Citations

Objective: To evaluate access, clinical outcomes, engagement, and satisfaction associated with an advanced musculoskeletal virtual care model. Design: Retrospective cohort study of adults with musculoskeletal complaints referred to advanced orthopedic virtual physical therapy by Physical Medicine and Rehabilitation providers between July 2024 and April 2025. Outcomes included access to care, patient-reported outcome measures, pain intensity, plan-of-care completion, and patient satisfaction. Results: Of 137 referred patients, 86 (62.8%) completed evaluations; 70.9% of those (n=61) completed full care episodes — exceeding national completion benchmarks (71% vs. 43%). Among completers, 96% achieved Minimal Clinically Important Differences. Functional improvements were significant: Oswestry Disability Index −32.4, Neck Disability Index −29.5, Lower Extremity Functional Scale +26.6 (all P <.001). Pain decreased from 6.1 to 0.9 (−85%). Average care required 5.6 visits versus national benchmarks of 6–10. Patient satisfaction was exceptional (Net Promoter Score=100). Conclusion: Among patients who completed a full episode of care, this advanced virtual musculoskeletal model was associated with substantial functional improvement, pain reduction, and high satisfaction while requiring fewer visits than national averages. Because outcome analyses were limited to completers, these findings may not represent all referred patients. Prospective controlled studies are needed to evaluate effectiveness and scalability.

Abstract Purpose This study evaluated and compared the marginal fit of CAD–CAM zirconia crown copings with and without a 3D‐printed control model. Materials and Methods This prospective in vitro trial involved 30 zirconia crown copings made from the same STL file. These were divided into two groups. Half of them had their own 3D‐printed control model made from the same STL file (With‐Printed‐Model group), whereas the other half lacked any control model (No‐Printed‐Model group). Both groups underwent manual adjustments in a systematic way. Their marginal gaps were evaluated using a digital optical microscope from eight zones: buccal, mesiobuccal, mesial, mesiopalatal, palatal, distopalatal, distal, and distobuccal. Results The mean values with standard deviations for the With‐Printed‐Model and No‐Printed‐Model groups were 15.18 ± 14.49 and 12.46 ± 14.09 µm, respectively. All crown copings from both groups were below 75 µm. Statistical analysis showed a significant difference between the two groups. Conclusion The No‐Printed‐Model group demonstrated superior marginal fit compared to the With‐Printed‐Model group. However, the largest marginal gaps from each group were still within the clinically acceptable range below 75 µm. Although the 3D‐printed control model did not improve marginal fit, its primary function is to effectively identify major manufacturing errors.

Abstract Genetic studies have significantly advanced our understanding of tauopathies, yet the genetic aetiology of Pick’s disease, a rare 3-Repeat tauopathy, remains unclear. The MAPT p.A152T variant has been identified as a risk factor for Alzheimer’s disease and progressive supranuclear palsy, but its role in Pick’s disease is unknown. In this study, we examined the prevalence of MAPT p.A152T in the largest series of neuropathologically confirmed Pick’s disease cases to date (n = 401). Through genotyping, we identified a single mutation carrier in the Pick’s disease cohort (minor allele frequency = 0.12%). We previously reported MAPT p.A152T at a 0.20% frequency in healthy controls (n = 2456), suggesting that it does not associate with 3-Repeat tauopathy risk. To further investigate the effect of the variant on MAPT transcript expression, we used bulk RNA sequencing in Alzheimer’s disease and progressive supranuclear palsy A152T mutation carriers. We did not detect significant differences in 4-Repeat tau levels, though preliminary trends may indicate more nuanced effects that need to be examined with long-read sequencing in a larger series. Overall, our study suggests that MAPT p.A152T does not increase Pick’s disease risk and may instead be linked to 4-Repeat or mixed tau pathologies, warranting further functional investigation.

Aims Testicular sex cord‐stromal tumours (TSCSTs) are rare neoplasms that arise from (or show differentiation to) elements derived from the sex cords or intertubular stroma. The current classification (World Health Organization, 2022) is based almost entirely on morphology, with many tumour types such as granulosa cell tumours being defined based on their resemblance to ovarian counterparts. Recent studies have uncovered new clinicopathological, molecular and biological nuances within this group of tumours, underscoring differences with ovarian homologues. Methods and results Considering the new data, a group of genitourinary pathology experts (Testicular Sex Cord‐Stromal Tumour [TESST] group) has proposed a revised ‘TESST classification’ that incorporates the best available evidence. This classification is structured and hierarchical, composed of the following tiers: (1) group, (2) category, (3) entity and (4) histological pattern. ‘Group’ refers to the histological compartment a specific tumour belongs to (sex cords, stroma or both), whereas ‘category’ is defined by the phenotype of the tumour, taking non‐neoplastic elements of the ovary and testis as a reference. The third tier, ‘entity’, refers to neoplasms with shared clinicopathological and/or molecular features that justify classifying them as distinct types. Lastly, ‘histological patterns’ are recurrent morphological variations within entities that are not linked to distinct clinicopathological or molecular features. Conclusions We propose a classification that will provide a framework to improve current clinical management and guide future research in the field.

ABSTRACT Background Transvenous lead extraction (TLE) is a commonly performed and generally safe procedure, though procedural complexity and risk can vary based on clinical and procedural factors. Objective This study aims to identify clinical and procedural factors associated with histologic evidence of subclinical vascular injury, defined by elastin positivity on extracted leads and its clinical significance. Methods Patients undergoing TLE with a lead dwell time of ≥ 1 year were included. Extracted leads with tissue were analyzed histologically using Verhoeff–Van Gieson staining to assess the presence of elastin. Demographic data, procedural and lead characteristics, and indication for extraction were obtained. Established extraction risk scores were calculated to determine efficacy in predicting subclinical vascular injury. Results The cohort included 49 patients with 92 leads extracted. A total of 25 patients (51%) had elastin‐positive leads. Complete procedural success occurred in 95.9% of cases. The multivariate regression model did not identify any independent predictors of elastin presence, including age (OR = 1.00; 95% CI 0.95–1.05; p = 0.89), female gender (OR = 3.04; 95% CI 0.67–13.65; p = 0.14), lead dwell time (OR = 1.13; 95% CI 0.98–1.29; p = 0.07). Additionally, no scoring system, such as the CCF, EROS, MB, SAFeTY, and LECOM, predicted the presence of elastin. Conclusion Subclinical venous injury was common following TLE, yet did not predict adverse clinical outcomes, reinforcing that TLE performed in experienced centers carries a favorable safety profile. Future studies in larger cohorts are needed to further characterize the clinical utility of subclinical vascular injury.

PURPOSE Precision medicine has revolutionized oncology; however, tumor biomarkers are not reflective of the heterogeneous cancer population. We evaluated NRG Oncology prostate cancer (PCa) clinical trials for demographic differences among patients with optional biospecimen collection (BC) consent and biospecimen submission (BSub). METHODS Data from 19 NRG PCa clinical trials closed before 2015 were analyzed. Patients who consented to BC and completed BSub were evaluated by race, ethnicity, median income, area deprivation index (ADI; categorized as highest v lowest three quartiles), age at enrollment, site, and year of enrollment. T/chi-square tests were used for continuous/categorical variables, respectively, followed by logistic regression. RESULTS Of the 15,648 randomized patients eligible for BC, 11,796 (75%) had specimens submitted. In all, 4,598 (82.2%) of 5,597 eligible patients consented for optional BC in nine clinical trials with a separate BC consent process (consent rates by race/ethnicity: 74.1% Black, 72.8% Hispanic/Latino, 83.8% White). A smaller proportion of Black and Hispanic/Latino patients consented to optional BC compared with those who did not (12.1% v 19.5% Black, P < .0001; 3.5% v 5.8% Hispanic, P = .0006). In univariable logistic regression models, high ADI (more socioeconomic disadvantage) was associated with a decreased likelihood for optional BC consent (odds ratio [OR], 0.67 [95% CI, 0.55 to 0.82]; P = .02), but not a decreased likelihood for BSub (OR, 0.74 [95% CI, 0.53 to 1.04]; P = .08). Multivariable models demonstrated that Black/Hispanic/Latino patients were less likely to consent to optional BC, and Black patients were less likely to have BSub ( P < .05 for all). CONCLUSION White/non-Hispanic patients and those with less socioeconomic disadvantage were more likely to consent to optional BC, whereas Black patients were less likely to have BSub. Targeted solutions are needed to improve biorepository representation so that precision medicine approaches better reflect the cancer population.

Importance There is no consensus on staging and surveillance imaging for cutaneous squamous cell carcinoma (CSCC). Although imaging has been shown to affect management, broad recommendations from the National Comprehensive Cancer Network have led to variability in clinical practice. Objective To develop multidisciplinary consensus recommendations on the use of staging and surveillance imaging of localized CSCC. Evidence Review A multidisciplinary expert panel across academic and clinical practice settings convened a Delphi consensus, with 3 iterative survey rounds from January to June 2025. Data were analyzed from February 2025 to January 2026. Eligibility defined by at least 1 to 2 CSCC publications during the previous 5 years, involvement in a relevant clinical trial, experience treating at least 3 patients monthly with CSCC, and/or 5 years or longer of clinical practice. Fifty-four experts were invited and 45 (83%) completed all 3 rounds and were included in the final analysis. Structured Delphi surveys evaluated clinical scenarios, imaging modalities, and surveillance strategies for CSCC. Consensus and near-consensus recommendations were generated, defined as 80% or greater and 70% to 79% agreement, respectively. Findings The 45 participants (21 female individuals [47%] and 24 male individuals [53%]; 14 Asian individuals [31%], 1 multiracial individual [2%], and 30 White individuals [67%]) consisted of dermatology (15 [33%]), medical oncology (7 [16%]), radiation oncology (9 [20%]), radiology (9 [20%]), surgery (3 [7%]), and otolaryngology specialists (2 [4%]). The Delphi panel recommended staging and surveillance for CSCCs with at least a 15% risk of metastasis. Consensus or near consensus was reached to recommend staging and surveillance imaging for tumors with a concern for metastasis, bone invasion, invasion beyond subcutaneous fat, large-caliber nerve invasion, or a diameter of 4 cm or larger or the combination of tumors with poorly differentiated histology and any of the following: diameter of 2 cm or larger, lymphovascular invasion and subcutaneous fat invasion, or lymphovascular invasion and small-caliber perineural invasion. Computed tomography imaging was the preferred modality for nodal staging (38 [84%]) and surveillance (35 [78%]). For surveillance duration, consensus was reached to provide imaging for at least 2 years, and near consensus was reached for at least 3 years. Conclusions and Relevance This study provides an expert consensus–based framework to standardize imaging in localized CSCC that may inform future guidelines.

TAF7, a core subunit of the general transcription factor TFIID, regulates transcription and additionally functions as an RNA chaperone that directs nascent nuclear RNAs to cytoplasmic polysomes, thereby influencing protein synthesis. Here, we identify a set of novel cytoplasmic interactors and a previously unappreciated cytoplasmic role for TAF7 in oncogenesis. BioID-mediated proximity labeling identified STAT3 and the CCT and WASH complexes as prominent cytoplasmic interactors of TAF7. These interactions were validated by co-immunoprecipitation and proximity ligation assays. We further showed that cytoplasmic TAF7 levels increased during oncogenesis in proportion to cancer cell pathogenicity. Notably, TAF7 engagement with STAT3, CCT and WASH complexes is markedly enhanced during cellular transformation, consistent with their functions in cancer progression. Together, these findings reveal a cytoplasmic TAF7 interactome and implicate elevated cytoplasmic TAF7 as associated with oncogenesis.

Abstract Background and Aims Clinical models incompletely capture the molecular pathways driving heart failure (HF) progression. This study evaluated whether molecular risk stratification provides incremental prognostic information beyond established clinical predictors in patients with HF. Methods A total of 2432 patients from the Global Congestive Heart Failure (G-CHF) registry with available genotyping, DNA methylation, and proteomic profiling were analysed. Three molecular scores were assessed: a composite cardiovascular polygenic risk score (PRS) from DNA sequence polymorphisms, a methylation risk score (MRS) derived from epigenome-wide associations, and a 23-protein-based score (ProteomicDeath23). Each score was tested individually and in combination with the clinical Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels for mortality prediction. Validation was performed in an HF subset of the UK Biobank (UKB). Results Over a median follow-up of 3.0 years in G-CHF, 523 patients died from any cause (7.64 per 100 person-years [PY]). In multivariable analyses, ProteomicDeath23 was the strongest independent predictor of all-cause mortality (hazard ratio [HR] per 1 standard deviation, 2.23), outperforming NT-proBNP (HR 2.00), MRSMortality (HR 1.66), PRSmetaCVD (HR 1.10), and the MAGGIC score (HR 1.70). A model combining ProteomicDeath23 with MAGGIC and NT-proBNP achieved the highest discrimination for mortality (C-index, 0.77). Addition of MRSMortality to this proteomic-clinical model resulted in only small improvements in discrimination (ΔC-index, +0.004, P = .0039), while the PRSmetaCVD provided no incremental benefit. Among patients with low NT-proBNP/MAGGIC score, mortality rates increased from 1.71 to 8.12 per 100 PY across ProteomicDeath23 tertiles. Consistent results were observed in the UKB-HF validation cohort. Conclusion A proteomic score was the strongest molecular predictor of mortality in HF. Integrating proteomic signatures with clinical risk factors significantly improved risk prediction.

Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with SCID had more than twofold hazard of death compared with non-Hispanic White patients. NBS was associated with earlier diagnosis, reduced infection at HCT, and elimination of survival disparities between Black and non-Hispanic White patients. These findings suggest that universal, system-level interventions such as NBS can mitigate disparities in outcomes for children with SCID.