Citations

Abstract Rehabilitation after musculoskeletal trauma is globally acknowledged as essential for restoring function and improving quality of life; however, significant variation exists in rehabilitation frameworks and services worldwide. Although certain principles—such as early intervention, structured care pathways, and multidisciplinary approaches—are universally recognized as important determinants of outcomes in trauma patients, their implementation and effectiveness vary considerably due to differences in health care infrastructure, economic resources, policy frameworks, and cultural contexts. Drawing on comparative analyses of rehabilitation frameworks across regions, including North America, Latin America, Europe, Asia-Pacific, and Africa, this paper identifies structural variations, systemic challenges, and innovations that can inform global rehabilitation efforts. Strategic international collaboration focusing on shared learning, standardized protocols, technology integration, and targeted investments is key to creating equitable and sustainable rehabilitation models, especially in resource-limited settings and aging populations.

Abstract Acute kidney injury (AKI) frequently follows hematopoietic cell transplantation (HCT). Soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker of AKI in the general population. We evaluated suPAR and its association with AKI requiring dialysis (AKI-D) in patients undergoing allogeneic HCT (alloHCT). Performance of suPAR was compared with serum creatinine (sCr) and neutrophil gelatinase-associated lipocalin (NGAL). Data were obtained from the Blood and Marrow Transplant Clinical Trials Network 1202 cohort, an observational study of 1709 alloHCT recipients. Adults aged ≥18 years with AKI-D after HCT were included. Adults who did not develop AKI were included as controls and matched 1:1. Periodic serum samples (7-90 days) were analyzed for NGAL, suPAR, and sCr. The 1:1 matched case-control groups (n = 62 each) were balanced in demographic variables, except for graft-versus-host disease prophylaxis. The median time from transplant to AKI-D was 2.6 months (range, 0.03-20.39). The day +7 suPAR level after HCT was higher in patients with AKI (median, 2.7 ng/mL) than in controls (2.1 ng/mL; P = .002). In the multivariate analysis, the day +7 suPAR level was associated with the development of AKI-D (P = .009). The area under the curve for the receiver operating characteristic curve for day +7 suPAR levels was 0.75. Neither NGAL nor sCr were associated with AKI-D. Elevated day +7 suPAR levels predicted AKI and lower overall survival (OS). The suPAR level at day +7 after HCT may be an early prognostic factor for the development of AKI-D and OS. Future prospective studies could evaluate this at different stages of AKI. This trial was registered at www.ClinicalTrial.gov as #NCT01879072.

Background: Longitudinal genomic profiling through serial circulating tumor DNA (ctDNA) testing offers a noninvasive method to monitor clonal evolution in advanced prostate cancer. This study evaluated the frequency and nature of newly emergent and potentially actionable genomic alterations detected through serial testing in a real-world setting. Methods: We conducted a retrospective analysis of advanced prostate cancer patients who underwent multiple Guardant360 ctDNA tests between October 2020 and March 2023. The study focused on identifying new genomic alterations absent in the initial test, with particular attention to alterations relevant for on-label therapies, therapies approved in other oncologic indications (i.e., off-label), or a clinical trial. Results: Among 479 patients with at least two ctDNA tests, the median interval between the first and second evaluable tests was 207 days. New and potentially actionable alterations emerged in 57.8% of patients, including potential targets for on-label therapies (16.7%), off-label therapies (16.5%), and clinical trials (55.7%). Tumor mutational burden (TMB) increased from “low” to “high” in 11% of patients, although none had microsatellite instability or mismatch repair deficiency. In a Mayo Clinic subset, ten patients received olaparib based on treatment-emergent alterations, but none achieved a prostate-specific antigen (PSA) response. Two patients who transitioned from low to high TMB received pembrolizumab, both with progressive disease as best response. Conclusions: In a large real-world cohort, serial ctDNA testing frequently identified new alterations that were not detected at baseline and are potentially actionable therapeutic targets, highlighting the value of serial genomic profiling for capturing clonal dynamics. Additional research is needed to better establish a framework for retesting and to clarify how these results should influence subsequent treatment decisions.

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease; however, the procedure can cause loss of cervical spine range of motion and potentially accelerate adjacent segment degeneration. Cervical disc arthroplasty (CDA) seeks to preserve native motion of the cervical spine, which can theoretically reduce the incidence of adjacent level degeneration. The literature regarding the relative efficacy of ACDF versus CDA remains inconsistent. In this study, the authors investigate the difference in outcomes between ACDF and CDA and identify factors contributing to the heterogeneity in the literature. METHODS The Ovid, Embase, Scopus, Cochrane, and ClinicalTrials.gov databases were systematically searched from inception to September 5, 2023, for randomized controlled trials (RCTs) comparing ACDF and CDA for degenerative disc disease. Studies were extracted by two authors and verified by a third. Random-effects meta-analysis was performed. The primary outcome was the difference in clinical outcomes between the two surgical groups. The secondary outcomes were the differences in radiological outcomes, surgical characteristics, complication rates, and hospital lengths of stay. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42023469204) and adhered to the PRISMA guidelines. RESULTS From 584 articles uploaded to the Covidence platform for screening, 35 studies derived from 25 RCTs were included in this systematic review and meta-analysis. A total of 4530 patients were treated with ACDF (2081) and CDA (2449). Forty-six percent of the patients (2063) were male, and the mean age of the study cohort was 45 ± 3 years. In terms of the primary outcome, CDA showed higher rates of neurological and overall success. Regarding the secondary outcomes, CDA demonstrated a significantly lower rate of adjacent level disease, higher rate of heterotopic ossification, and greater range of motion at the operated level. Additionally, CDA had lower rates of reoperation but significantly longer operative times than ACDF. The inclusion of myelopathic patients and variations in follow-up between the surgical groups contributed to the observed effect heterogeneity among studies. CONCLUSIONS In this study, CDA showed comparable or potentially greater success in overall and neurological outcomes, along with a lower incidence of adjacent level degeneration and reoperation rates but longer operative times.

ABSTRACT Objectives To explore the clinical impact of social determinants of health (SDoH) stress in bipolar disorder (BD) course of illness and to explore potential gender differences in SDoH stress endorsement. Methods 2280 individuals living with BD type I or II (62% women; 67.5% BD‐I) participating in the Mayo Clinic Bipolar Biobank who completed a questionnaire assessing positive and negative‐valent stressors in the 12 months prior to study enrollment were included for this analysis. Six negative stressors were used as proxies of SDoH. Generalized linear models were used to test the association between SDoH stressors and markers of illness severity as well as potential differences by sex by including an interaction term. Results After adjusting for age, sex, and recruitment site, SDoH‐related stressors were significantly associated with a more severe course of illness in both men and women. Except for unemployment rates, women reported more frequently SDoH‐related stress (i.e., lack of family support, financial problems, health coverage and access problems). Conclusions The study found significant gender differences in both the endorsement of specific SDoH stressors and in the prevalence of specific illness severity markers; however, it did not directly test the predictive relationship between gender differences in SDoH and illness severity markers. Future studies aiming to achieve health equity in mental health care should continue assessing social determinants of health stressors, incorporating a gender perspective to better understand their influence on bipolar disorder.

Abstract We investigated the influence of 55 583 autophagy-related single-nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across 4 independent populations comprising 5472 CLL cases and 726 465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the 4 populations identified, to our knowledge, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, and rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (P = 1.57 × 10−12). We also validated previously reported associations for FAS, BCL2, and BAK1 SNPs with CLL risk (P = 4.73 × 10−21 to 3.39 × 10−9). The CDKN2Ars3731204 and FASrs1926194 SNPs associated with increased CDKN2A and ACTA2 messenger RNA expression levels in the whole blood and/or lymphocytes (P = 5.1 × 10−7, P = 1.58 × 10−21, and P = 7.8 × 10−41), although no significant effect on autophagy flux was observed. However, associations were found between CDKN2A, BCL2, and FAS SNPs and various T-cell subsets, cytokine production, and circulating concentrations of interferon gamma, tumor necrosis factor–related apoptosis-inducing ligand, CD40, chemokine ligand 20, and interleukin-2 receptor subunit β proteins (P ≤ .005). No significant association was detected between autophagy variants and OS or TTFT, suggesting that these variants drive disease initiation rather than progression. In conclusion, this study identified 4 novel associations for CLL and provided insights into the biological pathways that influence CLL development.

Abstract Aims Chronotropic incompetence (CI) is a biomarker of cardiac autonomic dysfunction. The aim of the study is to assess the risk stratification value of CI during exercise or pharmacological stress echocardiography in patients with chronic coronary syndromes. Methods and results In a prospective, multicenter, international, observational study, we enrolled 13 445 patients with known or suspected chronic coronary syndromes who underwent stress echocardiography in 19 clinical sites from 10 countries using either exercise (n = 2594), dobutamine (n = 2440), or dipyridamole (n = 8411). Heart rate was automatically measured from the 1-lead ECG in the echocardiography monitor. We considered CI as failure to reach 85% of the maximal predicted (220-age) heart rate for exercise and dobutamine, and heart rate reserve (peak/rest heart rate) ≤ 1.22 (≤1.17 if in permanent atrial fibrillation) for dipyridamole stress. The primary outcome was all-cause death. CI was observed in 5045 patients (38%) and stress-induced regional wall motion abnormalities in 1648 (13%). Over a median follow-up time of 3.4 years (interquartile range, 1.6–9.1 years), there were 2426 (18%) deaths. The 10-year mortality was 39% in patients with and 21% in patients without CI (P < 0.0001). CI was associated with a significant increase in 10-year mortality in all age groups ranging from ≤54 years to ≥75 years (P < 0.0001). In addition, it was associated with increased mortality (P < 0.0001) irrespective of β-blocker use. Cox multivariable analysis revealed that CI was an independent predictor of mortality (HR: 1.60, 95% confidence interval: 1.47–1.74; P < 0.0001) together with age, male sex, diabetes mellitus, left ventricular ejection fraction, and resting heart rate. Conclusion In patients with chronic coronary syndromes, CI during exercise or pharmacological stress is a simple and objective predictor of survival.