1.Artificial intelligence-assisted screening reveals high prevalence of osteoporosis in Vietnamese adults using pelvic and hip radiographs
Dat Minh NGUYEN ; Chih-Hsing WU ; Tuan Van NGUYEN ; Lan T. HO-PHAM ; Kim Thi Hoang DANG ; Hy Van NGUYEN ; Sung-Yen LIN ; Chung-Hwan CHEN ; Ta-Wei TAI
Osteoporosis and Sarcopenia 2026;12(1):18-25
Objectives:
Osteoporosis is a silent disease with low screening rates in many developing countries. This study aimed to evaluate the feasibility of using an artificial intelligence (AI)-based system to screen osteoporosis from pelvic and hip radiographs in Vietnam.
Methods:
We conducted a cross-sectional study at a tertiary medical center in Central Vietnam in 2023. A total of 2000 consecutive pelvic and hip radiographs from patients aged ≥ 40 years were collected. After excluding poorquality images, 1987 radiographs were analyzed using an AI-based software designed to estimate bone mineral density (BMD) from plain radiographs and derive T-scores. Osteoporosis was defined as a T-score ≤ − 2.5. Patient characteristics, radiographic findings, and risk factors for osteoporosis were analyzed.
Results:
Among 1987 patients (mean age 66.4 ± 15.1 years; 41.3% men), osteoporosis was identified in 872 patients (43.9%). The prevalence increased with age and was higher in women than in men (58.7% vs 22.8%, P < 0.001). Osteoporosis was associated with femoral neck (OR = 3.8, 95% CI: 2.7–5.2) and intertrochanteric fractures (OR = 7.0, 95% CI: 4.5–11.0). Patients with lower T-scores had a higher risk of hip fractures, especially those with T-scores ≤ − 3.0 (OR = 11.5, 95% CI: 5.5–24.5).
Conclusions
AI-based analysis of pelvic and hip radiographs is a feasible and effective tool for osteoporosis screening in Vietnam. The prevalence of osteoporosis in this hospital-based setting was high, particularly among elderly women.AI-assisted screening may offer an accessible strategy for early detection of osteoporosis in resource-limited settings.
2.Laparoscopic management of Mirizzi syndrome type IV:a case report and review of minimal access surgery
Nhat Ba Minh NGUYEN ; Trieu Hai PHAM ; Trung Quoc PHAM ; Duc Van NGUYEN ; Phuc Hung NGUYEN
Journal of Minimally Invasive Surgery 2026;29(2):97-101
Mirizzi syndrome type IV, a rare and complex form of biliary obstruction, has traditionally required major open surgery. This case report describes a groundbreaking alternative: a 44-year-old woman successfully treated using a minimally invasive laparoscopic approach.The less invasive procedure resulted in rapid, complication-free recovery, with no evidence of biliary stricture at the 6-month follow-up. This outcome challenges conventional management and demonstrates that a minimally invasive approach can be both feasible and highly effective in carefully selected patients.
3.Validation of the Leuven Postprandial Distress Scale According to the Rome IV Criteria for Functional Dyspepsia
Cedric Van de BRUAENE ; Florencia CARBONE ; Karen Van den HOUTE ; Jolien SCHOL ; Bert BROEDERS ; Michael P JONES ; Alain VANDENBERGHE ; Tim VANUYTSEL ; Jan TACK
Journal of Neurogastroenterology and Motility 2026;32(1):99-108
Background/Aims:
The Leuven Postprandial Distress Scale (LPDS) is a validated patient reported outcome (PRO) measure for functional dyspepsia (FD)/postprandial distress syndrome (PDS) patients according to Rome III criteria. However, meal-related nausea or epigastric pain, part of PDS in Rome IV, were not addressed in this construct. Also, focus groups identified fatigue as a frequently reported complaint for which the European Medicines Agency requested further analysis. Our aim is to validate the LPDS in FD/PDS as defined by Rome IV criteria and to optimize the model by assessing the value of adding extra items to this questionnaire.
Methods:
The questionnaire was validated in 3 different Rome IV FD/PDS patient cohorts recruited for controlled clinical trials. Additional questions in the diary regarding symptom relationship to meal and fatigue were evaluated. Anchor scores were the patient assessment of gastrointestinal symptom severity index, Short-form Nepean dyspepsia index, the overall treatment evaluation and overall symptom severity questionnaires.
Results:
The LPDS Construct validity was confirmed for Rome IV-defined PDS. Psychometric analysis did not support inclusion of fatigue, nausea, meal-related or meal-unrelated, and meal-related epigastric pain, due to low loading or poor model fit.
Conclusions
The LPDS questionnaire showed good reliability and responsiveness, and can be confidently used as a validated tool in Rome IV PDS populations. Data did not support adding accessory symptoms to the construct, due to low loading or poor model fit.
4.Survival Outcomes of Gamma Knife Radiosurgery in EGFR-Mutant Non-Small Cell Lung Cancer Patients With 1–4Versus 5–10 Brain Metastases: A Vietnamese Study
Duc Linh TRAN ; Duc Lien NGUYEN ; Van Ba NGUYEN ; Thanh Duong PHAN ; Se-Hyuk KIM
Brain Tumor Research and Treatment 2026;14(2):74-81
Background:
In the targeted therapy era, the indication for stereotactic radiosurgery (SRS) has ex-panded to include patients with multiple brain metastases (BMs). This study aimed to compare treatment outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with 1–4 versus 5–10 BMs, all treated with tyrosine kinase inhibitors (TKIs) and upfront Gamma Knife radiosurgery.
Methods:
We retrospectively reviewed 74 consecutive EGFR-mutant NSCLC patients with 1–10synchronous BMs treated with first-line EGFR-TKIs and upfront Gamma Knife SRS at Vietnam National Cancer Hospital from 2021 to 2024. Patients were divided into 1–4 BMs (n=39) and 5–10 BMs (n=35) groups. Primary endpoints were intracranial progression-free survival (iPFS) and overall survival (OS).
Results:
Baseline characteristics were balanced between the two groups. Median iPFS wasnot reached in the 1–4 BMs group and 19 months in the 5–10 BMs group (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.95–1.17; p=0.31). Median OS was not reached in the 1–4 BMs group and was 23 months in the 5–10 BMs group (HR 1.03, 95% CI 0.91–1.16; p=0.41). Multivariate analysis revealed extracranial response (HR 4.30, p<0.01 for iPFS; HR 7.29, p<0.01 for OS) and presence of extracranial metastases (HR 3.20, p=0.01 for iPFS) as the only independent prognostic factors; number of BMs was not prognostic. Radionecrosis occurred in 6.8%, of which 2.7% were symptomatic.
Conclusion
In EGFR-mutant NSCLC patients receiving TKIs and upfront Gamma Knife radiosur-gery, the survival time in patients with 5–10 BMs was comparable to that with 1–4 BMs. The number of BMs should not be regarded as a contraindication for SRS in this subgroup.
5.Does the Benefit of Thrombectomy in Large Strokes Depend on Perfusion–Diffusion Mismatch? A Large Stroke Therapy Evaluation Trial Post Hoc Analysis
Adrien Ter SCHIPHORST ; Caroline ARQUIZAN ; Guillaume TURC ; Julien LABREUCHE ; Bertrand LAPERGUE ; David S. LIEBESKIND ; Hilde HENON ; Nasreddine NOURI ; Jean-François ALBUCHER ; Christophe COGNARD ; Gaultier MARNAT ; Igor SIBON ; Benjamin GORY ; Sébastien RICHARD ; Olivier NAGGARA ; Mariam ANNAN ; Grégoire BOULOUIS ; Eker F. OMER ; Tae-Hee CHO ; Federico Di MARIA ; Romain BOURCIER ; Benoit GUILLON ; Michael OBADIA ; Michel PIOTIN ; Anna FERRIER ; Emmanuel CHABERT ; Mònica MILLÁN ; Liesjet van DOKKUM ; Tudor G. JOVIN ; Emmanuelle Le BARS ; Vincent COSTALAT
Journal of Stroke 2026;28(1):115-125
Background:
and Purpose Whether perfusion-diffusion mismatch modifies treatment effect of mechanical thrombectomy (MT) for large strokes is poorly known. To address this question, we conducted a post hoc secondary analysis of the Large Stroke Therapy Evaluation (LASTE) randomized controlled trial (RCT).
Methods:
The LASTE RCT compared MT plus best medical treatment (BMT) to BMT alone in patients with large infarct (Alberta Stroke Program Early CT Score 0–5) in the 0–7-hour timewindow. This secondary analysis was restricted to patients with available baseline MR perfusionweighted imaging. We investigated the potential heterogeneity of MT treatment according to the presence of perfusion-diffusion mismatch, defined as a mismatch ratio ≥1.2, calculated as the time-to-maximum >6 seconds cerebral volume divided by ischemic core volume. The primary outcome was better functional outcome (favorable shift in the distribution of modified Rankin Scale [mRS] at 90 days, analyzed using generalized odds ratio [GenOR]).
Results:
A total of 102/324 patients were included, among whom 55 (54%) had a perfusiondiffusion mismatch. No significant treatment effect heterogeneity by diffusion-perfusion mismatch was observed for the primary outcome (GenOR for better functional outcome: 1.70 [95% confidence interval, CI, 0.95 to 3.05] and 1.04 [95% CI, 0.57 to 1.87] in patients with and without mismatch, respectively; ratio of GenORs: 1.63 [95% CI, 0.71 to 3.74]; P for heterogeneity=0.24) or for the secondary efficacy and safety outcomes.
Conclusions
Our study found no evidence of heterogeneity of treatment effect with respect to benefit or safety in patients with unrestricted infarct size at baseline treated with MT by presence of perfusion-diffusion mismatch. An individual participant-data meta-analysis of RCT is needed for definitive conclusions.
6.Fibroblast Dynamics Following Partial and Deep Burn Injury in a Reconstructed Human Skin Model
Britt van der LEEDEN ; H. Ibrahim KORKMAZ ; Sanne ROFFEL ; Chopie HASSAN ; Paul P. M. van ZUIJLEN ; Bouke K. H. L. BOEKEMA ; Hans W. M. NIESSEN ; Paul A. J. KRIJNEN ; Susan GIBBS
Tissue Engineering and Regenerative Medicine 2026;23(1):185-198
BACKGROUND:
Burn injuries are characterized by extensive and prolonged inflammatory responses that impair wound healing, especially in deep burns. Understanding the post-burn fibroblast dynamics in wound healing is critical to improve recovery and minimize scarring. This study aimed to develop a 3D reconstructed human skin (RhS) burn model to mimic superficial, partial-thickness, and deep burn injuries and assess fibroblast behavior over one week.
METHODS:
RhS consisted of a reconstructed epidermis on a fibroblast populated collagen hydrogel dermis. Papillary (fibroblast activation protein; FAP ?) and reticular (FAP-) fibroblasts located themselves in the upper and lower regions respectively within the dermal compartment in line with native skin. Burns of increasing temperatures (70 °C, 110 °C, and 140 °C) were introduced and RhS was analyzed up to one-week post-burn.
RESULTS:
Lactate dehydrogenase (LDH) staining for metabolic active cells in tissue sections enabled distinct histological zones to be observed in RhS with partial (110 °C) and deep burns (140 °C): including a viable fibroblast zone (zone V), a mixed dead and viable fibroblast zone (zone M), and a necrotic zone (zone N). Fibroblast migration from the wound edge (M) into the viable area (V) and changes in fibroblast phenotype, particularly an increase in papillary fibroblast markers (FAP ?), were observed, with a marked increased expression of Ki67 in fibroblasts at the burn wound edge (M).Additionally, burn temperature influenced the protein secretion of inflammatory and tissue remodeling mediators SAA, NGAL, MRP8/13, ICAM-1, CCL20, and MMP-9.
CONCLUSION
The RhS burn model enables complex fibroblast dynamics post-burn to be investigated in an organotypic model, providing a platform for studying burn pathophysiology which can be used for evaluating potential therapeutic strategies for enhancing burn wound healing and minimizing scarring in the future.
7.Non-Motor Fluctuations in Parkinson’s Disease: Underdiagnosed Yet Important
Iro BOURA ; Karolina POPLAWSKA-DOMASZEWICZ ; Cleanthe SPANAKI ; Rosabel CHEN ; Daniele URSO ; Riaan van COLLER ; Alexander STORCH ; Kallol Ray CHAUDHURI
Journal of Movement Disorders 2025;18(1):1-16
Non-motor fluctuations (NMFs) in Parkinson’s disease (PD) significantly affect patients’ well-being. Despite being identified over two decades ago, NMFs remain largely underrecognized, undertreated, and poorly understood. While they are often temporally associated with motor fluctuations (MFs) and can share common risk factors and pathophysiologic mechanisms, NMFs and MFs are currently considered distinct entities. The prevalence and severity of NMFs, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMFs on PD patients’ quality of life underscores the importance of further investigations via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMFs, ultimately enhancing clinicians’ diagnostic and treatment options in routine clinical practice.
8.Characteristics of RET gene mutations in Vietnamese medullary thyroid carcinoma patients: a single-center analysis
Van Hung PHAM ; Quoc Thang PHAM ; Minh NGUYEN ; Hoa Nhat NGO ; Thao Thi Thu LUU ; Nha Dao Thi MINH ; Trâm ĐẶNG ; Anh Tu THAI ; Hoang Anh VU ; Dat Quoc NGO
Journal of Pathology and Translational Medicine 2025;59(2):125-132
The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.
9.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
10.Factors Influencing Nerinetide Effect on Clinical Outcome in Patients Without Alteplase Treatment in the ESCAPE-NA1 Trial
Mayank GOYAL ; Bijoy K. MENON ; Johanna OSPEL ; Mohammed ALMEKHLAFI ; Charlotte ZERNA ; Raul NOGUEIRA ; Ryan MCTAGGART ; Andrew M. DEMCHUK ; Alexandre Y. POPPE ; Brian BUCK ; Kathy HEARD ; Manish JOSHI ; Diogo HAUSSEN ; Shawna CUTTING ; Shelagh B. COUTTS ; Daniel ROY ; Jeremy L. REMPEL ; Thalia S. FIELD ; Dar DOWLATSHAHI ; Brian van ADEL ; Richard SWARTZ ; Ruchir SHAH ; Eric SAUVAGEAU ; Volker PUETZ ; Frank L. SILVER ; Bruce CAMPBELL ; René CHAPOT ; Michael TYMIANSKI ; Michael D. HILL ;
Journal of Stroke 2025;27(1):95-101
Background:
and Purpose In the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial, treatment with nerinetide was associated with improved outcomes in patients who did not receive intravenous alteplase. We compared the effect of nerinetide on clinical outcomes in patients without concurrent intravenous alteplase treatment within different patient subgroups.
Methods:
ESCAPE-NA1 was a multicenter randomized trial in which acute stroke patients with baseline Alberta Stroke Program Early CT Score (ASPECTS) >4 undergoing endovascular treatment (EVT) were randomized to intravenous nerinetide or placebo. The primary outcome was independence (modified Rankin Scale [mRS] score 0–2) at 90 days. We assessed baseline, clinical, and imaging variables as predictors of outcome and for evidence of treatment effect modification. We constructed two multivariable models using variables known prior to randomization and variables known immediately post-EVT procedure to provide adjusted estimates of effect. We assessed for evidence of treatment effect modification using multiplicative interaction terms within each model.
Results:
Four hundred forty-six patients were included in the analysis. Clinical outcomes were better in patients randomized to the nerinetide arm (mRS 0–2: 59.4% vs. 49.8%). There was possible treatment effect modification by ASPECTS score; patients with ASPECTS 8–10 showed a larger treatment effect compared to those with lower ASPECTS score. Younger age, lower NIHSS score, lower baseline serum glucose, absence of atrial fibrillation at baseline, higher ASPECTS score, middle cerebral artery (vs. internal carotid artery) occlusion, use of conscious or no sedation (vs. general anesthesia), and faster treatment were all predictors of favorable outcome.
Conclusion
Patients in the nerinetide arm who were not treated with concurrent alteplase showed improved clinical outcomes and the treatment effect was larger among patients with favorable ASPECTS profiles.

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