Citations

Abstract Senescent cells drive tissue dysfunction through the senescence-associated secretory phenotype (SASP). We uncovered a central role for mitochondria in the epigenetic regulation of the SASP, where mitochondrial-derived metabolites, specifically citrate and acetyl-CoA, fuel histone acetylation at SASP gene loci, promoting their expression. We identified the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY) as critical for this process. Inhibiting these pathways selectively suppresses SASP without affecting cell cycle arrest, highlighting their potential as therapeutic targets for age-related inflammation. Notably, SLC25A1 inhibition reduces systemic inflammation and extends healthspan in aged mice, establishing mitochondrial metabolism as pivotal to the epigenetic control of aging.

Objective Extracorporeal cardiopulmonary resuscitation (ECPR) utilizes veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in cardiac arrest patients to reduce the risk of mortality and multiorgan dysfunction from systemic hypoperfusion. We aimed to compare clinical outcomes of patients receiving ECPR versus conventional cardiopulmonary resuscitation (CCPR) for refractory cardiac arrest. Data Sources This was a systematic review and meta-analysis. A librarian searched the main databases, Ovid MEDLINE (including epub ahead of print, in-process & other non-indexed citations), Ovid EMBASE and Ovid Cochrane Central Register of Controlled Trials from inception through July 2024. Study Selection We included randomized controlled trials and observational studies that compared the outcomes of ECPR to CCPR in cardiac arrest patients. Primary outcomes were neurological sequelae and survival. Data Extraction We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two reviewers independently screened articles, extracted data on selected articles and performed risk of bias assessments using ROBINS-I for non-randomized controlled trials and the revised Cochrane risk of bias tool for randomized controlled trials with disagreements settled by a third independent reviewer. Data Synthesis Out of 3458 studies identified and screened, 28 studies including 304,360 cardiac arrest patients met eligibility criteria and were included. Survival at hospital discharge was 20% for ECPR versus 3.3% for CCPR (OR 0.48 [CI 0.27, 0.84]). Favorable neurological outcome at hospital discharge was 11.8% for ECPR versus 1.9% for CCPR (OR 0.41 [CI 0.17, 1.01]). Complications from bleeding were ten times higher in the ECPR group (35.3% vs 3.7%; OR 0.08 [0.03, 0.24]). Conclusions ECPR appeared to be superior to CCPR for improved neurological outcome and survival in cardiac arrest patients, although bleeding was increased. There was large heterogeneity in the included studies and outcomes reported. Future prospective studies may improve the identification of subgroups of patients that will benefit most from ECPR. Systematic review and meta-analysis registration: PROSPERO - CRD42023394128.

Abstract Context A national assessment of osteoporosis drug therapy (ODT) use can inform the extent of underdiagnosis and undertreatment of osteoporosis. Objective The aim was to describe trends in ODT use by age, sex, fragility fracture, and documented osteoporosis. Methods This was a retrospective analysis of patient-quarter observations for adults aged ≥50 years with commercial or Medicare Advantage health insurance in the OptumLabs Data Warehouse between 2011 and 2022. The primary outcome was the proportion of patient-quarter observations with ODT use stratified by age, sex, fragility fracture, and documented osteoporosis. Cuzick tests were performed to assess trends ODT use. Results Analysis of 166 673 420 patient-quarter observations revealed that over 70% of patients with fragility fractures did not have documented osteoporosis. Among women aged ≥65 years with documented osteoporosis, ODT fill rates increased between 2011 and 2022 from 36.3% to 50.1% for women without fragility fractures (P < .001) and from 30.8% to 43.7% for women with fragility fractures (P < .001). However, ODT fill rates declined (9.2% to 7.4% between 2011 and 2022) for women with fragility fractures and no documented osteoporosis (P = .015). Similar trends were observed among women aged 50-64 years and men. Conclusion ODT use for patients with documented osteoporosis has increased but remains low. Low rates of ODT use for patients with fragility fractures in the absence of documented osteoporosis suggests that underdiagnosis of osteoporosis contributes to underuse of ODTs.

Progression of liver disease is dependent on intercellular signaling, including those mediated by extracellular vesicles (EVs). Within these EVs, microRNAs (miRNAs) are packaged to selectively silence gene expression in recipient cells for upregulating or downregulating a specific pathway. Injured hepatocytes secrete EV-associated miRNAs which can be taken up by liver sinusoidal endothelial cells, immune cells, hepatic stellate cells, and other cell types. In addition, these recipient cells will secrete their own EV-associated miRNAs to propagate a response throughout the tissue and the circulation. In this review, we comment on the implications of EV-miRNAs in the progression of alcohol-associated liver disease, metabolic dysfunction-associated steatohepatitis, viral and parasitic infections, liver fibrosis, and liver malignancies. We summarize how circulating miRNAs can be used as biomarkers and the potential of utilizing EVs and miRNAs as therapeutic methods to treat liver disease.

Background: Because of growing concerns regarding repeated head trauma, in 2016, the United States Soccer Federation (USSF) banned headers for athletes aged ≤10 years and limited athletes aged 11 to 13 years to practicing headers for 30 minutes per week. Purpose: To assess whether the USSF header policy was associated with fewer soccer-related concussions after the 2015 season. Study Design: Descriptive epidemiology study. Methods: A retrospective cohort from the National Electronic Injury Surveillance System database was assessed. Age, sex, and injury type were extracted for all soccer-related emergency department visits between January 1, 2012, and December 31, 2023. Univariate and multiple regression analyses were used to assess concussions as a percentage of all soccer-related injuries based on sex, age group (6-9, 10-13, and 14-17 years), and year. The following time frames were assessed: 2012-2015, 2016-2019, and 2020-2023. Results: The proportion of concussions decreased from 8.2% of all soccer-related injuries in 2012-2015 to 6.1% in 2020-2023 ( P < .01). The relative risk reduction for soccer-related concussions presenting to an emergency department in 2020-2023 compared with 2012-2015 was 25.6%. Overall, the proportion of concussions among 10- to 13-year-old and 14- to 17-year-old players was higher than for 6- to 9-year-old players (6.6% and 8.9% vs 4.9%, respectively; P < .01). Despite having a lower frequency of soccer-related injuries overall, female players had a greater proportion of concussions than male players (9.6% vs 6.2% of all soccer-related injuries; P < .01). In the multiple regression analysis, injuries that occurred in 2020-2023 were associated with lower odds of concussion compared with 2012-2015 (odds ratio [OR], 0.75 [95% CI, 0.69-0.81]). Compared with 6- to 9-year-old and male players, the 10- to 13-year-old (OR, 1.30 [95% CI, 1.16-1.45]), 14- to 17-year-old (OR, 1.79 [95% CI, 1.61-1.99]), and female players (OR, 1.53 [95% CI, 1.43-1.63]) were associated with higher odds of concussion. Conclusion: A 25.6% reduction in the relative risk of presenting to the emergency department with a soccer-related concussion was found when comparing 2020-2023 (after USSF header policy implementation) with 2012-2015 (before policy implementation). The USSF youth soccer header policy may improve player safety by reducing head impacts in the pediatric population.

Abstract Glenoid bone loss is a common sequela of recurrent anterior shoulder instability. When treated surgically, a bone augmentation procedure is more likely to provide a good outcome with a lower risk of recurrent instability compared with a soft‐tissue repair alone. There are several bone augmentation options to address glenoid bone loss, including coracoid transfer, iliac crest autograft, and distal tibial allograft (DTA). Both open and arthroscopic DTA techniques have been described using the lateral one‐third of the distal tibia oriented with the anterior aspect placed superiorly on the anterior glenoid. This graft orientation places its concavity in the superior‐to‐inferior direction. It may be preferred to have this concavity maximized toward the anterior direction so that it can further resist anterior displacement. The posterior one‐third of the distal tibia may provide a more optimal arc of resistance. However, no previous technique has used the posterior one‐third of the distal tibia to reconstruct the “half‐pipe” concavity of the anterior glenoid. We describe an all‐arthroscopic technique for a posterior third DTA oriented with the posterior tibial edge placed anteriorly on the glenoid, termed the “congruent‐arc DTA,” to address anterior shoulder instability with bone loss. Technique Video video See video under supplementary data.

Recent literature has emphasized the role of hand surgeons in screening patients with carpal tunnel syndrome (CTS) for amyloidosis by performing a carpal tunnel synovial biopsy during open carpal tunnel release (CTR). This has led to misconceptions about the diagnostic utility of synovial biopsy and the clinical evaluation of suspected amyloidosis. Controversy over carpal tunnel biopsy is exacerbated by minimally invasive advances in CTR procedures. This current perspective aims to determine the role of carpal tunnel synovial biopsy in amyloidosis and provide an update for hand surgeons regarding the nuances of amyloidosis. We conclude that carpal tunnel synovial biopsy should not be performed without CTS symptoms but only in patients meeting criteria for open CTR such as in those with severe symptoms which have failed nonoperative treatment and minimally invasive procedures are contraindicated. A screening approach for amyloidosis is proposed in patients presenting with CTS symptoms. Despite advances in the understanding, treatment, and diagnosis of amyloidosis, there remains a need for accurate, specific, and sensitive diagnostic tests.

Background: The treatment for Kienböck disease varies widely based on the status of the lunate. To date, there is no consensus regarding the optimal treatment for patients with coronal plane fractures of the lunate, or Lichtman Stage IIIC. Therefore, the purpose of this study was to assess whether coronal plane fractures of the lunate in Kienböck disease healed after surgical intervention, and to determine the outcomes after surgical fixation of the lunate compared with treatment with salvage procedures. Methods: A retrospective review of 36 patients with Lichtman IIIC Kienböck disease was conducted. Patients were classified into lunate reconstruction (vascularized bone graft [VBG] or non-VBG) or salvage procedures (proximal row carpectomy [PRC] or limited fusion). Preoperative and postoperative visual analog scale (VAS) pain, range of motion, grip strength, and Mayo Wrist Score (MWS) were analyzed. Radiographs and computed tomographic scans were reviewed for Lichtman stage, fracture location, union, modified carpal height ratio, Stahl index, and radioscaphoid angle. Results: Thirteen patients underwent lunate reconstruction, 13 underwent limited fusion, and 10 underwent PRC. The overall union rate was 45% after lunate reconstruction, with average time to union of 7 months. There were no differences in union rates between VBG and non-VBG. All 3 groups experienced improvement in their postoperative grip strength and MWS. There were no statistically significant differences in preoperative to postoperative changes in clinical outcome measures between the 3 cohorts; however, when we compared lunate reconstruction with all patients who underwent salvage procedures (limited carpal fusion and PRC), we noted the latter had improved functional outcomes ( P = .019). Four patients (31%) in the reconstruction cohort and 2 patients (8%) in the limited carpal fusion group required reoperation at latest follow-up. Conclusions: Union rate of coronal plane fractures in Kienböck disease remains variable. While the proportion of patients requiring reoperation was higher in the reconstruction group, all groups of patients experienced improvement in their clinical outcomes, without a significant difference between cohorts.