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The Sport Publication Observational Research Tool (SPORT): An Objective Tool to Score the Methodological Quality of Observational Clinical Sports Medicine Research
Kuhn, Andrew W. , Inclan, Paul M. , Haider, Ameer A. , Christy, Michele, Dunn, Warren, Alberton, Laura A. , Allen, Christina, Anderson, Kyle, Andrews, James, Azar, Fred, Baer, Geoffrey S. , Banffy, Michael B. , Bedi, Asheesh , Brockmeier, Stephen F., Brophy, Robert H. , Bush‐Joseph, Charles A., Carey, James R. , Carter, Thomas, Cohen, Steven, Farrow, Lutul D. , Flanigan, D. Preston, Franklin, Corinna C. , Hame, Sharon L. , Ioannis, Terzidis, Joseph, Sheeba, Kenter, Keith , Koh, Jason R., Krych, Aaron, LeClere, LT Lance, Levy, Bruce, McAllister, David, Morganti, Christina, Musahl, Volker , Nelson, Bradley , Noyes, Frank, Owens, COL Brett D., Pace, Lee, Paulos, Lonnie E., Rodeo, Scott, Safran, Marc, Savoie, Felix H. , Shelbourne, Donald K., Sherman, Seth L. , Singer, Ken, Smith, Matthew, Sonnery-Cottet, Bertrand, Spiker, Andrea M. , Stuart, Michael, Warren, Russell, Wittstein, Jocelyn R. , Wolcott, Michelle L., Wright, Rick, Matava, Matthew J. , Sherman, Seth L. , Kuhn, Andrew W , Dunn, Warren R., Brockmeier, Stephen F. , Brophy, Robert H. , Carey, James, Cohen, Steven B. , Flanigan, David, Krych, Aaron J. , LeClere, Lance E. , Lee, Cassandra Alda , Levy, Bruce, McAllister, David R. , Medvecky, Michael J. , Owens, Brett D. , Pace, J Lee , Redler, Lauren H. , Rodeo, Scott A. , Sonnery‐Cottet, Bertrand

Orthopaedic Journal of Sports Medicine | February 6, 2026 | Volume: 14 | Issue: 2 | Pages: No page available

10.1177/23259671251380883 | PMID 41660291 Get It

Background: A critical component of conducting systematic reviews or meta-analyses is assessing the methodological quality and bias of included studies. Several methodological quality assessment tools have been developed; however, these tools may not be relevant to observational sports medicine research, which carries numerous unique nuances and biases. Purpose: To develop the Sport Publication Observational Research Tool (SPORT), which evaluates and scores the methodological quality of observational sports medicine research. Study Design: Consensus statement. Methods: SPORT was developed through a modified Delphi approach involving members from the Herodicus Society and The FORUM. All active members were invited to participate in the process aimed at building consensus on SPORT content and scoring. After finalizing SPORT, a power analysis led to the independent selection of 55 observational clinical sports medicine studies, which were scored twice by 4 reviewers of varying training levels. Interrater and intrarater reliability for SPORT was assessed using intraclass correlation coefficients (ICCs). The distribution and percentiles for total SPORT score across the 55 studies were calculated. SPORT was also compared with the methodological index for non-randomized studies (MINORS), a commonly utilized quality assessment tool. Results: A total of 51 members participated and achieved 100%, 100%, 98.0%, and 98.0% completion rates for rounds 1 through 4, respectively. The final SPORT included 19 subscores related to methodological quality and bias and achieved 94% consensus approval. Mean SPORT completion time was 6 minutes and 19 seconds per study, which varied significantly by reviewer training level. The subscore "peer review" demonstrated unacceptable reliability and was removed. The remaining 18 subscores exhibited ICC ranges of 0.599 to 0.955 for interrater reliability and 0.530 to 0.936 for intrarater reliability. Total SPORT score demonstrated excellent agreement, for interrater (ICC, 0.967) and intrarater reliability (ICC, 0.966). Median SPORT score across the 55 studies was 20.0 and skewed toward lower scores. There was a moderate significant correlation between SPORT and MINORS ( r [53] = 0.575; P < .001). Conclusion: An objective tool to assess the methodologic quality of observational sports medicine research (SPORT) was successfully developed through a modified Delphi approach with numerous content experts in the field. This tool may be useful in assessing the methodological quality of primary observational sports medicine studies included in systematic reviews and meta-analyses.
Venous Abnormalities in Biopsy-confirmed Lipodermatosclerosis
Garimella, Vishal, Mukosera, George Tinotenda, Liedl, David , Todd, A., Davis, Mark D.P. , Rooke, Thom W., Alavi, A., Liedl, David A, Davis, Mark Denis P., Garimella, Vishal, Mukosera, George T. , Rooke, Thom W.

Advances in Skin & Wound Care | February 6, 2026 | Volume: 39 | Issue: 3 | Pages: 141-144

10.1097/asw.0000000000000421 | PMID 41649308 Get It

BACKGROUND: Lipodermatosclerosis (LDS) is a type of sclerosing panniculitis that predominantly involves the lower extremities and is characterized by erythema, hemosiderin pigmentation, and sclerotic skin lesions. LDS is a common reason for specialty consultations across clinical settings, including dermatology, vascular medicine, and occasionally the emergency department or internal medicine services. METHODS: To further evaluate the prevalence of venous hypertension in patients with LDS at the authors’ institution, they retrospectively reviewed the findings of lower extremity Doppler ultrasonography with or without segmental pressure (ie, venous ultrasonography) performed for adult patients with biopsy-confirmed LDS who were treated at the Clinic from January 1, 2000, through September 30, 2022. RESULTS: A total of 430 patients were included in the study. Venous ultrasonography findings were abnormal for 327 (76.0%) patients, whereas the other 103 (23.9%) patients had normal findings. Venous hemodynamics studies, including air plethysmography and continuous-wave Doppler ultrasonography, were performed for 33 patients with normal venous ultrasonography findings. Of these patients, 7 had mild valvular incompetence, 12 had abnormal calf muscle pump function, and 2 had pulsatility (backflow in the peripheral vein with elevated right atrial pressure) evident on continuous-wave Doppler ultrasonography. CONCLUSIONS: Overall, the findings extend previous observations that venous abnormalities are commonly present in patients with LDS and may contribute to its pathogenesis. However, a few patients with LDS have normal venous hemodynamics, which suggests that other factors also contribute to LDS pathogenesis.
Stoma-Free Survival Following Low Anterior Resection With Coloanal Anastomosis for Stage II and III Rectal Cancer
Cerkauskaite, Dovile , Sassun, Richard, Sileo, Annaclara, Brady, Justin T, Merchea, A., Stocchi, Luca, Perry, William R. G., Mathis, Kellie L. , Perry, William , Ng, Jyi Cheng , Perry, William R , Sassun, Richard , Sileo, Annaclara , Brady, Justin T. , Merchea, Amit , Stocchi, Luca , Behm, Kevin T. , Larson, David W.

Diseases of the Colon & Rectum | February 6, 2026 | Volume: 69 | Issue: 5 | Pages: 760-767

10.1097/dcr.0000000000004145 | PMID 41649030 Get It

BACKGROUND: Stoma-free survival represents a key quality-of-life outcome after surgery for locally advanced rectal cancer. Despite advances in neoadjuvant and surgical management, up to 30% of patients ultimately require a permanent fecal diversion. OBJECTIVE: To evaluate stoma-free survival and identify factors associated with permanent stoma formation in patients with locally advanced rectal cancer undergoing coloanal anastomosis. DESIGN: Retrospective cohort study. SETTINGS: Single tertiary referral center (2017–2021). PATIENTS: A total of 126 patients with clinical stage II and III rectal adenocarcinoma who received neoadjuvant therapy and underwent curative-intent resection with coloanal anastomosis were included. INTERVENTION: Curative-intent resection with coloanal anastomosis. MAIN OUTCOME MEASURES: The primary outcome was stoma-free survival. Secondary analyses examined factors associated with permanent fecal diversion. RESULTS: The medical records of 126 patients were analyzed, comprising 62.5% men, with a mean age of 54 ± 10 years and a median BMI of 27.7 (interquartile range 24.5–31.4). At a median follow-up of 53.0 months, the 5-year stoma-free survival rate was 88.9%. Univariate Cox regression analysis showed that BMI ≥35 (HR 3.80; 95% CI, 1.04–13.91, p = 0.044) and handsewn coloanal anastomosis with mucosectomy compared to stapled coloanal anastomosis without mucosectomy (HR 5.58; 95% CI, 1.71–18.14, p = 0.004), as well as local recurrence (HR 6.51; 95% CI, 1.44–29.46), were associated with worse stoma-free survival. The 30-day major morbidity rate was 7.9% after the index surgery. Sixteen patients required permanent fecal diversion due to bowel dysfunction (n = 11), disease recurrence (n = 4), or bowel obstruction (n = 1). LIMITATIONS: Retrospective, single-institution design with limited generalizability. CONCLUSIONS: Coloanal anastomosis in the era of total neoadjuvant therapy resulted in favorable 5-year stoma-free survival. BMI ≥35, handsewn coloanal anastomosis with mucosectomy, and local recurrence were associated with worse stoma-free survival. See Video Abstract . SUPERVIVENCIA SIN ESTOMA TRAS UNA RESECCIÓN ANTERIOR BAJA CON ANASTOMOSIS COLOANAL PARA EL CÁNCER RECTAL EN ESTADIO II-III ANTECEDENTES: La supervivencia sin estoma representa un resultado clave para la calidad de vida tras la cirugía de cáncer rectal localmente avanzado. A pesar de los avances en el tratamiento neoadyuvante y quirúrgico, hasta un 30 % de los pacientes requieren finalmente una derivación fecal permanente. OBJETIVO: Evaluar la supervivencia sin estoma e identificar los factores asociados con la formación de un estoma permanente en pacientes con cáncer rectal localmente avanzado sometidos a anastomosis coloanal. DISEÑO: Estudio de cohorte retrospectivo. ENTORNO: Centro terciario de referencia único, 2017-2021. PACIENTES: Se incluyó a un total de 126 pacientes con adenocarcinoma rectal en estadio clínico II-III que recibieron terapia neoadyuvante y se sometieron a una resección con intención curativa con anastomosis coloanal. INTERVENCIÓN: Resección con intención curativa con anastomosis coloanal. PRINCIPALES MEDIDAS DE RESULTADO: El resultado principal fue la supervivencia sin estoma. Los análisis secundarios examinaron los factores asociados con la derivación fecal permanente. RESULTADOS: Se analizaron 126 pacientes, de los cuales el 62,5 % eran hombres, con una edad media de 54 ± 10 años y un índice de masa corporal medio de 27,7 kg/m 2 (rango intercuartílico: 24,5-31,4 kg/m 2 ). Con una mediana de seguimiento de 53,0 meses, la tasa de supervivencia sin estoma a 5 años fue del 88,9 %. El análisis de regresión de Cox univariante mostró que el índice de masa corporal ≥ 35 kg/m 2 (razón de riesgo = 3,80, intervalo de confianza del 95 %: 1,04-13,91, p = 0,044) y la anastomosis coloanal cosida a mano con mucosectomía, en comparación con la anastomosis coloanal grapada sin mucosectomía (razón de riesgo = 5,58, intervalo de confianza del 95 %: 1,71-18,14, p = 0,004), así como la recurrencia local (razón de riesgo = 6,51, intervalo de confianza del 95 %: 1,44-29,46) se asociaron con una peor supervivencia sin estoma. La tasa de morbilidad grave a los 30 días fue del 7,9 % tras la cirugía índice. Dieciséis pacientes requirieron una derivación fecal permanente debido a disfunción intestinal (n = 11), recurrencia de la enfermedad (n = 4) u obstrucción intestinal (n = 1). LIMITACIONES: Diseño retrospectivo, de una sola institución, con una generalización limitada. CONCLUSIONES: La anastomosis coloanal en la era de la terapia neoadyuvante total dio lugar a una supervivencia sin estoma favorable a los 5 años. El índice de masa corporal ≥ 35 kg/m2, la anastomosis coloanal cosida a mano con mucosectomía y la recurrencia local se asociaron con una peor supervivencia sin estoma. (AI-generated translation )
Natural History of Patients With Histologically Proven Acute Eosinophilic Myocarditis
Ammirati, Enrico, Palazzini, Matteo , Lehtonen, Jukka , Potena, Luciano , Mäyränpää, Mikko I. , Rågback, Johanna, Uribarri, Aitor , Thiele, H, Vidal‐Burdeus, María , Freund, Anne, Gustafsson, F., Tschöpe, C., Elsanhoury, Ahmed , Ihle, Joshua , Rudi, Wolf‐Stephan , Grabmaier, Ulrich , Merlo, Marco, Weislova, Ivana, Jellinghaus, Stefanie, Linke, A, Baldovini, Chiara , Adorisio, R, Kuchyňka, Petr, Palecek, T, Krejčí, Jan, Poloczková, Hana , Caterino, Anna Laura, Lovell, Jana , Macomb, Elaine P., Shih, Jeffrey, Hong, Kimberly N. , Ruschitzka, Frank, Cavallini, Claudio, Riccini, Clara, Kamal, Mohamed, Groh, Matthieu, Garascia, Andrea , Lala, Anuradha, Shimokawa, Hiroaki, Sionis, A, Schmidt, Matthieu, Grosu, Aurelia, Bollano, Entela , Turco, Annalisa , Crespo-Leiro, M., Couto-Mallón, David, Cannata, Antonio, Narducci, M L, Cicchitti, Vincenzo , Ianni, Umberto , L, De Luca, Frea, Simone, Schroeder, J. W., Arias, Aníbal , Emdin, Michele, Corda, Marco , Pasqualucci, Daniele , Greulich, Simon , Gawaz, M, Manuylova, Tatiana, Martinez-Selles, M, Pérez, Francisco José Hernández, Centellas, Alba Martín , Trankle, Cory R. , Halushka, Marc K., Abbate, Antonio, Basso, Cristina, Sinagra, Gianfranco, Veronese, Giacomo , Camici, PG, Adler, Eric D., Cooper, Leslie T., Gustafsson, Finn , Tschöpe, Carsten , Thiele, Hölger , Ammirati, Enrico , Potena, Luciano , Ammirati, Enrico , Foà, Alberto , Uribarri, Aitor , Thiele, Holger , Vidal-Burdeus, María , Freund, Anne , Gustafsson, Finn , Tschöpe, Carsten , Elsanhoury, Ahmed , Ihle, Joshua , Grabmaier, Ulrich , Merlo, Marco , Melenovský, Vojtěch , Weislova, Ivana , Linke, Axel , Baldovini, Chiara , Kuchynka, Petr , Krejčí, Jan , Gilotra, Nisha A , Hong, Kimberly , Rossi, Valentina A , Ruschitzka, Frank T. , Kamal, Mohamed , Huang, Florent , Groh, Matthieu , Gentile, Piero , Garascia, Andrea , Shimokawa, Hiroaki , Vandenbriele, Christophe , Sionis, Alessandro , Schmidt, Matthieu , Bollano, Entela , Crespo-Leiro, Maria Generosa , Cannatà, Antonio , Bromage, Daniel I , Narducci, Maria Lucia , Cicchitti, Vincenzo , Ianni, Umberto , De Luca, Leonardo , Mistrulli, Raffaella , Frea, Simone , Raineri, Claudia , Schroeder, Jan W , Arias, Anibal Martin , Emdin, Michele , Greulich, Simon , Gawaz, Meinrad , Martínez-Sellés, Manuel , Hernández Pérez, Francisco José , Dominguez, Fernando , D'Alessandris, Nicoletta , Trankle, Cory , Halushka, Marc K , Moroni, Francesco , Abbate, Antonio , Basso, Cristina , Sinagra, Gianfranco , Veronese, Giacomo , Camici, Paolo G , Adler, Eric D , Bernasconi, Davide P , Klingel, Karin , Cooper, Leslie T , Foà, Alberto , Vidal-Burdeus, María , Merlo, M, Melenovský, Vojtěch , Adorisio, Rachele , Paleček, Tomáš , Krejčí, Jan , Cavallini, Claudio , Riccini, Clara, Gentile, Piero , Lala, Anuradha , Shimokawa, Hiroaki , Vandenbriele, Christophe , Couto‐Mallón, David , Luca, Leonardo De , Frea, Simone , Corda, Marco , Domínguez, Fernándo , Gaillet, Antoine , Halushka, Marc K. , Abbate, Antonio , Basso, Cristina , Cooper, Leslie T.

Circulation | February 6, 2026 | Volume: 153 | Issue: 9 | Pages: 634-652

10.1161/circulationaha.125.074797 | PMID 41645905 Get It

BACKGROUND: No large registries of patients with acute eosinophilic myocarditis (EM) are available. However, EM is perceived as a cardiac disease with high mortality, affecting mainly young and middle-aged adults according to small series and case reports. Awareness of the clinical presentation, associated systemic conditions, treatments, and outcomes of this uncommon condition is an unmet need. METHODS: In this international, multicenter, retrospective cohort study, 53 centers screened 193 patients with histologically proven acute EM between 1992 and 2023. After the exclusion of patients with insufficient data (n=10), symptoms lasting >30 days (n=19), or histological diagnosis not confirmed after review (n=8), 156 patients were included. RESULTS: Median age at presentation was 48 years (first to third quartile, 34–59 years) with male predominance (67.3%), and only 2 were pediatric cases (≤16 years of age; 1.3%). The main signs and symptoms at presentation were dyspnea (75.6%), fever (61.3%), and chest pain (53.2%). Unexpectedly, peripheral eosinophilia was reported in only 57.4% of cases, with a median cell count of 630 eosinophils/μL. The median left ventricular ejection fraction at presentation was 32% (first to third quartile, 25%–48%). The disorders most frequently associated with EM were eosinophilic granulomatosis with polyangiitis (22.4% of cases) and hypersensitivity forms (14.1%). Idiopathic/undefined forms accounted for 44.9% of cases, and miscellaneous causes accounted for 18.6%. In-hospital death or need for heart transplantation (HTx) occurred in 23 patients (14.7%; 22 deaths and 1 HTx), despite 43.6% being treated with temporary mechanical circulatory support and 92.9% being treated with immunosuppressive agents. Estimated rates of death or HTx at 1 and 3 years were 19.0% and 23.8%. Increased age, decreased left ventricular ejection fraction on admission, and no immunosuppressive therapy during hospitalization were independent predictors of death or HTx. A nonsignificant higher occurrence of deaths or HTx was observed in the hypersensitivity form (46.1%) compared with the eosinophilic granulomatosis with polyangiitis–associated form (13.1%) at 3 years ( P =0.15). CONCLUSIONS: Acute EM can often present without peripheral eosinophilia, and rates of in-hospital and midterm mortality or HTx are high. Endomyocardial biopsy is required to reach the final diagnosis of EM because relying on peripheral eosinophilia can lead to missing diagnosis. In-hospital immunosuppression is associated with HTx-free survival, although tailored immunosuppressive therapies are needed to improve outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06447935.
Genome and Transcriptome-Wide Analyses Identify Multiple Candidate Genes and a Significant Polygenic Contribution in Bicuspid Aortic Valve
Thériault, Sébastien , Holdcraft, Jacob A., Sharipova, Dinara , Dębiec, Radosław , Peloso, Gina M., Al‐Kassou, Baravan , Swan, Elena Ashikhmina , Ballotta, Andrea, Björck, Hanna M. , Braund, Peter S. , Corriveau, François, Dagenais, François, Francke, Michael, Gorbatov, Svetlana, Guo, Dongchuan, Habchi, Karam M, Scouarnec, Solena Le , Lichtner, Peter , Nguyen, Thy B., Norris, R., Pibarot, P, Simonet, Floriane, Tm, Sundt, Tessler, Idit , Willer, Cristen J., Wittmann, Susanne, Yang, Bo, Berezovets, Igor, Doppler, S. , Dreßen, Martina, Knoll, Katharina, Puehler, T., Schunkert, H, Bissell, Malenka M. , Bolger, Aidan, Brion, M, Citro, Rodolfo, Deeb, G. Michael, Corte, Alessandro Della, Dina, C., Eriksson, Per, Evangelista, Arturo , Franco-Cereceda, Anders, Gilon, Dan, Hetherington, Simon, Huggins, G S, Krane, Markus , Tourneau, Thierry Le, Limongelli, Giuseppe, Mathieu, P., Messika-Zeitoun, David, Michelena, Hector I., Milewicz, Dianna, Murdock, David R. , Nickenig, G., Nistri, Stefano, Nöthen, M, Samani, Nilesh J. , Schott, J., Webb, Tom R., Abdelilah-Seyfried, Salim, Schumacher, Johannes, Trenkwalder, Teresa , Body, Simon C. , Dina, Christian , Brión, Marı́a , Peloso, Gina M. , Webb, Tom R. , Faucherre, Adèle , Debiec, Radoslaw M , Peloso, Gina M , Al-Kassou, Baravan , Aranki, Sary , Ashikhmina Swan, Elena , Björck, Hanna M , Boureau, Anne Sophie , Braund, Peter S , Folkersen, Lasse , Guo, Dongchuan , Heydarpour, Mahyar , Isselbacher, Eric M , Jopling, Chris , Laporte, Fabien , Le Scouarnec, Solena , Li, Zhonglin , Lichtner, Peter , Maj, Carlo , Manikpurage, Hasanga D , Nguyen, Thy B , Norris, Russell A , Pibarot, Phillippe , Sarubbi, Berardo , Simonet, Floriane , Sundt, Thoralf , Surakka, Ida , Tessler, Idit , Yang, Bo , Doppler, Stefanie A , Dreßen, Martina , Knoll, Katharina , Puehler, Thomas , Schunkert, Heribert , Bissell, Malenka M , Bossé, Yohan , Bossone, Eduardo , Brion, María , Citro, Rodolfo , de Vincentiis, Carlo , Deeb, G Michael , Della Corte, Alessandro , Dina, Christian , Durst, Ronen , Ensminger, Stephan , Eriksson, Per , Evangelista, Arturo , Franco-Cereceda, Anders , Gilon, Dan , Giusti, Betti , Hetherington, Simon L , Huggins, Gordon S , Le Tourneau, Thierry , Limongelli, Giuseppe , Mathieu, Patrick , Messika-Zeitoun, David , Michelena, Hector I , Milewicz, Dianna M , Muehlschlegel, Jochen D , Murdock, David R , Nickenig, Georg , Nistri, Stefano , Nöthen, Markus M , Prakash, Siddharth K , Samani, Nilesh J , Jacques Schott, Jean , Webb, Tom R , Zaffran, Stéphane , Eagle, Kim , Body, Simon C , Holdcraft, Jacob A., Bellino, Michele , Dagenais, François, Forte, Amalia , Frigiola, Alessandro , Guo, Dongchuan , Isselbacher, Eric M. , Nelson, Christopher P. , Ong, Chin Siang , Roychowdhury, Tanmoy , Surakka, Ida , Willer, Cristen J , Aviérinos, Jean-François , Bolger, Aidan P. , Bossé, Yohan , Bossone, Eduardo , Citro, Rodolfo , Deeb, G. Michael , Corte, Alessandro Della , Gilon, Dan, Huggins, Gordon S. , Tourneau, Thierry Le , Mathieu, Patrick , Messika–Zeitoun, David , Nistri, Stefano , Nöthen, Markus M. , Pluchinotta, Francesca Romana , Prakash, Siddharth K. , Schott, Jean‐Jacques , Zaffran, Stéphane , Abdelilah‐Seyfried, Salim , Eagle, Kim A. , Schumacher, Johannes

Circulation | February 6, 2026 | Volume: 153 | Issue: 14 | Pages: 1060-1076

10.1161/circulationaha.125.074752 | PMID 41645906 Get It

BACKGROUND: Bicuspid aortic valve (BAV) is a frequent congenital heart defect with a high heritability. Despite this, only a limited number of genes have been associated with the disease, and the molecular mechanisms remain unexplained in most cases. This study aimed to further understand the genetic architecture of BAV. METHODS: A genome-wide association study meta-analysis including 9631 cases among 65 677 participants was performed. Genes were prioritized using transcriptomic analyses based on RNA sequencing in relevant tissues, including human fetal and adult aortic valves. The impact of the knockdown or knockout of 4 candidate genes on cardiac development was verified in zebrafish. A polygenic risk score was developed, its association with BAV was evaluated in an independent cohort, and its association with a wide range of phenotypes (n=976) was evaluated in UK Biobank (n=355 618 individuals). RESULTS: Thirty-six genomic loci were identified, including 32 that were not described previously. Among the prioritized genes, KANK2 and ERBB4 were identified as potentially causal through transcriptomic analyses, colocalization, and Mendelian randomization based on gene expression in human aortic valves (n=484), whereas PRDM6 and STRN were prioritized using similar analyses from aortic (n=326) and left ventricular tissues (n=326), respectively. Targeting 4 candidate genes ( WNT4 , LEF1 , STRN , and KANK2 ) in zebrafish led to disruption in cardiac development. A polygenic risk score was associated with an odds ratio of 2.07 (95% CI, 1.90–2.25; P =5.43×10 -62 ) per SD for BAV and significantly associated with thoracic aortic aneurysm and atrial fibrillation in UK Biobank. CONCLUSIONS: This study supports a significant polygenic contribution to BAV, where the combination of multiple common variants in genes involved in heart morphogenesis disrupts aortic valve development.
Shared Pathogenic Pathways Between REM Sleep Behavior Disorder and Neurodegenerative and Psychiatric Disorders
Zhang, Zhao, Somerville, Emma N. , Fang, Zih‐Hua , Liu, Lang, Asayesh, Farnaz , Ahmad, Jamil, Amiri, Saeid , Teferra, Meron, Dodet, P., Arnulf, Isabelle, Hu, Michele T.M., Desautels, A., Dauvilliers, Yves, Aktan-Süzgün, Merve , Stefani, A., Högl, Birgit, Gaig, Carles, Mayà, G., Iranzo, Alex, Serradell, Mònica , Valente, Mariarosaria, Dusek, P., Sommerauer, Michael , Röttgen, Sinah, Figorilli, M., Puligheddu, Monica, Mollenhauer, Brit, Trenkwalder, Claudia, Sixel-Doring, Friederike, Plazzi, G., Antelmi, E., Terzaghi, Michele, Fiamingo, Giuseppe , Ferini-Strambi, Luigi, Kulcsarova, Kristina, Bušková, J., Abril, Beatriz, Orso, B., Arnaldi, D., Boeve, Bradley F., Ju, Yo‐El S. , Ross, Owen A., Wu, Shih-Ying, Lee, Jonghun , Prilutsky, Daria, Blauwendraat, Cornelis, Leonard, Hampton, Postuma, Ronald B., Rouleau, Guy A., Gan-Or, Ziv, Arnulf, Isabelle , Hu, Michele T M , Desautels, Alex , Dauvilliers, Yves , Ibrahim, Abubaker , Stefani, Ambra , Högl, Birgit , Montini, Angelica , Maya, Gerard , Serradell, Monica , Gigli, Gian Luigi , Valente, Mariarosaria , Janes, Francesco , Sonka, Karel , Kemlink, David , Dušek, Petr , Figorilli, Michela , Puligheddu, Monica , Mollenhauer, Brit , Trenkwalder, Claudia , Sixel-Doring, Friederike , Plazzi, Giuseppe , Biscarini, Francesco , Antelmi, Elena , Cochen De Cock, Valérie , Terzaghi, Michele , Fiamingo, Giuseppe , Heidbreder, Anna , Ferini-Strambi, Luigi , Ostrozovicova, Miriam , Skorvanek, Matej , Kulcsarova, Kristina , Buskova, Jitka , Orso, Beatrice , Mattioli, Pietro , Arnaldi, Dario , Boeve, Brad , Ross, Owen A , Blauwendraat, Cornelis , Postuma, Ronald B , Rouleau, Guy Armand , Gan-Or, Ziv , Zhang, Zhao , Liu, Lang , Ahmad, Jamil, Teferra, Meron , Dodet, Pauline , Arnulf, Isabelle , Désautels, Alex , Dauvilliers, Yves , Ibrahim, Abubaker , Stefani, Ambra , Högl, Birgit , Gaig, Carles , Mayà, Gerard , Iranzo, Álex , Serradell, Mónica , Janes, Francesco , Bernardini, Andrea , Šonka, Karel , Dušek, Petr , Röttgen, Sinah , Figorilli, Michela , Puligheddu, Monica , Mollenhauer, Brit , Trenkwalder, Claudia , Sixel‐Döring, Friederike , Biscarini, Francesco , Antelmi, Elena, Heidbreder, Anna , Kulcsárová, Kristína , Mattioli, Pietro , Arnaldi, Dario , Boeve, Bradley F. , Blauwendraat, Cornelis , Postuma, Ronald B. , Gan‐Or, Ziv

No container title available | February 6, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.64898/2026.02.05.26345599 | PMID 41674635 Get It

Abstract Isolated/idiopathic rapid-eye-movement (REM)-Sleep Behavior Disorder (iRBD) is characterized by dream enactment behaviors associated with loss of REM atonia. iRBD is in most cases a prodromal synucleinopathy, and emerging evidence suggests associations between RBD and other neurological and psychiatric conditions. In this study, we performed pathway-based polygenic risk score (PRS) and rare variant burden analyses to examine these potential associations. Pathway-specific PRS were constructed from genome-wide association study summary statistics of five neurodegenerative and seven psychiatric traits across 10 biologically relevant pathway categories, including a total of 279 pathways, in 1,573 iRBD cases and 16,022 controls from the International RBD Study Group and UK Biobank. Rare variant burden tests were performed in 1,264 iRBD cases and 2,581 controls. We identified multiple potential pathways indicating shared polygenic risk between RBD and both neurodegenerative and psychiatric disorders. Lewy body diseases and post-traumatic stress disorder had the most shared polygenic risk pathways in neurological and psychiatric disorders, respectively. Two pathways, the serotonin transport pathway and the chaperone-mediated autophagy pathway, showed the strongest association with iRBD, and gene-based rare variants analyses revealed five genes associated with iRBD: GBA1 , PLEKHM1 , LRP2 , P2RX1 , and HAP1. Subsequent analysis of these genes in Parkinson’s disease and dementia with Lewy bodies replicated several associations. Together, these findings provide novel insights into the shared genetic architecture underlying iRBD, neurodegenerative disorders, and psychiatric traits, with implications for early identification and mechanistic understanding.
Prenatal Closure of Myeloschisis vs Myelomeningocele: Insights From the fMMC Consortium Registry
Hersh, David S. , Anuar, Amirul, Anadkat, Jagruti , Bennett, Kelly, Blumenfeld, Yair J. , Buchanan, Christopher Q., Clifford, Caitlin , Emery, Stephen P. , Gebb, Juliana , Goodnight, William H. , Herzeg, Akos , Heuer, Gregory G. , Hirose, Shinjiro , Jampa, Alekhya , Lillegard, Joseph B. , Lim, Foong-Yen, Luks, François I. , Moehrlen, Ueli, Moldenhauer, Julie S. , Cortes, M. Sanz, Schenone, Mauro H., Wagner, Amy J., Zaretsky, Michael V. , Crombleholme, Timothy M., Anadkat, Jagruti , Goodnight, William , Gebb, Juliana S , Moehrlen, Ueli , Cortes, Magdalena Sanz , Schenone, Mauro H , Tsao, KuoJen , Van Mieghem, Tim , Zaretsky, Michael V , Crombleholme, Timothy M , Lim, Foong‐Yen Y. , Miller, Jena L. , Shaaban, Aimen F.

Neurosurgery | February 5, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.1227/neu.0000000000003954 | PMID 41642007 Get It

BACKGROUND AND OBJECTIVES: Myelomeningocele is defined by the presence of a fluid-filled sac that contains the neural placode and cerebrospinal fluid (CSF) at the level of the spinal defect. Alternatively, the term myeloschisis is used when the neural placode is not contained within a CSF-filled sac. While both are eligible for prenatal closure, few studies have characterized the impact of the type of lesion on postnatal outcomes. This study compares the outcomes of these 2 types of open spinal dysraphism using data from the Fetal Myelomeningocele Consortium registry sponsored by the North American Fetal Therapy Network. METHODS: The prospective observational Fetal Myelomeningocele Consortium registry was used to extract deidentified data corresponding to patients who underwent fetal closure of myelomeningocele vs myeloschisis. Demographics, operative characteristics, perioperative complications, and postnatal outcomes were collected. RESULTS: A total of 1327 patients were identified, including 991 (74.7%) with myelomeningocele and 336 (25.3%) with myeloschisis. Compared with myelomeningocele, myeloschisis was associated with lower rates of prenatal talipes (11% vs 24%, P < .001) and higher rates of favorable prenatal movement (94% vs 86%, P < .001). Postnatally, myeloschisis conferred higher rates of leg movement (97% vs 90%, P = .002) and an increased likelihood of ambulation in the household (10.4% vs 4.1%, P = .009) and outside (7.2% vs 1.9%, P = .004) at 1 year. However, myeloschisis was also linked to greater use of skin patches during closure (49% vs 27%, P < .001), higher CSF leak rates among those with wound dehiscence (26% vs 8%, P = .014), and more frequent CSF diversion and tethered cord surgeries at follow-up. CONCLUSION: Myeloschisis and myelomeningocele demonstrate distinct clinical profiles. Although patients with myeloschisis may have favorable motor outcomes, they are also characterized by higher rates of CSF leakage, CSF diversion, and tethered cord surgery. These findings highlight the need for lesion-specific prognostication and may inform surgical planning and parental counseling in the context of prenatal spina bifida closure.
Left ventricular ejection fraction and benefit of tricuspid valve interventions: Insights from the international TRIGISTRY
Heitzinger, Gregor, Dreyfus, J, Topilsky, Y, Bonis, M De, Carnero-Alcazar, M, Rudolph, V, Crestanello, J, Lurz, P H I L I P, Bax, J J, Maisano, F, Enriquez-Sarano, M, Bartko, P E, Messika-Zeitoun, D, Heitzinger, Gregor , Dreyfus, Julien , Dannenberg, Varius , Topilsky, Yan , Taramasso, Maurizio , Bonis, Michele De , Carnero, Manuel , Crestanello, Juan A. , Bax, J J B, Maisano, Francesco , Enriquez‐Sarano, Maurice , Bartko, P E, Messika–Zeitoun, David

European Heart Journal | February 5, 2026 | Volume: 46 | Issue: Supplement_1 | Pages: No page available

10.1093/eurheartj/ehaf784.2363 Get It

Abstract Background The impact of treatment for tricuspid regurgitation (TR) across different levels of left ventricular ejection fraction (LVEF) remains uncertain. Purpose This study aimed to compare the outcomes of surgical and transcatheter tricuspid valve interventions (TTVI) to conservative (medical) management across all LVEF categories. Methods Patients with severe isolated TR from the TRIGISTRY, a multicenter international registry, were categorized based on LVEF (preserved EF-pEF:≥50%, mildly reduced EF-mrEF:41–49%, and reduced EF-rEF:≤40%). We assessed the impact of treatment modality and procedural success, defined as residual TR ≤mild-to-moderate, on two-year survival within each LVEF category. Results Among 2,384 patients, 1,383 had pEF, 400 had mrEF, and 601 had rEF. Compared to conservative management, surgery (P&lt;0.0005) and TTVI (P&lt;0.0001) were associated with a survival benefit in patients with pEF. No significant survival advantage was observed in patients with mrEF (P=0.28 for both), nor in those with rEF (P=0.76 and P=0.22 respectively). Similar results were obtained when surgical and transcatheter interventions were grouped together (P&lt;0.0001, P=0.17 and P=0.29 in patients with pEF, mrEF and rEF respectively). Patients with significant residual TR after TTVI exhibited a trend toward worse survival compared to those managed conservatively across all LVEF categories (P=0.47, P=0.33, and P=0.008 respectively)(Figure 1). Conclusion Tricuspid valve intervention, whether surgical or transcatheter-based, was associated with improved survival in patients with preserved LVEF but not in those with mildly reduced or reduced LVEF. Residual TR remained a significant prognostic factor across the entire LVEF spectrum. These findings highlight the need for careful patient selection when considering tricuspid interventions in individuals with reduced LVEF.Figure 1
Breast arterial calcifications on mammography and risk of stroke: a systematic review and meta-analysis
Ghozy, Sherief, Ali, Mohamed Ahmed, Sadiq, Muhayman, Pakzamir, Pedram, Fattahi, Mohammad Reza, Borkar, Rachana R. , Kadirvel, Ramanathan , Conners, Amy Lynn , Kallmes, David F., Ghozy, Sherief , Jazayeri, Seyed Behnam , Sadiq, Muhayman, Fattahi, Mohammad Reza, Ghadery, Abdolkarim Haji , Dmytriw, Adam A. , Kallmes, David F.

Frontiers in Neurology | February 5, 2026 | Volume: 17 | Issue: No issue available | Pages: No page available

10.3389/fneur.2026.1716747 | PMID 41725727 Get It

Background Breast arterial calcifications (BAC) are commonly observed as an incidental finding on screening mammography and have been linked to cardiovascular disease. Whether BAC is independently associated with stroke risk remains uncertain. Methods We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines. PubMed, Embase, and Scopus were searched from inception to May 2024 for cohort studies evaluating the association between BAC and stroke. Eligible studies included women undergoing mammography with documented BAC status and subsequent stroke outcomes. Data on patient characteristics and vascular risk factors were extracted. Study quality was appraised using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Random-effects meta-analyses with restricted maximum likelihood (REML) estimation were performed to pool risk ratios (RRs) and mean differences (MDs). Heterogeneity was assessed with the I 2 statistic, and publication bias with Egger’s test. Results Ten cohort studies including 52,413 women were analyzed. The presence of BAC was associated with more than a twofold increased risk of stroke (RR 2.09, 95% CI 1.58–2.75; I 2 = 64.4%). This association persisted after adjustment for age, diabetes, hyperlipidemia, and menopausal status. Compared with BAC-negative women, those with BAC were significantly older (MD 7.07 years, 95% CI 5.44–8.70) and more frequently hypertensive (RR 1.48, 95% CI 1.23–1.78), diabetic (RR 1.67, 95% CI 1.38–2.02), hyperlipidemic (RR 1.27, 95% CI 1.07–1.51), and postmenopausal (RR 1.26, 95% CI 1.00–1.59). Interestingly, BAC was less common among smokers (RR 0.62, 95% CI 0.45–0.86). Egger’s test showed no evidence of publication bias ( p = 0.143). Conclusion BAC detected on screening mammography is independently associated with an increased risk of stroke, even after accounting for traditional risk factors. These findings support BAC as a promising, underutilized imaging biomarker of cerebrovascular risk in women and highlight the need for standardized reporting and prospective validation.
Benefits of tricuspid valve intervention on outcomes based on underlying etiology in patients with severe functional tricuspid regurgitation: insights from the international TRIGISTRY
Iliadis, C, Dreyfus, J, Topilsky, Y, Bonis, M De, Carnero-Alcazar, M, Rudolph, V, Crestanello, J., Lurz, P H I L I P, Bartko, P E, Bax, J J, Enriquez-Sarano, M, Pfister, R, Messika-Zeitoun, D, Iliadis, Christos , Dreyfus, Julien , Topilsky, Yan , Taramasso, Maurizio , Bonis, Michele De , Carnero, Manuel , Bartko, P E, Bax, J J B, Maisano, Francesco , Enriquez‐Sarano, Maurice , Messika–Zeitoun, David

European Heart Journal | February 5, 2026 | Volume: 46 | Issue: Supplement_1 | Pages: No page available

10.1093/eurheartj/ehaf784.2376 Get It

Abstract Background While tricuspid regurgitation (TR) is predominantly functional, it can arise from various cardiac conditions. This study aimed to evaluate whether the benefits of tricuspid valve intervention, compared to conservative management, differ based on the underlying etiology. Methods In the TRIGISTRY international cohort, which includes consecutive patients with severe isolated functional TR across 33 centers in 10 countries, we compared mortality rates at 2 years between patients who underwent a tricuspid valve intervention (surgical or transcatheter) versus conservative management according to TR etiology. Patients were classified into three groups: (1) Isolated TR (ITR), defined as left ventricular ejection fraction (LVEF) &gt;60%, systolic pulmonary artery pressure (sPAP) &lt;50 mmHg, and no prior left-heart intervention (LHI); (2) LHI-TR, comprising patients with a history of LHI; and (3) Undetermined TR (UTR), which included those who did not meet the criteria for ITR or LHI, as well as those with missing sPAP data. Given previous findings indicating that intervention provided no survival benefit for patients with a high TRI-SCORE, the present analysis was restricted to individuals with low to intermediate TRI-SCORE (≤5). Survival outcomes between groups were compared using restricted mean survival time (RMST). Results A total of 1,552 patients (72±13 years; 56% female) with severe functional TR and a low (48%) or intermediate (52%) TRI-SCORE were included. Of these, 772 (50%) underwent an intervention, while 780 (50%) were conservatively managed. TR was classified as ITR in 201 patients (13%), LHI in 395 (25%), and UTR in 956 (62%). Overall, patients with ITR exhibited the lowest comorbidity burden, whereas those with UTR had the highest. After adjusting for comorbidities and TRI-SCORE, a survival benefit of a tricuspid valve intervention was observed in patients with ITR (survival estimate: 0.17, 95% CI [0.009, 0.32], P=0.039) and, to a lesser extent, in patients with UTR (survival estimate: 0.09, 95% CI [0.0, 0.184], P=0.048), but not in those with prior LHI (survival estimate: 0.06, 95% CI [-0.08, 0.2], P=0.4). Similar results were found when excluding patients with moderate or greater residual TR after intervention. Conclusion In TRIGISTRY, patients with ITR appeared to derive the greatest benefit from tricuspid valve intervention, followed to a lesser extent by those with UTR, while no benefit was observed in patients with prior LHI. However, the potential influence of unaccounted confounders cannot be excluded, and further studies are needed to better identify patients’ subsets that may derive the most benefit from a tricuspid valve intervention.