Citations

Abstract Studies have reported conflicting findings regarding the contribution of germline variants or somatic genomic drivers to racial disparities in multiple myeloma. To comprehensively investigate somatic drivers in relation to inherited genetics in multiple myeloma, we combined newly sequenced whole-genome sequencing data with publicly available datasets (total n = 1,286). Overall, we did not identify germline or somatic genomic differences that explain the different risk of developing multiple myeloma between patients with genetic similarity to African (AFR) or European (EUR) reference populations. A difference in the detectability and timing of APOBEC-associated and germinal center mutational activity was observed. Integrating epidemiologic data and mutational signature-based temporal estimates, we challenge the assumption that individuals in the AFR group develop multiple myeloma at a younger age. Finally, we demonstrate that, with equal access to efficacious therapies, patients in the AFR and EUR groups have equivalent clinical outcomes. Significance: Multiple myeloma is reported to occur at higher rates in individuals who self-identify as non-Hispanic Black. In this large dataset, genomic drivers occur at the same rate among ancestry groups, except for APOBEC mutagenesis. With equivalent therapy, clinical outcomes did not differ for patients grouped by genetic ancestry similarity.

Aging selectively impacts the function of type IIx/IIb fibers in the diaphragm muscle. We show that sarcopenia reduces maximum specific force, maximum shortening velocity, and peak power output, whereas endurance during repetitive contractions is preserved. These findings explain why higher force airway clearance behaviors decline with age, whereas fatigue-resistant breathing behavior remains resilient.

Background: Achilles tendon ruptures are among the most debilitating injuries in professional basketball, often leading to prolonged absence and long-term performance decline. While calf strains are common among National Basketball Association (NBA) athletes, their role as a precursor to Achilles rupture remains poorly understood. Hypothesis: A previous calf strain would be associated with increased odds of Achilles tendon rupture in NBA players and that affected players would experience significant post-injury performance declines. Study Design: Case-cohort study; Level of evidence, 3. Methods: Publicly available data on NBA players from 1958 to 2024 were analyzed, with the data search conducted in June 2025. Players with Achilles ruptures (n = 60) were compared with players with calf strains who did not sustain a rupture (n = 258). Logistic regression adjusted for age, body mass index, position, starter status, and workload. Pre- and postinjury performance was evaluated over 2 seasons using paired t tests. Descriptive analyses characterized injury laterality, game context, quarter, shoe type, and draft position. Video review assessed injury mechanisms. Results: Previous calf strain was associated with increased odds of Achilles rupture (odds ratio, 2.49; 95% CI, 1.16-5.22; P = .02). Among those with both injuries, 85.7% occurred on the same side, with a mean interval of 1.9 years. Of all players, a total of 75% returned to play. Postinjury declines were observed in player efficiency rating (−2.46), win shares (−3.23), games played (−260.3), and minutes per game (−5.19) (all P < .001). Return was more likely in younger players and those on multiyear contracts. Video analysis revealed a consistent “false step” mechanism in 95% of cases with footage. Most Achilles tendon ruptures occurred during in-game activity, while shoe type was evaluated descriptively and was not associated with player position or preinjury workload. Conclusion: Our study showed that previous calf strain is associated with an increased risk of Achilles tendon rupture in NBA players and may serve as a clinically identifiable risk marker. Rupture leads to substantial and sustained performance decline, even among those who return. Targeted rehabilitation and movement retraining may help mitigate progression to rupture in high-risk athletes.

ABSTRACT The term “clinical anatomy” is widely used in education and research, yet its conceptual boundaries continue to be interpreted in various ways. Prior consensus‐based efforts have emphasized integration, collaboration, and clinical relevance as central features of the field and have provided an important foundation for interdisciplinary engagement. At the same time, ongoing changes in academic structure, medical education, and interdisciplinary biomedical science raise important questions regarding how clinical anatomy can sustain its scientific identity and long‐term relevance. Building upon prior discussions, this article argues that the continued maturation of clinical anatomy depends on the integration of conceptual frameworks with the sustained production of rigorous, reproducible, and clinically meaningful scholarly contributions. Historical and contemporary examples alike demonstrate that the influence of clinical anatomy has been shaped through contributions that directly advanced clinical science and practice. Accordingly, continued emphasis on methodological rigor, reproducibility, clinically meaningful contribution, and educational accountability may be essential to the field's future development and relevance.

Resumo A glomerulopatia C3 (C3G) é uma entidade clinicopatológica caracterizada por inflamação glomerular com dominância de C3 à imunofluorescência. A microscopia eletrônica é utilizada para determinar a localização e o tipo de depósitos, o que permite subdividir a C3G em glomerulonefrite C3 (GNC3) e doença de depósitos densos (DDD) com base em achados ultraestruturais. Ambas as entidades são progressivas, com cerca de 60% dos pacientes evoluindo para doença renal terminal (DRT) em 10 anos. A recorrência após o transplante renal ocorre em até 60% dos casos de C3G. Novos conhecimentos sobre a fisiopatologia—diferentes padrões de lesão, escores histopatológicos, coloração para apolipoproteína E, desregulação da via alternativa do complemento, que inclui autoanticorpos e mutações em fatores reguladores do complemento, bem como análises proteômicas—permitiram uma melhor compreensão dos diferentes perfis fisiopatológicos e apresentações clínicas, possibilitando um tratamento individualizado. O papel da nefroproteção está bem estabelecido na C3G, assim como em outras doenças glomerulares. O tratamento não específico com corticosteroides e imunossupressores está associado a uma taxa de resposta variável. No entanto, mais recentemente, os resultados de ensaios clínicos com inibidores proximais da via alternativa do complemento demonstraram melhora significativa na proteinúria e atenuação da redução da taxa de filtração glomerular estimada (TFGe). Com base nos resultados desses ensaios com medicamentos que atuam especificamente nas vias do complemento a montante, incluindo a via alternativa, novas opções de tratamento tornaram-se disponíveis para pacientes com C3G.

Abstract C3 glomerulopathy (C3G) is a clinicopathologic entity characterized by glomerular inflammation with dominant staining for C3 on immunofluorescence microscopy. Electron microscopy is used to determine the location and type of deposits, which further divides C3G into C3 glomerulonephritis (C3GN) and dense deposit disease (DDD) based on ultrastructural findings. Both entities are progressive, with about 60% of patients progressing to end-stage kidney disease (ESKD) within 10 years. Recurrence after kidney transplantation occurs in up to 60% of C3G cases. New knowledge about the pathophysiology—different patterns of injury, histopathological scoring, apolipoprotein E staining, dysregulation of the alternative complement pathway (including both autoantibodies to and mutations in complement regulatory factors), as well as proteomic analyses—has allowed a better understanding of different pathophysiological profiles and clinical presentations, enabling individualized treatment. The role of nephroprotection is well established in C3G, as it is for other glomerular diseases. Non-specific treatment with corticosteroids and immunosuppression is associated with a variable response rate. However, more recently, results from clinical trials with proximal complement inhibitors have shown significant improvement in proteinuria and attenuation of the decline in estimated glomerular filtration rate (eGFR). Based on the results of these trials involving drugs that specifically target the upstream complement pathways, including the alternative pathway, new treatment options have recently become available for patients with C3G.