Citations

Introduction: Transcranial magnetic stimulation (TMS) is a promising intervention for adolescents with treatment-resistant depression (TRD). However, the durability of TMS-related improvement in adolescents is unclear. This 6-month study followed adolescents with TRD who had responded to TMS and provided TMS retreatment for adolescents with a partial relapse. Methods: The study enrolled adolescents (12–21 years) with TRD who had at least a partial response to sham or active TMS in a randomized controlled trial. Partial response was defined as ≥25% reduction of Hamilton Depression Rating Scale-24 (HAMD24). Participants with a partial relapse (≥1 point increase in Clinical Global Impression–Severity) received retreatment with daily 10 Hz TMS sessions until depressive symptom severity returned to the baseline score or after 30 TMS treatments. Results: There were 84 eligible participants, 66 were enrolled, and 41 completed the 6-month study. Twenty-eight participants (42%) were retreated with TMS. TMS retreatment courses had a mean of 22 sessions. At the 6-month follow-up, the complete sample exhibited reduced depressive symptoms (mean HAMD24 of 5.24) compared with baseline at entry into follow-up (mean HAMD24 of 8.21). Baseline depressive symptom severity was positively correlated with the risk of partial relapse, while the number of previous TMS interventions showed no correlation with the risk of partial relapse. TMS was well tolerated. Conclusions: This is the largest, long-term follow-up study with TMS retreatment for adolescents with TRD. These findings demonstrate the feasibility and clinical effects of a TMS retreatment protocol for adolescents with TRD, following a standard course of acute TMS.

ObjectiveTo determine which ear environment risk factors impact ossiculoplasty hearing outcomes and to generate a statistically‐valid grading system for ossiculoplasty outcome reporting.Study TypeRetrospective case series.MethodsA multi‐institutional database was generated from cases performed between 2011 and 2019. Preoperative and postoperative hearing thresholds were recorded alongside potential ear environment risk factors. Multiple variable linear regression statistical analyses of risk factors were applied to determine independent association with postoperative pure tone average air‐bone gap (PTA‐ABG). Significant factors were used to generate a statistically‐weighted grading scale of Ear Environment Risk (EER).Results1679 cases had a mean follow‐up time of 33.6 months (SD 36.3) and a mean postoperative PTA‐ABG of 21.2 (SD 12.8). Multiple revision status (p < 0.001), presence of canal wall down mastoidectomy cavity (p = 0.020), absent malleus (p < 0.001), absent stapes superstructure (p = 0.016), frequent otorrhea (p = 0.008), pediatric age (p < 0.001), and blunted/lateralized tympanic membrane (p = 0.003) were independently correlated with PTA‐ABG. These factors were incorporated into an EER Scoring System with four distinct risk groups wherein each risk group was significantly correlated with PTA‐ABG, and this grading system was better correlated with PTA‐ABG (Kendall's τ = 0.193) than other existing published grading scales.ConclusionGrading environment risk according to a novel EER scoring system generates meaningful risk groupings that correlate with ossiculoplasty postoperative PTA‐ABG, and this holds potential to frame reporting of hearing outcomes for future ossiculoplasty research.Level of Evidence3 Laryngoscope, 135:S1–S11, 2025

Introduction: The Mindfulness-Based Stress Reduction program for breast cancer survivors (MBSR [BCs]) is a stress-reducing program designed to increase cognitive functioning through four meditational practices. This randomized clinical trial aimed to determine if improvements in cognitive functioning and perceived cognitive abilities achieved from the MBSR(BC) were mediated through increased mindfulness, decreased rumination, and decreased perceived stress. Methods: Breast cancer survivors (BCSs) who met inclusion criteria of stage I, II, or III BC and received either chemotherapy (CT) or both CT and radiation were randomized to either the 6-week MBSR(BC), or Breast Cancer Education Support (BCES) program, or to a usual care (UC) regimen. Analysis of covariance was first implemented to identify potential mediators, followed by a formal mediational analysis to evaluate the effects of MBSR(BC) on 6-, 12-, and 26-week outcomes. Results: After consent, 212 BCS were randomized to MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31). The mean age was 56.5 and the majority of the BCS, 73.1%, were White and non-Hispanic. Results showed increases in “observing” as part of mindfulness as a potential mediator of MBSR(BC) effects on impairments on quality of life and logical memory at 6 months relative to UC. No mediation effects were identified for outcomes measured at 6 or 12 weeks and also when MBSR(BC) was compared with the BCES program. Discussion: These results partially supported our hypothesis that improvement in cognitive functioning would occur through increased mindfulness. Although few mediating relationships were identified, results showed a relationship between mindfulness and cognitive functioning. Both mediating relationships occurred through increases in “observing,” a subconcept of “mindfulness,” when compared to the MBSR(BC) with UC at 6 months. This study shows that mediators may help “optimize” clinical therapeutic treatment effects, thus contributing to the advancement of science. Trial Registration: ClinicalTrials.gov, www.ClinicalTrials.gov . Registration Number: NCT02786797.

Abstract The overall goal of the Alzheimer's Disease Neuroimaging Initiative (ADNI) is to optimize and validate biomarkers for clinical trials while sharing all data and biofluid samples with the global scientific community. ADNI has been instrumental in standardizing and validating amyloid beta (Aβ) and tau positron emission tomography (PET) imaging. ADNI data were used for the US Food and Drug Administration (FDA) approval of the Fujirebio and Roche Elecsys cerebrospinal fluid diagnostic tests. Additionally, ADNI provided data for the trials of the FDA‐approved treatments aducanumab, lecanemab, and donanemab. More than 6000 scientific papers have been published using ADNI data, reflecting ADNI's promotion of open science and data sharing. Despite its enormous success, ADNI has some limitations, particularly in generalizing its data and findings to the entire US/Canadian population. This introduction provides a historical overview of ADNI and highlights its significant accomplishments and future vision to pioneer “the clinical trial of the future” focusing on demographic inclusivity. Highlights The Alzheimer's Disease Neuroimaging Initiative (ADNI) introduced a novel model for public‐private partnerships and data sharing. It successfully validated amyloid and Tau PET imaging, as well as CSF and plasma biomarkers, for diagnosing Alzheimer's disease. ADNI generated and disseminated vital data for designing AD clinical trials.

Abstract The antiapoptotic protein, myeloid cell leukemia-1 (Mcl-1), contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models. This dose escalation study evaluated voruciclib in patients with previously treated hematologic malignancies. Initially, voruciclib was administered daily, continuously, on a 28-day cycle (group 1). After 2 patients with prior allogeneic stem cell transplantation had a dose-limiting toxicity (DLT) of interstitial pneumonitis at 100 mg, voruciclib administration was changed to days 1 to 14 of a 28-day cycle (group 2). Forty patients, 21 with AML and 19 with B-cell malignancies, were enrolled. Patients had a median of 3 prior lines of therapy (range, 1-8). Dose escalation in group 2 was stopped at 200 mg, a dose that achieved plasma concentrations sufficient for target inhibition, without DLTs observed. The most common adverse events were diarrhea (30%), nausea (25%), anemia (22%), fatigue (22%), constipation (17%), dizziness (15%), and dyspnea (15%). In AML, 1 patient achieved a morphologic leukemia-free state, and 2 had stable disease. Voruciclib treatment led to a decrease in MCL1 messenger RNA expression, downregulation of myelocytomatosis (MYC) and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase 2. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax for patients with previously treated AML. This trial was registered at www.clinicaltrials.gov as #NCT03547115.

Abstract As the healthcare burden caused by an increasingly aging population rapidly rises, a pressing need exists for innovative geroscience research that can elucidate aging mechanisms and precipitate the development of therapeutic interventions to support healthy aging. The Fifth Annual Midwest Aging Consortium Aging Research symposium, held from April 28 to 30, 2024, was hosted by The Ohio State University in Columbus, Ohio, and featured presentations from investigators across the Midwestern United States. This report summarizes the research presented at the symposium, whose topics included cellular senescence and the aging brain, metabolism and metabolic interventions, nutrition, redox mechanisms and biomarkers, and stress mechanisms. Abstract presentations and short talks highlighted early-stage and young investigators, whereas 2 keynote presentations anchored the symposium. Overall, this symposium showed the robustness of aging research in the Midwest and underscored the advantages of a collaborative approach to geroscience research.