep penetrating nevi (DPN) are rare melanocytic nevi, which can exhibit atypical histological features hampering the differentiation from malignant melanoma. DPN are considered benign melanocytic lesions, but rare spread to lymph nodes and unfavorable clinical outcomes associated with borderline/atypical DPN (B-DPN) has been reported. Since no guidelines are available for DPN and B-DPN, we aimed to review the literature on DPN and B-DPN to assess the management and prognosis. We screened 3,513 references from EMBASE, Scopus and Medline databases, and included 15 studies with a total of 355 DPN patients and 48 B-DPN patients. Therapeutic interventions ranged from simple excision to wide excisions and sentinel lymph node biopsy (SLNB), with block lymph node dissection in some positive SLNB cases. Follow-up periods ranged from 3 months to 23 years during which a total of five recurrences, two in DPN and three in B-DPN group, and three metastases, in B-DPN group, were reported. While some of the included studies comprised clinical and histopathological correlation, few included genetic assessment. The present review highlights the need for prospective cohort studies applying composite measures to identify effective regimens of diagnostic workup and treatment in DPN and B-DPN.
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http://dx.doi.org/10.3389/fonc.2020.00837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251176PMC
May 2020

Variations in Cardiovascular Structure, Function, and Geometry in Midlife Associated With a History of Hypertensive Pregnancy.

Hypertension 2020 06 20;75(6):1542-1550. Epub 2020 Apr 20.

From the Oxford Cardiovascular Clinical Research Facility, Division of Cardiovascular Medicine, Radcliffe Department of Medicine (H.B., M.L., A.V., R.U., A.B., R.D., C.S., Y.K., C.Y.L.A., W.W., O.H., A.J.L., P. Leeson), University of Oxford, United Kingdom.

Hypertensive pregnancy is associated with increased maternal cardiovascular risk in later life. A range of cardiovascular adaptations after pregnancy have been reported to partly explain this risk. We used multimodality imaging to identify whether, by midlife, any pregnancy-associated phenotypes were still identifiable and to what extent they could be explained by blood pressure. Participants were identified by review of hospital maternity records 5 to 10 years after pregnancy and invited to a single visit for detailed cardiovascular imaging phenotyping. One hundred seventy-three women (age, 42±5 years, 70 after normotensive and 103 after hypertensive pregnancy) underwent magnetic resonance imaging of the heart and aorta, echocardiography, and vascular assessment, including capillaroscopy. Women with a history of hypertensive pregnancy had a distinct cardiac geometry with higher left ventricular mass index (49.9±7.1 versus 46.0±6.5 g/m; =0.001) and ejection fraction (65.6±5.4% versus 63.7±4.3%; =0.03) but lower global longitudinal strain (-18.31±4.46% versus -19.94±3.59%; =0.02). Left atrial volume index was also increased (40.4±9.2 versus 37.3±7.3 mL/m; =0.03) and E:A reduced (1.34±0.35 versus 1.52±0.45; =0.003). Aortic compliance (0.240±0.053 versus 0.258±0.063; =0.046) and functional capillary density (105.4±23.0 versus 115.2±20.9 capillaries/mm; =0.01) were reduced. Only differences in functional capillary density, left ventricular mass, and atrial volume indices remained after adjustment for blood pressure (<0.01, =0.01, and =0.04, respectively). Differences in cardiac structure and geometry, as well as microvascular rarefaction, are evident in midlife after a hypertensive pregnancy, independent of blood pressure. To what extent these phenotypic patterns contribute to cardiovascular disease progression or provide additional measures to improve risk stratification requires further study.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682801PMC
June 2020

Safety of inter-hospital transfer of patients with acute ischemic stroke for evaluation of endovascular thrombectomy.

Sci Rep 2020 03 27;10(1):5655. Epub 2020 Mar 27.

Department of Neurology, Dresden Neurovascular Center, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.

Stroke networks facilitate access to endovascular treatment (EVT) for patients with ischemic stroke due to large vessel occlusion. In this study we aimed to determine the safety of inter-hospital transfer and included all patients with acute ischemic stroke who were transferred within our stroke network for evaluation of EVT between 06/2016 and 12/2018. Data were derived from our prospective EVT database and transfer protocols. We analyzed major complications and medical interventions associated with inter-hospital transfer. Among 615 transferred patients, 377 patients (61.3%) were transferred within our telestroke network and had transfer protocols available (median age 76 years [interquartile range, IQR 17], 190 [50.4%] male, median baseline NIHSS score 17 [IQR 8], 246 [65.3%] drip-and-ship i.v.-thrombolysis). No patient suffered from cardio-respiratory failure or required emergency intubation or cardiopulmonary resuscitation during the transfer. Among 343 patients who were not intubated prior departure, 35 patients (10.2%) required medical interventions during the transfer. The performance of medical interventions was associated with a lower EVT rate and higher mortality at three months. In conclusion, the transfer of acute stroke patients for evaluation of EVT was not associated with major complications and transfer-related medical interventions were required in a minority of patients.
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http://dx.doi.org/10.1038/s41598-020-62528-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101346PMC
March 2020
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