1.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.
2.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.
3.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.
4.Detection and characterization of novel respiratory viruses among native ducks (Anas luzonica) in Central Luzon, the Philippines
Milagros R Mananggit ; Joely T Ongtanco ; Xandre D Baccay ; Ronnie Domingo ; Mary Elizabeth Miranda ; Romeo Gundran ; Dan Drexel dela Cruz ; Frank YK Wong ; S Gabrielle Cody ; Laura A Pulscher ; Emily R Robie ; Emily S Bailey ; Gregory C Gray
Western Pacific Surveillance and Response 2025;16(2):23-28
Objective: This cross-sectional, prospective surveillance study sought to determine the prevalence of novel respiratory viruses among domestic ducks in Central Luzon that are known to have frequent contact with wild avian species. Such contact may lead to novel virus spillover events that may harm domestic poultry as well as humans.
Methods: From March 2019 to January 2020, cross-sectional and prospective surveillance for viruses among domestic ducks (Anas luzonica) was conducted by periodically collecting oropharyngeal swabs from ducks on 54 farms across three municipalities within Central Luzon (Region III). A flock of 30 sentinel domestic ducks was also sampled four times after being confined in the Candaba swamp. The resultant 1740 swab samples were pooled (5 samples/pool, 348 pools) by site and screened with molecular assays for respiratory viruses from multiple viral families.
Results: Two farms yielded samples positive for avian influenza virus in Candaba, where adolescent ducks are known to freely mix with wild birds as they graze in rice fields. Overall, the prevalence of avian influenza virus was 2.3% (8/348 pools). Sequencing revealed three pools with highly pathogenic avian influenza H5N6, one with low pathogenicity H5N8, and one with H5 with an unspecified neuraminidase. All the pooled specimens tested were negative for influenza C, adenoviruses, coronaviruses and enteroviruses.
Discussion: Although this study had several limitations, it found supportive evidence that domestic ducks are acquiring avian influenza viruses from wild bird species. These findings underscore recommendations that duck farmers should seek to prevent domestic ducks from mixing with wild avian species.
5.A Review of Finite Element Modeling for Anterior Cervical Discectomy and Fusion
Maohua LIN ; Rudy PAUL ; Utpal Kanti DHAR ; James DOULGERIS ; Timothy E. O’CONNOR ; Chi-Tay TSAI ; Frank D. VRIONIS
Asian Spine Journal 2023;17(5):949-963
The cervical spine poses many complex challenges that require complex solutions. Anterior cervical discectomy and fusion (ACDF) has been one such technique often employed to address such issues. In order to address the problems with ACDF and assess the modifications that have been made to the technique over time, finite element analyses (FEA) have proven to be an effective tool. The variations of cervical spine FEA models that have been produced over the past couple of decades, particularly more recent representations of more complex geometries, have not yet been identified and characterized in any literature. Our objective was to present material property models and cervical spine models for various simulation purposes. The outlining and refinement of the FEA process will yield more reliable outcomes and provide a stable basis for the modeling protocols of the cervical spine.
6.Survivorship Analysis in Asymptomatic COVID-19+ Hip Fracture Patients: Is There an Increase in Mortality?
Mason D. VIALONGA ; Luke G. MENKEN ; Alex TANG ; John W. YUREK ; Li SUN ; John J. FELDMAN ; Frank A. LIPORACE ; Richard S. YOON
Hip & Pelvis 2022;34(1):25-34
Purpose:
Mortality rates following hip fracture surgery have been well-studied. This study was conducted to examine mortality rates in asymptomatic patients presenting for treatment of acute hip fractures with concurrent positive COVID-19(+) tests compared to those with negative COVID-19(–) tests.
Materials and Methods:
A total of 149 consecutive patients undergoing hip fracture surgery during the COVID-19 pandemic at two academic medical centers were reviewed retrospectively. Patients were divided into two groups for comparative analysis: one group included asymptomatic patients with COVID-19+ tests versus COVID-19– tests. The primary outcome was mortality at 30-days and 90-days.
Results:
COVID-19+ patients had a higher mortality rate than COVID-19– patients at 30-days (26.7% vs 6.0%, P=0.005) and 90-days (41.7% vs 17.2%, P=0.046) and trended towards an increased length of hospital stay (10.1 ±6.2 vs 6.8±3.8 days, P=0.06). COVID-19+ patients had more pre-existing respiratory disease (46.7% vs 11.2%,P=0.0002). Results of a Cox regression analysis showed an increased risk of mortality at 30-days and 90-days from COVID-19+ status alone without an increased risk of death in patients with pre-existing chronic respiratory disease.
Conclusion
Factors including time to surgery, age, preexisting comorbidities, and postoperative ambulatory status have been proven to affect mortality and complications in hip fracture patients; however, a positive COVID-19 test result adds another variable to this process. Implementation of protocols that will promote prompt orthogeriatric assessments, expedite patient transfer, limit operating room traffic, and optimize anesthesia time can preserve the standard of care in this unique patient population.
7.Oncological and functional outcomes of transanal total mesorectal excision in a teaching hospital in the Netherlands
Joost A.G. VAN DER HEIJDEN ; Kelly G.H. VAN DE PAS ; Frank J.C. VAN DEN BROEK ; Francois M.H. VAN DIELEN ; Gerrit D. SLOOTER ; Adriana J.G. MAASKANT-BRAAT
Annals of Coloproctology 2022;38(1):28-35
Purpose:
Transanal total mesorectal excision (TaTME) was developed to overcome surgical difficulties experienced in distal pelvic dissection. Concerns have been raised about potential worse postoperative functional outcomes after TaTME. Also, the oncological safety was questioned. This study aimed to describe the functional, surgical, oncological outcomes and quality of life (QoL) after TaTME.
Methods:
All consecutive TaTME cases for rectal cancer without disseminated disease between December 2016 and April 2019 were included. The Wexner incontinence score, low anterior resection syndrome (LARS) score, fecal incontinence-related QoL, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-core questionnaire and 29-item module (EORTC QLQ-C30/CR29) were collected. Kaplan-Meier analysis was used to calculate local recurrence-free survival.
Results:
Thirty patients were eligible for analysis of which 23 received questionnaires. Response rate was 74%. After a median follow-up of respectively 20.0 and 23.0 months for functional and oncological outcomes, the median (interquartile range) of Wexner incontinence and LARS scores were 9.0 (7.0–12.0) and 33.1 (25.0–39.0). Major LARS was present in 73.3%. Fecal incontinence, general and colorectal-specific QoL subdomains that are associated with poor bowel function scored in line with previously reported data. The 2-year actuarial cumulative local recurrence rate was 3.7% (95% confidence interval, 2.4%–5.0%).
Conclusion
TaTME may lead to significant functional impairments. Patients should receive preoperative counseling on this topic and be fully aware of the potential consequences of their treatment. Oncological data were in line with other short- to moderate-term data and did not show alarming results.
8.Finding acute coronary syndrome with serial troponin testing for rapid assessment of cardiac ischemic symptoms (FAST-TRAC): a study protocol
W. Frank PEACOCK ; Alan S. MAISEL ; Christian MUELLER ; Stefan D. ANKER ; Fred S. APPLE ; Robert H. CHRISTENSON ; Paul COLLINSON ; Lori B. DANIELS ; Deborah B. DIERCKS ; Salvatore Di SOMMA ; Gerasimos FILIPPATOS ; Gary HEADDEN ; Brian HIESTAND ; Judd E. HOLLANDER ; Juan C. KASKI ; Joshua M. KOSOWSKY ; John T. NAGURNEY ; Richard M. NOWAK ; Donald SCHREIBER ; Gary M. VILKE ; Marvin A. WAYNE ; Martin THAN
Clinical and Experimental Emergency Medicine 2022;9(2):140-145
Objective:
To determine the utility of a highly sensitive troponin assay when utilized in the emergency department.
Methods
The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician’s clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible.Trial registration ClinicalTrials.gov Identifier NCT00880802
9.Biomechanical Study of Cervical Endplate Removal on Subsidence and Migration in Multilevel Anterior Cervical Discectomy and Fusion
Maohua LIN ; Rudy PAUL ; Stephen Z. SHAPIRO ; James DOULGERIS ; Timothy E. O’CONNOR ; Chi-Tay TSAI ; Frank D. VRIONIS
Asian Spine Journal 2022;16(5):615-624
Methods:
Model 1 (M1) was an intact C2C6 model with a 0.5 mm endplate. In model 2 (M2), a cage was implanted after removal of the C4–C5 and C5–C6 discs with preservation of the osseous endplate. In model 3 (M3), 1 mm of the osseous endplate was removed at the upper endplate. Model 4 (M4) resembles M3, except that 3 mm of the osseous endplate was removed.
Results:
The range of motion (ROM) at C2C6 in the M2–M4 models was reduced by at least 9º compared to the M1 model. The von Mises stress results in the C2C3 and C3C4 interbody discs were significantly smaller in the M1 model and slightly increased in the M2–M3 and M3–M4 models. Migration and subsidence decreased from the M2–M3 model, whereas further endplate removal increased the migration and subsidence as shown in the transition from M3 to M4.
Conclusions
The M3 model had the least subsidence and migration. The ROM was higher in the M3 model than the M2 and M4 models. Endplate preparation created small stress differences in the healthy intervertebral discs above the ACDF site. A 1 mm embedding depth created the best balance of mechanical strength and contact area, resulting in the most favorable stability of the construct.


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