Does Semaglutide Use Decrease Complications and Costs Following Total Knee Arthroplasty?

BACKGROUND: Diabetes mellitus (DM) and obesity are associated with total knee arthroplasty (TKA) complications. Semaglutide, a medication for DM and weight loss, can potentially affect TKA outcomes. This study investigated whether semaglutide use during TKA demonstrates fewer: (1) medical complications; (2) implant-related complications; (3) readmissions; and (4) costs. METHODS: A retrospective query was performed using a National database to 2021. Patients undergoing TKA for osteoarthritis with DM and semaglutide use were successfully propensity score-matched to controls semaglutide = 7,051; control = 34,524. Outcomes included 90-day postoperative medical complications, 2-year implant-related complications, 90-day readmissions, in-hospital lengths of stay, and costs. Multivariate logistical regressions calculated odds ratios (ORs), 95% confidence intervals, and P values (P < .003 as significance threshold after Bonferroni correction). RESULTS: Semaglutide cohorts had higher incidence and odds of myocardial infarction (1.0 versus 0.7%; OR 1.49; P = .003), acute kidney injury (4.9 versus 3.9%; OR 1.28; P < .001), pneumonia (2.8 versus 1.7%; OR 1.67; P < .001), and hypoglycemic events (1.9 versus 1.2%; OR 1.55; P < .001), but lower odds of sepsis (0 versus 0.4%; OR 0.23; P < .001). Semaglutide cohorts also had lower odds of prosthetic joint infections (2.1 versus 3.0%; OR 0.70; P < .001) and readmission (7.0 versus 9.4%; OR 0.71; P < .001), and trended toward lower odds of revisions (4.0 versus 4.5%; OR 0.86; P = .02) and 90-day costs ($15,291.66 versus $16,798.46; P = .012). CONCLUSION: Semaglutide use during TKA decreased risk for sepsis, prosthetic joint infections, and readmissions, but also increased risk for myocardial infarction, acute kidney injury, pneumonia, and hypoglycemic events.

Pharmacological Therapies for Connective Tissue Fibrosis in Orthopaedics.

Fibrosis is a common and debilitating pathological process that affects many organ systems and contributes to connective tissue disorders in orthopaedics. Tendons heal after acute and chronic injury through a process of fibrovascular scar tissue formation, and soft tissue joint capsules can be affected after traumatic joint injury, leading to arthrofibrosis. Although the precise underlying mechanisms are still being elucidated, fibrosis is thought to be a consequence of dysregulated immune and cytokine signaling that leads to myofibroblast activation and proliferation and subsequent excessive collagen deposition. Current treatments for connective tissue fibrosis include physical therapy and surgery, but there are no therapies that directly target the underlying cellular and molecular mechanisms of fibrosis. Many pharmacological agents have been used to successfully target fibrosis in other tissues and organ systems and thus are a promising treatment option to fill this gap. However, limited evidence is available to guide the use of these agents in musculoskeletal connective tissues. This article provides an overview of pharmacological therapies that have potential to treat connective tissue fibrosis in patients with musculoskeletal conditions, along with the current supporting evidence and future uses of each therapy.

Achilles Tendons Display Region-Specific Transcriptomic Signatures Associated With Distinct Mechanical Properties.

BACKGROUND: Previous studies have examined the transcriptomes and mechanical properties of whole tendons in different regions of the body. However, less is known about these characteristics within a single tendon. PURPOSE: To develop a regional transcriptomic atlas and evaluate the region-specific mechanical properties of Achilles tendons. STUDY DESIGN: Descriptive laboratory study. METHODS: Achilles tendons from 2-month-old male Sprague Dawley rats were used. Tendons were isolated and divided into proximal, middle, and distal thirds for RNA sequencing (n = 5). For mechanical testing, the Achilles muscle-tendon-calcaneus unit was mounted in a custom-designed materials testing system with the unit clamped over the musculotendinous junction (MTJ) and the calcaneus secured at 90° of dorsiflexion (n = 9). Tendons were stretched to 20 N at a constant speed of 0.0167 mm/s. Cross-sectional area, strain, stress, and Young modulus were determined in each tendon region. RESULTS: An open-access, interactive transcriptional atlas was generated that revealed distinct gene expression signatures in each tendon region. The proximal and distal regions had the largest differences in gene expression, with 2596 genes significantly differentially regulated at least 1.5-fold (q < .01). The proximal tendon displayed increased expression of genes resembling a tendon phenotype and increased expression of nerve cell markers. The distal region displayed increases in genes involved in extracellular matrix synthesis and remodeling, immune cell regulation, and a phenotype similar to cartilage and bone. There was a 3.72-fold increase in Young modulus from the proximal to middle region (P < .01) and an additional 1.34-fold increase from the middle to distal region (P = .027). CONCLUSION: Within a single tendon, there are region-specific transcriptomic signatures and mechanical properties, and there is likely a gradient in the biological and functional phenotype from the proximal origin at the MTJ to the distal insertion at the enthesis. CLINICAL RELEVANCE: These findings improve our understanding of the underlying biological heterogeneity of tendon tissue and will help inform the future targeted use of regenerative medicine and tissue engineering strategies for patients with tendon disorders.

Comparative analysis of metabolic risk factors for progression of non-alcoholic fatty liver disease.

AIM OF THE STUDY: Non-alcoholic fatty liver disease (NAFLD), a globally prevailing chronic liver condition, refers to a spectrum of disease ranging from bland steatosis to steatohepatitis causing fibrosis without significant alcohol intake. Prominent risk factors (RFs) include obesity, type 2 diabetes mellitus, and dyslipidemia. Currently, no established hierarchy exists for the influence of metabolic RFs on NAFLD progression. This retrospective cohort study investigated and ranked the independent and combined effects of three major RFs on NAFLD progression. MATERIAL AND METHODS: 652 NAFLD patients with ≥ 1 RF were categorized by RF combination to examine yearly changes in RF severity with liver stiffness measurement (LSM) over five years. Body mass index (BMI), hemoglo- bin A1c (HbA1c), total cholesterol (TC), and LSM were reviewed. RESULTS: In patients with any single improving RF, decreases in BMI were associated with a yearly LSM change of -1.26 kPa, while decreases in HbA1c and TC were associated with a change of -0.51 kPa and -0.56 kPa, respectively. In patients with any single worsening RF, increases in BMI were correlated with an LSM change of +0.74 kPa and increases in HbA1c and TC were correlated with a change of +0.43 kPa and +0.16 kPa, respectively. Patients with three RFs had the greatest LSM changes for both improving (-3.68 kPa) and worsening (+3.19 kPa) groups. The strongest predictors for LSM change were BMI and HbA1c, with standardized ß coefficients of 0.236 and 0.226 (p < 0.001), while TC had the least influence [0.112 (p < 0.01), F(3,647) = 11.458, p < 0.001, R 2 = 0.155]. CONCLUSIONS: Obesity was the most prominent RF. Treatment of all three RFs over a five-year period presented a high likelihood of fibrosis stage regression for NAFLD patients.