Racial Disparities Exist in 90-Day Unplanned Return to the Emergency Department Following Orthopaedic Trauma Surgery.

OBJECTIVES: Racial disparities in healthcare outcomes exist, including in orthopaedic trauma care. The aim of this study was to determine the impact of race, social deprivation, and payor status on 90-day emergency department (ED) revisits among orthopaedic trauma surgery patients at a Level 1 trauma academic medical center. DESIGN: Retrospective chart review analysis. SETTING: Level 1 trauma academic center in Durham, NC. PATIENT SELECTION CRITERIA: Adult patients undergoing orthopaedic trauma surgery between 2017 and 2021. OUTCOME MEASURES AND COMPARISONS: The primary outcome of this retrospective cohort study was 90-day return to the ED. Logistic regression analysis was performed for variables of interest [race, social deprivation (measured by the Area Deprivation Index), and payor status] separately and combined, with each model adjusting for distance to the hospital. Results were interpreted as odds ratios (ORs) of 90-day ED revisits comparing levels of the respective variables. Statistical significance was assessed at α = 0.05. RESULTS: A total of 3120 adult patients who underwent orthopaedic trauma surgery between 2017 and 2021 were included in the analysis. Black race (OR = 1.47; 95% confidence interval [CI]: 1.17-1.84, P < 0.001) and Medicaid coverage (OR = 1.63, 95% CI: 1.20-2.21, P = 0.002) were significantly associated with higher odds of return to ED compared with non-Black or non-Medicaid-covered patients. While ethnic minority (Hispanic/Latino or non-White) was statistically significant while adjusting only for distance to the hospital (OR = 1.23, 95% CI: 1.00-1.50, P = 0.047), it was no longer significant after adjusting for the other sociodemographic variables (OR = 1.13, 95% CI: 0.91-1.39, P = 0.27). The weighted Area Deprivation Index was not associated with a difference in odds of return to ED in any adjusted models. CONCLUSIONS: The results highlight the presence of racial and socioeconomic disparities in ED utilization, with Black race and Medicaid coverage significantly associated with higher odds of return to the ED. Future research should delve deeper into comprehending the root causes contributing to these racial and socioeconomic utilization disparities and evaluate the effectiveness of targeted interventions to reduce them. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Revision Total Ankle Arthroplasty Using the INBONE II System.

BACKGROUND: The utilization of total ankle arthroplasty (TAA) for managing severe ankle osteoarthritis has become increasingly common, leading to a higher occurrence of revision TAA procedures because of failure of primary TAA. This study aims to examine the clinical results associated with revision TAA using the INBONE II system. Given the growing number of TAA revision procedures and a focus on motion-preserving salvage options, we evaluated our early experience with revision TAA. METHODS: A retrospective analysis was conducted on a group of 60 presumed noninfected patients who underwent revision TAA with the INBONE II system. Detailed information was collected on patient demographics, implant characteristics, concurrent procedures, and complications. The implant survival was estimated using Kaplan-Meier analysis. RESULTS: The study revealed high complication rates but generally fair clinical outcomes for revision TAA using the INBONE II system. Complications were observed in 22 patients (36.7%), including persistent pain (n = 6), nerve injury/impingement (n = 5), infection (n = 3), fracture (n = 3), implant failure (n = 3), impaired wound healing (n = 2), and osteolysis (n = 3). The 3-year survivorship rate from reoperation was 92.0% (82.7%-100.0%) whereas the 3-year survivorship rate from major complications was 90.4% (80.8%-100.0%). CONCLUSION: We report high complication rates but generally fair clinical results for revision TAA utilizing the INBONE II system. LEVEL OF EVIDENCE: Level IV, retrospective case series study.

The association of pre-existing mental health conditions and patient outcomes after lower extremity orthopaedic trauma: a scoping review.

INTRODUCTION: Existing research has established a correlation between post-traumatic mental health conditions, including anxiety and depression, and various aspects of recovery, such as pain exacerbations, reduced functional recovery, and lowered patient satisfaction. However, the influence of pre-existing mental health conditions on orthopaedic trauma outcomes has not been thoroughly investigated. The objective of this study was to systematically review literature addressing the association between pre-existing mental health conditions and patient outcomes following surgical interventions for lower extremity fractures in non-geriatric populations. METHODS: A systematic literature review was conducted using Medline, Embase, and Scopus databases following PRISMA-ScR guidelines to select studies that examined lower extremity orthopaedic trauma outcomes in relation to pre-existing mental health conditions. Studies that evaluated patients with surgically treated lower extremity fractures and a history of mental health conditions such as anxiety, depression, or mood disorders were included. Studies with a mean patient age above 65 years of age were excluded to focus on non-geriatric injury patterns. RESULTS: The systematic review identified 12 studies investigating the relationship between surgical outcomes of orthopaedic lower extremity fractures and pre-existing mental health disorders in non-geriatric populations. Studies included patients with pelvis, femur, tibia, and ankle fractures. A majority (83%) of these studies demonstrated that patients with pre-existing mental health diagnoses had inferior functional outcomes, heightened pain levels, or an increase in postoperative complications. DISCUSSION: The presence of pre-existing mental health conditions, particularly anxiety and depression, may predispose orthopaedic trauma patients to an elevated risk of suboptimal functional outcomes, increased pain, or complications after surgical intervention for lower extremity fractures. Future research should focus on interventions that mitigate the impact of mental health conditions on orthopaedic outcomes and patient wellness in this population.

Unique Positive Cooperativity Between the ß-Arrestin-Biased ß-Blocker Carvedilol and a Small Molecule Positive Allosteric Modulator of the ß2-Adrenergic Receptor.

Among ß-blockers that are clinically prescribed for heart failure, carvedilol is a first-choice agent with unique pharmacological properties. Carvedilol is distinct from other ß-blockers in its ability to elicit ß-arrestin-biased agonism, which has been suggested to underlie its cardioprotective effects. Augmenting the pharmacologic properties of carvedilol thus holds the promise of developing more efficacious and/or biased ß-blockers. We recently identified compound-6 (cmpd-6), the first small molecule positive allosteric modulator of the ß2-adrenergic receptor (ß2AR). Cmpd-6 is positively cooperative with orthosteric agonists at the ß2AR and enhances agonist-mediated transducer (G-protein and ß-arrestin) signaling in an unbiased manner. Here, we report that cmpd-6, quite unexpectedly, displays strong positive cooperativity only with carvedilol among a panel of structurally diverse ß-blockers. Cmpd-6 enhances the binding affinity of carvedilol for the ß2AR and augments its ability to competitively antagonize agonist-induced cAMP generation. Cmpd-6 potentiates ß-arrestin1- but not Gs-protein-mediated high-affinity binding of carvedilol at the ß2AR and ß-arrestin-mediated cellular functions in response to carvedilol including extracellular signal-regulated kinase phosphorylation, receptor endocytosis, and trafficking into lysosomes. Importantly, an analog of cmpd-6 that selectively retains positive cooperativity with carvedilol acts as a negative modulator of agonist-stimulated ß2AR signaling. These unprecedented cooperative properties of carvedilol and cmpd-6 have implications for fundamental understanding of G-protein-coupled receptor (GPCR) allosteric modulation, as well as for the development of more effective biased beta blockers and other GPCR therapeutics. SIGNIFICANCE STATEMENT: This study reports on the small molecule-mediated allosteric modulation of the ß-arrestin-biased ß-blocker, carvedilol. The small molecule, compound-6 (cmpd-6), displays an exclusive positive cooperativity with carvedilol among other ß-blockers and enhances the binding affinity of carvedilol for the ß2-adrenergic receptor. Cooperative effects of cmpd-6 augment the ß-blockade property of carvedilol while potentiating its ß-arrestin-mediated signaling functions. These findings have potential implications in advancing G-protein-coupled receptor allostery, developing biased therapeutics and remedying cardiovascular ailments.

A Scalable CURE Using a CRISPR/Cas9 Fluorescent Protein Knock-In Strategy in Caenorhabditis elegans.

Genome editing with CRISPR/Cas9 technology has advanced from the lab bench to clinical application with multiple trials underway. This article introduces a course-based undergraduate experience (CURE) combining CRISPR/Cas9 genome editing (using a modified two-plasmid system) and the animal model Caenorhabditis elegans. This CURE is designed to be a scalable, semester-long laboratory that will introduce the students to literature searches, molecular biology, experiment planning, microscopy, CRISPR bioethics discussion, and scientific writing. Here, students challenged themselves to endogenously tag the C. elegans gene zmp-4, a matrix metalloproteinase enzyme, with a fluorescent protein marker and successfully generated a new worm strain. The knock-in was confirmed with genotyping and imaging and will be available for use by the entire worm community.