Citations

Background: Patellofemoral dislocations are often associated with chondral injuries. In adults, diagnostic arthroscopy (DA) has identified chondral injuries in up to one-third of cases where magnetic resonance imaging (MRI) was negative. However, the value of DA in detecting cartilage injuries in pediatric patients undergoing medial patellofemoral ligament reconstruction (MPFLR) has not been well studied. Purposes: To evaluate the utility of DA in diagnosing cartilaginous injuries in pediatric patients undergoing MPFLR with negative preoperative MRI findings and to compare postoperative outcomes between patients with and without chondral injury findings on DA. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A retrospective review was conducted on patients aged 0 to 18 years who underwent combined MPFLR and DA procedures from 2015 to 2023 at a single institution. The exclusion criteria were as follows: revision MPFLR; tibial tubercle osteotomy; multiligament reconstructions; and previous meniscal injury. MRI and DA reports were reviewed for chondral findings. Patients were classified into 3 groups: +MRI/+DA, –MRI/+DA, and –MRI/–DA. Subgroup analysis was performed within the –MRI/+DA group to compare outcomes in the immediate postoperative recovery period between those who underwent a chondroplasty versus those who did not. Results: Of the 155 patients included, follow-up averaged 7.8 months (median, 5 months [range, 0-41 months]). Among 89 patients with negative MRI findings, 39 (43.8%) had chondral injuries detected on DA. Targeted treatment was performed in 22 (56.4%) of these patients, a lower rate than in those with positive MRI findings (80.3%; P = .02). No significant differences were observed in knee flexion at 2 weeks postoperatively: +MRI/+DA (77.9°± 23°), –MRI/+DA (66.5°± 30.2°), and –MRI/–DA (73.3°± 30°) ( P = .14). Similarly, no significant differences were found at 12 weeks: +MRI/+DA (135.3°± 13°), –MRI/+DA (127.8°± 21°), and –MRI/–DA (134.1°± 13.4°) ( P = .10). Range of motion and complication rates were comparable across all groups ( P > .05). A subgroup analysis in the –MRI/+DA cohort comparing patients who underwent an arthroscopic procedure (n = 22) with those who did not (n = 17) showed no significant differences in range of motion or complication rates ( P > .05). Conclusion: Diagnostic arthroscopy detected cartilaginous injuries in 43.8% of pediatric patients with negative preoperative MRI undergoing MPFLR. This highlights the diagnostic value of DA in identifying injuries that would otherwise remain undetected.

BACKGROUND: MODULAR antitachycardia pacing (ATP), a multicenter, international trial, assesses a modular cardiac rhythm management system: a subcutaneous implantable cardioverter defibrillator in wireless communication with a leadless pacemaker (LP) capable of pace-terminating ventricular tachycardia. METHODS: Enrolees had one or more clinical risk factors for ventricular tachycardia and did not require chronic pacing. Complications included prespecified major LP system- and procedure-related complications, and any complication related to the LP, subcutaneous implantable cardioverter defibrillator, implantation, or study protocol. Survival analysis was performed to identify complication-free rates, therapy delivery, and all-cause mortality. RESULTS: The 297 patients enrolled had an ejection fraction of 35±13%, 43% secondary prevention indications, and 59% with prior ventricular arrhythmias. Of 286 patients undergoing LP implantation (100% success), 251 patients completed 12-month follow-up. Mortality rate was 6%, with none related to the implant procedure. Median follow-up duration was 23.4 months (interquartile range, 17.9–28.1). The LP major complication-free rate was 97.2%, exceeding the performance goal. The overall LP+ subcutaneous implantable cardioverter defibrillator system-related complication-free rate was 88.5%. Appropriate tachyarrhythmia-therapy (ATP+shock) rates were 14.4%, and appropriate shock rates were 8.5%. Inappropriate total tachyarrhythmia therapy was 9.5% of which 8.5% were shocks. ATP was 67.3% successful in terminating ventricular arrhythmia episodes and accelerated ventricular arrhythmias in 10.1% of episodes. Overall therapy burden (ATP+shock) was 96/100 patient-years, of which 44/100 patient-years was for shock delivery. CONCLUSIONS: One-year outcomes of the first modular pacing-defibrillator system reveal low system and LP complication rates and good ATP efficacy rates, suggesting that the modular cardiac rhythm management is a viable alternative to single-chamber implantable cardioverter defibrillators using low-energy pacing capability without the need for transvenous leads. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ ; Unique identifier: NCT04798768.

Abstract Purpose: CD4 T-cell immunity is associated with improved survival in patients with breast cancer. We previously reported a phase I trial evaluating a folate receptor alpha (FRα) vaccine administered with cyclophosphamide (CP), demonstrating excellent safety and immunogenicity. To simplify the vaccine strategy for ease of use, we report here the results of a randomized phase II trial evaluating a lower vaccine dose alongside the original dose, administered with or without CP pretreatment. Patients and Methods: Patients with triple-negative breast cancer who completed all systemic and local therapies were assigned to receive either low-dose (825 μg) or high-dose (2.5 mg) vaccine peptides plus GM-CSF in six 4-week cycles, with or without CP prior to vaccination. Safety was monitored, and immunogenicity was evaluated before and after vaccination. Results: A total of 80 patients were dosed with vaccine, and 58 patients were evaluable for immunogenicity. Vaccination was well tolerated and elicited immunity in 83% of patients. Levels of FRα-specific T cells were high, persistent, and comparable with T-cell levels against tetanus toxoid. No differences in immunity were observed between the two doses. CP pretreatment also did not affect the immune responses. Recurrences occurred in eight evaluable patients and were unrelated to the treatment arm. No patients died during the study because of their disease. Conclusions: The reduced-dose FRα vaccine is as effective as the original dose and does not require CP to generate maximal immunity. These findings may inform the design of trials testing efficacy in triple-negative breast cancer or other cancers.

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Abstract Approximately 17% of people aged 65 years and older are anemic, and 10% of death certificates report anemia as a secondary cause of death in the United States. Nonetheless, anemia remains unexplained in 30%-50% of older adults. This unexplained anemia of aging (UAA) is a diagnosis of exclusion. The mechanism, impact, and progression of UAA remain unknown. At older ages, anemia adds to pre-existing co-morbidities with significant adverse health consequences, representing a compelling unmet clinical concern. The National Institute on Aging held a workshop in 2024 to discuss current knowledge and research opportunities. Topics included the epidemiology of anemia at older age and its clinical implications; probable mechanism(s) underlying UAA, that is, low-grade inflammation’s effects on erythropoiesis; the role of microbiota in iron regulation in bone marrow; the importance of ruling out a diagnosis of leukemic clonal hematopoiesis (CH), which is more prevalent in older age; the role of senescence and aging governing hematopoiesis; and the effects of sex hormones on hematopoietic stem cell aging. Understanding the roles of these factors could reduce the proportion of the older anemic population whose anemia remains unexplained and offer insights into new potential diagnostic and intervention strategies. Speakers reviewed previous clinical trials in patients with UAA and CH. They discussed lessons learned and future research priorities, including efforts to develop new diagnostic algorithms and potential uses of machine learning.

Artificial intelligence (AI) is rapidly transforming the delivery of kidney care through predictive analytics, machine learning, deep learning, and generative AI technologies. To meet this challenge, the American Society of Nephrology convened an AI Workgroup to provide a framework for the responsible use of AI in nephrology. The group outlines foundational principles to guide AI development: prioritizing patient benefit, ensuring clinician oversight, and advancing innovation in high-burden disease areas. Its set of foundational assumptions are grounded in the physician always being in the loop and an overarching goal to benefit patients with kidney diseases. This review provides an overview of the clinical uses of AI in nephrology and offers practical guidance for nephrologists seeking to incorporate AI into CKD and AKI management, dialysis, and transplantation care. It also highlights key challenges—such as data quality, equity, transparency, and clinical integration—that must be addressed to ensure the responsible and effective implementation of AI in kidney care.

Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

Background: Age is the strongest factor determining disease expression in multiple sclerosis (MS). We previously demonstrated biological age acceleration in pediatric-onset MS (POMS) compared to controls with both epigenetic clocks (DNAm) and telomere length (TL). It is unknown whether these markers report overlapping or distinct aging-related processes. Objectives: To determine the correlation between DNAm and TL aging markers. Methods: We conducted a cross-sectional case–control study within the US Network of Pediatric MS Centers. We calculated age acceleration residuals for the Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks and measured TL from whole blood samples to estimate telomere to somatic DNA ratios (T/S ratio). We employed multivariable analysis of covariance to assess the correlation between DNAm estimates and TL. Results: We analyzed biological ages in 270 participants (125 POMS, mean 15.7 years; 145 controls, mean 15.3 years). There were moderate correlations among the different DNAm clocks, but no correlations between DNAm clocks and TL in pooled analyses. In a stratified analysis, only the control group showed a modest correlation between TL and PhenoAge clock ( r = 0.2, p = 0.06). Conclusions: DNAm did not correlate with TL in this sample of POMS and controls, suggesting that these biomarkers may capture complementary and non-overlapping elements of aging-related biology.