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Cardiovascular disease (CVD) is a significant health concern influenced by various determinants. Stigma and resilience have emerged as factors in CVD development and management. Women with HIV (WWH) have higher CVD rates than women without HIV. To improve cardiovascular health for WWH, a comprehensive understanding of how these factors interact, the understanding about individual awareness and willingness to engage in risk-reduction interventions are needed. Methods: As part of a study examining CVD risk among WWH aged >35 years old, 90-min focus groups were conducted (May 2022) in the English language. Focus groups aimed to elicit participants’ CVD risk knowledge and potential prevention strategies. Transcripts underwent a qualitative analysis. Results: Nineteen WWH participated in three focus groups. Participants experienced the following: (a) enacted stigma related to their HIV diagnosis (e.g., family, church member, healthcare staff); (b) a recent event (e.g., hospitalization of self/family, death in family, chest pain) triggered both heart health-promoting lifestyle changes and suboptimal health behaviors (e.g., COVID-19 pandemic: unhealthy snacking). Participants wanted to obtain more knowledge (“on a mission”) about CVD risk. In total, 100% expressed willingness to take medication or embark on other lifestyle changes to prevent future CVD events. Although participants identified preventative heart health behaviors (e.g., eating healthy foods; exercising; limiting stress, substances, and smoking), misconceptions were also identified (e.g., “catching” heart disease). Conclusions: Understanding the interplay of the different factors related to heart health is needed both at the provider and the patient level to inform interventions that reduce CVD risk amongst racial/ethnic minoritized women with HIV, living in the Southern region of the US.

ImportanceExposure to repetitive head impacts (RHI) is associated with increased risk for neurodegeneration. Accumulation of toxic proteins due to impaired brain clearance is suspected to play a role.ObjectiveTo investigate whether perivascular space (PVS) volume is associated with lifetime exposure to RHI in individuals at risk for RHI-associated neurodegeneration.Design, Setting, and ParticipantsThis cross-sectional study was part of the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of Chronic Traumatic Encephalopathy (DIAGNOSE CTE) Research Project, a 7-year multicenter study consisting of 4 US study sites. Data were collected from September 2016 to February 2020 and analyses were performed between May 2021 and October 2023. After controlling for magnetic resonance image (MRI) and processing quality, former American football players and unexposed asymptomatic control participants were included in analyses.ExposurePrior exposure to RHI while participating in American football was estimated using the 3 cumulative head impact indices (CHII-G, linear acceleration; CHII-R, rotational acceleration; and CHII, number of head impacts).Main Outcomes and MeasuresIndividual PVS volume was calculated in the white matter of structural MRI. Cognitive impairment was based on neuropsychological assessment. Linear regression models were used to assess associations of PVS volume with neuropsychological assessments in former American football players. All analyses were adjusted for confounders associated with PVS volume.ResultsAnalyses included 224 participants (median [IQR] age, 57 [51-65] years), with 170 male former football players (114 former professional athletes, 56 former collegiate athletes) and 54 male unexposed control participants. Former football players had larger PVS volume compared with the unexposed group (mean difference, 0.28 [95% CI, 0.00-0.56]; P = .05). Within the football group, PVS volume was associated with higher CHII-R (β = 2.71 × 10−8 [95% CI, 0.50 × 10−8 to 4.93 × 10−8]; P = .03) and CHII-G (β = 2.24 × 10−6 [95% CI, 0.35 × 10−6 to 4.13 × 10−6]; P = .03). Larger PVS volume was also associated with worse performance on cognitive functioning in former American football players (β = −0.74 [95% CI, −1.35 to −0.13]; P = .04).Conclusions and RelevanceThese findings suggest that impaired perivascular brain clearance, as indicated by larger PVS volume, may contribute to the association observed between RHI exposure and neurodegeneration.

Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive ductal and E-cadherin negative lobular morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct morphologies also have distinct biology and risk of recurrence. Our spatially resolved transcriptomic, genomic, and single-cell profiling revealed clinically significant differences between ductal and lobular tumor regions including distinct intrinsic subtype heterogeneity – e.g., MDLC with triple-negative breast cancer (TNBC) or basal ductal and estrogen receptor positive (ER+) luminal lobular regions, distinct enrichment of cell cycle arrest/senescence and oncogenic (ER and MYC ) signatures, genetic and epigenetic CDH1 inactivation in lobular but not ductal regions, and single-cell ductal and lobular subpopulations with unique oncogenic signatures further highlighting intraregional heterogeneity. Altogether, we demonstrated that the intratumoral morphological/histological heterogeneity within MDLC is underpinned by intrinsic subtype and oncogenic heterogeneity which may result in prognostic uncertainty and therapeutic dilemma.

2001 Background: Systemic treatments are limited for patients with meningiomas that have progressed after surgery and/or radiation. Loss of NF2and CDKN2A/Bare common in higher grade meningiomas and promote meningioma progression in preclinical models. We evaluated the efficacy of abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, as part of Alliance umbrella trial A071401, a genomically driven phase II study in recurrent or progressive meningiomas. Methods: Eligible patients (pts) with grade 2/3 tumors and NF2 mutations or CDK pathway alterations were treated with abemaciclib 200 mg orally twice daily until progressive disease. Two co-primary endpoints were used: progression-free survival at 6 months (PFS6) and response rate (RR) by Macdonald criteria; the trial would be declared positive if either endpoint was met. Twenty-four evaluable pts provided >85% power to detect a PFS6 >41.5% (vs. null 15%; alpha =0.02). The threshold for promising results for PFS6 was 8+/24 pts. For RR, 24 evaluable pts provided >89% power to detect RR >20% (vs. null 2.5%; alpha = 0.021). The threshold for promising results for RR was 3+/24 pts. Results: Of 83 pts screened while the abemaciclib arm was open between September 15, 2021 and October 3, 2022, 36 eligible pts received treatment. The mean number of treatment cycles administered was 7 and median follow-up since start of treatment was 11 months. The first 24 pts that met eligibility criteria and began treatment were considered evaluable for the primary endpoint analysis. Of the 24 pts evaluated, 58% were female and the median age was 62 years. The observed PFS6 rate was 54% (13/24 pts, 95% confidence interval 33-75%), thus the study met PFS6 endpoint. No objective responses were observed. Of the 36 pts who started treatment, eight had a grade 3 and two had a grade 4 adverse event at least possibly related to treatment. Grade 3 toxicities included anemia (2), neutropenia (2), leukopenia (1), blurry vision (1), diarrhea (2), fatigue (2), ALT elevation (1), dehydration (1), hyperkalemia (1), hyponatremia (1), dizziness (1), acute kidney injury (1), and thromboembolic event (1). Grade 4 toxicities included ALT elevation (1), AST elevation (1) and vomiting (1). Conclusions: Abemaciclib was well tolerated and resulted in an improved PFS6. The overall trial endpoint was met. Abemaciclib warrants further investigation for the treatment of patients with progressive grade 2/3 meningiomas. Support: U10CA180821, U10CA180882; UG1CA189867 (NRG Oncology); Eli Lilly; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02523014 .

TPS632 Background: Male breast cancer is a rare disease, and most cases are hormone receptor-positive (HR+). Due to a lack of clinical trials, male breast cancer has historically been treated based on data extrapolated from women. However, there are substantial knowledge gaps in the comparative efficacy, safety, and patient-reported outcomes of endocrine therapies for male breast cancer. While tamoxifen is the current standard of care, additional data are warranted for aromatase inhibitors (AI), gonadal suppression, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Methods: This is an open-label, multicenter, randomized, phase II trial designed to evaluate different endocrine therapies in men with HR+ and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. A total of 60 men will be enrolled across nine (9) sites within the Translational Breast Cancer Research Consortium (TBCRC). Key eligibility criteria include male sex and stage I, II, or III HR+/HER2- breast cancer before surgical resection of the primary tumor and axillary nodes. Key exclusion criteria include prior anti-cancer therapy for the current breast cancer or any other malignancy within the past 12 months, and inflammatory breast cancer. The trial has two phases. The first phase is a window of opportunity component in which newly diagnosed men are randomized 1:1:1 to either tamoxifen (Arm A), anastrozole (Arm B), or anastrozole plus degarelix (Arm C) given for three weeks. The primary endpoint for the window phase is Ki-67 reduction from the baseline diagnostic biopsy to the research biopsy at the end of the window phase. The second phase consists of neoadjuvant treatment, in which the tamoxifen group is randomized 1:1 to tamoxifen (Arm D) versus tamoxifen plus abemaciclib (Arm E), and the anastrozole alone (Arm B) and anastrozole plus degarelix (Arm C) groups are merged and then randomized 1:1 to anastrozole plus degarelix (Arm F) versus anastrozole plus degarelix plus abemaciclib (Arm G). The duration of the neoadjuvant phase is four (4) months, and the primary endpoint of this phase is residual cancer burden (RCB) index at time of surgery. The trial is powered for the RCB endpoint in a 2 x 2 factorial design to detect a 0.6 unit decrease in RCB index with 80% power and alpha=10%. For the Ki-67 endpoint, we assume an approximately 50% reduction in Arms A and B; Arm C will be of interest if it leads to ≥80% reduction in Ki-67. Secondary endpoints include: estradiol and testosterone levels at baseline, end of window, and during neoadjuvant phase; preoperative endocrine prognostic index (PEPI) score at surgery; adverse events; and patient-reported outcomes (including quality of life). Tumor tissue will be collected for correlative analyses. The study opened to enrollment at Dana-Farber in October 2023, and additional sites will open in 2024. Clinical trial information: NCT05501704 .

Abstract Background Alcohol is consumed by an estimated 137.4 million people in the United States 12 years of age and older, and, as a result, is estimated to have caused about 140 thousand deaths among people 20 to 64 years of age each year from 2015 up to and including 2019. Methods The proposed proposed review of the evidence on alcohol’s impact to health aims to produce conclusions to inform the Dietary Guidelines for Americans, 2026–2030. A multi-method approach will be utilized to formulate conclusions on (i) weekly (i.e., average) thresholds to minimize long-term and short-term risks of morbidity and mortality, (ii) daily thresholds to minimize the short-term risk of injury or acute illness due to per occasion drinking, (iii) alcohol use among vulnerable populations (e.g., pregnant women), and (iv) situations and circumstances that are hazardous for alcohol use. To inform expert discussions, this project will also include a systematic review of existing low-risk drinking guidelines, a systematic review of meta-analyses which examine alcohol’s impact on key attributable disease and mortality outcomes, and of estimates of the lifetime absolute risk of alcohol-attributable mortality and morbidity based on a person’s sex and average level of alcohol use. The preliminary conclusions produced as a result of this project will undergo public consultation, and data from these consultations will be analyzed using both quantitative and qualitative methods. The results of the public consultations will be used to further revise and refine the project’s conclusions. Discussion This project will establish a scientific consensus concerning alcohol’s impact on health. This consensus is imperative for informing the upcoming Dietary Guidelines for Americans, 2026–2030, and for better informing individuals about the health risks associated with alcohol use.

Abstract Unlike many other subspecialties in radiology, breast radiologists practice in a patient-facing and interdisciplinary environment where team building, communication, and leadership skills are critical. Although breast radiologists can improve these skills over time, strong mentorship can accelerate this process, leading to a more successful and satisfying career. In addition to providing advice, insight, feedback, and encouragement to mentees, mentors help advance the field of breast radiology by contributing to the development of the next generation of leaders. During the mentorship process, mentors continue to hone their listening, problem-solving, and networking skills, which in turn creates a more supportive and nurturing work environment for the entire breast care team. This article reviews important mentorship skills that are essential for all breast radiologists. Although some of the principles apply to all mentoring relationships, ensuring that every breast radiologist has the skills to be both an effective mentor and mentee is key to the future of the profession.

AbstractMeningeal solitary fibrous tumors (SFT) are rare and have a high frequency of local recurrence and distant metastasis. In a cohort of 126 patients (57 female, 69 male; mean age at surgery 53.0 years) with pathologically confirmed meningeal SFTs with extended clinical follow‐up (median 9.9 years; range 15 days–43 years), we performed extensive molecular characterization including genome‐wide DNA methylation profiling (n = 80) and targeted TERT promoter mutation testing (n = 98). Associations were examined with NAB2::STAT6 fusion status (n = 101 cases; 51 = ex5‐7::ex16‐17, 26 = ex4::ex2‐3; 12 = ex2‐3::exANY/other and 12 = no fusion) and placed in the context of 2021 Central Nervous System (CNS) WHO grade. NAB2::STAT6 fusion breakpoints (fusion type) were significantly associated with metastasis‐free survival (MFS) (p = 0.03) and, on multivariate analysis, disease‐specific survival (DSS) when adjusting for CNS WHO grade (p = 0.03). DNA methylation profiling revealed three distinct clusters: Cluster 1 (n = 38), Cluster 2 (n = 22), and Cluster 3 (n = 20). Methylation clusters were significantly associated with fusion type (p < 0.001), with Cluster 2 harboring ex4::ex2‐3 fusion in 16 (of 20; 80.0%), nearly all TERT promoter mutations (7 of 8; 87.5%), and predominantly an “SFT” histologic phenotype (15 of 22; 68.2%). Clusters 1 and 3 were less distinct, both dominated by tumors having ex5‐7::ex16‐17 fusion (respectively, 25 of 33; 75.8%, and 12 of 18; 66.7%) and with variable histological phenotypes. Methylation clusters were significantly associated with MFS (p = 0.027), but not overall survival (OS). In summary, NAB2::STAT6 fusion type was significantly associated with MFS and DSS, suggesting that tumors with an ex5::ex16‐17 fusion may have inferior patient outcomes. Methylation clusters were significantly associated with fusion type, TERT promoter mutation status, histologic phenotype, and MFS.

Subharmonic aided pressure estimation (SHAPE) is a technique that utilizes subharmonic signals from microbubble contrast agents for pressure estimation. Validation of the SHAPE technique relies on synchronous measurements of in vivo pressures using contrast microbubbles and a pressure catheter (reference standard). For the guidance and placement of pressure catheter in vivo, iodinated contrast is used with fluoroscopy. Therefore, during data acquisition for validation studies of the SHAPE technique, both contrast microbubbles and iodinated contrast are present simultaneously within the vasculature. This study aims to elucidate the effects of iodinated contrast (Visipaque, GE HealthCare) on subharmonic signal amplitude from contrast microbubbles (Definity, Lantheus Medical Imaging, Inc.). In an acrylic water tank, 0.06 mL of Definity and varied amounts of Visipaque (0.14, 0.43, 0.85, and 1.70 mL) were added to 425 mL of deionized water. Ultrasound scanning was performed with a SonixTablet scanner (BK Medical Systems) using optimized parameters for SHAPE with Definity ( f transmit/receive = 3.0/1.5 MHz; chirp down pulse). Subharmonic data was acquired and analyzed at 9 different incident acoustic outputs ( n = 3). Results showed an increase in subharmonic signal amplitude from Definity microbubbles in the presence of 0.14 mL Visipaque by 2.8 ± 1.3 dB ( p < .001), no change with 0.85 mL Visipaque (0.7 ± 1.2 dB; p = .09) and a decrease in subharmonic amplitude in the presence of 1.70 mL Visipaque by 1.9 ± 0.7 dB ( p < .001). While statistically significant effect on subharmonic signal amplitude of Definity microbubbles was noted due to the mixture, the magnitude of the effect was minimal (~2.8 dB) and unlikely to impact in vivo SHAPE measurements.