Citations

Abstract Aging, a major risk factor for delirium, is associated with accumulation of senescent cells in many tissues of the body. Senescent cells produce a host of proinflammatory and tissue remodeling factors collectively termed the senescence-associated secretory phenotype (SASP), which are secreted into circulation. The relationship between increased senescent cell burden and risk of delirium is not known. This study aimed to determine whether changes in circulating SASP proteins are associated with increased risk of postoperative delirium in cognitively intact older adults. Participants were recruited among patients scheduled for surgical or transcatheter aortic valve replacement, and blood was obtained at the presurgical visit. SASP factors were measured using commercially available multiplex magnetic bead immunoassays based on Luminex xMAP multianalyte profiling platform and analyzed on a MAGPIX system. Activin A concentration was determined by a Quantikine ELISA kit. Delirium cases were identified by manual chart abstraction, utilizing the problem list, ICD-10 codes, clinical notes, and nursing flowsheets. Eight of 62 (12.9%) of patients within the cohort developed postoperative delirium. Length of stay was significantly longer for patients who developed delirium (10.6 days) versus patients without delirium (6 days). Concentrations of SASP factors Activin A and PAPP-A were significantly higher in plasma of patients with delirium vs. those who did not develop delirium. IL-1 alpha concentration was significantly lower in patients with delirium vs without delirium. Other SASP factors measured were not statistically different between groups. More study is needed to determine whether these changes are directly related to increased senescent cell burden.

AbstractSenescent cells compromise tissue structure and function in older organisms. We recently identified senescent fibroadipogenic progenitors (FAPs) with activated chemokine signaling pathways in the skeletal muscle of old mice, and hypothesized these cells may contribute to the age‐associated accumulation of immune cells in skeletal muscle. In this study, through cell–cell communication analysis of skeletal muscle single‐cell RNA‐sequencing data, we identified unique interactions between senescent FAPs and macrophages, including those mediated by Ccl2 and Spp1. Using mouse primary FAPs in vitro, we verified increased expression of Ccl2 and Spp1 and secretion of their respective proteins in the context of both irradiation‐ and etoposide‐induced senescence. Compared to non‐senescent FAPs, the medium of senescent FAPs markedly increased the recruitment of macrophages in an in vitro migration assay, an effect that was mitigated by preincubation with antibodies to either CCL2 or osteopontin (encoded by Spp1). Further studies demonstrated that the secretome of senescent FAPs promotes polarization of macrophages toward an M2 subtype. These data suggest the unique secretome of senescent FAPs may compromise skeletal muscle homeostasis by recruiting and directing the behavior of macrophages.

Case: This report describes the case of an athletic 12-year-old boy who presented with a 64° left proximal humeral varus angulation deformity and physeal bar secondary to multiple operations for a proximal humeral metaphyseal cystic lesion and pathologic fracture. Using a combined lateral closing and medial opening-wedge osteotomy, a 68° valgus correction was achieved with excellent clinical and functional outcomes at 16-month follow-up. Forward flexion increased from 120 to 170° preoperatively to postoperatively while abduction improved from 110° preoperatively to 170° postoperatively. Conclusion: A combined lateral closing and medial opening-wedge osteotomy of the proximal humerus can successfully treat cases of extreme proximal humerus varus in the growing shoulder where unilateral or dome osteotomies are not suitable.

Purpose To compare the cost‐effectiveness of an initial trial of nonoperative treatment to that of early arthroscopic debridement for stable osteochondritis dissecans (OCD) lesions of the capitellum. Methods A Markov Chain Monte Carlo probabilistic model was developed to evaluate the outcomes and costs of 1,000 simulated patients undergoing nonoperative management versus early arthroscopic debridement for stable OCD lesions of the capitellum. Health utility values, treatment success rates, and transition probabilities were derived from the published literature. Costs were determined on the basis of the typical patient undergoing each treatment strategy at our institution. Outcome measures included costs, quality‐adjusted life‐years (QALYs), and the incremental cost‐effectiveness ratio (ICER). Results Mean total costs resulting from nonoperative management and early arthroscopic debridement were $5,330 and $21,672, respectively. On average, early arthroscopic debridement produced an additional 0.64 QALYS, resulting in an ICER of $25,245/QALY, which falls well below the widely accepted $50,000 willingness‐to‐pay (WTP) threshold. Overall, early arthroscopic debridement was determined to be the preferred cost‐effective strategy in 69% of patients included in the microsimulation model. Conclusions Results of the Monte Carlo microsimulation and probabilistic sensitivity analysis demonstrated early arthroscopic debridement to be a cost‐effective treatment strategy for the majority of stable OCD lesions of the capitellum. Although early arthroscopic debridement was associated with higher total costs, the increase in QALYS that resulted from early surgery was enough to justify the cost difference based on an ICER substantially below the $50,000 WTP threshold. Level of Evidence Level III, economic computer simulation model.