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Transgender and gender-diverse (TGD) persons represent a small but growing population in the United States. Accessing inclusive, equitable, and evidence-based healthcare remains a challenge for this patient population. Many TGD persons seek gender-affirming care, including gender-affirming hormonal therapy (GAHT) and gender-affirming surgery (GAS), to help ameliorate the physical and mental aspects of their gender incongruence. Both GAHT and GAS induce clinically important histopathologic and anatomic changes in breast tissue. Consequently, breast care in TGD persons has become an increasingly recognized topic of importance in gender-affirming care. However, there remains a scarce but growing base of literature specifically addressing the unique healthcare needs of breast care in TGD patients. This article will review how to establish trusting patient–provider relationships for TGD patients, gender inclusivity in breast clinics and imaging centers, the influence of GAHT and GAS on breast tissue, breast cancer screening recommendations and barriers, and breast cancer risk and treatment considerations in TGD persons.

Objective Our goal is to address the health literacy gap concerning cleft lip and palate using artificial intelligence (AI), specifically OpenAI's ChatGPT-4, to enhance the readability of patient educational materials (PEMs). Additionally, we aim to explore the integration of interactive educational materials into these resources. Design A cross-sectional study. Setting Websites of craniofacial teams approved by the American Cleft Palate-Craniofacial Association (ACPA). Patients/Participants PEMs collected from these websites. Interventions First, we examined the PEMs for interactive educational content such as videos, photos, case examples, and audio clips. Subsequently, we used the WebFX online readability calculator and Grammarly to evaluate the texts’ readability and clarity. After that, we used ChatGPT-4 to simplify the PEM texts to a 6th-grade reading level and re-evaluated their readability and clarity. Main Outcome Measure(s) Readability levels (grade level) and clarity scores of PEMs before and after AI modification, and the presence of interactive educational content. Results Initial evaluations using the Flesch-Kincaid Grade Level formula showed that the texts were written at a median 9th-grade reading level. Modifications using ChatGPT-4 significantly improved readability, achieving a median 6th-grade level and enhanced clarity. Only 27% of the websites featured interactive educational content, indicating a gap in utilizing educational enhancements. Conclusion The use of AI improved the readability and clarity of patient educational materials, aligning with recommended standards. However, the underutilization of interactive tools suggests a need for broader integration of these resources to optimize patient education and engagement.

Objectives: Ice hockey is a physically demanding sport, with young athletes prone to anterior cruciate ligament (ACL) injuries. Currently, there is a paucity of data examining the results of ACL reconstruction (ACLR) in competitive hockey players. The purpose of this study was to assess return to hockey (RTH) and reoperation rates following ACLR for ACL injuries in a cohort of competitive hockey players. Methods: All competitive ice hockey players (including, youth, high school, juniors, collegiate, or professional) with a history of ACL injury and subsequent ACLR at a single academic institution between 2000 and 2022 were identified. Exclusion criteria included ACL injuries that did not occur during hockey, history of ACLR prior to hockey injury, and recreational hockey players. Graft failure was defined as a retear (as determined via clinical or advanced imaging evaluation) and/or revision ACLR. Results: Ultimately, 50 knees in 44 hockey players were included at a mean (± standard deviation) follow-up time of 7.0 years ± 5.4 years (Table 1). The mean age at the time of index surgery was 18.9 years ± 3.0 years, with 38 males (76%), and the distribution of bone-patellar tendon-bone (BPTB) and hamstring tendon (HT) autografts was 40 (80%) and 10 (20%), respectively. RTH occurred in 66% of hockey players at a mean of 10.2 months ± 6.2 months. Graft failure occurred in 9 knees (18%) at a mean of 5.9 years ± 5.8 years after the index ACLR. All patients who sustained a retear underwent reoperation. Kaplan-Meier survivorship free from surgical failure of the entire cohort was 94% at 1 year, 88% at 5 years, 74% at 10 years, and 67% at 15 years (Figure 1A). BPTB autograft demonstrated a lower failure rate compared with HT autograft (13% vs 40%; P = 0.041) and was associated with better survival compared with HT autograft up to 15 years after the index ACLR (80% vs 39%; P = 0.047; Figure 1B). Conclusions: ACL injury remains a concern for competitive hockey players after ACLR. Return to competitive ice hockey was observed in 66% of athletes after ACLR, with 18% of hockey players experiencing graft failure and undergoing subsequent reoperation. BPTB autograft was associated with better survival than HT autograft.

Objectives: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. The purpose of this study is to evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. Methods: All RCTs comparing PRP to alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse fragility index (RFI) were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from one or more trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. Results: In total, this analysis included outcomes from 1993 patients with a mean (± standard deviation) age of 58.0 ± 3.8 years. The mean number of events required to reverse significance (FI) was 4.57 ± 5.85. This corresponded to a fragility quotient of 0.060 ± 0.075, meaning the significance of the results was contingent on 6 events per 100 participants. For non-significant outcome events, the mean number of events required to reverse statistical nonsignificance (RFI) was 4.41 ± 2.22. This corresponded to a reverse fragility quotient of 0.065 ± 0.056, meaning the non-significance of the results was contingent on 6.5 events per 100 participants (Figure 1). Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared to hyaluronic acid (p = 0.002, odds ratio 95% CI = 2.19 [1.33-3.62]) (Figure 2) as well as higher rates of patient-reported symptom relief (p = 0.019, odds ratio [95% CI] = 1.55 [1.07-2.24]) (Figure 3), not requiring a reintervention after the initial injection treatment (p = 0.002, odds ratio [95% CI] = 2.17 [1.33-3.53]) (Figure 4), and achieving the minimal clinically important difference (MCID) for pain improvement (p = 0.007, odds ratio [95% CI] = 6.19[1.63-23.42]) when compared to all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. Conclusions: Individual RCTs evaluating PRP for knee OA possess slight robustness. Upon meta-analysis, PRP demonstrated a significant advantage over HA as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared to alternative, nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and healthcare. Future RCTs and meta-analyses should consider reporting fragility indices and quotients to facilitate interpretation of results in their proper context. In addition, the robustness of these findings suggests that reconsideration of the American Academy of Orthopaedic Surgeons clinical practice guidelines around the use of PRP for knee OA may be warranted.

Objectives: The role of psychological factors in the clinical presentation and outcomes of treated is increasingly recognized in orthopaedic surgery. Particularly, in prearthritic hip disorders, young adult hip patients often have significant psychological undertones. Patient resiliency, as quantified by the brief resiliency scale (BRS), is a static patient characteristic and has been increasingly recognized for its potential role in pain and symptomatology. The purpose of the current study was to investigate the correlation between BRS and traditional hip patient-reported outcome measures (PROMs). Methods: A prospective multicenter cohort study of 696 patients undergoing femoroacetabular impingement (FAI) primary hip arthroscopy surgery was performed and utilized for the current study. Inclusion criteria are patients aged 14 to 45 years old with idiopathic FAI not caused by childhood disease. Exclusion criteria are previous ipsilateral hip procedures or disease processes such as neuromuscular disease or high-grade osteoarthritis. PROMs included the Patient-Reported Outcomes Measurement Information System (PROMIS) domains of pain interference, physical function, mobility, anxiety, and depression, as well as hip disability and osteoarthritis and outcome score (HOOS), modified Harris hip score (mHHS), international hip outcome tool (iHOT-12), and short form-12 (SF-12). Resiliency was divided into low resiliency (score < 3), normal resiliency (score 3 to 4.3), and high resiliency (score > 4.3) as described by Smith et al 1 to use as categorical variables to compare to the other patient-reported scores. The Pearson correlation coefficient (r) was calculated and the Kruskall Willis test was used to measure association between BRS and the other PROMs for continuous and categorical values, respectively. R values ≥0.7, ≥0.4, and ≥0.1 signify a strong, moderate, and weak correlation, respectively. For categorical analysis, P values < 0.05 were considered significant. Results: The cohort of 696 patients had mean age was 24.9 ± 7.9 years and a female predominance at 56%. Average BRS scores were 3.7 ± 0.7. Overall, 13.7% of patients had low resiliency, while 65.8% had normal resiliency and 20.5% had high resiliency. Linear correlation, using Pearson coefficients, found associations between BRS and all other scores. There were only weak associations between BRS scores and PROs (all r < 0.25) except a moderate correlation with PROMIS depression (r = -0.476, p < 0.001) and PROMIS anxiety (r = -0.481, p < 0.001). Patients in higher resiliency groups reported less severe symptoms in HOOS – quality of life (p < 0.001), HOOS – sports and recreation (p = 0.004), HOOS – activities of daily living (p = 0.004), HOOS – pain (p = 0.026), iHOT-12 (p = 0.01), mHHS (p = 0.004), SF-12 mental (p < 0.001), PROMIS physical function (p = 0.003), PROMIS pain (p < 0.001), PROMIS mobility (p < 0.001), PROMIS depression (p < 0.001), and PROMIS anxiety (p < 0.001). Patients with higher activity levels (UCLA ≥9) demonstrated higher resiliency (p = 0.04). Conclusions: In FAI patients, patient resiliency appears to influence baseline PROs. Overall, 14% of patients had low resiliency while 21% had high resiliency. Further studies are needed to investigate this relationship and whether concurrent psychological treatment will help improve patient outcomes after hip arthroscopy for FAI. [Figure: see text]

Objectives: Injury to the Medial Ulnar Collateral Ligament (MUCL) is a common setback experienced by many throwing athletes often requiring reconstruction with 12-18 months of rehabilitation. Current reconstructive techniques fail to anatomically restore the MUCL which may contribute to the prolonged course of rehabilitation. In recent years, we described an anatomic MUCL reconstruction with internal brace augmentation which demonstrated improved biomechanical strength when compared to the docking technique in cadaveric specimens. The purpose of this study was to evaluate the postoperative course of both amateur and professional throwing athletes that underwent anatomic MUCL reconstruction with internal brace augmentation. We hypothesized that throwers would return to the same level of play and that return to play (RTP) would be a shorter duration compared to current reported outcomes. Methods: In this surgical technique, the native MUCL is formally repaired. The graft and a suture tape are folded over a suspensory loop and secured in a socket of the medial epicondyle of the humerus to maximize tendon to bone contact. On the ulnar side, the graft and internal brace are secured proximally by two suture anchors on either side of the sublime tubercle and further secured across the sublime tubercle ridge distally to re-create the anatomic triangular insertion of the native ligament. All surgeries were performed by a single surgeon. Patient reported outcomes in addition to date of RTP, level of play, and functional outcomes were retrospectively gathered. All patients initially followed an Accelerated Rehabilitation Protocol and were converted to a Standard Paced protocol if setbacks were encountered. Results: A total of 26 baseball players underwent primary (n=23) or revision (n=3) MUCL reconstruction with the Anatomic Technique. Of these, 15 were professional and 11 were amateur athletes. 92% of throwers returned to play at a mean of 9.9 months following reconstruction. 89% were able to advance through the accelerated postoperative protocol without issues and 85% returned to the same role and level of play. Post injury KJOC scores improved from 41 to 86.9 and SANE scores improved from 32.5 to 95.5. No significant difference was identified in pre-injury versus post-reconstruction throwing velocity, ball spin rate, or horizontal/vertical ball movement. Conclusions: Anatomic reconstruction of the MUCL with internal bracing is a viable option for MUCL injuries. Advantages include increased tendon-bone contact of the reconstruction, multiple fixation points, and anatomic restoration of the MUCL. This technique allowed an expedited return to sport for these baseball athletes.

Background: Doxorubicin (DOX)-induced cardiotoxicity (DICT) has become a serious health burden for cancer survivors. The detrimental effects of CXCR4-mediated excessive inflammation in myocardium and the protective effects of CXCR7 in cardiomyocytes have been demonstrated. Aims: We tested the protective effects against DICT of a dual-targeting compound TC14012, which has specific antagonistic activity against CXCR4 and potent agonistic activity on CXCR7. Methods: Eight-week-old male C57BL/6J mice were injected with DOX for consecutive 5 weeks, during which mice were treated with TC14012 twice a week. One week after the last dose injection, mice were euthanized after heart function examination. Markers of cardiac inflammation and fibrosis were evaluated. Cardiac RNA-seq was performed to explore the underlying molecular pathways. Key findings: TC14012 supplement significantly prevented DOX-induced cardiac systolic dysfunction, reflected by improved ejection fraction and fraction shortening, along with remarkable attenuation of DOX-induced cardiac perivascular and interstitial collagen deposition and neutrophils and macrophage infiltration. RNA-seq revealed that TC14012 prevention of DICT was accompanied with a remarkable stimulation of signals involving in cardiac contraction and energy reserve metabolic process, particularly glycogen and glucan metabolism that are crucial for meeting the cardiac energy demand in response to DOX induction. These signals could be further enriched into AMPK signaling pathway and validated by upregulation of AMPK phosphorylation. Besides, TC14012 prevention of DICT was accompanied with a significant reduction in cardiac mast cell activation and degranulation. These signals could be further enriched into Rap1 signaling pathway, and TC14012 was validated to inhibit Rap1 activity and mast cell activation. Most importantly, TC14012 treatment did not affect the suppressive effects of DOX on tumor growth in a syngeneic EL4 lymphoma-bearing, immunocompetent mouse model. Conclusions: We preliminary conclude that TC14012 prevents DICT by activating cardiac CXCR7 to reprogram cardiomyocyte metabolism and prevent cardiac damage and dysfunction via activating AMPK, and by antagonizing CXCR4 to inhibit cardiac mast cell infiltration and activation via blunting Rap1 activity but does not affect the anti-tumor activity of DOX.

Introduction: Cardiac differentiation protocols enable derivation of cardiomyocytes (CM). from human induced pluripotent stem cell (iPS). However, limited tools are available to ensure enhanced iPS-CM maturation without the need for prolonged and complex culture. Research Question: This study assessed whether the mesodermal and cardiopoiesis inductor, Brachyury (T), complements standard cardiac differentiation and augments structural and functional maturation of iPS-CM. Aims: The impact of T mRNA introduction prior to initiation of cardiac differentiation was characterized on: i) cardiac transcription factor expression; ii) structural and functional hallmarks of maturity; and iii) cardiotoxicity. Methods: RT-qPCR was employed to monitor the expression of cardiac-specific transcription factors. Transmission electron microscopy enabled the assessment of cellular ultrastructure. Seahorse measurements were used to determine basal respiration. Fluo4 staining was used to measure calcium transients with external field stimulation. Cardiotoxicity was measured as the impact of doxorubicin on calcium handling and cell survival. Results: Transfection with T prompted early and sustained upregulation of the cardiac transcription factors Nkx2.5 (10-fold; FDR<0.001) and MEF2C (7.2-fold; FDR<0.001). Mitochondrial area was increased with T transfection (P<0.001) and T-transfected iPS-CM exhibited greater basal respiration (FDR<0.05), greater calcium handling resilience in response to field stimulation, and a more mature transient morphology. Following doxorubicin exposure T transfected iPS-CM exhibited a greater compromise in calcium handling (FDR<0.001), and exaggerated cell death. Conclusion: Induction of human iPS with T prior to initiation of cardiac differentiation enhanced signatures of structural and functional maturity, and provided more robust readouts of drug toxicity.