1.Non-Inferiority Trials in Stroke Research: What Are They, and How Should We Interpret Them?
Linxin LI ; Vasileios-Arsenios LIOUTAS ; Ralph K. AKYEA ; Stefan GERNER ; Kui Kai LAU ; Emily RAMAGE ; Aristeidis H. KATSANOS ; George HOWARD ; Philip M. BATH
Journal of Stroke 2025;27(1):41-51
Randomized clinical trials are important in both clinical and academic stroke communities with increasing numbers of new design concepts emerging. One of the “less traditional” designs that have gained increasing interest in the last decade is non-inferiority trials. Whilst the concept might appear straightforward, the design and interpretation of non-inferiority trials can be challenging. In this review, we will use exemplars from clinical trials in the stroke field to provide an overview of the advantages and limitations of non-inferiority trials and how they should be interpreted in stroke research.
2.Reinforcement of Transdural Angiogenesis: A Novel Approach to Treating Ischemic Stroke With Cerebral Perfusion Impairment
Journal of Stroke 2025;27(1):30-40
Cerebral hypoperfusion plays a critical role in early neurological deterioration and long-term outcomes in patients with acute ischemic stroke, which remains a major global health challenge. This review explored transdural angiogenesis as a promising therapeutic strategy to restore cerebral perfusion in patients with ischemic stroke. The multiple burr hole procedure has been preliminarily used as an indirect revascularization method to induce transdural arteriogenesis. Theoretically, its efficacy could be enhanced by combining it with angiogenic boosters, such as erythropoietin. Recent clinical and preclinical studies have revealed that this combination therapy promotes angiogenesis and arteriogenesis, leading to successful revascularization across the dura mater and improved cerebral blood flow. This strategy may be particularly beneficial for high-risk patients with recurrent ischemic events, such as those with moyamoya disease or intracranial arterial occlusion, representing an effective strategy when conventional medical treatments are insufficient. This review highlights the potential of transdural angiogenesis enhancement as a novel intervention for ischemic stroke, offering an alternative to thrombolysis or endovascular treatment, particularly in acute stroke patients with impaired cerebral perfusion. This approach has the potential to bridge the treatment gap for patients outside the therapeutic window for acute stroke interventions. Although further research is required to refine this technique and validate its efficacy in broader clinical settings, early results have revealed promising outcomes at reducing stroke-related complications and improving patient prognosis. This review indicates that this novel strategy may offer hope for managing ischemic stroke and related conditions associated with significant cerebral hypoperfusion.
3.Long-Term Incidence of Gastrointestinal Bleeding Following Ischemic Stroke
Jun Yup KIM ; Beom Joon KIM ; Jihoon KANG ; Do Yeon KIM ; Moon-Ku HAN ; Seong-Eun KIM ; Heeyoung LEE ; Jong-Moo PARK ; Kyusik KANG ; Soo Joo LEE ; Jae Guk KIM ; Jae-Kwan CHA ; Dae-Hyun KIM ; Tai Hwan PARK ; Kyungbok LEE ; Hong-Kyun PARK ; Yong-Jin CHO ; Keun-Sik HONG ; Kang-Ho CHOI ; Joon-Tae KIM ; Dong-Eog KIM ; Jay Chol CHOI ; Mi-Sun OH ; Kyung-Ho YU ; Byung-Chul LEE ; Kwang-Yeol PARK ; Ji Sung LEE ; Sujung JANG ; Jae Eun CHAE ; Juneyoung LEE ; Min-Surk KYE ; Philip B. GORELICK ; Hee-Joon BAE ;
Journal of Stroke 2025;27(1):102-112
Background:
and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes.
Methods:
We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data.
Results:
Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4.
Conclusion
Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.
7.Direct and Indirect Effects of Prolonged Exposure to Long Working Hours on Risk Stroke Subtypes in the CONSTANCES Cohort
Marc FADEL ; Grace SEMBAJWE ; Jian LI ; Annette LECLERC ; Fernando PICO ; Alexis SCHNITZLER ; Eric Richard FADEL ; Yves ROQUELAURE ; Alexis DESCATHA
Journal of Stroke 2025;27(1):154-157
8.Recanalization Outcomes and Procedural Complications in Patients With Acute Ischemic Stroke and COVID-19 Receiving Endovascular Treatment
João Pedro MARTO ; Davide STRAMBO ; George NTAIOS ; Thanh N NGUYEN ; Pawel WRONA ; Simon ESCALARD ; Simona MARCHESELLI ; Ossama Yassin MANSOUR ; Blanca FUENTES ; Malgorzata DOROBEK ; Marta NOWAKOWSKA-KOTAS ; Elena Oana TERECOASA ; Jonathan M. COUTINHO ; Mariana CARVALHO-DIAS ; Patricia CALLEJA ; João SARGENTO-FREITAS ; Ana PAIVA-NUNES ; Martin ŠRÁMEK ; Priyank KHANDELWAL ; Torcato MEIRA ; Mohamad ABDALKADER ; Pascal JABBOUR ; Martin KOVÁŘ ; Oscar AYO-MARTIN ; Patrik MICHEL ; Roman HERZIG ; Anna CZŁONKOWKSA ; Jelle DEMEESTERE ; Raul G. NOGUEIRA ; Alexander SALERNO ; Susanne WEGENER ; Philipp BAUMGARTNER ; Carlo W. CEREDA ; Giovanni BIANCO ; Morin BEYELER ; Marcel ARNOLD ; Emmanuel CARRERA ; Paolo MACHI ; Valerian ALTERSBERGER ; Leo BONATI ; Henrik GENSICKE ; Manuel BOLOGNESE ; Nils PETERS ; Stephan WETZEL ; Marta MAGRIÇO ; João NUNO RAMOS ; Rita MACHADO ; Carolina MAIA ; Egídio MACHADO ; Patrícia FERREIRA ; Teresa PINHO-E-MELO ; André PAULA ; Manuel Alberto CORREIA ; Pedro CASTRO ; Elsa AZEVEDO ; Luís ALBUQUERQUE ; José NUNO-ALVES ; Joana FERREIRA-PINTO ; Torcato MEIRA ; Liliana PEREIRA ; Miguel RODRIGUES ; André ARAÚJO ; Marta RODRIGUES ; Mariana ROCHA ; Ângelo PEREIRA-FONSECA ; Luís RIBEIRO ; Ricardo VARELA ; Sofia MALHEIRO ; Manuel CAPPELLARI ; Cecilia ZIVELONGHI ; Giulia SAJEVA ; Andrea ZINI ; Gentile MAURO ; Forlivesi STEFANO ; Ludovica MIGLIACCIO ; Maria SESSA ; Sara La GIOIA ; Alessandro PEZZINI ; Davide SANGALLI ; Marialuisa ZEDDE ; Rosario PASCARELLA ; Carlo FERRARESE ; Simone BERETTA ; Susanna DIAMANTI ; Ghil SCHWARZ ; Giovanni FRISULLO ; Pierre SENERS ; Candice SABBEN ; Michel PIOTIN ; Benjamin MAIER ; Guillaume CHARBONNIER ; Fabrice VUILLIER ; Loic LEGRIS ; Pauline CUISENIER ; Francesca R. VODRET ; Gaultier MARNAT ; Jean-Sebastien LIEGEY ; Igor SIBON ; Fabian FLOTTMANN ; Gabriel BROOCKS ; Nils-Ole GLOYER ; Ferdinand O. BOHMANN ; Jan Hendrik SCHAEFER ; Christian H. NOLTE ; Heinrich AUDEBERT ; Eberhard SIEBERT ; Marek SYKORA ; Wilfried LANG ; Julia FERRARI ; Lukas MAYER-SUESS ; Michael KNOFLACH ; Elke-Ruth GIZEWSKI ; Jeffrey STOLP ; Lotte J. STOLZE ; Paul J. NEDERKOORN ; Ido VAN-DEN-WIJNGAARD ; Joke DE MERIS ; Robin LEMMEN ; Sylvie DE RAEDT ; Fenne VANDERVORST ; Matthieu Pierre RUTGERS ; Antoine GUILMOT ; Anne DUSART ; Flavio BELLANTE ; Fernando OSTOS ; Guillermo GONZALEZ-ORTEGA ; Paloma MARTÍN-JIMÉNEZ ; Sebastian GARCÍA-MADRONA ; Antonio CRUZ-CULEBRAS ; Rocio VERA ; Maria-Consuelo MATUTE ; María ALONSO-DE-LECIÑANA ; Ricardo RIGUAL ; Exuperio DÍEZ-TEJEDOR ; Soledad PÉREZ-SÁNCHEZ ; Joan MONTANER ; Fernando DÍAZ-OTERO ; Natalia PEREZ-DE-LA-OSSA ; Belén FLORES-PINA ; Lucia MUÑOZ-NARBONA ; Angel CHAMORRO ; Alejandro RODRÍGUEZ-VÁZQUEZ ; Arturo RENÚ ; Francisco HERNANDEZ-FERNANDEZ ; Tomas SEGURA ; Herbert TEJADA-MEZA ; Daniel SAGARRA-MUR ; Marta SERRANO-PONZ ; Thant HLAING ; Isaiah SEE ; Robert SIMISTER ; David J. WERRING ; Espen Saxhaug KRISTOFFERSEN ; Annika NORDANSTIG ; Katarina JOOD ; Alexandros RENTZOS ; Libor ŠIMU˚NE ; Dagmar KRAJÍČKOVÁ ; Antonín KRAJINA ; Robert MIKULÍK ; Martina CVIKOVÁ ; Jan VINKLÁREK ; David ŠKOLOUDÍK ; Martin ROUBEC ; Eva HURTIKOVA ; Rostislav HRUBÝ ; Svatopluk OSTRY ; Ondrej SKODA ; Marek PERNICKA ; Lubomír KOČÍ ; Zuzana EICHLOVÁ ; Martin JÍRA ; Michal PANSKÝ ; Pavel MENCL ; Hana PALOUŠKOVÁ ; Aleš TOMEK ; Petr JANSKÝ ; Anna OLŠEROVÁ ; Roman HAVLÍČEK ; Petr MALÝ ; Lukáš TRAKAL ; Jan FIKSA ; Matěj SLOVÁK ; Michał KARLIŃSK ; Maciej NOWAK ; Halina SIENKIEWICZ-JAROSZ ; Anna BOCHYNSKA ; Tomasz HOMA ; Katarzyna SAWCZYNSKA ; Agnieszka SLOWIK ; Ewa WLODARCZYK ; Marcin WIĄCEK ; Izabella TOMASZEWSKA-LAMPART ; Bartosz SIECZKOWSKI ; Halina BARTOSIK-PSUJEK ; Marta BILIK ; Anna BANDZAREWICZ ; Justyna ZIELIŃSKA-TUREK ; Krystian OBARA ; Paweł URBANOWSKI ; Sławomir BUDREWICZ ; Maciej GUZIŃSKI ; Milena ŚWITOŃSKA ; Iwona RUTKOWSKA ; Paulina SOBIESZAK-SKURA ; Beata ŁABUZ-ROSZAK ; Aleksander DĘBIEC ; Jacek STASZEWSKI ; Adam STĘPIEŃ ; Jacek ZWIERNIK ; Grzegorz WASILEWSKI ; Cristina TIU ; Razvan-Alexandru RADU ; Anca NEGRILA ; Bogdan DOROBAT ; Cristina PANEA ; Vlad TIU ; Simona PETRESCU ; Atilla ÖZCAN-ÖZDEMIR ; Mostafa MAHMOUD ; Hussam EL-SAMAHY ; Hazem ABDELKHALEK ; Jasem AL-HASHEL ; Ismail IBRAHIM ISMAIL ; Athari SALMEEN ; Abdoreza GHOREISHI ; Sergiu SABETAY ; Hana GROSS ; Piers KLEIN ; Kareem EL NAAMANI ; Stavropoula TJOUMAKARIS ; Rawad ABBAS ; Ghada-A MOHAMED ; Alex CHEBL ; Jiangyong MIN ; Majesta HOVINGH ; Jenney-P TSAI ; Muhib-A KHAN ; Krishna NALLEBALLE ; Sanjeeva ONTEDDU ; Hesham-E MASOUD ; Mina MICHAEL ; Navreet KAUR ; Laith MAALI ; Michael ABRAHAM ; Ivo BACH ; Melody ONG ; Denis BABICI ; Ayaz-M. KHAWAJA ; Maryam HAKEMI ; Kumar RAJAMANI ; Vanessa CANO-NIGENDA ; Antonio ARAUZ ; Pablo AMAYA ; Natalia LLANOS ; Akemi ARANGO ; Miguel A. VENCES ; José-Domingo BARRIENTOS ; Rayllene CAETANO ; Rodrigo TARGA ; Sergio SCOLLO ; Patrick YALUNG ; Shashank NAGENDRA ; Abhijit GAIKWAD ; Kwon-Duk SEO ;
Journal of Stroke 2025;27(1):128-132
9.Neurovascular Complications of Acute Aortic Syndrome
Dean ZELDICH ; Matthew BIEROWSKI ; Leah SHABO ; Sridhara YADDANAPUDI ; Gregary MARHEFKA
Journal of Stroke 2025;27(1):19-29
Acute aortic syndromes (AAS) such as aortic dissection, intramural hematoma, and penetrating aortic ulcer pose significant neurovascular risks, affecting patient outcomes. This review examines the incidence, clinical presentation, and outcomes of neurovascular complications in AAS patients. Common complications include stroke, spinal cord ischemia, and transient ischemic attacks, with stroke being the most prevalent. Managing aortic dissection necessitates careful blood pressure control to prevent dissection progression while avoiding compromised cerebral and spinal perfusion. Carotid involvement, particularly dissection, increases stroke and transient ischemic attack risks. Emergency surgical interventions, though essential to prevent rupture or repair dissection, carry risks of perioperative neurovascular complications. The use of electroencephalography and transcranial Doppler can aid in the early detection and monitoring of neurovascular events. We discuss the pros and cons of certain blood pressure medications in the acute treatment of aortic dissection. A multidisciplinary approach involving cardiovascular surgeons, neurologists, and critical care specialists is vital for optimizing outcomes and mitigating risks. Early recognition and management of neurovascular complications are crucial, and further research is needed to develop targeted prevention and treatment strategies.
10.Predictive Modeling of Symptomatic Intracranial Hemorrhage Following Endovascular Thrombectomy: Insights From the Nationwide TREAT-AIS Registry
Jia-Hung CHEN ; I-Chang SU ; Yueh-Hsun LU ; Yi-Chen HSIEH ; Chih-Hao CHEN ; Chun-Jen LIN ; Yu-Wei CHEN ; Kuan-Hung LIN ; Pi-Shan SUNG ; Chih-Wei TANG ; Hai-Jui CHU ; Chuan-Hsiu FU ; Chao-Liang CHOU ; Cheng-Yu WEI ; Shang-Yih YAN ; Po-Lin CHEN ; Hsu-Ling YEH ; Sheng-Feng SUNG ; Hon-Man LIU ; Ching-Huang LIN ; Meng LEE ; Sung-Chun TANG ; I-Hui LEE ; Lung CHAN ; Li-Ming LIEN ; Hung-Yi CHIOU ; Jiunn-Tay LEE ; Jiann-Shing JENG ;
Journal of Stroke 2025;27(1):85-94
Background:
and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking.
Methods:
This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance.
Results:
Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal.
Conclusions
The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

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