Preoperative prediction model for risk of readmission after total joint replacement surgery: a random forest approach leveraging NLP and unfairness mitigation for improved patient care and cost-effectiveness.

BACKGROUND: The Center for Medicare and Medicaid Services (CMS) imposes payment penalties for readmissions following total joint replacement surgeries. This study focuses on total hip, knee, and shoulder arthroplasty procedures as they account for most joint replacement surgeries. Apart from being a burden to healthcare systems, readmissions are also troublesome for patients. There are several studies which only utilized structured data from Electronic Health Records (EHR) without considering any gender and payor bias adjustments. METHODS: For this study, dataset of 38,581 total knee, hip, and shoulder replacement surgeries performed from 2015 to 2021 at Novant Health was gathered. This data was used to train a random forest machine learning model to predict the combined endpoint of emergency department (ED) visit or unplanned readmissions within 30 days of discharge or discharge to Skilled Nursing Facility (SNF) following the surgery. 98 features of laboratory results, diagnoses, vitals, medications, and utilization history were extracted. A natural language processing (NLP) model finetuned from Clinical BERT was used to generate an NLP risk score feature for each patient based on their clinical notes. To address societal biases, a feature bias analysis was performed in conjunction with propensity score matching. A threshold optimization algorithm from the Fairlearn toolkit was used to mitigate gender and payor biases to promote fairness in predictions. RESULTS: The model achieved an Area Under the Receiver Operating characteristic Curve (AUROC) of 0.738 (95% confidence interval, 0.724 to 0.754) and an Area Under the Precision-Recall Curve (AUPRC) of 0.406 (95% confidence interval, 0.384 to 0.433). Considering an outcome prevalence of 16%, these metrics indicate the model's ability to accurately discriminate between readmission and non-readmission cases within the context of total arthroplasty surgeries while adjusting patient scores in the model to mitigate bias based on patient gender and payor. CONCLUSION: This work culminated in a model that identifies the most predictive and protective features associated with the combined endpoint. This model serves as a tool to empower healthcare providers to proactively intervene based on these influential factors without introducing bias towards protected patient classes, effectively mitigating the risk of negative outcomes and ultimately improving quality of care regardless of socioeconomic factors.

Correction to "Shifting the Antibody-Drug Conjugate Paradigm: A Trastuzumab-Gold-Based Conjugate Demonstrates High Efficacy against Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Mouse Model".

[This corrects the article DOI: 10.1021/acsptsci.3c00270.].

Outcomes after débridement, antibiotics, and implant retention for prosthetic joint infection in shoulder arthroplasty.

BACKGROUND: Patients who undergo total shoulder arthroplasty usually have excellent long-term outcomes. However, a subset of patients is diagnosed with a prosthetic joint infection (PJI) requiring revision procedures and prolonged recovery. The purpose of this study was to evaluate rates of recurrent shoulder PJI in patients undergoing débridement, antibiotics, and implant retention (DAIR), single-stage revision, and 2-stage revision. We also sought to compare outcomes and complications across procedures. METHODS: Retrospective chart review was conducted for patients diagnosed with PJI after primary shoulder arthroplasty between January 2010 and August 2021. Patients were included if they underwent treatment with DAIR, single-stage revision, or 2-stage revision. Demographic information, surgical details, complications, laboratory data, postoperative antibiotic regimen, and infectious pathogen were collected. Postoperative patient-reported outcomes were collected: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, Shoulder Activity Scale, and PROMIS Upper Extremity. Chi-square, t test, and 1-way analysis of variance were used as appropriate to evaluate each factor. RESULTS: Sixty-five patients were included in the study, 26% treated with DAIR, 9% treated with single-stage revision, and 65% treated with 2-stage revision. There were no significant differences in patient comorbidities. Patients undergoing DAIR were diagnosed significantly earlier than those undergoing single- and 2-stage revision procedures (12.6 ± 22.9 months vs. 49.6 ± 48.4 vs. 25.0 ± 26.6, P = .010). Recurrent PJI was noted in 23.1% of patients: 29.4% of DAIR patients, no single-stage patients, and 23.8% of 2-stage patients (P = .330). Patients undergoing 2-stage revision with treatment failure had a significantly higher Elixhauser Comorbidity Index (0.2 ± 3.7 vs. 3.7 ± 3.9, P = .027). There was no significant difference in patient-reported outcomes across groups. CONCLUSION: Patients undergoing treatment of shoulder PJI with DAIR did not have an increased rate of reinfection compared with single-stage and 2-stage revision procedures. Patients treated with DAIR were diagnosed with PJI significantly earlier than those undergoing single-stage and 2-stage revision procedures. There was no difference in complication rates between groups. This information adds to the body of work detailing outcomes after DAIR for shoulder PJI and provides encouraging data for use in this patient population. Future studies with a larger sample size may be conducted to further investigate specific pathogens, infection timelines, and antibiotic regimens that reduce the risk of treatment failure.

Predictors of dislocations after reverse shoulder arthroplasty: a study by the ASES complications of RSA multicenter research group.

BACKGROUND: Instability after reverse shoulder arthroplasty (RSA) is one of the most frequent complications and remains a clinical challenge. Current evidence is limited by small sample size, single-center, or single-implant methodologies that limit generalizability. We sought to determine the incidence and patient-related risk factors for dislocation after RSA, using a large, multicenter cohort with varying implants. METHODS: A retrospective, multicenter study was performed involving 15 institutions and 24 American Shoulder and Elbow Surgeons members across the United States. Inclusion criteria consisted of patients undergoing primary or revision RSA between January 2013 and June 2019 with minimum 3-month follow-up. All definitions, inclusion criteria, and collected variables were determined using the Delphi method, an iterative survey process involving all primary investigators requiring at least 75% consensus to be considered a final component of the methodology for each study element. Dislocations were defined as complete loss of articulation between the humeral component and the glenosphere and required radiographic confirmation. Binary logistic regression was performed to determine patient predictors of postoperative dislocation after RSA. RESULTS: We identified 6621 patients who met inclusion criteria with a mean follow-up of 19.4 months (range: 3-84 months). The study population was 40% male with an average age of 71.0 years (range: 23-101 years). The rate of dislocation was 2.1% (n = 138) for the whole cohort, 1.6% (n = 99) for primary RSAs, and 6.5% (n = 39) for revision RSAs (P < .001). Dislocations occurred at a median of 7.0 weeks (interquartile range: 3.0-36.0 weeks) after surgery with 23.0% (n = 32) after a trauma. Patients with a primary diagnosis of glenohumeral osteoarthritis with an intact rotator cuff had an overall lower rate of dislocation than patients with other diagnoses (0.8% vs. 2.5%; P < .001). Patient-related factors independently predictive of dislocation, in order of the magnitude of effect, were a history of postoperative subluxations before radiographically confirmed dislocation (odds ratio [OR]: 19.52, P < .001), primary diagnosis of fracture nonunion (OR: 6.53, P < .001), revision arthroplasty (OR: 5.61, P < .001), primary diagnosis of rotator cuff disease (OR: 2.64, P < .001), male sex (OR: 2.21, P < .001), and no subscapularis repair at surgery (OR: 1.95, P = .001). CONCLUSION: The strongest patient-related factors associated with dislocation were a history of postoperative subluxations and having a primary diagnosis of fracture nonunion. Notably, RSAs for osteoarthritis showed lower rates of dislocations than RSAs for rotator cuff disease. These data can be used to optimize patient counseling before RSA, particularly in male patients undergoing revision RSA.

Shifting the Antibody-Drug Conjugate Paradigm: A Trastuzumab-Gold-Based Conjugate Demonstrates High Efficacy against Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Mouse Model.

Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutics to target cancers without toxicity to normal tissue. Clinically, most chemotherapeutic ADCs are based on complex organic molecules, while the conjugation of metallodrugs to mAbs has been overlooked, despite the resurgent interest in metal-based drugs as cancer chemotherapeutics. In 2019, we described the first gold ADCs containing gold-triphenylphosphane fragments as a proof of concept. The ADCs (based on the antibody trastuzumab) were selective and highly active against HER2-positive breast cancer cells. In this study, we developed site-specific ADCs (Thio-1b and Thio-2b) using the cysteine-engineered trastuzumab derivative THIOMAB antibody technology with gold(I)-containing phosphanes and a maleimide-based linker amenable to bioconjugation (1b and 2b). In addition, we developed lysine-directed ADCs with gold payloads based on phosphanes and N-heterocyclic carbenes featuring an activated ester moiety (2c and 5c) with trastuzumab (Tras-2c and Tras-5c) and another anti-HER2 antibody, pertuzumab (Per-2c and Per-5c). Both sets of ADCs demonstrated significant anticancer potency in vitro assays. Based on these results, one ADC (Tras-2c), containing the [Au(PEt3)] fragment present in FDA-approved auranofin, was selected for an in vivo antitumor efficacy study. Immunocompromised mice xenografted with the HER2-positive human cancer cell line SKBR-3 exhibited almost complete tumor reduction and low toxicity with intravenous administration of Tras-2c. With this highly selective targeting system, we demonstrated that a subnanomolar cytotoxicity profile in cells is not required for an impressive antitumor effect in a mouse xenograft model.

Minimally Invasive Versus Transcatheter Aortic Valve Replacement: An Updated Meta-Analysis and Systematic Review.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) has arisen as a viable alternative to surgery. Similarly, minimally invasive surgical aortic valve replacement (mini-SAVR), such as ministernotomy and minithoracotomy, have also gained interest. We conducted a pairwise meta-analysis to further investigate the efficacy of TAVR versus mini-SAVR. METHODS: Medical databases were comprehensively searched for studies comparing TAVR with a mini-SAVR modality, defined as minimally invasive aortic surgery, ministernotomy, minithoracotomy, or rapid-deployment or sutureless SAVR. Random-effects meta-analysis was conducted using the generic inverse variance method. Primary outcomes included 30-day mortality, midterm mortality, 30-day stroke, acute kidney injury (AKI), paravalvular leak (PVL), new permanent pacemaker (PPM), new-onset atrial fibrillation, and postintervention mean and peak valve pressure gradients and were pooled as risk ratio (RR), mean difference (MD), or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: A total of 5,071 patients (2,505 mini-SAVR vs 2,566 TAVR) from 12 studies were pooled. Compared with TAVR, mini-SAVR showed significantly lower rates of both 30-day (RR = 0.63, 95% CI: 0.42 to 0.96, P = 0.03) and midterm mortality at 4 years of follow-up (HR = 0.76, 95% CI: 0.67 to 0.87, P < 0.001). Furthermore, mini-SAVR was protective against 30-day PVL (RR = 0.07, 95% CI: 0.04 to 0.13, P < 0.001) and new PPM (RR = 0.25, 95% CI: 0.11 to 0.57, P < 0.001). Conversely, TAVR was protective against 30-day AKI (RR = 1.67, 95% CI: 1.20 to 2.32, P = 0.002) and postinterventional mean gradients (MD = 1.65, 95% CI: 0.25 to 3.05, P = 0.02). No difference was observed for 30-day stroke (RR = 0.84, 95% CI: 0.56 to 1.24, P = 0.38), new-onset atrial fibrillation (RR = 1.79, 95% CI: 0.93 to 3.44, P = 0.08), or postinterventional peak gradients (MD = 3.24, 95% CI: -1.10 to 7.59, P = 0.14). CONCLUSIONS: Compared with TAVR, mini-SAVR was protective against 30-day and midterm mortality, 30-day PVL, and new permanent pacemaker, while TAVR patients had lower 30-day AKI. Future randomized trials comparing the efficacy of mini-SAVR approaches with TAVR are needed.

Risk factors of acromial and scapular spine stress fractures differ by indication: a study by the ASES Complications of Reverse Shoulder Arthroplasty Multicenter Research Group.

BACKGROUND: Both patient and implant related variables have been implicated in the incidence of acromial (ASF) and scapular spine fractures (SSF) following reverse shoulder arthroplasty (RSA); however, previous studies have not characterized nor differentiated risk profiles for varying indications including primary glenohumeral arthritis with intact rotator cuff (GHOA), rotator cuff arthropathy (CTA), and massive irreparable rotator cuff tear (MCT). The purpose of this study was to determine patient factors predictive of cumulative ASF/SSF risk for varying preoperative diagnosis and rotator cuff status. METHODS: Patients consecutively receiving RSA between January 2013 and June 2019 from 15 institutions comprising 24 members of the American Shoulder and Elbow Surgeons (ASES) with primary, preoperative diagnoses of GHOA, CTA and MCT were included for study. Inclusion criteria, definitions, and inclusion of patient factors in a multivariate model to predict cumulative risk of ASF/SSF were determined through an iterative Delphi process. The CTA and MCT groups were combined for analysis. Consensus was defined as greater than 75% agreement amongst contributors. Only ASF/SSF confirmed by clinical and radiographic correlation were included for analysis. RESULTS: Our study cohort included 4764 patients with preoperative diagnoses of GHOA, CTA, or MCT with minimum follow-up of 3 months (range: 3-84). The incidence of cumulative stress fracture was 4.1% (n = 196). The incidence of stress fracture in the GHOA cohort was 2.1% (n = 34/1637) compared to 5.2% (n = 162/3127) (P < .001) in the CTA/MCT cohort. Presence of inflammatory arthritis (odds ratio [OR] 2.90, 95% confidence interval [CI] 1.08-7.78; P = .035) was the sole predictive factor of stress fractures in GHOA, compared with inflammatory arthritis (OR 1.86, 95% CI 1.19-2.89; P = .016), female sex (OR 1.81, 95% CI 1.20-2.72; P = .007), and osteoporosis (OR 1.56, 95% CI 1.02-2.37; P = .003) in the CTA/MCT cohort. CONCLUSION: Preoperative diagnosis of GHOA has a different risk profile for developing stress fractures after RSA than patients with CTA/MCT. Though rotator cuff integrity is likely protective against ASF/SSF, approximately 1/46 patients receiving RSA with primary GHOA will have this complication, primarily influenced by a history of inflammatory arthritis. Understanding risk profiles of patients undergoing RSA by varying diagnosis is important in counseling, expectation management, and treatment by surgeons.

Remote Blood Oxygen Estimation From Videos Using Neural Networks.

Peripheral blood oxygen saturation (SpO 2) is an essential indicator of respiratory functionality and received increasing attention during the COVID-19 pandemic. Clinical findings show that COVID-19 patients can have significantly low SpO 2 before any obvious symptoms. Measuring an individual's SpO 2 without having to come into contact with the person can lower the risk of cross contamination and blood circulation problems. The prevalence of smartphones has motivated researchers to investigate methods for monitoring SpO 2 using smartphone cameras. Most prior schemes involving smartphones are contact-based: They require using a fingertip to cover the phone's camera and the nearby light source to capture reemitted light from the illuminated tissue. In this paper, we propose the first convolutional neural network based noncontact SpO 2 estimation scheme using smartphone cameras. The scheme analyzes the videos of an individual's hand for physiological sensing, which is convenient and comfortable for users and can protect their privacy and allow for keeping face masks on. We design explainable neural network architectures inspired by the optophysiological models for SpO 2 measurement and demonstrate the explainability by visualizing the weights for channel combination. Our proposed models outperform the state-of-the-art model that is designed for contact-based SpO 2 measurement, showing the potential of the proposed method to contribute to public health. We also analyze the impact of skin type and the side of a hand on SpO 2 estimation performance.

Factors associated with humeral stem revision in anatomic to reverse total shoulder arthroplasty revision.

BACKGROUND: Recent advances in implant technology have allowed for modular or platform humeral stem insertion during initial anatomic total shoulder arthroplasty (TSA). These systems allow for humeral stem retention during conversion to reverse TSA (RTSA). However, some patients still require humeral stem revision when undergoing revision to RTSA. The purpose of this study was to evaluate the association between patient-specific factors and radiographic parameters with humeral stem revision vs. retention during conversion from TSA to RTSA. METHODS: Retrospective chart review was conducted for patients who underwent a revision TSA to RTSA between January 2010 and May 2022 at a single institution. Patients were included if their prosthesis included a convertible humeral stem. Patient demographic information, surgical details, and postoperative outcomes and complications were collected. Radiographic parameters were measured by 2 graders on radiographs taken prior to the revision procedure. The need for humeral stem revision and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) scores (preoperative and 2 years) were also noted. Statistical analysis was performed using chi-square test for categorical variables and t test for continuous variables. RESULTS: One hundred seven patients were included, with 52 undergoing humeral stem revision. Patients were revised an average of 51.0 ± 54 months after primary TSA. Younger patient age (63.6 vs. 68.5 years, P = .017) and use of a lateralized glenosphere (1.6 mm vs. 0.4 mm, P < .001) were significantly associated with need for humeral stem revision. Glenoid to humeral head cut distance (28.3 mm vs. 26.3 mm, P = .076) approached significant association with the need for humeral stem revision. All other measurements were not associated with the need for humeral stem revision. Improvement of ASES scores at 2 years' follow-up was higher in the nonrevised group (increase of 33.4 points) than the revision group (23.3), but this did not reach significance (P = .149). Estimated blood loss and surgical time were significantly higher in the stem revision group than the non-revised group (P = .048 and P < .001, respectively). CONCLUSION: Younger patients and those receiving a lateralized glenosphere were more likely to undergo humeral stem revision during conversion from TSA to RTSA. Glenoid to the humeral head cut distance should be studied further as a potential indication for humeral stem revision, as it correlates with the space available for a revision implant. This information can guide surgeons with preoperative planning for a revision arthroplasty.

How accurate are positive preoperative aspiration culture results in shoulder periprosthetic joint infection? A concordance study.

BACKGROUND: The concordance between preoperative synovial fluid cultures and intraoperative tissue cultures for identifying pathogenic microorganisms in shoulder periprosthetic joint infection (PJI) remains poorly understood. The purpose of our study was to examine the diagnostic accuracy of positive synovial fluid culture results in early pathogen identification for shoulder PJI. METHODS: A total of 35 patients who met the Musculoskeletal Infection Society criteria for PJI following primary anatomic or reverse arthroplasty and the study inclusion criteria were identified retrospectively from a single institution (multiple surgeons) from January 2011 to June 2021. The inclusion criteria required a positive preoperative intra-articular synovial fluid sample within 90 days analyzed within the same institution and intraoperative tissue cultures at the time of arthrotomy. Concordance was determined when the organism(s) identified from the aspirate correlated with the intraoperative specimens. RESULTS: Overall concordance was identified in 28 of 35 patients (80%), with similar concordance for anatomic (21 of 24, 88%) and reverse (7 of 11, 64%) shoulder arthroplasties (P = .171). Culture discordance occurred in 7 of 35 patients (20%): of these, 5 (14%) had no corresponding intraoperative culture growth whereas 2 (6%) had polymicrobial intraoperative cultures. Monomicrobial Cutibacterium acnes PJI cases were the most common (24 of 35, 69%) and had an overall concordance rate of 79%. Of 5 discordant C acnes patients, 2 had polymicrobial intraoperative cultures and 3 had negative intraoperative culture results; all the patients with negative intraoperative culture results had received antibiotics between the time of aspiration and surgery. Considered separately, concordance in patients who had a positive aspirate finding for C acnes and did not receive antibiotics prior to surgery was 19 of 21 (90%), with a sensitivity of 100% (95% confidence interval, 82%-100%) and a corresponding positive predictive value of 0.91 (95% confidence interval, 58%-93%). CONCLUSION: Preoperative positive aspiration culture results demonstrated favorable sensitivity and specificity when compared with intraoperative tissue cultures in identifying pathogenic microorganisms in shoulder PJI patients. These findings are congruent with literature from hip and knee arthroplasty. Ultimately, confidence in the accuracy of positive preoperative aspiration culture results in shoulder PJI may facilitate the development of early, targeted treatment strategies while directing patient expectations and risk.

No Difference in Complication or Reoperation Rates Between Arthroscopic and Open Debridement for Lateral Epicondylitis: A National Database Study.

PURPOSE: To compare complication rates and 5-year reoperation rates between open debridement (OD) and arthroscopic debridement (AD) for lateral epicondylitis. METHODS: The PearlDiver MUExtr database (2010-2019) was reviewed for patients diagnosed with lateral epicondylitis (queried by International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision [ICD-10] codes) undergoing OD or AD of the common extensor tendon without repair (queried by Current Procedural Terminology codes). Patients were stratified into 2 cohorts: those who underwent AD and those who underwent OD. Nonoperative treatment modalities were reported for both groups within 1 year before index procedure. The rates of 90-day postoperative complications were compared, and multivariate logistic regression analysis was used to identify risk factors for complications. The 5-year reoperation rates, using laterality-specific ICD-10 codes, were also compared between the 2 groups. RESULTS: In total, 19,280 patients (OD = 17,139, AD = 2,141) were analyzed in this study. The most common nonoperative treatments for patients who underwent OD or AD were corticosteroid injections (49.5% vs 43.2%), physical therapy (24.8% vs 25.7%), bracing (2.8% vs 3.2%), and platelet-rich plasma injections (1.3% vs 1.0%). There were no significant differences in radial nerve injuries, hematomas, surgical site infections, wound dehiscence, and sepsis events between the 2 procedures (P = .50). The 5-year reoperation rate was not significantly different between the AD (5.0%) and OD (3.9%) cohorts (P = .10). CONCLUSIONS: For lateral epicondylitis, both AD and OD of the extensor carpi radialis brevis (without repair) were found to have low rates of 90-day adverse events, with no significant differences between the 2 approaches. Similarly, the 5-year reoperation rate was low and not statistically different for those treated with OD or AD. LEVEL OF EVIDENCE: Level III, cross-sectional study.

Open Debridement Alone Versus Open Debridement With Tendon Repair for Lateral Epicondylitis: A Comparison of Complications and 5-Year Reoperation Rates From a Large Insurance Database.

Background: Open debridement (OD) of the extensor carpi radialis brevis tendon, both with and without repair to the lateral epicondyle, are effective treatments for recalcitrant lateral epicondylitis. However, few comparative studies exist within the literature. Purpose: To (1) compare the 5-year reoperation rates of patients who underwent OD alone versus OD with tendon repair (ODR) and (2) identify the 90-day adverse event rates, total same-day reimbursement amounts, and national usage trends for these 2 procedures from 2010 to 2019. Study Design: Cohort study; Level of evidence, 3. Methods: The PearlDiver MUExtr database was reviewed for patients diagnosed with lateral epicondylitis who underwent OD alone and ODR or reattachment between January 2010 and December 2019. These patients were stratified into 2 cohorts: the OD cohort and ODR cohort. The 5-year reoperation rates were assessed and compared, and the incidence of 90-day postoperative complications and risk factors were identified. The number of ODs and ODRs performed each year and the mean same-day reimbursement amounts (in US$) for both procedures were assessed. Results: Overall, 41,932 lateral epicondylitis patients who underwent debridement were identified, with 17,139 OD patients and 24,793 ODR patients. There were no significant changes in the proportion of OD versus ODR procedures performed during the study period (P = .18). A significantly higher incidence of hematoma was seen after OD compared with ODR (0.19% vs 0.12%; P = .04), but ODR had a significantly lower 5-year reoperation rate than OD (2.8% vs 3.9%; P = .006), with an absolute risk reduction of 1.1% and a number needed to treat of 91. Finally, ODR ($1683.17 ± $12.15) had a higher mean same-day reimbursement than OD ($1479.05 ± $15.78) (P = .001). Conclusion: Both OD and ODR had low complication rates. The 5-year reoperation rates were low for both procedures, but they were significantly higher for OD. Over the 10-year study period, there were no significant changes in the relative percentages of OD versus ODR performed. ODR had a significantly higher mean same-day reimbursement.

BRCA2 BRC missense variants disrupt RAD51-dependent DNA repair.

Pathogenic mutations in the BRCA2 tumor suppressor gene predispose to breast, ovarian, pancreatic, prostate, and other cancers. BRCA2 maintains genome stability through homology-directed repair (HDR) of DNA double-strand breaks (DSBs) and replication fork protection. Nonsense or frameshift mutations leading to truncation of the BRCA2 protein are typically considered pathogenic; however, missense mutations resulting in single amino acid substitutions can be challenging to functionally interpret. The majority of missense mutations in BRCA2 have been classified as Variants of Uncertain Significance (VUS) with unknown functional consequences. In this study, we identified three BRCA2 VUS located within the BRC repeat region to determine their impact on canonical HDR and fork protection functions. We provide evidence that S1221P and T1980I, which map to conserved residues in the BRC2 and BRC7 repeats, compromise the cellular response to chemotherapeutics and ionizing radiation, and display deficits in fork protection. We further demonstrate biochemically that S1221P and T1980I disrupt RAD51 binding and diminish the ability of BRCA2 to stabilize RAD51-ssDNA complexes. The third variant, T1346I, located within the spacer region between BRC2 and BRC3 repeats, is fully functional. We conclude that T1346I is a benign allele, whereas S1221P and T1980I are hypomorphic disrupting the ability of BRCA2 to fully engage and stabilize RAD51 nucleoprotein filaments. Our results underscore the importance of correctly classifying BRCA2 VUS as pathogenic variants can impact both future cancer risk and guide therapy selection during cancer treatment.

Epidemiology of Sports-Related Traumatic Hip Dislocations Reported in United States Emergency Departments, 2010-2019.

Background: Traumatic hip dislocations are rare injuries that most commonly occur in motor vehicle accidents. There is a paucity of literature that describes sports-related hip dislocations. Purpose: To estimate the incidence of sports-related hip dislocations and determine any sport- or sex-related epidemiological trends using the National Electronic Injury Surveillance System (NEISS) database. Study Design: Descriptive epidemiology study. Methods: Data regarding sports-related hip dislocations from 2010 to 2019 were retrieved from the NEISS, a database that catalogs injury information during emergency department visits from 100 hospitals across the United States to produce nationwide estimates of the injury burden. The estimated number of injuries was calculated using weights assigned by the NEISS database. The injuries were then stratified by sport and sex to determine any epidemiological patterns. Results: A total of 102 hip dislocation injuries were identified over the surveyed 10 years, indicating 2941 estimated injuries nationwide. Overall, 10 (9.8%) of 102 sports-related hip dislocations presented with concomitant acetabular fractures, representing an estimated 288 injuries nationally over 10 years. Male athletes sustained more sports-related hip dislocations than female athletes, with a relative incidence of 12.51 (P < .001). Adolescents aged 15 to 19 years recorded the highest number of hip dislocations. There were 17 sports identified as having caused at least 1 hip dislocation over the 10-year period. More hip dislocation injuries were sustained from contact sports (91.2%) than noncontact sports (8.8%) (P < .001). Football (estimated 164 injuries per year; 55.6%), snowboarding (28 per year; 9.5%), skiing (26 per year; 8.8%), and basketball (21 per year; 7.1%) had the highest rates of hip dislocation. Additionally, 43 (82.7%) football-related injuries were caused by tackling mechanisms, and 9 (17.3%) were caused by nontackling mechanisms (P < .001). Conclusion: The incidence of traumatic sports-related hip dislocations was extremely low in the United States during the study period. Male adolescents, aged 15 to 19 years, sustained the greatest number of injuries during football. Significantly more hip dislocations occurred in contact sports, most commonly football, snowboarding, skiing, and basketball, compared with noncontact sports. As adolescent athletes may have limited treatment options if osteonecrosis occurs, these data serve to increase the clinical awareness of these injuries.

Biomechanical analysis of anterior stability after 15% glenoid bone loss: comparison of Bankart repair, dynamic anterior stabilization, dynamic anterior stabilization with Bankart repair, and Latarjet.

BACKGROUND: Dynamic anterior shoulder stabilization (DAS) with Bankart repair is a recently described stabilization technique thought to be more robust than an isolated Bankart repair while avoiding many coracoid transfer-related complications and technical demands. DAS involves transfer of the long head biceps through a subscapularis split to the anterior glenoid to create a sling effect. We hypothesize that DAS with Bankart repair will restore anterior stability in a human-cadaveric model with subcritical (15%) glenoid bone loss. METHODS: Eight cadaveric shoulders were tested using an established shoulder simulator to record glenohumeral translations with an accuracy of ±0.2 mm. Shoulders were tested in 5 states-intact soft tissues, Bankart defect with 15% bone loss, isolated Bankart repair, DAS with Bankart repair, isolated DAS, and Latarjet. A 45 N anterior force was applied through the pectoralis major tendon, and translation of the humeral head was recorded and compared with repeated measures analysis of variance. RESULTS: The anterior translation in the intact (native) glenoid was 4.7 mm at neutral position and 4.6 mm at 45° external rotation. Anterior translation significantly increased after introducing a Bankart defect with 15% glenoid bone loss to 9.1 mm (neutral, P = .002) and 9.5 mm (45° external rotation, P < .001). All repair conditions showed a significant decrease in anterior translation relative to Bankart defect. DAS with Bankart repair decreased anterior translation compared with the Bankart defect: 2.7 mm (neutral, P < .001) and 2.1 mm (45° external rotation, P < .001). DAS with Bankart repair significantly decreased anterior translation compared with the isolated Bankart repair (2.7 mm vs. 4.7 mm, P = .023) and the isolated DAS (2.7 mm vs. 4.3 mm, P = .041) in neutral position. The Latarjet procedure resulted in the greatest reduction in anterior translation compared with the Bankart defect: 1.2 mm (neutral, P < .001) and 1.9 mm (45° external rotation, P < .001). CONCLUSIONS: DAS with Bankart repair is a viable alternative to restore anterior glenohumeral stability with a 15% glenoid defect at a greater degree than either DAS or Bankart repair alone. The Latarjet procedure was the most effective in reducing anterior translation but restrained the anterior translation significantly more than the native glenoid.

Minimum 15-year follow-up for clinical outcomes of arthroscopic rotator cuff repair.

BACKGROUND AND HYPOTHESIS: Arthroscopic rotator cuff repair surgery is one of the most common shoulder procedures performed in the United States. Although several studies have shown considerable symptomatic relief in the short term following surgery, a relatively high rate of recurrent defects has led surgeons to question the long-term durability of this operation. We hypothesized that outcomes at a minimum of 15 years of follow-up in patients who underwent all-arthroscopic rotator cuff repair would be maintained and would remain significantly improved compared with the preoperative status. METHODS: All-arthroscopic rotator cuff repairs were performed in 193 patients from 2003 to 2005. Patient-reported outcomes were collected preoperatively and at 1, 2, 5, and ≥15 years postoperatively. The primary outcome was the American Shoulder and Elbow Surgeons (ASES) score. Secondary outcomes included Single Assessment Numeric Evaluation (SANE), Shoulder Activity Scale (SAS), visual analog scale, and Patient-Reported Outcomes Measurement Information System (PROMIS)-Upper Extremity (UE) scores. Patient demographic characteristics, revision surgical procedures, and complications were recorded. Generalized estimating equations were used to model scores over time, and multiple comparisons between time points were performed using Tukey adjustment. RESULTS: This study included 60 patients with a mean follow-up period of 16.5 years (range, 15.8-17.7 years). The mean ASES score improved from 60.2 ± 18.8 preoperatively to 93.0 ± 9.4 at ≥15 years (P < .0001). The mean visual analog scale pain score decreased from 4.1 ± 0.7 preoperatively to 0.7 ± 0.3 at ≥15 years (P < .0001). The average SANE, SAS, and PROMIS-UE scores at ≥15 years were 87.8 ± 14.8, 8.8 ± 4.3, and 49.6 ± 10.2, respectively. Of 60 patients, 7 underwent revision surgery. Older age and female sex were associated with lower SAS scores at 15 years, whereas female sex was associated with lower PROMIS-UE scores. There were no factors predictive of ASES or SANE scores. CONCLUSION: At long-term follow-up (≥15 years), the patient-reported outcomes of all-arthroscopic rotator cuff repair show significant improvement from baseline preoperative function and remain durable over a period of 15 years. This information is useful in counseling patients regarding the long-term results of this procedure.

Biomechanical comparison of 3 latissimus dorsi transfer sites for reverse total shoulder arthroplasty in the absence of teres minor.

BACKGROUND: Reverse total shoulder arthroplasty is often performed to treat rotator cuff tear arthropathy with irreparable rotator cuff tears. Patients with full-thickness tears involving the posterior cuff and teres minor specifically lose active external rotation of the humerus, limiting activities of daily living. A latissimus dorsi transfer has been described as one potential solution, but few studies have compared different latissimus dorsi transfer sites. This study assesses the biomechanics of 3 latissimus dorsi transfer sites, examining external rotation, deltoid muscle forces, and force across the glenoid for specific activities. METHODS: The Newcastle Shoulder Model was modified to include a Delta III reverse shoulder arthroplasty and was used to model the effects of 3 latissimus dorsi transfer sites-anterior, posterolateral, and posterodistal-in the setting of teres minor deficiency. The latissimus dorsi was represented by 5 muscle elements approximating anatomic fascicle divisions. Kinematic data sets representing common activities were input into the model, allowing calculation of muscle forces and glenoid loads. RESULTS: Each of the 3 latissimus dorsi transfer sites demonstrated a change of moment arm from internal to external rotation with increased magnitude. Average maximum deltoid muscle forces and glenoid loading across all motions decreased for each of the 3 transfer sites, with the greatest decreased force noted for the posterior deltoid. This decrease in deltoid force and glenoid loading was significantly greater with the anterior and posterolateral transfer sites, relative to the posterodistal site. DISCUSSION: Latissimus dorsi transfer to all 3 sites in the setting of reverse total shoulder arthroplasty and posterior rotator cuff deficiency resulted in large external rotation moment arms. The transferred latissimus dorsi shared the external rotation load and resulted in decreased deltoid forces and glenoid loading with very small differences between the 3 transfer sites. The posterodistal location reduced deltoid force and glenoid loading to a lower degree compared with other sites, but it also showed that it did not alter the tendon length compared with the native shoulder.

Backside polyethylene wear in reverse shoulder arthroplasty.

BACKGROUND: Aseptic loosening from implant-associated osteolysis in reverse shoulder arthroplasty (RSA) may contribute to premature implant failure. Although articular side polyethylene (PE) damage has been well documented in the literature, no studies to date have investigated backside wear in RSA. The aims of this investigation were to (1) document and compare the damage between the backside and articular surface in explanted RSA components, (2) assess whether certain quadrants have a greater propensity for damage, and (3) report the most common mode(s) of backside PE damage. METHODS: Twenty-one RSA humeral liners retrieved during revision procedures between 2005 and 2014 were included for analysis. The mean time between implantation and extraction was 16 months (10 days-88 months). Diagnoses at the time of revision included dislocation (10), infection (4), mechanical failure (3), loosening (2), and unknown (2). Liners were examined under light microscopy (×10-30 magnification) and damage on the articular and backside of the liner surface was graded using the modified Hood score. The location and damage modality were compared between the articular side and backside of the implant. RESULTS: Damage was noted on the articular surfaces of all 21 liners and on the backside surface of 20 liners. The total damage in all the quadrants was higher on the articular surface than on the backside of the component, with a mean difference in total quadrant damage scores of 11.74 ± 3.53 (P < .001). There was no difference in damage among the quadrants on the backside (P = .44) or the articular surface (P = .08). The articular side exhibited greater scratching, abrasion, and surface deformation than the backside (P < .001). CONCLUSIONS: This short-term retrieval study demonstrated that backside PE damage occurs on the humeral component of RSA implants. There was greater damage to the articular side of the liner but wear to the backside was present in almost all liners. The clinical importance of backside wear in RSA and its overall contribution to PE particulate disease and osteolysis needs further investigation.

Outcomes of shoulder arthroplasty by year of index procedure: are we getting better?

BACKGROUND: The purpose of this study was to determine whether postoperative patient-reported outcomes improved over time following anatomic total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). METHODS: We performed a retrospective analysis of prospectively collected patient-reported outcomes from our institution's registry between 2008 and 2018 (N = 1899). American Shoulder and Elbow Surgeons (ASES) scores at a minimum of 2 years postoperatively were required. Univariable linear models were used to test the association between year of surgery and improvement in ASES scores at 2- and 5-year follow-up, as well as any association with age, sex, primary or revision surgery, hand dominance, American Society of Anesthesiologists classification, rotator cuff status, primary diagnosis, and Walch classification. Multivariable models were created to analyze ASES score improvement by index year while controlling for significant factors. RESULTS: In the univariable analysis, 5-year ASES difference scores increased each year by a mean of 1.65 (P < .001; 95% confidence interval [CI], 0.75-2.55) for TSA, 2.50 (P = .014; 95% CI, 0.52-4.49) for RTSA, and 1.64 (P < .001; 95% CI, 0.81-2.47) for the overall population. Patient sex, American Society of Anesthesiologists classification, rotator cuff status, primary diagnosis, Walch classification, and revision procedures were also significant factors affecting ASES scores. On multivariable analysis controlling for these factors, 5-year ASES difference scores were still significantly associated with year of surgery, increasing each year by a mean of 2.20 (P < .001; 95% CI, 0.91-3.50) for TSA, 4.83 (P < .001; 95% CI, 1.17-8.49) for RTSA, and 1.66 (P < .001; 95% CI, 0.81-2.51) for the entire population. CONCLUSION: Both anatomic TSA and RTSA patients reported increasing ASES difference scores at 5-year follow-up as time passed. These findings may indicate that advances in shoulder arthroplasty have resulted in better patient outcomes over time. Further research is needed to clarify which factors influence improvements in outcomes, particularly for revision procedures.