Citations

We previously reported 5-year results of 57 patients with major acetabular defects (Paprosky 2B through 3B) who underwent full (31) or half (26) cup-cage reconstructions. This study provides an update with 8.8-year mean follow-up. The 10-year cumulative incidence of and survivorship free from revision, reoperation, and complications were estimated. The 10-year cumulative incidence of revision was 14% for full and 12% for half constructs. The incidence of revision for aseptic loosening was 4.3% and 4.6%, respectively. The 10-year survivorship free from aseptic loosening for patients with pelvic discontinuity was 88.9% (95% confidence interval [CI], 70.6% to 100%) and 85.7% (95% CI, 61.8% to 100%), respectively; no patient without pelvic discontinuity required revision for aseptic loosening. The 10-year cumulative incidence of complications was 42% for all patients, including a 15% incidence of dislocation. Thus, both full and half cup-cage constructs provided durable fixation for complex acetabular bone loss at 10 years, although dislocation remains a concern. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Abstract Background: Endocrine therapies remain central to estrogen receptor alpha-positive (ERα+) breast cancer treatment, yet their predominantly cytostatic effects highlight the need for combinatorial approaches that promote tumor cell death. We therefore tested BH3 mimetics as single agents and in combination with (Z)-endoxifen (ENDX) across endocrine sensitive and endocrine resistant ERα+ breast cancer models. Methods: Six BH3 mimetics were tested in MCF7 and T47D cells and matched ENDX-resistant and fulvestrant-resistant derivatives. ENDX combinations were assessed using 2D proliferation and synergy assays, 3D RASTRUM® bioprinted cultures, migration assays, and in vivo MCF7 xenograft studies. Results: BH3 mimetics showed broad anti-proliferative activity as single agents in endocrine sensitive and resistant models. ENDX combinations were predominantly additive in 2D assays, with limited synergy confined to specific dose windows. In 3D culture, selected combinations of an MCL1 inhibitor (MCL1i) or navitoclax with ENDX produced greater suppression than single agents and, in several conditions, reduced growth below baseline, consistent with loss of viability. Combination treatment also enhanced suppression of migration under select concentrations. In MCF7 xenograft studies, ENDX robustly suppressed tumor growth; however, adding MCL1i or navitoclax did not provide additional antitumor benefit at the doses, schedules, and timeframes tested. Conclusion: BH3 mimetics show activity in ERα+ breast cancer models in vitro , including endocrine resistant models. Although ENDX combination benefit did not translate in vivo under the conditions tested, these data support further study of optimized BH3 mimetic combinations, including evaluation of dose, ratio, schedule, tumor target engagement, and other clinically advanced agents.

Most genetic variants associated with complex traits are hypothesized to regulate gene expression. To understand the genetics underlying gene expression variability, we characterized 14,324 RNA-sequencing samples from the Trans-Omics for Precision Medicine program and performed expression and splicing quantitative trait locus (e/sQTL) analyses in six tissues and cell types, including whole blood ( n = 6454) and lung ( n = 1291). We detected tens of thousands of secondary cis-e/sQTLs, showing that secondary cis-e/sQTL discovery remains unsaturated. We fine-mapped UK Biobank–derived genome-wide association study (GWAS) signals from 164 traits and identified e/sQTL colocalizations for 10,611 GWAS signals, including 7096 that colocalize with secondary e/sQTLs. Our results suggest that even larger e/sQTL analyses will uncover additional secondary e/sQTLs, further benefiting GWAS interpretation.

Down syndrome (DS), the genetic condition caused by trisomy 21 (T21), is characterized by lifelong immune dysregulation leading to high rates of autoimmune disorders, elevated risk of complications from infections, immune hypersensitivity, and a unique form of immunodeficiency. It is now appreciated that DS shares key hallmarks with interferonopathies, with vast remodeling of all branches of the immune system, hypercytokinemia, and widespread autoantibody production. Here within, we review the existing literature with an emphasis on clinical considerations toward monitoring, management, and therapeutic opportunities. We highlight recent research advances that illuminate diagnostic approaches to evaluate immune dysregulation in DS. We also discuss the evidence supporting specific immunomodulatory strategies that could have multidimensional benefits in this population, including JAK inhibitors, intravenous immunoglobulin, and B cell–depleting agents.

ABSTRACT Objective(s) Fetal pleural effusion is a rare condition that may significantly impact fetal and neonatal outcomes. Currently, no universal standardized approach exists for diagnosing and managing primary fetal pleural effusions. This study aimed to develop structured, expert‐based clinical guidelines for the diagnosis, monitoring, management, and follow‐up care of primary fetal pleural effusion. Methods A Delphi method was employed to achieve consensus among an international panel of experts in fetal medicine. Experts were selected based on their clinical expertise, affiliations, and relevant publications. A three‐round anonymous electronic survey was sent to the full panel. In the initial two rounds, participants rated each statement on a Likert scale (1–5) and provided suggestions for modifications. Statements with a median score of five and no suggested changes were accepted as consensus. Statements with a median score below four were rejected. Statements scoring a median of four were revised according to suggestions and reconsidered in the subsequent round. In the final round, participants indicated their agreement or disagreement with the remaining statements. Consensus was defined as agreement from more than 70% of participants with no suggestions for further changes. Results A total of 101 expert clinicians accepted the invitation and completed the first round with 73 (72%) completing all three rounds. Consensus statements were achieved on aspects of diagnosis, monitoring, intervention, post‐intervention management, and delivery. Key recommendations concerning the diagnosis of primary fetal pleural effusion include the use of ultrasound as the primary modality for identifying fetal pleural effusion and excluding secondary causes through detailed genetic, infectious, and metabolic evaluations. Management strategies emphasized thoracoamniotic shunting as the preferred intervention in hydropic fetuses with primary pleural effusion. Experts reached consensus that shunt placement could be offered as early as 16 weeks. No consensus was reached for isolated effusion without hydrops, as management was considered case‐dependent. The importance of ultrasonographic monitoring of fetal status at least weekly post‐intervention was strongly endorsed. Conclusion(s) The Delphi method facilitated the development of a consensus‐based protocol for diagnosing and managing primary fetal pleural effusion. These standardized guidelines are intended to enhance clinical practice across various settings, improve perinatal outcomes, and serve as a foundation for future research for this high‐risk fetal condition.

ABSTRACT Background Implementation of remote robotic‐assisted surgery (rRAS) has the potential to significantly improve access to high‐quality surgical care for patients worldwide. Advances in robotic systems and telecommunications now enable highly reliable, low latency, and cybersecure connectivity. These technological developments, together with the broader adoption of telemedicine, have driven an increasing interest in the implementation of rRAS. Methods The Clinical Robotic Surgery Association (CRSA) convened a conference to develop international clinical recommendations for rRAS using the Danish Model of Consensus. The society identified five key issue categories and invited a panel of experts to address specific questions for each. Panel members and a jury of 10 unbiased, non‐expert in rRAS professionals participated in a day‐long conference on November 19, 2025 (Los Angeles, USA). During the conference, participants presented, discussed, and reached consensus on specific guidelines relevant to each category. Immediately after the conference, the jury reviewed and approved the recommended guidelines. Results Multiple recommendations were approved for each of the following categories: Operating Models, Roles and Responsibilities (2 recommendations), Clinical Pathway (2 recommendations), Emergency Management (8 recommendations), Technical Considerations (5 recommendations), and Medico‐legal and Ethical Considerations (4 recommendations). Conclusions There was consensus that with recent advances in telecommunication and robotic technologies, rRAS can be offered safely and effectively if the identified safeguards are realized. Adoption of rRAS is expected to continue advancing rapidly.

Background: Greater trochanteric (GT) fractures after total hip arthroplasty (THA) are typically managed nonoperatively. However, outcome data for patient counseling remain limited. We evaluated the nonoperative results, focusing on fracture union rates and the presence of persistent limp in relation with fracture location, displacement magnitude, and direction. Methods: We retrospectively reviewed 82 postoperative GT fractures not associated with trochanteric osteolysis following primary THA performed between 1984 and 2020. The mean follow-up was 9 years. Fracture location was classified relative to the contralateral lesser trochanter as tip, waist, or base. Initial displacement, migration, final displacement, and bony union were assessed radiographically. Clinical outcomes included the presence of a persistent limp and Harris Hip Score. Multivariable analyses were performed to identify factors associated with nonunion and limp. Results: Fractures were classified as tip (n = 32), waist (n = 29), or base (n = 21). The mean initial displacement was 8.9 mm, with 43% displaced >10 mm. Initial displacement was significantly lower in base fractures (4.8 mm) compared with tip (10.1 mm) or waist (10.8 mm) fractures (p < 0.05). The mean final displacement was 14.6 mm. 45% of fractures achieved complete bony union, and 38% of patients demonstrated a persistent limp. In multivariable analysis, greater final displacement (>12 mm), and tip and waist fractures were independently associated with nonunion. Posterior fracture displacement was significantly associated with persistent limp. Conclusions: Outcomes following nonoperative management of GT fractures after THA depend on fracture morphology and displacement characteristics. Tip and waist fractures and fractures with final displacement >12 mm have a higher risk of nonunion, whereas posterior and superior displacement is associated with persistent limp. Greater than 20 mm of displacement is associated with both limp and nonunion. These findings may assist surgeons in counseling patients and in identifying fracture patterns at higher risk for adverse outcomes of nonoperative management. Level of Evidence: Level III (Prognostic Study). See Instructions for Authors for a complete description of levels of evidence.