Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

BACKGROUND: Obesity and type 2 diabetes are prevalent in patients with heart failure with preserved ejection fraction and are characterized by a high symptom burden. No approved therapies specifically target obesity-related heart failure with preserved ejection fraction in persons with type 2 diabetes. METHODS: We randomly assigned patients who had heart failure with preserved ejection fraction, a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more, and type 2 diabetes to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: A total of 616 participants underwent randomization. The mean change in the KCCQ-CSS was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4; P<0.001), and the mean percentage change in body weight was -9.8% with semaglutide and -3.4% with placebo (estimated difference, -6.4 percentage points; 95% CI, -7.6 to -5.2; P<0.001). The results for the confirmatory secondary end points favored semaglutide over placebo (estimated between-group difference in change in 6-minute walk distance, 14.3 m [95% CI, 3.7 to 24.9; P = 0.008]; win ratio for hierarchical composite end point, 1.58 [95% CI, 1.29 to 1.94; P<0.001]; and estimated treatment ratio for change in CRP level, 0.67 [95% CI, 0.55 to 0.80; P<0.001]). Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group. CONCLUSIONS: Among patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes, semaglutide led to larger reductions in heart failure-related symptoms and physical limitations and greater weight loss than placebo at 1 year. (Funded by Novo Nordisk; STEP-HFpEF DM ClinicalTrials.gov number, NCT04916470.).

Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.

BACKGROUND: Heart failure with preserved ejection fraction is increasing in prevalence and is associated with a high symptom burden and functional impairment, especially in persons with obesity. No therapies have been approved to target obesity-related heart failure with preserved ejection fraction. METHODS: We randomly assigned 529 patients who had heart failure with preserved ejection fraction and a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or higher to receive once-weekly semaglutide (2.4 mg) or placebo for 52 weeks. The dual primary end points were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations) and the change in body weight. Confirmatory secondary end points included the change in the 6-minute walk distance; a hierarchical composite end point that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6-minute walk distance; and the change in the C-reactive protein (CRP) level. RESULTS: The mean change in the KCCQ-CSS was 16.6 points with semaglutide and 8.7 points with placebo (estimated difference, 7.8 points; 95% confidence interval [CI], 4.8 to 10.9; P<0.001), and the mean percentage change in body weight was -13.3% with semaglutide and -2.6% with placebo (estimated difference, -10.7 percentage points; 95% CI, -11.9 to -9.4; P<0.001). The mean change in the 6-minute walk distance was 21.5 m with semaglutide and 1.2 m with placebo (estimated difference, 20.3 m; 95% CI, 8.6 to 32.1; P<0.001). In the analysis of the hierarchical composite end point, semaglutide produced more wins than placebo (win ratio, 1.72; 95% CI, 1.37 to 2.15; P<0.001). The mean percentage change in the CRP level was -43.5% with semaglutide and -7.3% with placebo (estimated treatment ratio, 0.61; 95% CI, 0.51 to 0.72; P<0.001). Serious adverse events were reported in 35 participants (13.3%) in the semaglutide group and 71 (26.7%) in the placebo group. CONCLUSIONS: In patients with heart failure with preserved ejection fraction and obesity, treatment with semaglutide (2.4 mg) led to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater weight loss than placebo. (Funded by Novo Nordisk; STEP-HFpEF ClinicalTrials.gov number, NCT04788511.).

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

BACKGROUND: In the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups. METHODS: We conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m2, New York Heart Association class II-IV symptoms, and a Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; a measure of heart failure-related symptoms and physical limitations) of less than 90 points. In STEP-HFpEF, people with diabetes or glycated haemoglobin A1c concentrations of at least 6·5% were excluded, whereas for inclusion in STEP-HFpEF DM participants had to have been diagnosed with type 2 diabetes at least 90 days before screening and to have an HbA1c of 10% or lower. In both trials, participants were randomly assigned to either 2·4 mg semaglutide once weekly or matched placebo for 52 weeks. The dual primary endpoints were change from baseline to week 52 in KCCQ-CSS and bodyweight in all randomly assigned participants. Confirmatory secondary endpoints included change from baseline to week 52 in 6-min walk distance, a hierarchical composite endpoint (all-cause death, heart failure events, and differences in changes in KCCQ-CSS and 6-min walk distance); and C-reactive protein (CRP) concentrations. Heterogeneity in treatment effects was assessed across subgroups of interest. We assessed safety in all participants who received at least one dose of study drug. FINDINGS: Between March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group. INTERPRETATION: In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated. FUNDING: Novo Nordisk.

Biomarkers of transfusion transmitted occult hepatitis B virus infection: Where are we and what next?

Blood transfusion is a vital procedure, where transfusion-transmitted infection of hepatitis B virus (HBV) remains an important issue, especially from blood donors with occult hepatitis B virus infection (OBI). Occult hepatitis B virus infection is a complex entity to detect using surrogate blood biomarkers for intrahepatic viral transcriptional activity, requiring a continually refined battery of tests utilised for screening. This review aims to critically evaluate the latest advances in the current blood biomarkers to guide the identification of OBI donors and discuss novel HBV markers that could be introduced in future diagnostic practice. Challenges in detecting low HBV surface antigen levels, mutants, and complexes necessitate ultrasensitive multivalent dissociation assays, whilst HBV DNA testing requires improved sensitivity but worsens inaccessibility. Anti-core antibody assays defer almost all potentially infectious donations but have low specificity, and titres of anti-surface antibodies that prevent infectivity are poorly defined with suboptimal sensitivity. The challenges associated with these traditional blood HBV markers create an urgent need for alternative biomarkers that would help us better understand the OBI. Emerging viral biomarkers, such as pre-genomic RNA and HBV core-related antigen, immunological HBV biomarkers of T-cell reactivity and cytokine levels, and host biomarkers of microRNA and human leucocyte antigen molecules, present potential advances to gauge intrahepatic activity more accurately. Further studies on these markers may uncover an optimal diagnostic algorithm for OBI using quantification of various novel and traditional blood HBV markers. Addressing critical knowledge gaps identified in this review would decrease the residual risk of transfusion-transmitted HBV infection without compromising the sustainability of blood supplies.

Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Short-term learning of the vestibulo-ocular reflex induced by a custom interactive computer game.

Retinal image slip during head rotation drives motor learning in the rotational vestibulo-ocular reflex (VOR) and forms the basis of gaze-stability exercises that treat vestibular dysfunction. Clinical exercises, however, are unengaging, cannot easily be titrated to the level of impairment, and provide neither direct feedback nor tracking of the patient's adherence, performance, and progress. To address this, we have developed a custom application for VOR training based on an interactive computer game. In this study, we tested the ability of this game to induce VOR learning in individuals with normal vestibular function, and we compared the efficacy of single-step and incremental learning protocols. Eighteen participants played the game twice on different days. All participants tolerated the game and were able to complete both sessions. The game scenario incorporated a series of brief head rotations, similar to active head impulses, that were paired with a dynamic acuity task and with a visual-vestibular mismatch (VVM) intended to increase VOR gain (single-step: 300 successful trials at ×1.5 viewing; incremental: 100 trials each of ×1.13, ×1.33, and ×1.5 viewing). Overall, VOR gain increased by 15 ± 4.7% (mean ± 95% CI, P < 0.001). Gains increased similarly for active and passive head rotations, and, contrary to our hypothesis, there was little effect of the learning strategy. This study shows that an interactive computer game provides robust VOR training and has the potential to deliver effective, engaging, and trackable gaze-stability exercises to patients with a range of vestibular dysfunctions.NEW & NOTEWORTHY This study demonstrates the feasibility and efficacy of a customized computer game to induce motor learning in the high-frequency rotational vestibulo-ocular reflex. It provides a physiological basis for the deployment of this technology to clinical vestibular rehabilitation.

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups.

BACKGROUND AND OBJECTIVES: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors. MATERIALS AND METHODS: Three hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays. RESULTS: Eighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups. CONCLUSION: Using two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro.

ChatGPT-4 Performs Clinical Information Retrieval Tasks Utilizing Consistently More Trustworthy Resources Than Does Google Search for Queries Concerning the Latarjet Procedure.

PURPOSE: To assess the ability for ChatGPT-4, an automated Chatbot powered by artificial intelligence (AI), to answer common patient questions concerning the Latarjet procedure for patients with anterior shoulder instability and compare this performance to Google Search Engine. METHODS: Using previously validated methods, a Google search was first performed using the query "Latarjet." Subsequently, the top ten frequently asked questions (FAQs) and associated sources were extracted. ChatGPT-4 was then prompted to provide the top ten FAQs and answers concerning the procedure. This process was repeated to identify additional FAQs requiring discrete-numeric answers to allow for a comparison between ChatGPT-4 and Google. Discrete, numeric answers were subsequently assessed for accuracy based on the clinical judgement of two fellowship-trained sports medicine surgeons blinded to search platform. RESULTS: Mean (±standard deviation) accuracy to numeric-based answers were 2.9±0.9 for ChatGPT-4 versus 2.5±1.4 for Google (p=0.65). ChatGPT-4 derived information for answers only from academic sources, which was significantly different from Google Search Engine (p=0.003), which used only 30% academic sources and websites from individual surgeons (50%) and larger medical practices (20%). For general FAQs, 40% of FAQs were found to be identical when comparing ChatGPT-4 and Google Search Engine. In terms of sources used to answer these questions, ChatGPT-4 again used 100% academic resources, while Google Search Engine used 60% academic resources, 20% surgeon personal websites, and 20% medical practices (p=0.087). CONCLUSION: ChatGPT-4 demonstrated the ability to provide accurate and reliable information about the Latarjet procedure in response to patient queries, using multiple academic sources in all cases. This was in contrast to Google Search Engine, which more frequently used single surgeon and large medical practice websites. Despite differences in the resources accessed to perform information retrieval tasks, the clinical relevance and accuracy of information provided did not significantly differ between ChatGPT-4 and Google Search Engine.

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.

Ultrasensitive PCR system for HBV DNA detection: Risk stratification for occult hepatitis B virus infection in English blood donors.

Occult hepatitis B (HBV) infection (OBI), characterized by low viral loads, accounts for much of the risk of HBV transfusion-transmitted infection. With anticore antibodies (anti-HBc) screening introduced in England, the imperative to identify OBI donors has increased. We aimed to develop an ultra-sensitive PCR system and investigate risk factors for HBV DNA presence in blood donations. Seven extraction methods and three PCR assays were compared. The optimal system was sought to determine HBV DNA presence in anti-HBc-positive donations. Predictors of DNA positivity were subsequently investigated. Extraction from 5 mL of plasma increased sample representation and resulted in HBV DNA detection in low viral load samples (~0.5 IU/mL). Screening of 487 763 donations in 2022 identified two OBI donors and 2042 anti-HBc-positive donors, 412 of the latter with anti-HBs < 100 mIU/mL. Testing of 134 anti-HBc-positive donations utilizing the 5 mL extraction method identified two further HBV DNA-positive donations. Higher anti-HBc titer and anti-HBs negativity were significant predictors of DNA detectability in anti-HBc-positive donations. An ultrasensitive PCR assay identified potentially infectious donations increasing HBV DNA detection in anti-HBc-positive donors from 0.5% to 1.9%. Anti-HBc titers may further complement the risk stratification for DNA positivity in anti-HBc screening and minimize unnecessary donor deferral.

PROMIS physical function and pain perform poorly psychometrically in patients undergoing medial patellofemoral ligament reconstruction.

PURPOSE: The purpose of this study was to assess the validity, floor and ceiling effects, and dimensionality of PROMIS Physical Function (PF) and Pain compared to legacy patient reported outcome (PRO) measures in patients undergoing medial patellofemoral ligament (MPFL) reconstruction. METHODS: Patients who underwent MPFL reconstruction between 2018 to 2020 were retrospectively reviewed. Preoperatively, patients completed the IKDC, VR-12, Kujala, SF-12, KOOS JR, PROMIS PF and Pain surveys. Inter-survey convergence was assessed with Spearman correlations. Psychometric analysis included investigations of inter-survey convergent validity, intra-survey floor and ceiling effects, and Rasch analyses with person-item fit and iterative question elimination model fit testing. RESULTS: A total of 76 patients (mean age: 22.6 ± 8.4 years) who completed preoperative surveys were included (compliance: 91.7-96.2%). Preoperatively, age was significantly associated with both PROMIS PF (coefficient: - 0.291, P = 0.005) and Pain scores (coefficient: 0.294, P = 0.002). PROMIS PF had a Very Good correlation with IKDC and PROMIS Pain had a Very Good correlation with KOOS JR. Other correlations ranged from Poor to Good. No significant floor or ceiling effects were observed for any PRO. On iterative question elimination Rasch modelling, only two questions from PROMIS PF remained after 6 rounds of elimination while PROMIS Pain had no questions remaining after 3 rounds of elimination. CONCLUSION: Preoperative PROMIS PF and Pain provided only Fair to Good correlations with most legacy PROs. Although no significant floor and ceiling effects were observed, PROMIS PF and Pain did not perform well psychometrically in this population of patients undergoing MPFL reconstruction. These results suggest PROMIS questionnaires should be used with caution in this population, especially if used in isolation, when discussing clinical expectations with patients. The authors recommend continued use of legacy PROs specific to assessment of patellar instability and function that have established validity in patellar instability populations. LEVEL OF EVIDENCE: Level IV.

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.

Shoulder arthroplasty device clearance: an ancestral network analysis.

BACKGROUND: The US Food and Drug Administration (FDA) oversees medical device regulation and oversight in the United States, and the majority of shoulder arthroplasty devices are cleared via the 510(k) pathway, in which a device demonstrates "substantial equivalence" to a previously cleared predicate. The purpose of this study was to determine an interconnected ancestral network of shoulder arthroplasty devices and determine equivalency ties to devices subsequently recalled by the FDA for design-related issues. METHODS: The FDA 510(k) database was used to identify all legally marketed shoulder arthroplasty devices from May 28, 1976, to July 1, 2021. Direct predicate information obtained via clearance summary documents associated with each device was used to generate an ancestral genealogy network for all shoulder arthroplasty devices cleared between July 1, 2020, and July 1, 2021. FDA design recalls were analyzed, and the number of descendant devices was calculated for each recalled device. RESULTS: An evaluation of all 476 510(k) premarket notification pathway-cleared shoulder devices since 1976 identified 0-313 descendant devices for each. Eighty of these devices (16.8%) have since been recalled, of which 10 recalls were directly related to implant design issues. Furthermore, among 29 of the most recently cleared devices (July 1, 2020-July 1, 2021), 16 (55.2%) claim predicates devices that have subsequently been withdrawn from the market because of design-related failures. CONCLUSIONS: Shoulder arthroplasty devices are linked together via an interconnected FDA 510(k) equivalency approval network dating back to 1976 despite substantive changes in material specifications and device design, many of which have since been recalled. Many of the cleared modern devices claim predicates based on subsequently recalled prostheses.

Artificial intelligence for automated identification of total shoulder arthroplasty implants.

BACKGROUND: Accurate and rapid identification of implant manufacturer and model is critical in the evaluation and management of patients requiring revision total shoulder arthroplasty (TSA). Failure to correctly identify implant designs in these circumstances may lead to delay in care, unexpected intraoperative challenges, increased morbidity, and excess health care costs. Deep learning (DL) permits automated image processing and holds the potential to mitigate such challenges while improving the value of care rendered. The purpose of this study was to develop an automated DL algorithm to identify shoulder arthroplasty implants from plain radiographs. METHODS: A total of 3060 postoperative images from patients who underwent TSA between 2011 and 2021 performed by 26 fellowship-trained surgeons at 2 independent tertiary academic hospitals in the Pacific Northwest and Mid-Atlantic Northeast were included. A DL algorithm was trained using transfer learning and data augmentation to classify 22 different reverse TSA and anatomic TSA prostheses from 8 implant manufacturers. Images were split into training and testing cohorts (2448 training and 612 testing images). Optimized model performance was assessed using standardized metrics including the multiclass area under the receiver operating characteristic curve (AUROC) and compared with a reference standard of implant data from operative reports. RESULTS: The algorithm classified implants at a mean speed of 0.079 seconds (±0.002 seconds) per image. The optimized model discriminated between 8 manufacturers (22 unique implants) with AUROCs of 0.994-1.000, accuracy of 97.1%, and sensitivities between 0.80 and 1.00 on the independent testing set. In the subset of single-institution implant predictions, a DL model identified 6 specific implants with AUROCs of 0.999-1.000, accuracy of 99.4%, and sensitivity >0.97 for all implants. Saliency maps revealed key differentiating features across implant manufacturers and designs recognized by the algorithm for classification. CONCLUSION: A DL model demonstrated excellent accuracy in identifying 22 unique TSA implants from 8 manufacturers. This algorithm may provide a clinically meaningful adjunct in assisting with preoperative planning for the failed TSA and allows for scalable expansion with additional radiographic data and validation efforts.

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.

A Systematic Review of Lower-Body Kinematic and Strength Factors Associated With Pitch Velocity in Adult Baseball Pitchers.

CONTEXT: Ball velocity for baseball pitchers is influenced by a multitude of factors along the kinetic chain. While a vast amount of data currently exist exploring lower-extremity kinematic and strength factors in baseball pitchers, no previous study has systematically reviewed the available literature. OBJECTIVE: The aim of this systematic review was to perform a comprehensive assessment of the available literature investigating the association between lower-extremity kinematic and strength parameters and pitch velocity in adult pitchers. EVIDENCE ACQUISITION: Cross-sectional studies that investigated the association between lower-body kinematic and strength factors and ball velocity in adult pitchers were selected. A methodological index for nonrandomized studies checklist was used to evaluate the quality of all included studies. EVIDENCE SYNTHESIS: Seventeen studies met the inclusion criteria comprising a total of 909 pitchers (65%, professional, 33% college, and 3% recreational). The most studied elements were hip strength and stride length. The mean methodological index for nonrandomized studies score was 11.75 of 16 (range = 10-14). Pitch velocity was found to be influenced by several lower-body kinematic and strength factors including the following: (1) hip range of motion and strength of muscles around the hip and pelvis, (2) alterations in stride length, (3) alterations in lead knee flexion/extension, and (4) several pelvic and trunk spatial relationships throughout the throwing phase. CONCLUSIONS: Based on this review, we conclude that hip strength is a well-established predictor of increased pitch velocity in adult pitchers. Further studies in adult pitchers are needed to elucidate the effect of stride length on pitch velocity given mixed results across multiple studies. This study can provide a basis for trainers and coaches to consider the importance of lower-extremity muscle strengthening as a means by which adult pitchers can improve pitching performance.

Mid-life extrapyramidal symptoms predict cognitive impairment 23 years later.

OBJECTIVES: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later. MATERIALS & METHODS: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73. RESULTS: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later. CONCLUSIONS: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline.

Patient-level comparison of heart failure patients in clinical phenotype and prognosis from China and Sweden.

BACKGROUND: Clinical phenotype and prognosis of heart failure (HF) may be variable among different racial populations. Therefore, a patient-level comparison of hospitalized HF patients in two university hospitals from China and Sweden was performed. METHODS AND RESULTS: This study was a pooled data analysis of the patients prospectively enrolled in two single-center studies in China (n = 949) and Sweden (n = 1639) from 2011 to 2015. Clinical characteristics and 6-month all-cause mortality were collected. Higher systolic blood pressure (126.1 ± 20.3 vs. 114.2 ± 15.4 mmHg, p < 0.001) and NT-proBNP level (4540 vs. 3251 pg/mL, p = 0.013) were found in the Swedish cohort, also more patients with ischemic heart disease (32.0% vs. 19.2%), hypertension (64.2% vs. 36.8%), valvular heart disease (40.9% vs.31.6%) and atrial fibrillation (55.3% vs. 39.6%) (all p < 0.001). The use of ACEIs/ARBs (48.8% vs. 80.8%) or beta-blockers (58.8% vs. 86.5%) (both p < 0.001) was lower in Chinese cohort. Given younger age in Chinese cohort (61.6 vs. 76.4 years, p < 0.001), age-stratified analyses were conducted, as there were similar patient numbers in 50-74 years in Chinese (n = 550) and Swedish (n = 554) cohorts, therefore baseline characteristics and prognosis were further compared. The age- and sex-adjusted outcome (HR 0.80 [95% CI 0.55-1.19], p = 0.273) was comparable between the two populations. The NT-proBNP and eGFR independently predicted 6-month mortality in both Chinese (HR [95% CI] 1.006 [1.003-1.008], 0.986 [0.976-0.999]) and Swedish cohort (1.003 [1.000-1.007], 0.988 [0.976-0.999]). CONCLUSIONS: Patient-level comparison of real-world HF populations from China and Sweden demonstrated different clinical phenotypes and therapy but similar prognosis and their predictors.

Cumulative incidence and predictors of acquired aortic stenosis in a large population of men followed for up to 43 years.

BACKGROUND: Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. METHODS: We included a random sample of men (n = 9998) born 1915-1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25-43, 30-43 and 35-43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. RESULTS: The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20-22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25-27.5 kg/m2, 27.5-30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12-3.55), 2.98 (95% CI 1.65-5.40) and 3.55 (95% CI 1.84-6.87), respectively. CONCLUSIONS: The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

Echocardiographic diagnosis of heart failure with preserved ejection fraction in elderly patients with hypertension.

Objectives. The aim of this study is to evaluate the diagnostic performance of echocardiography for the diagnosis of heart failure with preserved ejection fraction (HFpEF) in the elderly and to validate the Heart Failure Association diagnostic algorithm (HFA-PEFF). Design. A case-control study was conducted in patients with hypertension with or without HFpEF who were matched for age (n = 33; 78.4 ± 5.3 years) and sex. Participants underwent echocardiography including assessment of left atrial (LA) volume index (LAVI), early mitral filling to early diastolic mitral annulus velocity ratio (E/e'), LA reservoir strain (LASr), tissue Doppler LA contraction (a'), right ventricular isovolumic relaxation time (RVIVRT), and a 6-minute walk test (6-MWT). The filling pressure algorithm from the European association of cardiovascular imaging (EACVI) 2021 was applied. The HFA-PEFF score was also applied, using echocardiography parameters and the value of NT pro-BNP, without considering symptomatic status. Results. Echocardiographic parameters identified patients with HFpEF with an area under the curve (AUC) >0.9 for E/e', RVIVRT, LASr, a', and the ratio of LAVI/a'. LASr correlated with 6-MWT (r = 0.59, p = .0003). The EACVI algorithm classified all controls with normal filling pressure and 94% of patients with HFpEF with increased filling pressure. When the HFA-PEFF diagnostic algorithm was validated, a high score (≥5 points) had 100% sensitivity for HFpEF, while 88% of controls had intermediate scores (2-4 points). Conclusion. The EACVI filling pressure algorithm, RVIVRT, LASr, and the ratio LAVI/a' were accurate for diagnosing HFpEF in elderly patients with hypertension. The HFA-PEFF score had high sensitivity but limited ability to exclude HFpEF.