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Background: The multidimensional prognostic index (MPI), an established tool to predict adverse outcomes, classifies frailty using an aggregate-weighted tripartite scoring system based on 8 domains (low, moderate, or severe risk). However, this approach may fail to capture specific patient phenotypes that can be characterized by separate MPI domains and for whom health outcome risk also differs.
Objective: We sought to identify latent patient phenotypes based on MPI domain data and to determine their association with mortality in older patients with atrial fibrillation (AF).
Methods: Using data from the European Study of Older Subjects With Atrial Fibrillation, we used latent class analysis to identify phenotypes using individual MPI domains and Cox regression models to examine their association with 12-month mortality.
Results: Four MPI domain phenotypes were identified in 2019 patients with AF (mean age 82.9 years [standard deviation, 7.5]; 57% females): phenotype 1 (relatively fit, few comorbidities; n = 672, 33%), phenotype 2 (functionally impaired, polypharmacy, comorbidities; n = 685, 34%), phenotype 3 (multidimensional frailty, comorbidities; n = 161, 8%), and phenotype 4 (relatively fit, polypharmacy, comorbidities; n = 501, 25%). Compared with phenotype 1, 12-month mortality was higher in phenotype 3 (adjusted hazard ratio [aHR], 4.68; 95% confidence interval [CI], 3.41-6.43), phenotype 2 (aHR, 1.98; 95% CI, 1.53-2.57), and phenotype 4 (aHR, 1.44; 95% CI, 1.07-1.94).
Conclusion: In a cohort of older patients with AF, latent class analysis identified 4 MPI domain phenotypes with different risks of mortality. Pending confirmatory studies, the identified subgroups might allow more targeted interventions to improve outcomes in this population.
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http://dx.doi.org/10.1016/j.hrthm.2025.05.012 | DOI Listing |
Am J Hum Genet
September 2025
Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, Rotterdam 3000 CA, the Netherlands.
Microtubule-actin cross-linking factor 1 (MACF1) is a large protein of the spectraplakin family, which is essential for brain development. MACF1 interacts with microtubules through the growth arrest-specific 2 (Gas2)-related (GAR) domain. Heterozygous MACF1 missense variants affecting the zinc-binding residues in this domain result in a distinctive cortical and brain stem malformation.
View Article and Find Full Text PDFTurk J Pediatr
September 2025
West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
Background: The α-actinin-4 (ACTN4) gene encodes an actin-binding protein, which plays a crucial role in maintaining the structure and function of podocytes. Previous studies have confirmed that ACTN4 mutations can lead to focal segmental glomerulosclerosis-1 (FSGS1), a rare disease primarily manifesting in adolescence or adulthood, characterized by mild to moderate proteinuria, with some cases progressing slowly to end-stage renal disease.
Case Presentation: We report a 12.
Introduction: Frailty, characterized by a reduction in intrinsic capacity across multiple physiological systems, is a key concern in healthy aging. Insight in the trajectory of an individual's functional ability and intrinsic reserve capacity in a relatively younger population of older adults is lacking. This study aims to investigate the early stages of frailty by tracking trajectories of physical indicators of intrinsic capacity before frailty becomes clinically evident.
View Article and Find Full Text PDFJ Neurooncol
September 2025
Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Purpose: NOTCH3 is increasingly implicated for its oncogenic role in many malignancies, including meningiomas. While prior work has linked NOTCH3 expression to higher-grade meningiomas and treatment resistance, the metabolic phenotype of NOTCH3 activation remains unexplored in meningioma.
Methods: We performed single-cell RNA sequencing on NOTCH3 + human meningioma cell lines.
Kaohsiung J Med Sci
September 2025
Department of Medical Oncology, Haikou People's Hospital, Haikou, Hainan, People's Republic of China.
Inhibition of cuproptosis contributes to the development of non-small cell lung cancer (NSCLC). The expression of RNA-binding motif protein 15 (RBM15) is upregulated in NSCLC. Nonetheless, its relationship with cuproptosis remains unclear.
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