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.

The use of machine learning for predicting candidates for outpatient spine surgery: a review.

While spine surgery has historically been performed in the inpatient setting, in recent years there has been growing interest in performing certain cervical and lumbar spine procedures on an outpatient basis. While conducting these procedures in the outpatient setting may be preferable for both the surgeon and the patient, appropriate patient selection is crucial. The employment of machine learning techniques for data analysis and outcome prediction has grown in recent years within spine surgery literature. Machine learning is a form of statistics often applied to large datasets that creates predictive models, with minimal to no human intervention, that can be applied to previously unseen data. Machine learning techniques may outperform traditional logistic regression with regards to predictive accuracy when analyzing complex datasets. Researchers have applied machine learning to develop algorithms to aid in patient selection for spinal surgery and to predict postoperative outcomes. Furthermore, there has been increasing interest in using machine learning to assist in the selection of patients who may be appropriate candidates for outpatient cervical and lumbar spine surgery. The goal of this review is to discuss the current literature utilizing machine learning to predict appropriate patients for cervical and lumbar spine surgery, candidates for outpatient spine surgery, and outcomes following these procedures.

Prevalence and antibiotic resistance of Staphylococcus aureus associated with a college-aged cohort: life-style factors that contribute to nasal carriage.

Staphylococcus aureus is an opportunistic human pathogen that can frequently be found at various body locations, such as the upper respiratory tract, nostrils, skin, and perineum. S. aureus is responsible for causing a variety of conditions, which range from minor skin infections and food poisoning to life-threatening sepsis and endocarditis. Furthermore, S. aureus has developed resistance to numerous antimicrobial agents, which has made treatment of S. aureus infections difficult. In the present study, we examined lifestyle factors that could increase the likelihood of S. aureus carriage, the overall prevalence of S. aureus, as well as assessed the antibiotic resistance profiles of the S. aureus isolates among a population of college students. Five hundred nasal samples were collected and analyzed via selective growth media, coagulase and protein A testing, as well as polymerase chain reaction and DNA sequencing. One hundred four out of the 500 samples collected (21%) were identified as containing S. aureus. The S. aureus isolates were resistant to penicillin (74%), azithromycin (34%), cefoxitin (5%), ciprofloxacin (5%), tetracycline (4%), and trimethoprim (1%), but sensitive to gentamicin and rifampin. Lastly, we identified several lifestyle factors (i.e., pet exposure, time spent at the university recreational facility, musical instrument usage, and tobacco usage) positively correlated with S. aureus nasal colonization.

Analysis of Patient Factors Affecting In Vitro Characteristics of Subacromial Bursal Connective Tissue Progenitor Cells during Rotator Cuff Repair.

Unsatisfactory failure rates following rotator cuff (RC) repair have led orthopaedic surgeons to explore biological augmentation of the healing enthesis. The subacromial bursa (SB) contains abundant connective tissue progenitor cells (CTPs) that may aid in this process. The purpose of the study was to investigate the influence of patient demographics and tear characteristics on the number of colony-forming units (CFUs) and nucleated cell count (NCC) of SB-derived CTPs. In this study, we harvested SB tissue over the supraspinatus tendon and muscle in 19 patients during arthroscopic RC repair. NCC of each sample was analyzed on the day of the procedure. After 14 days, CFUs were evaluated under a microscope. Spearman's rank correlation coefficient was then used to determine the relationship between CFUs or NCC and patient demographics or tear characteristics. The study found no significant correlation between patient demographics and the number of CFUs or NCC of CTPs derived from the SB (p > 0.05). The study did significantly observe that increased tear size was negatively correlated with the number of CFUs (p < 0.05). These results indicated that increased tear size, but not patient demographics, may influence the viability of CTPs and should be considered when augmenting RCrepairs with SB.