Citations

Purpose To evaluate the effects of this graft preparation technique on histologic evidence of tenocyte mechanical damage. Methods A consecutive series of patients undergoing biceps tenodesis for shoulder pathology were evaluated. After suprapectoral tenodesis, 27 mm of the long head of the biceps was secured for compression into the patch. The remaining length of the residual tendon was longitudinally split, resulting in 2 equal lengths of remnant tendon from the same zone. One sample was sent to pathology with no preparation, and the other was prepared as a compressed biceps autograft patch according to the manufacturer’s recommendations. Both grafts were sent to pathology for evaluation of tenocyte morphology. Records were reviewed to determine if compression resulted in mechanical damage to the tenocytes at the time of biceps augmentation. Results Fifty‐five shoulder procedures and 110 samples were sent for pathology analysis. Forty‐two of the 55 (76%) specimens demonstrated morphologically normal tenocytes in both the compressed and noncompressed groups, and 7 (13%) cases showed evidence of tenocyte necrosis or mechanical damage in both groups. The difference in abnormal tenocyte morphology between the compressed and native groups was not statistically significant ( P = .625). Conclusions Autograft biceps compression into a point‐of‐care patch did not result in mechanical damage to tenocyte morphology at the time of insertion for augmentation of rotator cuff pathology. Clinical Relevance Free proximal biceps tendon compression can result in a patch that does not mechanically damage the tenocyte. The patch can be used as a biologic autograft to enhance shoulder rotator cuff repair, as well as subscapularis repair in the setting of shoulder arthroplasty.

Background. The impact of induction type or high-risk viral discordance on older kidney transplant recipients is unclear. Herein, we analyzed the association between induction type, viral discordance, and outcomes for older recipients. Methods. We analyzed the Scientific Registry of Transplant Recipients standard analysis file for all primary kidney transplant recipients older than 55 y who were transplanted between 2005 and 2022. All transplants were crossmatch negative and ABO-compatible. Recipients were discharged on tacrolimus and mycophenolate ± steroids. Recipients were categorized into 3 groups by induction received: rabbit antithymocyte globulin (r-ATG; N = 51 079), interleukin-2 receptor antagonist (IL-2RA; N = 22 752), and alemtuzumab (N = 13 465). Kaplan-Meier curves were generated for recipient and graft survival, and follow-up was censored at 10 y. Mixed-effect Cox proportional hazard models examined the association between induction type, high-risk viral discordance, and outcomes of interest. Models were adjusted for pertinent recipient and donor characteristics. Results. Induction type did not predict recipient survival in the multivariable model, whereas Epstein-Barr virus high-risk discordance predicted 14% higher mortality (1.14 [1.07-1.21], P < 0.01). In the multivariable model for death-censored graft survival, alemtuzumab, but not IL-2RA, was associated with an increased risk of graft loss (1.18 [1.06-1.29], P < 0.01) compared with r-ATG. High-risk cytomegalovirus discordance predicted 10% lower death-censored graft survival (1.10 [1.01-1.19], P < 0.02). Live donor and preemptive transplantation were favorable predictors of survival. Conclusions. In this large cohort of older transplant recipients, alemtuzumab, but not IL-2RA, induction was associated with an increased risk of graft loss compared with r-ATG. Cytomegalovirus and Epstein-Barr virus high-risk viral discordance portended poor graft and recipient survival, respectively.

AbstractThe tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies. In this context, designing the most efficient development programs to translate promising targets and treatments from preclinical studies to early‐phase clinical trials is vital. In September 2022, the Rainwater Charitable Foundation convened an international expert workshop focused on the translation of tauopathy therapeutics through early‐phase trials. Our report on the workshop recommends a framework for principled drug development and a companion lexicon to facilitate communication focusing on reproducibility and achieving common elements. Topics include the selection of targets, drugs, biomarkers, participants, and study designs. The maturation of pharmacodynamic biomarkers to demonstrate target engagement and surrogate disease biomarkers is a crucial unmet need.Highlights Experts provided a framework to translate therapeutics (discovery to clinical trials). Experts focused on the “5 Rights” (target, drug, biomarker, participants, trial). Current research on frontotemporal degeneration, progressive supranuclear palsy, and corticobasal syndrome therapeutics includes 32 trials (37% on biologics) Tau therapeutics are being tested in Alzheimer's disease; primary tauopathies have a large unmet need.

SummaryBackground and AimsMachine learning (ML) can identify the hidden patterns without hypothesis in heterogeneous diseases like acute‐on‐chronic live failure (ACLF). We employed ML to describe and predict yet unknown clusters in ACLF.MethodsClinical data of 1568 patients with ACLF from a tertiary care centre (2015–2023) were subjected to distance‐, density‐ and model‐based clustering algorithms. Final model was selected on best cluster separation, viz. Silhouette width and Dunn's index (for distance‐ or density‐based algorithms) and minimum BIC (for model‐based algorithms). Cluster assignments, patient trajectories and survival were analysed through inferential statistics. Supervised ML models were trained in 70% data that predicted clusters in remaining 30% data followed by an temporal validation.ResultsThe cohort was male‐predominant (87%), aged 44.3 years, with alcohol‐associated hepatitis (62.9%) and survival of 50.5%. Due to poor performance of distance‐ and density‐based algorithms and better explainability, the latent class model (LCM) was selected for exploration. LCM revealed four clusters with distinct trajectories, reversibility and survival (independent of MELD, CLIF‐C ACLF and AARC scores). Cluster1 had patients with none/one organ failure and highest reversibility. Cluster2 had females with viral hepatitis and two organ failures. More‐than‐one acute precipitant, severity, infections, organ failures and irreversibility escalated from clusters 1 to 4. Circulatory and renal failures critically influenced cluster assignments. Incorporating clusters to CLIF‐C ACLF, infection and ACLF definition improved the discriminative accuracy of CLIF‐C‐ACLF by 11%. Extreme gradient boost and decision trees could predict clusters with AUCs of 0.989 (0.979–0.995) and 0.875 (0.865–0.890). MELD, CLIF‐C‐OF, haemoglobin, lactate, CLIF‐C‐ACLF and ALT were critical variables for cluster prediction. Clusters with distinct survival were documented in a temporal validation cohort.ConclusionsML for the first time could identify clusters with distinct phenotypes, trajectories and outcomes in ACLF. Stratification into clusters can address heterogeneity, guide prognosis, recruitment in trials, resource allocation and liver transplant discussions in ACLF.

Abstract Introduction Prostate cancer (CaP) significantly impacts Black men, who face higher morbidity despite lower overall mortality. The disease and its treatments profoundly affect sexuality, relationships, and quality of life (QoL), necessitating robust support systems. Healthcare, spousal support, community involvement, and interactions with other survivors are crucial for enhancing survivors' self-esteem and daily functioning. Virtual town halls offer a platform to share trusted information and foster community support, overcoming geographic and structural barriers. This town hall event will explore Black CaP survivors' experiences, focusing on sexuality post-diagnosis and related medical and psychological needs. MethodsOn June 13, 2024, The University of Oklahoma and Stephenson Cancer Center will host the 5th town hall event (via Microsoft Teams) to address Black CaP survivors' sexual health concerns. Previous town halls averaged 70 attendees and covered various aspects of the CaP journey. This event will include storytelling and panel discussions, with presentations from two CaP survivors and their spouses on personal experiences and coping strategies. A urologic oncologist will discuss treatment advancements and early detection, while a clinical health psychologist will address psychological and emotional aspects of survivorship. Simultaneous watch parties will be held in Milledgeville, Georgia, and Dallas, Texas. Interactive Q&A sessions will allow participant engagement. Attendees will complete a post-event survey to assess the session's impact and collect clinical and sociodemographic data. Quantitative data will be analyzed using SPSS v28, and audio-recorded sessions will be transcribed and thematically analyzed using Nvivo. Results will be available by the end of June and presented at the conference. Expected Results Participants will gain a deeper understanding of the intersection between CaP and sexuality in Black men's health. Discussions will highlight the psychological impact of a cancer diagnosis, challenges in maintaining sexual health during and after treatment, and the role of mental health support. The town hall aims to emphasize the importance of a strong support system, providing valuable coping skills through shared experiences and expert insights. Topics will include the emotional and psychological impact of sexual health challenges, partner support, and the necessity of open communication with healthcare providers. The event seeks to improve CaP survivors' QoL by emphasizing continuous education and integrating sexual health into overall survivorship care. Conclusion This town hall event aims to bridge gaps in understanding and addressing Black CaP survivors' sexual health concerns. By fostering open dialogue and providing expert insights, we hope to improve these men's QoL and survivorship care, emphasizing mental health support, spousal support, and continuous education. Citation Format: Motolani Ogunsanya, Ernie Kaninjing, Parisa Ghasemi, Skyler Danker, Daniel Morton, Kathleen Dwyer, Mary Ellen Young, Folakemi T. Odedina, Yaw Nyame, Amy Siston, Jordan Neil, Adam C Alexander, Perry Cole, Patrick Beckford, Donald Reese, Thomas Mitchell, Everett Montgomery, Roland Odeleye, Darla E. Kendzor. Beyond the diagnosis: A town hall event to explore black men’s journey with prostate cancer and sexuality [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B028.

Objectives: The purpose of this study was to characterize content posted by orthopaedic surgeons on social media (SM) while investigating patient perceptions of this content from various regions of the United States. Analysis was included regarding how this content may influence the respondents’ healthcare decisions. Methods: SM posts by orthopaedic surgeons were reviewed and categorized. A patient survey was written to assess respondent SM usage practices as well as respondent perceptions of these categories. The survey was administered in the clinic of 13 separate orthopaedic surgeons via QR code. Survey results were analyzed for differences in SM utilization. Patient responses were assessed to judge perception of social medial content types. Results: There were 674 completed patient surveys. The 18-24 (89.3%) and 25-34 (87.6%) age groups were more likely to report daily use (p=0.002), but SM utilization was high among all age groups. 23% of patients reported using SM to see information about their healthcare at least once per month, 38% of patients reported reviewing the SM account of a physician at least once per month, and 23% of patients reported that they were likely or very likely to view the SM account of their own physician. 26% of patients reported that SM content is likely or very likely to influence which physician they see. Patients held the most consistently positive view of posts educating patients regarding common injuries, discussing sports team coverage, providing patient testimonials, and posts illustrating examples of imaging used to diagnose and treat patients. Patients held consistently neutral views of posts educating colleagues, discussing research and presentations at national meetings, displaying aspects of surgeons’ personal lives, and supporting marginalized groups. Several post categories elicited negative or highly polarized responses including those discussing research publications, showing surgical techniques or pictures/videos taken during surgery, or political statements. Conclusions: SM is an increasingly useful tool to help physicians interact with patients or build a practice. Physicians who wish to interact with patients should consider posting content viewed most positively including posts educating patients, discussing sports team coverage, and patient testimonials. Content that is viewed less favorably should be posted sparingly or with a sensitive tag. The most effective way to reach large patient populations appears to be through Instagram, Facebook, Tik Tok, Snapchat, and LinkedIn, in that order. Further ongoing study is required to understand the differences between physician SM content focused on interacting with patients compared to content focused on interacting with other physicians.

ObjectiveDe novo variants in cullin‐3 ubiquitin ligase (CUL3) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here, we aimed to collect sporadic cases carrying rare variants in CUL3, describe the genotype–phenotype correlation, and investigate the underlying pathogenic mechanism.MethodsGenetic data and detailed clinical records were collected via multicenter collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient‐derived T‐cells.ResultsWe assembled a cohort of 37 individuals with heterozygous CUL3 variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 35 have loss‐of‐function (LoF) and 2 have missense variants. CUL3 LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin‐protein conjugates in vitro. Notably, we show that 4E‐BP1 (EIF4EBP1), a prominent substrate of CUL3, fails to be targeted for proteasomal degradation in patient‐derived cells.InterpretationOur study further refines the clinical and mutational spectrum of CUL3‐associated NDDs, expands the spectrum of cullin RING E3 ligase‐associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism. ANN NEUROL 2025;97:76–89

PURPOSE Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131 I-apamistamab with conventional care. METHODS SIERRA (ClinicalTrials.gov identifier: NCT02665065 ) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131 I-apamistamab–led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population. RESULTS The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively. CONCLUSION The 131 I-apamistamab–led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.