Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

PURPOSE: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation. METHODS: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation. RESULTS: Part 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1. CONCLUSIONS: While there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.

Modifiable Patient Factors Demonstrate No Increased Risk for 30-Day Complication Rate for Elective 1-2 Level Posterior Lumbar Fusion Surgery: A Comparison Between a National Database and Local Registry.

BACKGROUND: While national databases provide large datasets that can be used to understand trends over time, their correlation with prospectively collected data from local registries has not been established. The purpose of the study was to compare differences in patient demographics and adverse events for patients undergoing elective posterior spinal fusion (PSF) between a national database and institutional registry. METHODS: A retrospective chart review was performed. A total of 14,618 patients (13,678 patients from the National Surgical Quality Improvement Program [NSQIP] database and 940 patients from the institutional registry) who underwent elective 1- to 2-level PSF were included in the study. Preoperative patient demographics and comorbidities of each cohort were compared. In addition, postoperative 30-day complications and readmission were collected. A multivariate analysis was performed to examine for differences in risk factors for 30-day adverse events between the 2 cohorts. RESULTS: A total of 13,678 patients from the NSQIP database and 940 patients from the institutional cohort were included for analysis. Mean age was similar between patient cohorts (60.8 ± 13.1NSQIP vs 58.8 ± 12.9registry), with NSQIP having significantly more patients over the age of 65 (41.4% vs 33.2%, P < 0.001). Overall complication rate was similar between NSQIP (6.8%) and the institutional registry (8.4%). Both found age and female sex to be significant predictors of 30-day adverse events, while obesity, hypertension, and smoking were only found to be predictive in the NSQIP database. CONCLUSIONS: Age and female sex were found to be independent risk factors for 30-day adverse events between both cohorts, while only NSQIP found modifiable comorbidities to be significant predictors. Although large databases allow for trends in quality over time, subtleties in practice variation and data collection methods at the individual institution level need to be considered when generalizing findings, especially as it pertains to modifiable factors. CLINICAL RELEVANCE: Quality metrics and risk factors for patient outcomes are often derived from national databases. This study highlights the differences between study results when outcomes are derived from an institutional registry compared to a national database.