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Haj Mohamad Ebrahim Ketabforoush A, Hosseinpour A, Habibi MA, Ariaei A, Farajollahi M, Chegini R, Mirzaasgari Z. Optimizing Acute Ischemic Stroke Outcomes: The Role of Tenecteplase Before Mechanical Thrombectomy. Clin Ther 2024; 46:e10-e20. [PMID: 39266330 DOI: 10.1016/j.clinthera.2024.08.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 08/09/2024] [Accepted: 08/13/2024] [Indexed: 09/14/2024]
Abstract
PURPOSE Acute ischemic stroke (AIS) is a life-threatening condition demanding prompt reperfusion to salvage brain tissue. Thrombolytic drugs, like tenecteplase (TNK), offer clot dissolution, but time constraints and contraindications limit their use. Mechanical thrombectomy (MT) revolutionized AIS treatment, especially for large vessel occlusions (LVO). Recent evidence suggests that administering TNK before MT improves recanalization and outcomes, challenging the dominance of alteplase. METHODS Relevant articles focusing on TNK before MT were retrieved from PubMed, Scopus, and Web of Science, looking for randomized controlled trials (RCT), clinical trials, and meta-analyses in humans until 2024. FINDINGS TNK, a genetically engineered thrombolytic, exhibits superior fibrin specificity and a longer half-life than alteplase. Clinical trials comparing TNK and alteplase before MT showcase enhanced recanalization, functional outcomes, and safety with TNK. Advanced neuroimaging aids patient selection, though its cost-effectiveness warrants consideration. Dosing studies favor a 0.25 mg/kg dose for efficacy and reduced complications. Clinical guidelines from various associations acknowledge TNK's potential as an alteplase alternative for AIS treatment, particularly for LVOs eligible for thrombectomy. IMPLICATIONS In conclusion, TNK emerges as a promising option for bridging therapy in AIS, displaying efficacy and safety benefits, especially when administered before MT. Its fibrin specificity, longer half-life, and potential for improved outcomes position TNK as a viable alternative to alteplase, potentially transforming the landscape of AIS treatment strategies. While limitations like small sample sizes and variations in protocols exist, future research should focus on large-scale RCT, subgroup analyses, and cost-effectiveness evaluations to further elucidate TNK's role in optimizing AIS management.
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Affiliation(s)
| | - Ali Hosseinpour
- Department of Neurology, Clinical Research Development Unit (CRDU) of Shahid Rajaei Hospital, Alborz University of Medical Sciences, Karaj, Iran
| | - Mohamad Amin Habibi
- Clinical Research Development Center, Shahid Beheshti Hospital, Qom University of Medical Sciences, Qom, Iran
| | - Armin Ariaei
- School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | | | - Rojin Chegini
- Metabolic liver disease research center, Isfahan University of medical sciences, Isfahan, Iran
| | - Zahra Mirzaasgari
- Department of Neurology, Firouzgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
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Prasad S, Jones EM, Gebreyohanns M, Kwon Y, Olson DM, Anderson JA, Savitz SI, Cruz-Flores S, Warach SJ, Rhodes CE, Goldberg MP, Ifejika NL. Multicenter exploration of tenecteplase transition factors: A quantitative analysis. J Stroke Cerebrovasc Dis 2024; 33:107592. [PMID: 38266690 DOI: 10.1016/j.jstrokecerebrovasdis.2024.107592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 01/02/2024] [Accepted: 01/20/2024] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.
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Affiliation(s)
- Sidarrth Prasad
- University of Texas Southwestern Medical Center, United States
| | - Erica M Jones
- University of Texas Southwestern Medical Center, United States
| | | | - Yoon Kwon
- University of Texas Southwestern Medical Center, United States
| | - DaiWai M Olson
- University of Texas Southwestern Medical Center, United States
| | | | - Sean I Savitz
- University of Texas Health Science Center at Houston, United States
| | | | - Steven J Warach
- Dell Medical School, The University of Texas at Austin, United States
| | - Charlotte E Rhodes
- The University of Texas Health Science Center at San Antonio, United States
| | - Mark P Goldberg
- The University of Texas Health Science Center at San Antonio, United States
| | - Nneka L Ifejika
- University of Texas Southwestern Medical Center, United States.
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Tang J, Tang J, Liao Y, Bai L, Luo T, Xu Y, Liu Z. An in vitro comparative study on clot lysis efficiency of urokinase and reteplase with the synergy of ultrasound needle. Heliyon 2024; 10:e26624. [PMID: 38463819 PMCID: PMC10920158 DOI: 10.1016/j.heliyon.2024.e26624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 02/16/2024] [Accepted: 02/16/2024] [Indexed: 03/12/2024] Open
Abstract
Objectives Ultrasound Needle, which is an improved ultrasonic horn device, has shown great potential for promoting the diffusion of thrombolytic drugs within clots and enhancing clot lysis efficiency. However, the clot lysis efficiency of different thrombolytic drugs with the synergy of Ultrasound Needle remains unknown. In this study, we aimed to compare the lysis efficiency of the non-fibrin-specific drug urokinase and fibrin-specific drug reteplase with the synergy of Ultrasound Needle. Materials and methods Twenty-five milliliters of human blood was incubated for 1.5 h to form in vitro clots and then received the corresponding treatment protocols: control group (normal saline), US group (10 min of Ultrasound Needle treatment), UK group (30000IU of urokinase), r-PA group (2 mg of reteplase), US + UK group, and US + r-PA group. After treatment, the morphological changes of the clots were analyzed by B-mode ultrasound imaging and hematoxylin and eosin (H&E) staining. Lysis efficiency was evaluated based on the relative end weight (final weight/initial weight). The fibrin density of the different groups after treatment was assessed by immunofluorescence staining. Results Morphological examination and relative end weight analysis showed that combination therapies induced a more thorough dissolution of clots compared with single therapies, and the US + r-PA group exhibited higher lysis efficiency than the US + UK group. In addition, immunofluorescence staining showed that the US + r-PA group had fewer remaining thrombus fibrins than the US + UK group after treatment. Conclusions The Ultrasound Needle can significantly improve the clot lysis efficiency of both fibrinolytic drugs, and fibrin-specific reteplase exhibited superior lysis efficiency over non-fibrin-specific urokinase with the synergy of the Ultrasound Needle.
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Affiliation(s)
| | | | - Yiyi Liao
- Department of Ultrasound, Xinqiao Hospital, Army Medical University, Chongqing, PR China
| | - Luhua Bai
- Department of Ultrasound, Xinqiao Hospital, Army Medical University, Chongqing, PR China
| | - Tingting Luo
- Department of Ultrasound, Xinqiao Hospital, Army Medical University, Chongqing, PR China
| | - Yali Xu
- Department of Ultrasound, Xinqiao Hospital, Army Medical University, Chongqing, PR China
| | - Zheng Liu
- Department of Ultrasound, Xinqiao Hospital, Army Medical University, Chongqing, PR China
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Prasad S, Jones EM, Gebreyohanns M, Aguilera V, Olson DM, Anderson JA, Savitz SI, Flores SC, Warach SJ, Rhodes CE, Goldberg MP, Ifejika NL. A qualitative study of barriers and facilitators to using tenecteplase to treat acute ischemic stroke. J Stroke Cerebrovasc Dis 2024; 33:107458. [PMID: 37956644 DOI: 10.1016/j.jstrokecerebrovasdis.2023.107458] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 10/03/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. METHODS Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. RESULTS Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. CONCLUSION Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment.
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Affiliation(s)
- Sidarrth Prasad
- University of Texas Southwestern Medical Center, United States
| | - Erica M Jones
- University of Texas Southwestern Medical Center, United States
| | | | | | - DaiWai M Olson
- University of Texas Southwestern Medical Center, United States
| | | | - Sean I Savitz
- University of Texas Health Science Center at Houston, United States
| | | | - Steven J Warach
- Dell Medical School, The University of Texas at Austin, United States
| | - Charlotte E Rhodes
- The University of Texas Health Science Center at San Antonio, United States
| | - Mark P Goldberg
- The University of Texas Health Science Center at San Antonio, United States
| | - Nneka L Ifejika
- University of Texas Southwestern Medical Center, United States.
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Checkouri T, Gerschenfeld G, Seners P, Yger M, Ben Hassen W, Chausson N, Olindo S, Caroff J, Marnat G, Clarençon F, Baron JC, Turc G, Alamowitch S. Early Recanalization Among Patients Undergoing Bridging Therapy With Tenecteplase or Alteplase. Stroke 2023; 54:2491-2499. [PMID: 37622385 DOI: 10.1161/strokeaha.123.042691] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 07/25/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND Intravenous thrombolysis (IVT) with alteplase or tenecteplase before mechanical thrombectomy is the recommended treatment for large-vessel occlusion acute ischemic stroke. There are divergent data on whether these agents differ in terms of early recanalization (ER) rates before mechanical thrombectomy, and little data on their potential differences stratified by ER predictors such as IVT to ER evaluation (IVT-to-EReval) time, occlusion site and thrombus length. METHODS We retrospectively compared the likelihood of ER after IVT with tenecteplase or alteplase in anterior circulation large-vessel occlusion acute ischemic stroke patients from the PREDICT-RECANAL (alteplase) and Tenecteplase Treatment in Ischemic Stroke (tenecteplase) French multicenter registries. ER was defined as a modified Thrombolysis in Cerebral Infarction score 2b-3 on the first angiographic run, or noninvasive vascular imaging in patients with early neurological improvement. Analyses were based on propensity score overlap weighting (leading to exact balance in patient history, stroke characteristics, and initial management between groups) and confirmed with adjusted logistic regression (sensitivity analysis). A stratified analysis based on pre-established ER predictors (IVT-to-EReval time, occlusion site, and thrombus length) was conducted. RESULTS Overall, 1865 patients were included. ER occurred in 156/787 (19.8%) and 199/1078 (18.5%) patients treated with tenecteplase or alteplase, respectively (odds ratio, 1.09 [95% CI, 0.83-1.44]; P=0.52). A differential effect of tenecteplase versus alteplase on the probability of ER according to thrombus length was observed (Pinteraction=0.003), with tenecteplase being associated with higher odds of ER in thrombi >10 mm (odds ratio, 2.43 [95% CI, 1.02-5.81]; P=0.04). There was no differential effect of tenecteplase versus alteplase on the likelihood of ER according to the IVT-to-EReval time (Pinteraction=0.40) or occlusion site (Pinteraction=0.80). CONCLUSIONS Both thrombolytics achieved ER in one-fifth of patients with large-vessel occlusion acute ischemic stroke without significant interaction with IVT-to-EReval time and occlusion site. Compared with alteplase, tenecteplase was associated with a 2-fold higher likelihood of ER in larger thrombi.
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Affiliation(s)
- Thomas Checkouri
- AP-HP, Service des Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Hôpital Saint-Antoine, Sorbonne Université, Paris, France (T.C., G.G., M.Y., S.A.)
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France (T.C., G.G., M.Y., S.A.)
| | - Gaspard Gerschenfeld
- AP-HP, Service des Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Hôpital Saint-Antoine, Sorbonne Université, Paris, France (T.C., G.G., M.Y., S.A.)
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France (T.C., G.G., M.Y., S.A.)
| | - Pierre Seners
- Service de Neurologie, GHU Paris Psychiatrie et Neurosciences, France (P.S.)
- Université de Paris, INSERM U1266, FHU Neurovasc, France (P.S., W.B.H., N.C., J.-C.B., G.T.)
- Service de Neurologie, Hôpital Fondation Rothschild, Paris, France (P.S.)
| | - Marion Yger
- AP-HP, Service des Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Hôpital Saint-Antoine, Sorbonne Université, Paris, France (T.C., G.G., M.Y., S.A.)
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France (T.C., G.G., M.Y., S.A.)
| | - Wagih Ben Hassen
- Université de Paris, INSERM U1266, FHU Neurovasc, France (P.S., W.B.H., N.C., J.-C.B., G.T.)
- Service de Neuroradiologie, GHU Paris Psychiatrie et Neurosciences, France (W.B.H.)
| | - Nicolas Chausson
- Université de Paris, INSERM U1266, FHU Neurovasc, France (P.S., W.B.H., N.C., J.-C.B., G.T.)
- Service de Neurologie, Unité Neuro-vasculaire, Hôpital Sud Francilien, Corbeil-Essonnes (N.C.)
| | | | - Jildaz Caroff
- AP-HP, Service de Neuroradiologie interventionnelle (NEURI), Hôpital Bicêtre, Université Paris-Saclay, Le Kremlin-Bicêtre, France (J.C.)
| | - Gaultier Marnat
- Service de Neuroradiologie diagnostique et interventionnelle (G.M.), France
- CHU de Bordeaux, France (G.M.)
| | - Frédéric Clarençon
- AP-HP, Service de Neuroradiologie, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France (F.C.)
| | - Jean-Claude Baron
- Université de Paris, INSERM U1266, FHU Neurovasc, France (P.S., W.B.H., N.C., J.-C.B., G.T.)
| | - Guillaume Turc
- Université de Paris, INSERM U1266, FHU Neurovasc, France (P.S., W.B.H., N.C., J.-C.B., G.T.)
| | - Sonia Alamowitch
- AP-HP, Service des Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Hôpital Saint-Antoine, Sorbonne Université, Paris, France (T.C., G.G., M.Y., S.A.)
- STARE team, iCRIN, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France (T.C., G.G., M.Y., S.A.)
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Wang YD, Lin JF, Huang XY, Han XD. Successful treatment of veno-arterial extracorporeal membrane oxygenation complicated with left ventricular thrombus by intravenous thrombolysis: A case report. World J Clin Cases 2023; 11:3323-3329. [PMID: 37274033 PMCID: PMC10237126 DOI: 10.12998/wjcc.v11.i14.3323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/22/2023] [Accepted: 04/04/2023] [Indexed: 05/16/2023] Open
Abstract
BACKGROUND Left ventricular thrombus is a rare condition, for which appropriate treatments are not extensively studied. Although it can be treated by thrombectomy, such surgery can be difficult and risky, and not every patient can tolerate the surgery.
CASE SUMMARY We report a case of a middle-aged man receiving veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for acute myocardial infarction who developed left ventricular thrombus despite systemic anticoagulation. After systemic thrombolysis with urokinase, the left ventricular thrombus disappeared, ECMO was successfully withdrawn 9 days later, and the patient recovered and was discharged from hospital.
CONCLUSION Systemic thrombolysis is a treatment option for left ventricular thrombus in addition to anticoagulation and thrombectomy.
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Affiliation(s)
- Ya-Dong Wang
- Intensive Care Medicine, Nantong Third People's Hospital, Nantong 226000, Jiangsu Province, China
| | - Jin-Feng Lin
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong 226000, Jiangsu Province, China
| | - Xiao-Ying Huang
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong 226000, Jiangsu Province, China
| | - Xu-Dong Han
- Critical Care Medicine, Nantong Third People’s Hospital, Nantong 226000, Jiangsu Province, China
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Yu W. Vasospasm and Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: Recent Advances and Future Directions in Translational Research. Transl Stroke Res 2023; 14:119-120. [PMID: 35501554 DOI: 10.1007/s12975-022-01028-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 04/25/2022] [Accepted: 04/25/2022] [Indexed: 11/25/2022]
Affiliation(s)
- Wengui Yu
- Department of Neurology, University of California, Irvine, USA.
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Masomi-Bornwasser J, Fabrig O, Krenzlin H, König J, Tanyildizi Y, Kempski O, Ringel F, Keric N. Systematic Analysis of Combined Thrombolysis Using Ultrasound and Different Fibrinolytic Drugs in an in Vitro Clot Model of Intracerebral Hemorrhage. ULTRASOUND IN MEDICINE & BIOLOGY 2021; 47:1334-1342. [PMID: 33549380 DOI: 10.1016/j.ultrasmedbio.2021.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 01/07/2021] [Accepted: 01/07/2021] [Indexed: 06/12/2023]
Abstract
Adequate removal of blood clots by minimally invasive surgery seems to correlate with a better clinical outcome in patients with intracerebral hemorrhages (ICHs). Moreover, neurotoxic effects of recombinant tissue plasminogen activator have been reported. The aim of this study was to improve fibrinolysis using an intra-clot ultrasound application with tenecteplase and urokinase in our established ICH clot model. One hundred thirty clots were produced from 25 or 50 mL of human blood, incubated for different periods and equipped with drainage, through which an ultrasound catheter was placed in 65 treatment clots for 1 h, randomly allocated into three groups: administration of ultrasound, administration of 60 IU of tenecteplase or administration of 30,000 IU urokinase. Relative end weights were compared. This study found a significant increase in thrombolysis caused by a combination of ultrasound and fibrinolytic drugs, whereas ultrasound and tenecteplase are significantly more effective in the treatment of larger and aged clots.
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Affiliation(s)
- Julia Masomi-Bornwasser
- Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
| | - Oliver Fabrig
- Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Harald Krenzlin
- Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Jochem König
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Centre of the Johannes Gutenberg University, Mainz, Germany
| | - Yasemin Tanyildizi
- Department of Neuroradiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Oliver Kempski
- Institute for Neurosurgical Pathophysiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Florian Ringel
- Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
| | - Naureen Keric
- Department of Neurosurgery, University Medical Center of the Johannes Gutenberg University, Mainz, Germany
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