Citations

Background Overhead athletes are susceptible to shoulder injuries, among which rotator cuff injuries are common and often directly associated with muscle weakness. Therefore, valid and reliable measures of rotator cuff strength at sport specific positions may be a vital part of sports physical therapy practice. Purpose: The current study aimed to determine the inter- and intra-tester reliability of measuring shoulder internal rotation (IR) and external rotation (ER) strength at a novel testing position, 130° of abduction and compared to the 90°/90° position. A secondary aim was to assess concurrent validity between measurements taken with the Humac® Norm™ Isokinetic Dynamometer (IKD) and Microfet® 2 hand-held dynamometer (HHD). Study Design Inter-Rater and Intra-Rater Reliability and Criterion Validity Methods Twenty-five (n=25) healthy participants were recruited for this study. Exclusion criteria included prior shoulder surgery, shoulder injury within the last three months, and contraindications to exercise according to ACSM guidelines. Participants performed maximal isometric shoulder external and internal rotation strength testing at both 90° and 130° of shoulder abduction. On the first day, participants were tested on the IKD at both positions, followed by each tester using the HHD. Participants returned 7-14 days later for repeat testing using the HHD only. ICC values were calculated for each rater, instrument, and testing position. Bland-Altman plots were created to establish limits of agreement. Minimal detectable change values were calculated. Results Inter- and intra-rater reliability for testing isometric strength using a hand-held dynamometer was good to excellent for both shoulder positions with ICC values consistently above 0.8. Concurrent validity between the HHD and IKD was poor to moderate with ICC values ranging from 0.1-0.4. However, Bland-Altman plots demonstrated that the difference in strength measures was within the limits of agreement. Conclusion Shoulder IR and ER strength testing at 130° of abduction shows strong inter-rater and intra-rater reliability for measurement in sport specific positions. Level of Evidence Level 3

Abstract Background: Osteochondral allograft and autograft transplantation for femoral head defects have emerged as promising treatments for concomitant cartilage and subchondral bone injuries in young patients. The purpose of this study was to evaluate the clinical and radiological outcomes of patients who underwent osteochondral allograft or autograft transplantation for femoral head defects and access any risk factors that may lead to conversion to THA. Methods: All patients who underwent osteochondral allograft or autograft transplantation for femoral head defects were analyzed. All patients had symptomatic femoral head osteochondral defects identifiable on advanced imaging such as computed tomography or magnetic resonance imaging. Clinical outcomes were assessed at final follow-up with the modified Harris Hip Score (mHHS), Hip Outcome Score – Activities of Daily Living (HOS-ADL), Hip Outcome Score – Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool (iHOT-12). Additionally, patients were assessed radiographically preoperatively and at a final postoperative visit using anterior-posterior and lateral radiographs for osteoarthritis using Tönnis grading. Results: A total of 27 patients were included in this study (19 osteochondral allograft transplantation, 8 osteochondral autograft transplantation). The overall mean follow-up was 4.7 years. The average mHHS, HOS-ADL, HOS-SSS, and iHOT-12 for the allograft cohort were 86.7, 92.8, 81.4, and 79.0, respectively, while for the autograft cohort it was 87.6, 92.7, 83.1, and 82.0, respectively. For the allograft cohort, there were a total of 5 reoperations (26.3%) consisting of 4 THA at a mean of 1.9 years and 1 trochanteric osteotomy nonunion at 0.7 year. For the remaining allograft patients who did not undergo treatment failure, only one (6.7%) had radiographic osteoarthritis progression. None of the patients in the autograft cohort underwent THA. Overall, conversion to THA was 14.8%. Conclusion: Osteochondral allograft and autograft transplantation for femoral head defects demonstrated overall favorable clinical outcomes and conversion to THA at mean 5-year follow-up and should be considered for patients with focal femoral head defects.

Abstract Studies have identified genetic and epidemiologic factors associated with mammographic density (MD) phenotypes. However, MD-associated genetic variants only account for a small proportion of the total estimated heritability. Interrogating interactions between genetic and epidemiologic factors could potentially identify additional MD-associated loci, expand our understanding of the genetic basis of MD phenotypes, and clarify how epidemiologic factors modulate relationships between genetic variants and MD. We conducted six separate genome-wide, gene–environment (GxE) interaction analyses, applying 2 degrees of freedom (df) and 1df interaction tests, for each of three MD phenotypes (percent density, dense area (DA), and nondense area (NDA)). The six epidemiologic factors considered were height, ever parous, parity, ever menopausal hormone therapy, ever breastfeeding, and months of breastfeeding. We included European ancestry participants from multiple studies within the Markers of Density consortium and the Breast Cancer Association Consortium (n = 4895-16 218 depending on specific analyses). We identified 11 loci with genome-wide significant (P < 5 × 10−8) interaction tests including two novel common genetic signals interacting with parity (8p21.2) and ever breastfeeding (19p13.2) for NDA. Our results suggest that epidemiologic risk factors might influence relationships between common genetic variants and MD phenotypes at particular genomic loci.

ABSTRACTImmune thrombotic thrombocytopenic purpura (iTTP) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular occlusion secondary to acquired ADAMTS13 deficiency. Contemporary data regarding iTTP treatment practices in the US, including the use of caplacizumab, are lacking. We aimed to characterize the demographics and therapies, including medications and apheresis practices, in patients with iTTP in the US. We retrospectively analyzed iTTP cases at 15 sites in the US that provide comprehensive care for patients with iTTP. The time‐period assessed was from January 1, 2017 to December 31, 2021. Our primary objective was to analyze data by iTTP episode, inclusive of initial episodes and relapses. A total of 390 iTTP episodes were reported for 280 unique individuals (187 females, 93 males). Thirty‐day mortality was 3.7% (14/374), and 6‐month mortality was 7.4% (27/367). TPE details were reported for 343 episodes, among which 261 underwent at least one procedure (median 6, IQR 3–11). Among the 261 episodes with at least one therapeutic plasma exchange (TPE) performed, 82.0% (214/261) used only plasma. Caplacizumab was used either alone or in combination with other agents in 43 (11.0%) episodes. Management strategies for iTTP remain varied across centers in the US, with a variety of combinations for TPE replacement fluids and therapeutic agents, as well as limited use of caplacizumab. Further research and standardization of treatment regimens may further reduce mortality in this condition.

Abstract Introduction: Femoroacetabular impingement commonly causes labral and cartilage damage. Understanding what clinical and CT-morphological factors are associated with increased labral and acetabular cartilage damage may give insight into the FAI pathophysiology. The present study aims to identify factors associated with labral and cartilage damage. Method: This is a prospective, multicenter cohort of patients undergoing primary arthroscopy for treatment of symptomatic FAI. Enrollment was between 2020 and 2022. The current study investigated predictive factors of advanced labral damage (detachment or full-thickness tear length >4cm) and advanced acetabular cartilage damage (delamination or full-thickness defect ≥200mm2). Finally, we performed external validation for the previously reported RAPID score that predicts high-grade cartilage injury. Results: There were 647 patients in the cohort. For labral injuries, there were 384/647 (59.4%) detachments and 154/647 (23.8%) full-thickness defects, with labral tears ≥4cm was present in 100/558 (17.9%) hips. Older age (OR:1.04, p=0.002), males (OR:1.83,p=0.005), and larger alpha angles at 2:00 (OR:1.02,p=0.04) were associated with full-thickness labral injuries. Older age (OR:1.06,p<0.001) and larger alpha angles at 2:00 (OR:1.03,p=0.01) were associated with tears ≥4cm. 258/679 (38.0%) patients had delamination or full-thickness cartilage defects. Older age (OR:1.09,p<0.001), males (OR:1.91 p=0.003), decreased IRF (OR:0.95,p<0.001), higher femoral version (OR:1.02,p=0.04), and larger alpha angles at 1:30 (OR:1.06,p<0.001) were associated with delamination or defect cartilage injuries. Advanced acetabular cartilage damage ≥200mm2 was present in 109/679 (16.8%) hips and was associated with larger alpha angles at 2:00 (OR:1.07,p<0.001), decreased IRF (OR:0.95,p<0.001), and males (OR:2.52,p=0.002), and age (OR:1.05,p=0.002). For RAPID score external validation, we used our data for their model (sex, Tonnis OA Grade, radiographic alpha angle) and found an AUC of 0.685. With an adjusted model using CT alpha angles, AUC improved to 0.703. Our final model improved the AUC to 0.809 and included age, sex, IRF, femoral version, and CT alpha angles. Conclusion: FAI commonly has associated labral and cartilage injuries. The current study found multiple predictive factors for advanced labral and cartilage injuries as well as for larger lesions. A model including age, sex, IRF, femoral version, and CT alpha angles appears to best predict acetabular cartilage damage. Further research should investigate how these affect outcomes.

Abstract Background and Aims Classification and risk stratification in aortic (AR), mitral (MR), and tricuspid regurgitation (TR) remains a significant clinical challenge. This study aimed to develop an artificial intelligence (AI) system to assess valvular regurgitation and stratify MR-progression risk. Methods Using transthoracic echocardiograms (TTEs) at two sites (internal development/test, external test), the DELINEATE-Regurgitation system was developed to classify AR, MR, and TR severity using colour Doppler videos. Methods of summating video-level classifications into study-level predictions were tested, comparing single-view with multiview approaches integrating predictions across multiple videos. Model agreement with cardiologists was assessed by weighted kappa. A separate AI system (DELINEATE-MR-Progression) analysing colour Doppler videos was developed to predict which patients with mild, mild–moderate, and moderate MR were most likely to progress to moderate–severe or severe MR with analysis by Kaplan–Meier and Cox proportional hazards models. Results A total of 71 660 TTEs with 1 203 980 colour Doppler videos were included. The weighted kappa in internal/external test sets for regurgitation classification was 0.81/0.76 for AR, 0.76/0.72 for MR, and 0.73/0.64 for TR using a multiview approach taking all colour Doppler videos in a study, demonstrating substantial agreement with cardiologist interpretation with superiority of multiview over single view approaches. In the progression analysis, the AI score stratified MR-progression risk even when controlled for clinical factors known to be associated with MR progression [internal test set hazard ratio 4.1 (95% confidence interval 2.5–6.6)]. Conclusions An AI system can accurately classify AR, MR, and TR and predict MR progression beyond currently known risk factors.

Abstract Excessively restrictive inclusion and exclusion criteria in clinical trials are one of many barriers to clinical trial enrollment for patients with myelodysplastic syndromes/neoplasms (MDSs). Many organizations are developing efforts to increase clinical trial eligibility; yet, several recent publications focused on patients with MDS suggest that many patients with this disease may be excluded from clinical trials unnecessarily. Clinical trial eligibility should reflect the phase of the study and risks of the agent being studied. Phase 3 trials should be less restrictive than early-phase trials to represent the real-world population as closely as possible. We hypothesize that many clinical trials, particularly phase 3 trials, have unnecessarily restrictive eligibility criteria. This study aims to evaluate the most common eligibility criteria according to phase of trial and to determine whether criteria correspond with drug safety signals. We identified MDS clinical trials registered on ClinicalTrials.gov from 1 January 2000 to 1 September 2023 and analyzed the eligibility criteria of 191 therapeutic MDS trials. We found that categorical inclusion and exclusion criteria are remarkably similar in representation across trial phases. Additionally, only 13% of trials are concordant with drug safety signals, suggesting that the eligibility criteria are often arbitrary. On behalf of the icMDS (International Consortium for Myelodysplastic Syndromes), an association of international MDS experts, we provide a position statement on restrictive eligibility criteria for MDS clinical trials that should be avoided with the aim of removing barriers to clinical trial enrollment.