Citations

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.

Introduction: Neonatal pig hearts exhibit remarkable regenerative capacity within two days post-birth. In this study, we propose that a comprehensive multiomics analysis encompassing circRNA, miRNA, and mRNA data from neonatal mouse hearts can unveil intricate circRNA-miRNA-mRNA relationships associated with cardiac regeneration. Our aim is to identify new novel circRNAs and miRNAs implicated in cardiomyocyte proliferation through leveraging multiomics analysis. Methods: Utilizing neonatal mouse hearts, we conducted circRNA, miRNA, and mRNA sequencing across four different postnatal days (P1, P3, P7, and P28; n=6, encompassing both males and females). We employed integrative bioinformatics analyses across distinct experimental designs (P1 vs P3, P1 vs P7, and P1 vs P28). Back splice junctions generated by CIRCexplorer2’s parse command was utilized to annotate sequenced circRNAs as known or novel. Validation of circRNA, miRNA, and mRNA expression levels was achieved through qRT-PCR, while protein expression levels were assessed via western blotting. Fluorescence in situ hybridization (FISH) technology was employed to determine circRNA localization. The functional significance of key genes involved in cardiomyocyte proliferation was assessed via siRNA-mediated knockdown of circRNAs and miRNAs, accompanied by cell cycle assessment using bioluminescence assay and immunostaining. Results: Intersection of differentially expressed target genes from circRNA, miRNA, and mRNA analyses at each experimental design facilitated the construction of circRNA-miRNA-mRNA regulatory networks, aiding in the development of cardiac regeneration-related regulatory networks and inference of novel relationships between circRNA, miRNA, and mRNA. Integrative bioinformatics analysis revealed significant alterations in circRNA-miRNA-mRNA expression profiles during postnatal cardiomyocyte maturation in mice. Pathway enrichment analysis identified several differentially expressed circRNAs enriched in cell division and proliferation-related pathways. qPCR and cell cycle studies identified 17 potential circRNAs associated with cardiomyocyte proliferation in mice, with knockdown of these circRNAs significantly impacting cardiomyocyte cell cycle. Conclusion: Our findings suggest a crucial role for circRNAs in the regulation of neonatal myocardial regeneration.

Background: Facial shape is significantly influenced by the underlying facial bony skeleton. Sexual dimorphisms in these structures are crucial for craniofacial, aesthetic, and gender-affirming surgery. Previous studies have examined the orbits and upper face, but less is known about the midface. This study aimed to elucidate the sexual dimorphism in the midface region, focusing on the maxilla and zygomatic bones. Methods: A retrospective review was conducted using facial computed tomography scans from 101 White patients aged 20–79 years, using Materialise Mimics and 3-Matics for segmentation and 3D reconstruction. Measurements and statistical shape modeling of the midfacial skeleton were performed. Results: Our results show a distinct sexual dimorphism in the midfacial skeletal structure across all age groups. Women typically had a narrower bizygomatic width by 1.5 mm (P = 0.04), a shallower maxillary depth by 1.6 mm (P < 0.01), and a midfacial vertical height that was 4 mm shorter than that of men (P = 0.018). In contrast, men exhibited a greater distance between the frontozygomatic sutures by 5.4 mm (P < 0.01), a 3-mm greater interorbitale distance (P < 0.01), and a 2.1-mm wider infraorbital foramina distance (P = 0.007). There were no significant differences in the pyriform and maxillary angles (P = 0.15 and P = 0.52, respectively). Conclusions: Our analysis of midfacial skeletal anatomy revealed sexual dimorphism differences. Men exhibited more pronounced facial features than women, with a broader horizontal midfacial skeleton, a longer midfacial vertical height, and greater maxillary depths compared with women.

Importance Historically, women with aortic stenosis have experienced worse outcomes and inadequate recognition compared to men, being both underdiagnosed and undertreated, while also facing underrepresentation in clinical trials. Objective To determine whether women with small aortic annuli undergoing transcatheter aortic valve replacement have better clinical and hemodynamic outcomes with a self-expanding valve (SEV) or balloon-expandable valve (BEV). Design, Setting, Participants The Small Annuli Randomized to Evolut or SAPIEN Trial (SMART) was a large-scale randomized clinical trial focusing on patients with small aortic annuli undergoing transcatheter aortic valve replacement, randomized to receive SEVs or BEVs and included 716 patients treated at 83 centers in Canada, Europe, Israel, and the US from April 2021 to October 2022. This prespecified secondary analysis reports clinical and hemodynamic findings for all 621 women enrolled in SMART. Data for this report were analyzed from February to April 2024. Interventions Transcatheter aortic valve replacement with an SEV or a BEV. Main Outcomes and Measures The composite coprimary clinical end point comprised death, disabling stroke, or heart failure–related rehospitalization. The coprimary valve function end point was the incidence of bioprosthetic valve dysfunction, both assessed through 12 months. Secondary end points included the incidence of moderate or severe prosthesis-patient mismatch. Results A total of 621 women (mean [SD] age, 80.2 [6.2] years; 312 randomized to the SEV group and 309 to the BEV group) were included in the present analysis. At 12 months, there were no significant differences in the coprimary clinical end point between the SEV and BEV groups (9.4% vs 11.8%, absolute risk difference −2.3%; 95% CI −7.2 to 2.5, P = .35). However, SEV implantation was associated with less bioprosthetic valve dysfunction (8.4% vs 41.8%; absolute risk difference, −33.4%; 95% CI, −40.4 to −26.4; P &amp;lt; .001). SEV implantation resulted in lower aortic valve gradients and larger effective orifice areas at 30 days and 12 months and less mild or greater aortic regurgitation at 12 months compared to BEV implantation. Prosthesis-patient mismatch was significantly lower with SEVs, regardless of the definition used and adjustment for body mass index. Use of SEVs was associated with better quality of life outcomes as assessed by the Valve Academic Research Consortium-3 ordinal quality of life measure. Conclusions and Relevance Among women with severe symptomatic aortic stenosis and small aortic annuli undergoing transcatheter aortic valve replacement, the use of SEVs, compared to BEVs, resulted in similar clinical outcomes and a markedly reduced incidence of bioprosthetic valve dysfunction through 12 months, including a lower risk of prosthesis-patient mismatch and better 12-month quality of life. Trial Registration ClinicalTrials.gov Identifier: NCT04722250

ObjectivesTo analyze demographic trends in laryngology fellowship training in the United States from 1993 to 2022, comparing periods before and after formalization of the fellowship within the National Resident Matching Program (NRMP) in 2012.MethodsA national database of fellowship‐trained laryngologists (FTLs) and non‐fellowship‐trained laryngologists (nFTLs) practicing primarily laryngology was created by methodically compiling laryngologists via Internet search, with corroboration by regional laryngologists and vetting by senior laryngologists on this manuscript. Demographic variables included residency and/or fellowship graduation year, gender, race and ethnicity inferred through individuals' photos and surnames. NRMP match data from 2012 to 2022 were obtained from the American Laryngological Association.ResultsAn average of 21 programs offered 23 positions in the NRMP match, with 14 programs (66.4%) filling 16 positions (68.8%) from 2012 to 2022. The 10‐year FTL growth rate decreased from 25.4% (1993–2002) to 10.5% and 6.6% in subsequent periods. In May 2023, there were 349 active laryngologists, including 303 FTLs, in the United States. A total of 189 (62.4%) FTLs were men, 114 (37.6%) were women; 201 (66.2%) were White, 102 (33.8%) were non‐White. Between the pre‐NRMP and post‐NRMP periods, the percentage of male FTLs decreased from 71.5% to 55.5%, female FTLs increased from 28.5% to 44.5%, and White FTLs decreased from 69.2% to 64.2%. Chi‐squared analysis yielded a statistically significant association between gender and training period for FTLs (p = 0.004), but no statistically significant difference between race and training period.ConclusionsThe post‐NRMP period saw an expansion of laryngology fellowships and workforce diversification, reflecting trends observed in otolaryngology and medicine overall.Level of EvidenceNA Laryngoscope, 135:794–800, 2025