The buffalo is an important species in many regions of the world, particularly in Asia, Africa and parts of Europe. Among the various species of buffalo, the water buffalo (Bubalus bubalis) is the most widespread, and it is well-known for its ability to thrive in wet and humid environments. In Europe, Italy is one of the leading producers of buffalo milk, and is particularly renowned for the production of Mozzarella di Bufala, a cheese made from the milk of water buffalo. Scientific knowledge on applied physiology, health, husbandry and reproduction in buffalo remains limited. This may be partly due to the fact that the species has historically been of greatest economic importance in regions where production systems are predominantly traditional and research investment has been limited. More recently, research has increasingly focused on production and feeding strategies and breeding practices. In addition, much of the research on the reproductive biology and management has concentered on the female buffalo, with particular emphasis on seasonality, oestruses detection and induction, whereas relatively little attention has been paid to male reproduction.This review discusses the reproductive physiology and behaviour of the male domestic buffalo in relation to differences in management and environmental conditions under which the species is reared, with a particular focus on the Italian Mediterranean buffalo breed (IMB).
The 2022 transition of United States Medical Licensing Examination (USMLE) Step 1 from numeric to pass/fail scoring represents a fundamental shift in neurosurgery residency applicant selection. Historically, Step 1 scores served as a key objective metric. With numeric scores no longer available, programs may place greater emphasis on alternative metrics. To the authors' knowledge, this study is the first that aimed to evaluate how predictors of neurosurgery match outcomes have shifted before and after Step 1 became pass/fail. We conducted a retrospective cohort analysis of neurosurgery residency applicant data from pre-pass/fail (Step 1 numeric) and post-pass/fail eras. Data were used from the 2023 and 2024 application cycles. Variables included demographics, USMLE Step 2 clinical knowledge (CK) scores, Step 1 pass status, research output variables, dedicated research years, postgraduate training after medical school graduation, Alpha Omega Alpha (AOA) membership, home institution status, and other academic metrics. Descriptive statistics were compared for matched and unmatched applicants within each era. Independent predictors of match success were identified through multivariable logistic regression analysis. In the pre-pass/fail era, matched applicants had higher Step 2 CK scores and more review article, neurosurgery-specific, neurosurgery-specific first-author, and total publications than unmatched applicants (p < 0.001 for all). Independent predictors of match success included Step 2 CK score and review article productivity. Research year and postgraduate training were negative predictors. In the post-pass/fail era, Step 2 CK, home institution, AOA membership, research year, neurosurgery-specific publications, and basic science publications were significant positive predictors. Review articles no longer predicted match success. The transition to pass/fail Step 1 has shifted the emphasis of neurosurgery residency applicant selection from general research productivity and review articles toward specialty-specific scholarship, home institution affiliation, AOA membership, and dedicated research experience. Step 2 CK has remained a consistent predictor across eras.
Strict adherence to follow-up ophthalmic care after emergency department visits is critical not only for monitoring disease progression, assessing therapeutic response, and preventing avoidable complications, but also because ophthalmic examinations may provide one of the few opportunities to identify otherwise unrecognized systemic disease. To identify variables associated with loss to follow-up (LTFU) care after emergency department ophthalmology consultations, and to characterize similarities and differences between self-reported race. Retrospective cohort study examining emergency department ophthalmology consultations between January 1st, 2019, and December 31st, 2021, at a level 1 trauma center serving Western New York, Northern Pennsylvania and Southern Ontario. Single center study at Erie County Medical Center in Buffalo, New York, USA. A total of 2323 ophthalmology consultations were analyzed. The primary outcome was the rate of LTFU, defined as failure to attend a scheduled outpatient appointment. Demographic, diagnostic, and socioeconomic variables were analyzed across all patients and stratified by self-reported racial group (White, African American/Black, and Other). Logistic regression analysis was performed. Of the 1697/2323 (73.1%) patients that required an outpatient follow-up at The Ira G. Ross Eye Institute, 1003 (59.1%) identified as White, 489 (28.8%) identified as African American/Black and 205 (12.1%) identified as Other. The overall rate of LTFU was 41.8%, with no significant difference in follow-up rates by racial group on multivariable analysis. In the overall patient cohort, LTFU was significantly more common among patients residing in ZIP codes with lower rates of high school completion, those with a longer interval between the emergency department visit and the scheduled follow-up appointment, and those who presented with near-normal visual acuity (close to 20/20). Among White patients, glaucomatous and retinal diagnoses were associated with lower rates of LTFU. Older age, corneal diagnoses and orbital diagnoses were associated with lower rates of LTFU among African American/Black patients. This study identified both shared and distinct factors associated with LTFU across racial groups. These findings provide a foundation for future studies investigating the mechanisms underlying follow-up adherence and may help inform efforts to improve outpatient follow-up.
Abatacept is approved for the treatment of moderate-severe RA, JIA and PsA in the USA and elsewhere. The purpose of this study was to estimate the incidence/birth prevalence of selected maternal and infant outcomes in pregnancies exposed to abatacept. Pregnant women exposed to any dose of abatacept from the first day of the last menstrual period to the end of the first trimester who resided in the USA or Canada were enrolled in the Organization of Teratology Information Specialists Abatacept Pregnancy Exposure Registry between 2007 and 2019. Data on exposures, outcomes and covariates were collected by maternal interviews, medical records and study-related physical examinations up to 1 year postpartum. The sample consisted of 30 abatacept-exposed pregnancies. Sixteen were enrolled prospectively and were treated for RA or PsA; 14 did not meet the prospective criteria and were enrolled in an exposure series. Of those prospectively enrolled, 2/13 (15.4%) involved an infant with a major birth defect, 2/16 (12.5%) ended in spontaneous abortion and 2/13 (15.4%) delivered preterm. In the exposure series, 5/14 livebirths (35.7%) ended with an infant with a major birth defect, 2 of which were chromosomal or genetic, and 6/14 (42.9%) delivered preterm. There were no patterns of major or minor birth defects identified in either group. In the exposure series, selected adverse outcomes were more frequent, likely due to biases that led to exclusion of these pregnancies from the prospective cohort.
Orthostatic dizziness and lightheadedness are frequent complaints in patients age 60 and above, whereas various common and uncommon etiologies need to be considered, including medication side effects, cardiovascular and metabolic causes and neurologic disorders. Autonomic dysfunction is a common etiology that warrants comprehensive medical and neurologic evaluations for identification of neurogenic orthostatic hypotension, prodromal Parkinson's disease, Lew body dementia, pure autonomic failure and others. In this article, key historical details, physical exam findings and diagnostic investigations for orthostatic dizziness are discussed. Patients' report of chronic and persistent orthostatic intolerance, even in the absence of objective orthostatic hypotension, should serve as a reliable and sufficient key feature should prompt an evaluation for autonomic and neurodegenerative disorders.
Major advances in pulp biology, biomaterials, and tissue engineering have fuelled the development of regenerative strategies aimed at preserving or restoring pulp vitality. Despite this progress, the clinical translation of these discoveries remains limited or absent. Although there is a global agenda to reduce and replace animal use in medical research, we believe that a critical missing link in the translational pipeline of regenerative endodontics innovations is the lack of rigorously validated, clinically relevant preclinical models to use in advancing promising in vitro findings through regulatory processes to human application. While novel alternative methodologies (NAMs), including microfluidics, organoids, and organ-on-chip systems, offer human-relevant in vitro models and are rapidly transforming early-stage screening and mechanistic studies, they are currently insufficient to replicate the complex systemic elements provided by animal models, which are essential for demonstrating in vivo efficacy of regenerative therapies. Regulatory approval of devices, drugs, and biologics continues to require robust preclinical evidence generated in whole-organism systems, particularly when complex interactions involving immunity, vascularisation, innervation, and aging are central to therapeutic success. In this perspective article, we discuss key scientific, methodological, and logistical considerations for the systematic development and validation of orthotopic animal models in regenerative endodontics research. We place particular emphasis on vital pulp treatment as a biologically and clinically relevant framework for studying pulp repair and in demonstrating the efficacy of novel therapies. We highlight the challenges that have hindered consensus in model selection and standardisation, and emphasise the need for coordinated transdisciplinary efforts to overcome these barriers. We argue that prioritising standardised orthotopic vital pulp treatment models, in combination with evolving NAMs, represents a critical step to bridge the gap between mechanistic discoveries and clinical translation in regenerative endodontics.
Older adults with cognitive disorders, including dementia and mild cognitive impairment, are particularly vulnerable to adverse effects from centrally acting medications. Cognitive potentially inappropriate medications (CogPIMs), including anticholinergics, antipsychotics, benzodiazepines (BZDs), and non-benzodiazepine hypnotics (Z-drugs), may worsen well-being and increase healthcare utilization in this population. This study evaluates CogPIMs exposure and its association with health-related quality of life (HRQoL) and healthcare utilization among community-dwelling older adults with cognitive disorders. We conducted a cross-sectional analysis of 2011-2022 Medical Expenditure Panel Survey (MEPS) data from adults aged ≥ 65 with cognitive disorders. CogPIMs exposure was defined as ≥ 1 prescription of anticholinergics, antipsychotics, BZDs, or Z-drugs. Outcomes included (1) annual prevalence of CogPIMs exposure, (2) healthcare utilization, and (3) HRQoL measured by SF-12 physical and mental component scores. Inverse probability of treatment weighting was used to adjust for confounding. Temporal trends were assessed using Joinpoint regression. Survey-weighted logistic and negative binomial regression models estimated adjusted associations. A total of 2796 older adults with cognitive disorders were identified in MEPS from 2011 to 2022, representing a weighted analytic sample of 29.7 million individuals. Overall CogPIM exposure declined from 39.3% in 2011 to 29.3% in 2022 (Annual Percentage Change: -1.9%, p < 0.01). CogPIM exposure was not associated with poor physical HRQoL but was associated with higher odds of poor mental HRQoL (adjusted Odds Ratio: 1.72 [1.31-2.25], p < 0.01). CogPIM exposure was also associated with higher rates of emergency department visits (adjusted incidence rate ratios (aIRR) = 1.41 [1.24-1.60], p < 0.01) and hospitalizations (aIRR = 1.38 [1.19-1.59], p < 0.01), but not outpatient visits (aIRR = 1.27 [0.75-1.54], p = 0.31). Among community-dwelling older adults with cognitive disorders, CogPIM exposure remains common and is associated with poorer mental HRQoL and increased acute care utilization. Future longitudinal and interventional studies are needed to determine whether modifying exposure to CogPIM can improve well-being and reduce potentially preventable acute care utilization.
This randomized clinical trial examines 1-year safety and efficacy outcomes in patients who underwent intra-arterial thrombectomy or medical management following an acute ischemic stroke with large-core infarcts.
Submaximal aerobic exercise is an evidence-informed strategy for concussion management. However, its impact on the concussed pediatric brain remains poorly understood. A seminal adult study reported stability of default mode network (DMN) functional connectivity before and immediately after aerobic exercise in adults with mild traumatic brain injury. Comparable data do not exist in children, despite known developmental neurophysiological differences between children and adults. This study examined DMN network stability before and after submaximal aerobic exercise in pediatric sport-related concussion. In a controlled cohort design, 18 concussed participants (within 4 weeks of injury; 15.2 ± 1.8 years; 33% female) and 18 age- and sex-matched controls (14.5 ± 2.1 years; 50% female) completed resting-state functional magnetic resonance imaging scans pre- and post-exercise. Exercise intensity was set to 85% of the individualized symptom-limited heart rate achieved on a Buffalo Concussion Treadmill Test performed 24-48 h prior. Functional connectivity was assessed across four DMN regions of interest (posterior cingulate cortex, medial prefrontal cortex, left lateral parietal cortex, right lateral parietal cortex). Graph theory analyses conceptualized each region as a network node. Region of interest-based analyses demonstrated reduced pre- to post-exercise correlations across DMN pairs in both groups. Mean percent change was -25.8% (±12.7%) in concussion and -15.0% (±7.2%) in controls. However, no statistically significant within- or between-group correlational differences were observed, consistent with adult findings. In contrast, graph theory revealed significant post-exercise reductions in network efficiency (β = -0.17, p = 0.015), cost (β = -0.18, p = 0.014), and degree centrality (β = -0.53, p = 0.001) exclusively in the concussion group, driven primarily by the right lateral parietal cortex. While correlational analyses suggest DMN stability similar to adults, graph metrics indicate reduced network connectedness following exercise in pediatric concussion. These findings underscore the need to move beyond symptom-based frameworks and examine exercise-related neurophysiological responses in youth concussion.
Myocardial infarction (MI) is a major global health concern influenced by diverse risk factors. Despite growing evidence of oral-systemic connections, current MI models largely exclude oral health indicators, reflecting the longstanding separation between dental and medical paradigms. This study introduces a multidomain, interpretable machine learning framework that integrates detailed periodontal and oral hygiene variables, marking one of the first efforts to quantitatively incorporate these features into MI incidence identification. A population-based case-control dataset comprising 1,355 individuals and heterogeneous variables was used to train and evaluate seven supervised classifiers via nested cross-validation. Among them, XGBoost achieved the best performance (AUC = 0.88 ± 0.01; F1 score = 0.74 ± 0.03) and was further probability-calibrated using isotonic regression, yielding a mean Brier score of 0.14 ± 0.01 and demonstrating well-aligned predicted probabilities. SHAP values confirmed the importance of conventional cardiovascular predictors, while several periodontal indicators such as mean clinical attachment loss, plaque index, and gingival bleeding emerged among the most influential features. Sex-stratified SHAP analysis revealed sex-specific patterns in the relative impact of oral features. Additionally, individual-level waterfall plots illustrated how oral inflammation may contribute independently or in combination with conventional factors to MI incidence identification. These findings support a systems-level view of periodontitis as a modifiable, biologically relevant factor in cardiovascular health and underscore the value of considering oral-health markers within screening and management frameworks.
Significance: Sensory and subjective effects contribute to consumer response toward electronic nicotine delivery systems (ENDS). Evaluating the relative contributions of nicotine concentration, form (salt vs freebase), and carrier concentration (PG/VG ratio) is important to understanding why formulations may be more attractive. Methods: Participants were 78 adults (age ≥21) with no sensory deficits who used ENDS daily, randomized to one of two sub-studies. In Study A, 38 participants sampled tobacco-flavored e-liquids varying in PG/VG ratio (30/70, 60/40, 100/0) and nicotine concentration (0, 18, 36 mg/mL freebase). In Study B, 40 participants sampled e-liquids varying in nicotine form (salt, freebase) and concentration (0, 18, 36 mg/mL). Questionnaires assessed sensory and subjective effects. Generalized estimating equation (GEE) models examined the effects of experimental factors on these ratings. Results: Nicotine concentration was strongly related to a wide array of sensory and subjective effects measures, generally following a dose-response pattern. PG/VG showed relationships with a subset of hedonic effects independent of nicotine. There were no significant differences observed for sensory or subjective measures between salt versus freebase nicotine. Conclusions: Nicotine concentration showed consistent associations with sensory response to e-liquids when delivered in the same device. Sensory and behavioral responses to different e-liquid compositions may help contextualize ENDS usage patterns, risk perceptions, and behaviors.
CD73 is an enzyme that generates extracellular adenosine and has been implicated in tumor-associated immune suppression, but its biological and clinical significance in pancreatic ductal adenocarcinoma (PDAC) remains incompletely understood. We investigated the prognostic relevance and biological functions of CD73 in PDAC using transcriptomic analyses, in vitro functional assays, and in vivo mouse models. Transcriptomic analyses consistently showed that CD73 expression was correlated with hypoxia, glycolysis related, and cell-cycle programs. In agreement with these findings, hypoxic exposure induced CD73 mRNA expression in a subset of PDAC cell lines, and CD73 knockdown modestly affected glycolysis related extracellular acidification (ECAR) in a cell line dependent manner, and modulation of CD73 expression altered PDAC cell growth. CD73 expression was also associated with reduced intratumoral CD8+ T cell infiltration and cytolytic activity in human PDAC cohorts. In vivo, CD73 overexpression accelerated cancer progression and shortened survival in immunocompetent mice, whereas this effect was abrogated in immunodeficient NSG mice. Flow cytometric analysis further demonstrated reduced intratumoral CD8+ T cell infiltration in CD73 overexpressing tumors. Clinically, high CD73 expression was consistently associated with worse survival in multiple PDAC cohorts. Collectively, these findings suggest that CD73 is associated with multiple features of PDAC progression, including hypoxia-related metabolic programs, tumor growth, and suppression of anti-tumor immunity. CD73 may therefore represent a biologically relevant biomarker and a potential therapeutic target in PDAC.
Despite strong links between emotion regulation (ER) difficulties and problem drinking, few studies have directly addressed whether interventions that target ER positively impact drinking outcomes. In a prior Stage 1a/1b behavioral therapies development study, we developed an Emotion Regulation Treatment (ERT) for alcohol use disorder (AUD) that included strategies addressing prolonged direct experiencing of emotion, mindfulness, and coping and distress tolerance. Results demonstrated the feasibility and initial efficacy of ERT as a supplement to cognitive behavioral therapy (CBT) for AUD. Based on this initial success, the current study reports on a fully powered stage II randomized clinical efficacy trial to compare CBT plus ERT (CBT + ERT) to CBT plus an active health and lifestyles (HLS) control (CBT + HLS) and explore potential mechanisms of action. Adults (n = 194) with moderate-to-severe AUD were enrolled in 12 week outpatient treatment and randomized to either the CBT + ERT or CBT + HLS treatment condition. Analyses evaluated (1) the impact of treatment condition on percent days abstinent (PDA) and percent heavy drinking days (PHDD) at end of treatment (EOT) and 3, 6, and 12 months posttreatment, and (2) whether change trajectories of negative affect, craving, mindfulness, cognitive reappraisal, or adaptive alcohol coping, assessed daily or weekly during treatment, partially accounted for associations between treatment condition and EOT alcohol outcomes. The CBT + ERT group had greater PDA at all posttreatment follow-ups relative to the CBT + HLS group. There were no group differences in PHDD. Levels of PDA and PHDD did not change across posttreatment follow-ups for either group. The CBT + ERT group exhibited greater adaptive alcohol coping across the first week of treatment, which in turn was associated with higher PDA and lower PHDD at EOT. No other mediation effects were detected. CBT + ERT was associated with greater PDA at EOT relative to CBT + HLS, an association that was partially explained by greater adaptive coping early in treatment.
African American/Black breast cancer (BC) survivors experience higher rates of sleep disturbance than their White counterparts, which may contribute to worse survival and quality of life; however, whether adherence to cancer-related lifestyle guidelines (adiposity, physical activity, and diet) is associated with post-diagnosis sleep disturbance in Black women remains unexplored. We evaluated whether adherence to World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations was associated with lower risk of sleep disturbance in a population-based cohort of Black BC survivors, the Women's Circle of Health Follow-Up Study. Pre-diagnosis lifestyle factors were assessed during home visits among 682 participants. Lifestyle pattern scores were calculated using the WCRF/AICR scoring system (range: 0-7; higher scores indicating greater adherence). Sleep disturbance was assessed ∼2 years post-diagnosis using the Pittsburgh Sleep Quality Index, with a score >5 indicating sleep disturbance. Robust Poisson regression estimated relative risks (RRs) and 95% confidence intervals (CIs) for associations between lifestyle pattern scores and sleep disturbance. The mean (SD) pre-diagnosis lifestyle pattern score was 3.0 (1.1), and 59.8% of survivors had post-diagnosis sleep disturbance. Compared with women in the lowest quartile of lifestyle pattern score (0-2.25), those in the highest quartile (≥4) had a 21% lower risk of sleep disturbance (RR = 0.79, 95% CI: 0.65, 0.97) after multivariable adjustment. Higher lifestyle pattern scores were associated with better domain scores for subjective sleep quality, sleep disturbance, and daytime dysfunction. Adherence to cancer-related lifestyle guidelines may reduce the risk of sleep disturbance among Black BC survivors.
Risky drinking and sexual violence (SV; i.e., sexual harassment, sexual assault) affect U.S. military personnel, potentially compromising operational readiness. Drinking and SV often co-occur in social settings, making a behavioral risk intervention focused on peers ideal for implementation with military personnel. Here, we present findings from phase 1 of a 3-phase project to develop a peer-based motivational intervention (PMI) aimed at reducing risky drinking and SV among U.S. service members. In this phase we sought to understand sailors' perspectives on alcohol use and SV in the military and to obtain feedback on the relevance, acceptability, and feasibility of the PMI. Active duty sailors aged 18-24 years were recruited via the Defense Manpower Data Center (N = 23, 52.2% male) to view a video prototype of the PMI and provide feedback via an online interview. Interview transcripts were analyzed qualitatively. Analyses were aimed at answering 2 research questions: (a) How do sailors view risky drinking and SV in the military context? and (b) How do sailors perceive the relevance, acceptability, and feasibility of the PMI to prevent risky drinking and SV among service members? Sailors described unique features of military culture that perpetuate risky alcohol use and SV, including the normalization of these behaviors, working within a hierarchy, and deployment. Overall, sailors appreciated the PMI's emphasis on commitment to peers, planning, and the engaging nature of the intervention. They also identified challenges to getting busy service members to participate and made suggestions for enhancing participation. A PMI may be a promising way to address drinking and SV in military contexts.
Cardiovascular function is tightly linked to tissue architectures, where the spatial organization of cells, extracellular matrix (ECM), vascular networks, and remodeling processes governs physiological performance and disease progression. Spatial proteomics has, therefore, emerged as a powerful framework for understanding cardiovascular biology and cardiovascular disease mechanisms by revealing spatially organized protein regulation across various physiological and pathological states. In this review, we focus on spatial proteomics strategies most relevant to cardiovascular research and discuss their applications through representative examples. These approaches can be broadly categorized into region-of-interest-based methods, which enable precise characterization of localized cellular heterogeneity, and tissue mapping strategies, which capture spatial organization and biologically relevant region-to-region variability across larger tissue domains. In addition, spatial proteomics platforms differ in their capacity for targeted or untargeted protein analysis, influencing both proteome coverage and their suitability for hypothesis-driven versus discovery-based studies. We evaluate the strengths and limitations of state-of-the-art technologies across 3 key parameters, molecular depth, spatial coverage, and spatial resolution, and discuss how these parameters shape study design and biological understanding. Building on these considerations, we argue that a comprehensive understanding of cardiovascular tissue biology requires spatial proteomics strategies that capture both localized molecular details and spatial organization across large tissue areas, as neither alone is sufficient to explain complex tissue behavior. We propose an integrated workflow in which untargeted, whole-tissue mapping of thousands of proteins is first used to unbiasedly discover spatial patterns and generate hypotheses by identifying candidate regions and proteins of interest, followed by hypothesis testing and validation using high-precision region-of-interest-based proteomics and targeted protein imaging. This sequential framework leverages the complementary strengths of tissue-wide mapping and region-of-interest-based approaches to provide multiscale, mechanistic insights into spatially organized disease processes. Finally, we discuss emerging directions that are poised to expand the scope of spatial proteomics in cardiovascular research.
The interest in microdosing psychedelics continues to grow within academic and recreational contexts. However, microdosing practices have changed over time, and warrants examination of use patterns within a large, global sample of consumers. The Global Psychedelic Survey 2025 (GPS 2025) was an online, anonymous, cross-sectional survey conducted from May 1-23, 2025. The survey was available in 19 languages and inquired about a wide range of topics surrounding psychedelic use. This manuscript focuses on the primary outcomes for the microdosing component of the survey, examining the substances consumed, dosing regimens employed, reasons for use, as well as the typical 'set and setting' while microdosing. In this sample, 5399 participants reported microdosing during their lifetime, of whom 69.8% (n = 3768) used a microdose within the past year. Psilocybin was the most commonly microdosed substance (n = 4377; 81.1%, 95% CI: 80.0%-82.1%), followed by LSD (n = 2136; 39.6%, 95% CI: 38.3%-40.9%). This was consistent across global regions. The 'Fadiman protocol' (i.e. one day on, two days off) was the most reported dosing regimen among regular microdosers (n = 1203; 24.3%, 95% CI: 23.1%-25.6%). While microdosing, respondents reported often spending time in nature (n = 3087; 58.9%), focusing inwards (n = 2977; 56.8%), or spending leisure time (n = 2253; 43%), demonstrating preliminary evidence supporting the integration of set and setting in the context of microdosing. This study provides a snapshot of psychedelic microdosing practices using the largest psychedelic-specific global survey to date. These findings highlight real-world practices that can guide both clinical study designs and inform harm-reduction practices in naturalistic settings.
To determine the efficacy and safety of darolutamide, exemestane, and leuprolide acetate in recurrent adult-type ovarian granulosa cell tumor (AGCT). This single-arm Phase II cooperative group study included patients with recurrent AGCT who had progressed on a prior aromatase inhibitor. The treatment regimen consisted of darolutamide 600 mg by mouth twice daily, exemestane 25 mg by mouth once daily, and leuprolide acetate 7.5 mg by intramuscular injection every four weeks. Patient accrual occurred from January 2024 to April 2024 with sample size determined using Simon's Optimal two-stage design. The primary measure of efficacy was objective response rate (ORR) measured by Response Evaluation Criteria in Solid Tumors 1.1. Secondary objectives included duration of response, progression-free survival (PFS), overall survival (OS), and safety of the treatment regimen. Seventeen patients were enrolled to complete target accrual of the first stage. Of the 16 evaluable patients, there was one partial response (ORR = 6.25%). The trial did not continue to the second stage as it did not meet its prespecified endpoint. Ten patients (62.5%) were confirmed to have stable disease and five patients (31.25%) were confirmed to have progressive disease. Median PFS was 8.5 months (95% CI: 3.1 months - 12.0 months). Median OS was not reached. There were no grade 4 or grade 5 adverse events attributable to the treatment regimen. Though the trial did not meet its primary endpoint, there was one partial response to the treatment regimen. Clinically meaningful PFS was demonstrated. Clinical Trial Registration Number NCT06169124.
Cancer remains a leading cause of mortality in the United States. This study aimed to examine trends and disparities in the prevalence of selected cancers-any cancer, breast, cervical, prostate, and skin cancer-among U.S. adults from 2019 to 2023. This cross-sectional study used data from the National Center for Health Statistics (NCHS) Interactive Summary Health Statistics for Adults. Cancer prevalence was based on self-reported physician diagnoses. Joinpoint regression analysis assessed temporal trends, with annual percentage change (APC) estimates and 95% confidence intervals (CI) reported. Analyses were stratified by year, gender, age, race/ethnicity, nativity, veteran status, employment status, geographic region, metropolitan statistical area (MSA), and Social Vulnerability Index (SVI). The overall prevalence of any cancer remained stable from 2019 (9.6%, 95% CI: 9.3-9.9) to 2023 (9.8%, 95% CI: 9.5-10.1). However, notable disparities were observed. In 2023, White adults had the highest prevalence (11.7%, 95% CI: 11.3-12.2), while Asians had the lowest (3.5%, 95% CI: 2.6-4.8). Breast cancer prevalence in females rose slightly from 3.2% (95% CI: 2.9-3.5) in 2019 to 3.5% (95% CI: 3.2-3.8) in 2023, though not significantly. Cervical cancer in females significantly declined from 1.1% (95% CI: 0.9-1.3) to 0.9% (95% CI: 0.8-1.1) (APC: -6.05, 95% CI: -10.87 to -0.99). Prostate cancer in males rose slightly from 2.3% (95% CI: 2.1-2.6) to 2.5% (95% CI: 2.3-2.8), with Black males having the highest prevalence (3.6%, 95% CI: 2.7-4.7). Skin cancer in females significantly increased from 3.0% (95% CI: 2.7-3.3) to 3.3% (95% CI: 3.0-3.6) (APC: 2.25, 95% CI: 1.11 to 3.36), with the highest prevalence among White adults (4.7%, 95% CI: 4.4-5.0). Higher prevalence was generally observed among older adults, residents of non-MSA areas and the Midwest, individuals with low social vulnerability, the unemployed, U.S.-born individuals, and veterans. Although overall cancer prevalence remained relatively stable between 2019 and 2023, significant disparities persist across demographic, geographic, and socioeconomic groups. These findings emphasize the need for targeted cancer control strategies to address ongoing inequities.
Classic Hodgkin lymphoma (cHL) associated with Epstein-Barr virus (EBV) positivity as well as non-nodular sclerosis (non-NS) histologic subtypes have demonstrated poorer outcomes compared to EBV-negative and nodular sclerosis cases. We report a prespecified subset analysis of patients enrolled in the phase III SWOG S1826 trial to evaluate outcomes based on EBV status and histologic subtype in patients treated with nivolumab-AVD (N-AVD) or brentuximab vedotin (BV)-AVD. In the phase III SWOG S1826 trial, patients with stage III-IV cHL were randomized to N-AVD or BV-AVD. Of 970 eligible patients, 522 had known EBV status. N-AVD improved 3-year progression-free survival (PFS) in EBV-positive (91% v 70%; HR, 0.30; P = 0.01) and EBV-negative patients (90% v 84%; HR, 0.64; P = 0.09). Among 664 patients with slides available for histology review, 102 (15.4%) had non-NS subtypes. N-AVD prolonged 3-year PFS in patients with non-NS (86% v 63%; HR, 0.33; P = 0.006) and NS histologic subtype (93% v 86%; HR, 0.53; P = 0.01). Non-NS histology independently was associated with inferior outcomes (HR, 2.54; P < 0.0001) after adjusting for treatment in the entire cohort. However, N-AVD treatment still had favorable PFS within this high-risk group. In addition, patients with EBV positivity or non-NS histology cHL treated with BV-AVD had significantly worse PFS (HR, 1.97; P = 0.03 for EBV; and HR, 3.08; P < 0.0001 for histology). N-AVD substantially abrogated the historically poor prognosis associated with EBV positivity and non-NS histology in advanced-stage cHL. These results support N-AVD as frontline standard of care, particularly in high-risk biologic subgroups. (NCT03907488).