Citations

Prostate-specific antigen (PSA) screening has played a critical role in reducing prostate cancer mortality but remains controversial due to concerns regarding overdiagnosis, overtreatment, and inconsistent screening guidelines. In 2012, the United States Preventive Services Task Force (USPSTF) issued a grade D recommendation against PSA screening, leading to a national decline in PSA testing and prostate biopsy rates. This was followed by an increase in the incidence of metastatic prostate cancer at diagnosis. The USPSTF has since revised its recommendation to grade C, emphasizing shared decision-making for men aged 55 to 69 years. However, variability in screening recommendations across professional societies has resulted in clinical uncertainty, particularly for primary care physicians (PCPs), who frequently initiate PSA testing and urology referrals. This review provides an evidence-based overview of PSA screening tailored for the PCP. We performed a comprehensive literature review using Ovid MEDLINE, PubMed, Embase, and the Cochrane Library, including systematic reviews published between January 2020 and April 2025, and current guidelines from the American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EAU), and American Cancer Society (ACS). We summarize the evolving landscape of PSA screening and its integration with contemporary tools such as shared decision-making, multiparametric magnetic resonance imaging (mpMRI), and transperineally targeted biopsy. We advocate for initiating PSA screening between the ages of 45 and 49 in men with average or elevated risk, based on long-term evidence demonstrating the value of an early baseline PSA level and risk-stratified follow-up. This approach, coupled with improved diagnostic tools, can help PCPs navigate guideline variability and implement a rational, common-sense strategy to maximize early detection while minimizing harm.

Abstract Geroscience research benefits from interdisciplinary approaches, team science, and collaborations, which collectively facilitate the discovery of aging mechanisms and their translation into tangible, clinical interventions. Since its inception in 2019, the Midwest Aging Consortium (MAC) has provided an engaging platform for aging researchers in the United States’ Midwest to connect, collaborate, and exchange ideas. The Sixth Annual Research Symposium of the MAC held at the Mayo Clinic in Rochester, Minnesota, in April 2025 highlighted the continued impact of the MAC in bringing together aging researchers, including many trainees and early career investigators, into a collaborative environment. This record-setting event featured interdisciplinary research on key aging mechanisms, including lipid metabolism, mitochondrial dysfunction, stress response, cellular senescence, and immune adaptations across organ systems. New therapeutic concepts and clinical trial approaches were presented. Cutting-edge methodologies including single-cell and spatial transcriptomics, metabolomics, and organoid cultures, to dissect aging process in tissue-specific and systemic contexts also were presented. Overall, the MAC symposium underscored the translational potential of geroscience and reinforced the MAC’s mission to accelerate aging research through regional collaborations and innovation.

Hearing loss is a highly prevalent disease state affecting almost 1 in 5 individuals globally. Growing research shows that untreated or undertreated hearing loss carries significant long-term sequelae, including increased risk of social isolation, depression, and cognitive decline, among other ramifications. Limited awareness and common misperceptions among the general US adult population and primary care providers contribute to low rates of referral to hearing specialty clinics and underutilization of hearing aids, cochlear implants, and other rehabilitative devices. Comprised of diverse membership, the Hearing Health Collaborative (HHC) was formed in May 2021 to identify and overcome challenges impacting good health care practices and public policy on hearing care in connection with healthy aging. This editorial documents a recent outcome of the HHC derived from a structured A3 process. Specifically, initiative 2, a proposal to develop a simple, clinically anchored staging system primarily for use by frontline providers and patients, is presented. Unlike other common disorders that harbor long-term health sequelae, a corresponding pragmatic clinical staging system—leveraging precedent disease staging convention, based on clinically meaningful outcomes and prognosis for acquired hearing loss—does not exist. The development of this staging system will potentially allow for improved communication across providers and patients, facilitate referral pathways, and ultimately enable patient access to timely and appropriate care.

Traumatic brain injury (TBI) is one of the leading causes of death and neurological disability worldwide. The search for biomarkers that indicate TBI severity and prognosis with greater accuracy is ongoing. This study aimed to evaluate the significance of several neuroinflammatory cytokines and chemokines, assessing their potential as biomarkers in pediatric TBI (pTBI). This was an exploratory analysis of inflammatory cytokines and chemokines measured in a subset of 26 children aged 0–18 years with TBI and 21 controls. TBI severity was determined by GCS. The functional outcome was measured via the GOS-E score at 6 weeks and 3, 6, 9, and 12 months post-injury. Serum samples were analyzed for ICAM-1, VCAM-1, SAA, CRP, IFN-g, IL-10, IL-12p70, IL-13, IL-1b, IL-2, IL-4, IL-6, IL-8, TNF-a, TNF-b, eotaxin, eotaxin-3, IP-10, MCP-1, MCP-4, MDC, MIP-1a, MIP-1b and TARC. Levels of IL-6, IL-10, IL-13, IL-16, MDC, and GM-CSF were increased, and IFN-γ, IL-5, IL-8, and eotaxin-3 were decreased at enrollment when compared with controls. Elevated IL-6 and IL-10 at enrollment were associated with severe TBI (AUC of 1, p = 0.0002 and p = <0.0001, respectively). IL-6, IL-10, IL-16, and TNF-β at enrollment and IL-5 at 24 h were elevated in children with unfavorable outcomes, with an AUC > 0.8, suggesting biomarker potential. Our data indicate that several cytokines and chemokines measured after TBI may aid in the assessment of pTBI severity and prognosis. IL-6, IL-10, and IL-16 may show potential as biomarkers for pTBI severity and outcomes.

Abstract Objectives There are striking differences among caregivers of people with dementia in their health and well-being during active caregiving and after caregiving has ended. A key factor influencing caregiver health is the emotional quality of the caregiver–care recipient relationship, which may be reflected in the emotional language caregivers use when describing this relationship. The present study assessed whether caregivers’ positive and negative language is associated with their current and future depression trajectories. Methods Active caregivers responded to an open-ended question about a recent time they felt connected to the care recipient. We summed the number of positive and negative emotion words and divided them by the total words in the response. We evaluated whether caregivers’ emotional language (a proxy for the emotional quality of the caregiver–care recipient relationship) was associated with their depression assessed both concurrently (N = 347 active caregivers) and longitudinally (N = 224 former caregivers). Results Neither positive nor negative emotional language significantly correlated with caregiver depression during active caregiving. Structural equation modeling revealed caregivers’ greater positive emotional language (accounting for baseline depression) was associated with less steep increases in depression after the care recipient’s death. Results were robust when accounting for negative emotional language and covariates. Negative emotional language was not significantly associated with changes in caregiver depression. Discussion Caregivers who use more positive words when describing their connection with the care recipient may be more resilient, underscoring the potential role of positive emotional qualities of the caregiving relationship in preserving caregivers’ mental health after caregiving ends.

PURPOSE To compare patient-reported and clinical outcomes between radical cystectomy (RC) and bladder-sparing therapy (BST) in patients with recurrent high-grade non–muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS This pragmatic, prospective observational cohort study was designed with patients, who selected and prioritized outcomes. Eligible adults were candidates for both RC or BST, had previous induction Bacillus Calmette-Guérin (BCG), and received their last treatment within 12 months. The primary outcome was the EORTC-QLQ-C30 physical function scale at 12 months. Secondary outcomes included other EORTC-QLQ-C30 scales, depression, anxiety, bladder cancer–specific quality of life (QOL), financial burden, and cancer-specific outcomes. Targeted maximum likelihood estimation (TMLE) was used to calculate average treatment effect (ATE) estimates between arms. Inverse probability weighted risk ratios (wRR) were calculated using quasi-Poisson regression. RESULTS Of 570 participants (mean age 71.4 years; 21% female), 371 selected BST and 199 selected RC. Physical function was significantly worse in the RC arm at 3 months; by 9 months, there was no difference between arms, and at 12 months, physical function did not differ (ATE, 0.9; 95% CI, –0.6 to 2.4; P = .22). RC was associated with better emotional function, generic health-related QOL, and financial burden, and lower depression and anxiety, while BST was associated with better bowel and sexual health. Cancer-specific survival was 99% for BST versus 96% for RC (wRR, 0.99; 95% CI, 0.97 to 1.01). RC was associated with a higher risk of adverse events and serious adverse events, including a 90-day mortality rate of 2.5%. CONCLUSION Most patient-prioritized outcomes were similar or better among participants who chose RC compared with BST. These findings support the continued role of RC in managing recurrent high-grade NMIBC.

Carotid blowout is the rupture of a carotid artery or branch vessel, a dangerous complication in post-treatment head and neck cancer patients. The purpose of this retrospective case review is to identify imaging features suggestive of eminent carotid blowout on routine surveillance post-treatment neck imaging, so that a prompt neuroendovascular consult is obtained and the patient is preemptively treated, thus improving patient outcomes. It is important to carefully interrogate the carotid vessels with appropriate window/leveling for irregularity, adjacent tissue ulceration, exposed vessel to either air or fluid, surrounding tumor, and pseudoaneurysm.

PURPOSE Low-grade serous carcinoma (LGSOC) of the ovary, fallopian tube, or peritoneum is a hormonally driven, relatively chemoresistant malignancy with limited treatment options in the recurrent setting. Given frequent estrogen receptor (ER) expression and dysregulation of the cyclin-dependent kinases 4 and 6 (CDK4/6)–p16–Rb pathway, features shared with hormone receptor–positive breast cancer, dual endocrine, and CDK4/6 inhibition is a biologically rational strategy. This phase II trial evaluated ribociclib plus letrozole in recurrent LGSOC. METHODS This open-label, single-arm, multicenter phase II study enrolled women with measurable, recurrent LGSOC. Patients received ribociclib (600 mg orally, once daily, days 1-21 of a 28-day cycle) and letrozole (2.5 mg orally, once daily). The primary end point was investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary end points included clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Of 74 patients screened, 51 were enrolled and 49 treated. The confirmed ORR was 30.6% (90% CI, 19.9 to 43.2), including one complete and 14 partial responses. Among responders, the median duration of response was 21.2 months. The CBR was 84% (90% CI, 72.5 to 91.6). The median PFS was 14.5 months (90% CI, 10.1 to 28.8), and the median OS was 44.5 months (90% CI, 31.8 to not reached). The most common grade ≥3 adverse event (AE) was neutropenia (47%), managed with dose modifications. Three grade 5 events (6%) occurred but were unrelated to treatment. Treatment discontinuation because of AEs occurred in 4%. No dose-limiting toxicities were observed. CONCLUSION Ribociclib plus letrozole met the primary end point, achieving meaningful response rates and durable disease control in recurrent LGSOC. The safety profile was consistent with prior CDK4/6 inhibitor studies. This combination represents a therapeutic option in this rare and genomically distinct subtype.

Abstract The benefit of rituximab maintenance after first-line (1L) bendamustine-rituximab (BR) in patients with mantle cell lymphoma (MCL) remains uncertain, with inconsistent results from the phase 2 MAINTAIN trial and several retrospective studies. We conducted a large retrospective study at 27 US and Canadian academic centers to examine the benefit of rituximab maintenance after BR. A total of 911 patients received 1L BR between 2010 and 2020, and 703 had an objective response and no evidence of disease progression at the 3-month post-BR landmark. Among those, 394 (56%) received rituximab maintenance and 309 (44%) did not, with largely similar baseline patient and disease characteristics. In the landmark analysis, rituximab maintenance was associated with improved event-free survival (EFS; median, 49.9 vs 29.7 months; P&lt; .001) as well as overall survival (OS; median, 109.5 vs 74.2 months; P&lt; .001). The EFS and OS benefits were observed across most of the subgroups. EFS and OS differences were statistically significant in those who achieved a complete response to 1L BR (n = 590; median EFS, 62.7 vs 31.1 months [P&lt; .001]; median OS, 136.1 vs 75.3 months [P&lt; .001]), but the analysis among those who achieved a partial response to 1L BR was limited by the small sample size. These results provide additional evidence for the survival benefit of rituximab maintenance after BR in MCL and support its use in clinical trial design and routine practice.