Citations

Importance Currently, there are no standardized outcome domains or measures in clinical trials for facial aging. Heterogeneity in outcome domains and measurement instruments across clinical trials creates difficulty in directly comparing interventions, determining superior therapies, and developing high-quality meta-analyses. Objective To develop a core outcome set (COS) of essential domains to be reported in clinical trials evaluating the efficacy of interventions for facial aging. Evidence Review PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials, and CINAHL were searched from September 2005 to September 2015. An updated search of the same databases was performed from September 2015 to February 2026. Studies were included if (1) they were randomized clinical trial or controlled clinical trial in design, (2) they assessed the efficacy or safety of an intervention for facial aging, (3) they were published in English, and (4) they involved human participants. Complementary sources, including patient interviews, were used to capture further relevant outcomes. Two rounds of Delphi surveys, followed by consensus meetings, were used to identify outcome domains considered most important by both patient and physician stakeholders. Findings The final COS consists of 6 outcome domains: (1) overall convenience of treatment; (2) time to return to normal work and social activity; (3) overall assessment of focused area of treatment (at the point in time when treatment is expected to provide peak benefit); (4) duration of treatment effect; (5) severity of persistent local or systemic adverse events, including pigmentary change, skin texture change, delayed healing, scarring, and serious adverse events; and (6) patient satisfaction with treatment. Conclusions and Relevance The 6 outcome domains identified through a Delphi consensus are recommended for reporting in future facial aging trials to ensure that outcomes that matter most to patients and clinicians are measured and that results are comparable across interventions.

Abstract Studies have reported conflicting findings regarding the contribution of germline variants or somatic genomic drivers to racial disparities in multiple myeloma. To comprehensively investigate somatic drivers in relation to inherited genetics in multiple myeloma, we combined newly sequenced whole-genome sequencing data with publicly available datasets (total n = 1,286). Overall, we did not identify germline or somatic genomic differences that explain the different risk of developing multiple myeloma between patients with genetic similarity to African (AFR) or European (EUR) reference populations. A difference in the detectability and timing of APOBEC-associated and germinal center mutational activity was observed. Integrating epidemiologic data and mutational signature-based temporal estimates, we challenge the assumption that individuals in the AFR group develop multiple myeloma at a younger age. Finally, we demonstrate that, with equal access to efficacious therapies, patients in the AFR and EUR groups have equivalent clinical outcomes. Significance: Multiple myeloma is reported to occur at higher rates in individuals who self-identify as non-Hispanic Black. In this large dataset, genomic drivers occur at the same rate among ancestry groups, except for APOBEC mutagenesis. With equivalent therapy, clinical outcomes did not differ for patients grouped by genetic ancestry similarity.

ABSTRACT Reversion mutations (REVs) restore homologous recombination repair (HRR) and confer resistance to PARP inhibitors (PARPi) in HR-deficient cancers. Yet, their prevalence, mechanisms, and biological constraints remain undefined. We analyzed genomic profiling of 609,464 tissue and liquid biopsy samples across multiple cancer types to delineate the pan-cancer landscape of REVs. REVs were identified in eight HRR genes, most frequently BRCA2 and BRCA1 and notably never in ATM or CHEK2 . REVs exclusively impacted truncating pathogenic variants, predominantly through large in-frame and exon-level deletions, associated with repetitive sequences. Conserved functional domains are relatively depleted of REVs. Structural modeling and functional studies support that exon-level deletions preserve critical domain architecture and confer PARPi resistance. The study establishes HRR reversion as a structurally permissive, yet evolutionarily constrained, resistance mechanism with implications on response, monitoring, and therapeutic strategy. One Sentence Summary Homologous recombination reversion evolves through structurally tolerated, microhomology-driven alterations that restore DNA repair under therapeutic selection across cancers.

Autoimmune diseases arise when B and T lymphocytes lose tolerance to self. Yet in most disorders, the underlying molecular determinants, including autoantibodies, epitopes and lymphocyte clones that drive tissue injury remain undefined. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare and often fatal pediatric neuroendocrine syndrome with strong evidence of antigen-driven paraneoplastic autoimmunity, including association with the intracellular autoantigen ZSCAN1. However, the effector immune circuit and the epitope-level determinants operating within the hypothalamus and brainstem have remained unknown. To address this challenge in ROHHAD and more broadly in autoimmune disease, we developed the Autoimmune Epitope and immunoGlobulin/Immune-receptor identification System (AEGIS), an integrated framework that links immune repertoires to their cognate self-epitopes. AEGIS combines B cell and T cell receptor profiling from sites of tissue injury with high-resolution epitope mapping, direct sequencing of antigen-specific autoantibodies, in silico antibody-antigen folding, selection, and T cell antigen discovery. Applied to a deeply phenotyped child with ROHHAD, AEGIS revealed a compartmentalized, clonally restricted immune response in which brain-deposited IgG and expanded cerebrospinal fluid B cell and CD4 T cell clonotypes converged on shared ZSCAN1 epitopes, resolved to minimal determinants and peptide-MHC ligands. These findings provide a clone- and epitope-linked mechanistic map of ROHHAD autoimmunity and establish a generalizable framework for identifying candidate pathogenic clones and antigens across diverse autoimmune diseases.

Background: Little is known about how silicone metacarpophalangeal (MCP) arthroplasty outcomes compare between rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Methods: Using our single institutional data from 2000 to 2022, we propensity matched 46 primary silicone MCP arthroplasties in 33 OA patients 1:2 to 92 arthroplasties in 54 RA patients based on age, sex, body mass index, operative digit, and if the surgery was on the dominant hand. We used Kaplan-Meier estimates and cluster-robust Cox proportional hazard models to compare survival free from revision, all-cause reoperation, and development of coronal plane deviation >10°. Results: There was comparable 10-year survival free of revision (94% OA, 91% RA) and all-cause reoperation (91% OA, 87% RA), with no difference in risk for each outcome between groups. Revision in OA patients occurred early (mean 0.6 years) for recurrent deformity (n = 2) and periprosthetic joint infection (n = 1). Revision in the RA cohort occurred later (mean 6.3 years postoperatively) for recurrent deformity (n = 3) and dislocation (n = 1). Osteoarthritis patients had less coronal plane deviation at the final radiographic follow-up (6.5° vs 16.2°, P < .001), higher 10-year survival free from coronal deviation > 10° (79% vs 17%), and lower risk of progressive coronal deformity (hazard ratio 0.15, P < .001). Conclusions: Silicone MCP arthroplasty remains a durable option with low reoperation rates for RA and OA. Osteoarthritis patients experience less coronal deviation and late reoperation for deformity than RA patients, likely due to their more robust soft-tissue stabilizers and noninflammatory disease process.

Abstract Purpose: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor, with a median survival of only 15 months. Effective therapeutic advances remain limited, with few clinical trial patients exhibiting robust responses to experimental therapies. This has led to efforts to identify molecular biomarker signatures capable of stratifying patient responses either prognostically (pre-treatment) or diagnostically (post-treatment). This study aims to assess the robustness and reproducibility of published transcriptional GBM biomarker signatures for predicting clinical outcomes in GBM trials. Methods: We analyzed published RNA-seq data from 4 clinical trials involving oncolytic virotherapy and immune checkpoint inhibitors, as well as multiple cohorts of patients treated via the Stupp protocol. The performance of reported immune gene signatures was evaluated across all datasets using both grouped and continuous survival modeling. Intra-patient signature variation between different biopsy sites and timepoints was assessed using longitudinal, multi-site sampling collected by the Break Through Cancer Accelerating GBM Therapies TeamLab. LASSO, multivariate Cox regression, and risk scoring with FDR adjustment were used to identify novel signatures with cross-cohort utility. Key Findings: No single published signature consistently predicted survival across all analyzed trials. A post-treatment ssGSEA antitumor cytokine signature that was associated with survival in the CAN-3110 OV trial (R = 0.74, p &lt; 0.01) was also significantly associated with improved survival in an adjuvant anti-PD1 trial (R = 0.75, p = 0.03) and neoadjuvant anti-PD1 trial (R = 0.30, p = 0.05), but not in standard-of-care controls. PAM clustering of MCP immune signatures, as reported for the DNX-2401 OV+Anti-PD1 trial, also stratified post-treatment survival in the CAN-3110 OV trial (p &lt; 0.01), with the coldest TME subtype consistently predicting worse survival. However, the prognostic value of the most immune enriched TME subtype was inconsistent and did not extend to the Anti-PD1 trials. Furthermore, multi-site, longitudinal biopsy samples revealed marked heterogeneity in biomarker signatures between biopsies from individual patients, even when assessed at the same timepoint. We’ve identified several candidate transcriptomic signatures that show promise for generalizable prognostic value in GBM patient cohorts and are characterizing their spatiotemporal variability. Conclusions: While no individual immune signature is universally predictive in GBM immunotherapy, certain post-treatment cytokine signatures and TME stratifications are significant in multiple immunotherapy contexts, though not in standard-of-care patient cohorts. Marked spatiotemporal heterogeneity in these signatures underscores the need for composite prognostic markers resilient to sampling variance. Citation Format: Christopher M. Jannotta, C Zoe Linke, Charles A. Whittaker, Vikas Patil, Accelerating GBM Therapies TeamLab, Farshad Nassiri, Gelareh Zadeh, E Antonio Chiocca, Alexander L. Ling. Assessing biomarker reproducibility for glioblastoma patient response stratification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1055.

Abstract Introduction The effectiveness of temporary uterine artery ligation (TUAL) in reducing blood loss during laparoscopic myomectomy (LM) is uncertain, despite increased use as an adjunct to improve surgical safety. This study aims to evaluate the safety and efficacy of TUAL in LM for the management of uterine myomas. Material and Methods We conducted a systematic review and meta‐analysis of comparative studies evaluating LM with and without TUAL. Electronic databases were searched up to October 7, 2024. Eligible studies were randomized controlled trials or observational comparative studies published in English that reported at least one primary outcome. The primary outcomes were intraoperative estimated blood loss and perioperative change in hemoglobin. Secondary outcomes included operative time, number and size of myomas removed, length of hospital stay, recurrence, and complication rates. Data extraction and analysis were performed using a random‐effects model. This review was registered prospectively with PROSPERO (CRD42024595684). Results Seven studies met the inclusion criteria, comprising five randomized controlled trials and two retrospective case–control studies, with a total of 857 women (352 undergoing LM with TUAL and 505 undergoing LM alone). TUAL was associated with a reduction in intraoperative estimated blood loss (mean difference [MD]: −84.7 mL; 95% Cl: −89.0; −80.0) and postoperative reduction in hemoglobin level (MD: −0.4 g/dL; 95% Cl: −0.7; −0.2) compared with LM without TUAL. However, TUAL was associated with increased operative time (MD: 16.5 min; 95% Cl: 3.4; 29.6). Conclusions TUAL appears to be a possible adjunct to LM for selected patients in the management of uterine myomas. Our study demonstrated that TUAL with LM could be associated with a reduction in estimated blood loss, despite an increase in operative time. Nonetheless, further studies with a larger sample size and long‐term follow‐up, as well as stratification of outcomes based on ligation technique, are warranted to elucidate the benefits of TUAL.

Background: Anti-cyclic citrullinated peptide antibodies (ACPAs) are associated with more aggressive rheumatoid arthritis disease. We aimed to determine the effect of ACPA serostatus on survival free from revision, all-cause reoperation, and recurrence of coronal plane deformity in patients with rheumatoid arthritis (RA) undergoing silicone metacarpophalangeal (MCP) arthroplasty. Methods: We retrospectively identified silicone MCP arthroplasties performed in patients with RA with known ACPA serostatus from 2000 to 2022. Kaplan-Meier estimates were used to report survival free from revision, all-cause reoperation, and recurrence of coronal plane deviation >10° on postoperative radiographs. We analyzed ACPA serostatus as a risk factor for these endpoints using cluster-robust Cox proportional hazard models, adjusting for patient sex. Results: We included 133 joints in 39 ACPA seropositive patients (9.0 years mean follow-up) and 63 joints in 21 ACPA seronegative patients (5.7 years mean follow-up). Survival free from revision, all-cause reoperation, and recurrent coronal deformity was higher in seropositive patients than in seronegative patients. Anti-cyclic citrullinated peptide antibody seropositivity was significantly associated with lower risk for revision (hazard ratio [HR] = 0.16), all-cause reoperation (HR = 0.20), and recurrent coronal plane deviation >10° (HR = 0.28). Seropositive patients had longer average time to recurrent coronal deviation >10° (3.5 years vs 1.3 years) and less coronal deviation at final radiographic follow-up (15.9° vs 21.5°). Conclusions: Anti-cyclic citrullinated peptide antibody seropositivity is associated with improved silicone MCP implant survivorship and lower risk of recurrent coronal plane deformity in patients with rheumatoid arthritis. More work is needed to better understand the biologic basis of these findings.