Citations

Objective: To examine microsurgical outcomes of medial sporadic vestibular schwannoma (VS), defined as a spherical tumor within the cerebellopontine angle (CPA) without tubular internal auditory canal (IAC) extension, compared with a referent cohort of “typical” VS with IAC extension. Study design: Historical matched cohort study. Setting: Tertiary referral center. Patients: Forty patients with medial sporadic VS who met the inclusion criteria were each matched to 3 referent patients by age, CPA tumor size, preoperative hearing class, and surgical approach. Interventions: Microsurgical resection. Main outcome measures: Extent of resection, immediate and long-term postoperative facial nerve weakness (House-Brackmann grade >I), and long-term hearing preservation were compared between patients with medial VS and the referent cohort using conditional logistic regression. Results: Medial VS and matched patients with IAC extension were not statistically significantly different in nongross total extent of resection (OR: 1.04, 95% CI: 0.47-2.31), immediate (OR: 0.82, 95% CI: 0.40-1.67) or long-term (OR: 0.59, 95% CI: 0.23-1.48) postoperative facial nerve weakness, or long-term nonserviceable hearing (OR: 0.84, 95% CI: 0.17-4.22). Conclusions: In this matched cohort study of medial VS, we found no statistically significant differences in the extent of resection, facial nerve function, or hearing preservation between tumors with and without IAC extension.

According to the current WHO classification, noninvasive germ cell neoplasia of the testis comprises germ cell neoplasia in situ (GCNIS), specific forms of intratubular germ cell neoplasia, and gonadoblastoma. Because type II germ cell tumors (GCT, type II) arise from GCNIS, accurate detection of precursor lesions is diagnostically important. In preparation for the 2024 International Society of Urological Pathology (ISUP) Consensus Conference on genitourinary precursor lesions, which took place in Florence, Italy, an anonymous survey was distributed to ISUP members to assess current diagnostic practices regarding testicular precursor lesions. The literature and current WHO classification affirm the significance of precursor lesions in testicular tumours. Working Group 4—Precursor Lesions of the Testis—focused on their practical application by individual pathologists rather than establishing consensus from scientific data. There is strong agreement that GCNIS is the preferred and appropriate term for GCT precursor lesions and that its presence should be reported in cases of invasive GCT. Respondents also agree that “seminoma with intratubular nonseminoma” is the appropriate terminology for seminoma with an associated noninvasive nonseminomatous (embryonal carcinoma, yolk sac tumor, trophoblasts, or teratoma) component. Most pathologists prefer to use OCT3/4 as the primary immunohistochemical marker, and a panel was generally not considered necessary. No consensus is reached regarding the requirement for immunohistochemistry to confirm GCT precursor lesions in the testis. Three questions remain open: the value of subtyping intratubular lesions, the immunohistochemical approach to gonadoblastoma, and the criteria distinguishing Sertoli cell nodules from Sertoli cell tumors.

ABSTRACT Interactions between clinical pharmacists and industry partners continue to evolve as health care increases in complexity and technology assumes a more dominant role. To address the corresponding ethical challenges, the 2025 Industry Relations Committee of the American College of Clinical Pharmacy (ACCP) was charged with updating the 2008 ACCP position statement, Pharmacists and Industry: Guidelines for Ethical Interactions . This update expands its perspective, reflecting the broader and more influential roles pharmacists play across the health care ecosystem. All clinical pharmacist–industry interactions should be grounded in improving patient care. Through this lens, six recommendations are provided: (1) Pharmacists should not engage in industry partnerships or collaborations that might unduly influence objectivity, independence, or fairness in clinical and professional judgments; (2) Pharmacists should disclose and mitigate financial, consulting, or other relationships that constitute potential conflicts of interest and should not participate in activities where an existing conflict cannot be resolved; (3) Pharmacists who participate in industry‐sponsored research should follow accepted ethical, regulatory, and scientific standards; (4) Pharmacists providing continuing education programs or developing drug information materials should maintain control of content; ensure their content is fair, balanced, and free from bias; and disclose and mitigate any conflicts; (5) Formal instruction on ethical interactions with industry professionals should begin early and continue through all stages of pharmacist education, training, and professional development; (6) Pharmacists should maintain the confidentiality and privacy of patients and other health care professionals when working with industry partners. Questions to guide personal industry interactions are provided. This paper does not detail every emerging area (e.g., artificial intelligence, social media), but recommendations are applicable wherever clinical pharmacists leverage their professional expertise. By maintaining a critical, discerning, and ethical approach to industry collaborations, clinical pharmacists can uphold professional obligations while contributing to the advancement of evidence‐based practice, ultimately prioritizing patient welfare.

Introduction Cerebellar transcranial direct current stimulation (tDCS) combined with language therapy can aid in chronic aphasia recovery, but the neural mechanisms and biomarkers of treatment efficacy remain uncertain. Methods In this secondary analysis of data from a previously conducted clinical trial, we used a randomized, double-blind, sham-controlled, within-subject crossover design with a study sample of 19 participants with post-stroke aphasia. We assessed the degree to which baseline properties of cerebro-cerebellar white matter tracts can predict or moderate longitudinal treatment effects at three time points: post-treatment, 2 weeks post-treatment, and 2 months post-treatment. Tract properties were measured by fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI). We also tested whether there are differential effects between trained and untrained language tasks and between cerebellar tDCS polarity (anodal and cathodal). Results Baseline measures of tracts connecting the left lesioned cortex to the right posterolateral cerebellum (stimulation target) influenced treatment gains for untrained tasks, relative to sham control. In contrast, for the trained task, treatment gains were influenced by baseline measures of tracts connecting the non-stimulated left cerebellum with the contralateral right cerebral cortex. Although there were no consistent effects from cerebellar tDCS polarity, a highly consistent pattern emerged across all tasks and tracts. Specifically, language improvements were predicted by a baseline tract profile (i.e., higher FA and lower MD) typically associated with higher white matter integrity, especially within the context of stroke-induced white matter decline. Discussion These findings corroborate the potential for baseline tract properties as a biomarker of treatment efficacy and support the notion that adjuvant (cerebellar tDCS + language) therapy preferentially benefits individuals with relatively preserved structural connections within functionally relevant networks. Clinical trial registration ClinicalTrials.gov , identifier (NCT02901574).

Background and Objectives: Despite wide agreement on the importance of building research capacity to the specialty of family medicine, no standard exists for defining or measuring that growth. Previous work to address this gap yielded the Productivity and Capacity Evaluation in Research (PACER) Tool, a list of quantitative research metrics grouped into seven categories. We surveyed family medicine department chairs to understand which categories of PACER metrics they considered most valuable in evaluating their department’s research capacity. We also aimed to compare reported research capacity in 2024 with answers given by family medicine department chairs in 2021. Methods: A cross-sectional survey administered through the Council of Academic Family Medicine Educational Research Alliance (CERA) was used to gather information from family medicine department chairs in the United States and Canada. One question asked chairs to evaluate their department’s research capacity, and nine questions assessed the relative importance of the seven PACER Tool categories. Results: A total of 218 surveys were delivered, with 111 (50.9%) completed. Survey results demonstrated that program chairs determined funding to be the most impactful category. We found no clear trend in the second most important or least important categories. Results also showed no statistically significant change in reported research capacity between 2021 and 2024. Conclusions: Funding emerged as the category of research metrics viewed as most important by the greatest number of family medicine department chairs. Although other categories of metrics also were viewed as important, this survey demonstrated no clear pattern of their relative importance in this population.

Abstract Few prospective benchmark studies exist to characterize the evolving contemporary real-world practice for peripheral T-cell lymphoma (PTCL). We report the patterns of first-line care and outcomes for 720 patients with systemic PTCL enrolled in 2 related prospective cohort studies, Lymphoma Epidemiology of Outcomes (LEO) from 2015 to 2020 and Molecular Epidemiology Resource (MER) from 2002 to 2015, both followed to 2024. The primary end points were event-free survival (EFS) and overall survival (OS) using Kaplan-Meier estimator and Cox regression model. Secondary end points included correlations of clinical and treatment factors with survival. The most common induction regimens were CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) based (70%), given as CHOP (36%), CHOP plus etoposide (23%), or CHOP-like plus novel agents (11.5%, including 5% BV-CHP [brentuximab plus cyclophosphamide, doxorubicin, and prednisone]). Consolidative autologous stem cell transplant was performed in 102 patients (14%). Within nodal PTCL, EFS and OS were adversely associated with International Prognostic Index 2 to 5, prognostic index for T-cell lymphoma score 1 to 4, and non–anaplastic large-cell lymphoma (ALCL) subtypes. Within LEO, which captured increasing first-line etoposide and brentuximab vedotin, adding etoposide to CHOP was associated with better OS in anaplastic lymphoma kinase-negative ALCL. BV-CHP showed a trend toward OS improvement in ALCL. Patients failing EFS6 and EFS24 had 5-year subsequent OS of 12% and 17%, respectively. The inferior outcomes in non-ALCL subtypes and patients failing EFS6 and EFS24 highlight unmet needs with CHOP-based induction, where clinical trials with targeted therapy should be prioritized. This trial was registered at www.clinicaltrials.gov as NCT02736357.

Background Effective leadership is critical to the success of complex multidisciplinary healthcare organisations. As the organisation emerged from the global pandemic, Mayo Clinic recognised a need to transform its traditional, linear care model into a dynamic, platform-based approach to support its strategy. This required a new leadership model that could support and equip leaders with the skills needed to drive patient-centred healthcare transformation from within. Objective To develop and validate a new leadership competency framework capable of supporting future-ready leadership. Methods A multiphase, evidence-based approach was employed: (1) a visionary interview, goal setting and literature review; (2) focus groups with 23 leaders from across the organisation; (3) iterative competency framework development; and (4) a validation study involving a stratified sample of 129 physician leaders who rated competencies on importance and differentiation, and a qualitative verification by key stakeholders. Results Five core competencies with 23 behaviours were identified. The validation analysis established all behaviours as important for differentiating leadership performance. Stakeholder review confirmed the competencies were actionable and applicable across leadership roles at all levels. Conclusion The Leads Self, Leads Others, Inspires Others, Forward Thinking and Engages Others (abbreviated LLIFE) competency model positions a healthcare organisation to advance leadership excellence in a rapidly evolving healthcare environment that requires comprehensive transformation. It aligns with strategic goals, embeds values-based behaviours and supports continuous development, establishing a model that other healthcare institutions may learn from and adapt.

Abstract Background: Treatment for patients with triple-negative breast cancer (TNBC) relies on non-specific chemotherapy, underscoring the need for precision-based approaches. Our lab discovered that MALT1, the effector protein of the CARMA3-BCL10-MALT1 (CBM) signaling complex, is activated downstream of several oncogenic G protein-coupled receptors (GPCRs) implicated in breast cancer, including the thrombin (PAR1), angiotensin II (AGTR1), and lysophosphatidic acid (LPAR) receptors. When activated, MALT1 functions as a protease to cleave select protein substrates. Based on our finding that CBM activity in TNBC cells promotes tumor growth in immunocompetent but not in immunodeficient mouse models, we hypothesized that MALT1 protease activity induces a pro-tumor secretome that creates an immune-suppressed tumor immune microenvironment (TIME). Methods/Results: We confirmed by western that MALT1 protease is active in multiple human and mouse TNBC cell lines. Next, to identify MALT1-dependent secreted factors, we performed transcriptomic and proteomic analyses comparing TNBC cells treated with or without MALT1 protease inhibitors. We found that several secreted factors, including GM-CSF, CXCL1, and Pentraxin 3, were reduced by MALT1 protease inhibition. To assess the functional impact of the MALT1 protease-dependent secretome, we performed media transfer experiments comparing the effects of conditioned media (CM) from TNBC cells treated with or without MALT1 protease inhibitors. To account for species differences, experiments were performed evaluating human TNBC cell CM added to human PBMCs and mouse TNBC cell CM added to murine bone marrow cells. We found that the MALT1 protease-dependent secretome reduces the expression of iNOS in both human and murine macrophages. For use in validating our findings in human TNBC clinical specimens, we developed a “MALT1 protease active gene signature” using RNA-seq analysis. Conclusions/Future Directions: Our studies indicate that MALT1 protease activity in TNBC cells promotes expression of numerous immune-suppressive factors. In both human and mouse systems, blockade of MALT1 protease alters the tumor cell secretome and promotes an increase in expression of the anti-tumor M1-like marker iNOS in macrophages. Future studies will evaluate how this change in iNOS expression impacts functional properties of TNBC-associated macrophages. We will also assess the influence of the TNBC MALT1-dependent secretome on the TIME in vivo by comparing the effects of intratumoral injection of CM from MALT1 wild-type or MALT1 protease-deficient TNBC cells. Finally, we will utilize our MALT1 activity gene signature to evaluate TNBC clinical specimens for an association between MALT1 activity and tumor immune contexture, with an emphasis on tumor-associated macrophages. Our studies could nominate MALT1 protease as a potential therapeutic target for improving anti-tumor immunity in TNBC. Since multiple MALT1 protease inhibitors are in clinical trial, our findings could be rapidly translated to improve outcomes for patients with TNBC. Citation Format: John W. Little IV, Jeffrey A. Meridew, Dong Hu, Juliana Hofstätter Azambuja, Linda M. McAllister-Lucas, Peter C. Lucas. The GPCR-MALT1 protease signaling axis drives an immunosuppressive secretome in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr B046.