Citations

Abstract Objectives Erdheim-Chester disease (ECD) is one of 3 major types of histiocytic neoplasms, along with Rosai-Dorfman disease and Langerhans cell histiocytosis. It was first recognized as a neoplasm in the 2016 World Health Organization Classification of Haematolymphoid Tumours. About 80% to 90% of cases harbor MAPK pathway mutations. Methods We discuss the diagnosis of ECD using 3 illustrative cases, consider interpretative challenges, and present a diagnostic algorithm. Results Erdheim-Chester disease is a systemic disease that shows a characteristic pattern of organ involvement including bone, perinephric soft tissue, skin, heart, and central nervous system. Histologically, ECD shows a spectrum of xanthogranulomatous, lymphohistocytic, or fibrohistiocytic infiltrates. By immunohistochemistry, the neoplastic histiocytes have a macrophage phenotype with expression of CD163, negative to focal S100, and negative CD1a and langerin. These features alone are not specific and thus insufficient for diagnosis. Immunohistochemistry for cyclin D1 and BRAF V600E, correlation with clinical and imaging findings, and mutational analysis for MAPK pathway mutations all play important roles in establishing an ECD diagnosis. Conclusions The diagnosis of ECD is often challenging due to its clinical and histologic overlap with reactive inflammatory processes. Correlation of histology features with clinical findings, immunohistochemistry, and genetic studies is essential for an accurate and timely diagnosis.

Abstract Black/African American populations, globally, bear the greatest prostate cancer (CaP) burden compared to other racial/ethnic groups. Addressing CaP disparities in Black men is complex, requiring a patient-centered, community-centric and comprehensive approach. This study integrates iCCaRE Consortium findings and broader literature to address unmet needs in survivorship care. The iCCaRE Consortium implemented five complementary pilot studies using mixed-methods designs, including feasibility trials, qualitative research, and observational analyses across the United States and sub-Saharan Africa. Descriptive statistics, subgroup analyses, and qualitative thematic analyses were performed across these studies. Collectively, projects addressed multilevel determinants including social, behavioral, and biological drivers of disparities. Project 1 implemented a Virtual Reality Assistant (ViRA) across clinical and community settings, with ongoing evaluation in pragmatic trials. Project 2 showed strong patient preference for home-based cancer care. Project 3 enrolled demonstrated trends toward improved health-related quality of life. Project 4 identified key themes influencing survivorship experiences. Project 5 identified biological mechanisms linking stress, immune modulation, and symptom burden. The iCCaRE pilot projects demonstrate the feasibility and early impact of a consortium-based, transdisciplinary approach to addressing CaP disparities in Black men. These findings highlight the importance of integrating patient-centered interventions, community engagement, and biological insights to inform scalable strategies aimed at improving survivorship outcomes and advancing health equity. The iCCaRE Consortium demonstrates that a transatlantic, patient-centered, and multidisciplinary approach integrating social, clinical, and biological factors can generate scalable strategies to improve survivorship outcomes and advance equity in CaP care for Black men.

ABSTRACT Purpose Despite 5‐year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%–20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non‐Hispanic Black (NHB) and Hispanic (vs. non‐Hispanic White [NHW]) patients experienced higher post‐relapse mortality. It is unknown whether post‐relapse disparities persist when second‐line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. Methods A pooled analysis of individual‐level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001–2016) was conducted. The Kaplan–Meier method estimated 3‐year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. Results Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow‐up of 4.9 years, 3‐year OS was 82.1% (95% confidence interval [CI], 75.3%–87.1%) and did not differ by race and ethnicity ( p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment ( p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity ( p = 0.43). Conclusion Post‐relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.

BACKGROUND: Technetium-based cardiac amyloid radionuclide imaging enables noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), but conventional planar and visual semiquantitative approaches have important limitations. We developed the quantitative 3-dimensional Mayo 3D Score, defined as the ratio of mean left ventricular myocardial radiotracer uptake to right atrial blood-pool uptake using computed tomography (CT)-fused single-photon emission CT (SPECT) volumes of interest, and sought to validate its diagnostic performance against myocardial pathology. METHODS: Consecutive patients who underwent 99m Tc-pyrophosphate SPECT/CT at Mayo Clinic for suspected ATTR-CM between June 2017 and January 2025 with archived myocardial tissue were included. Baseline characteristics, including demographics, echocardiogram, biomarkers, visual semiquantitative, and Mayo 3D Score metrics, were collected. Myocardial specimens underwent histopathologic confirmation of amyloid, with amyloid subtype determination and further semiquantitative grading of amyloid burden and deposition patterns. RESULTS: Among 230 patients (median age, 72 years; 78% male), 107 (47%) had ATTR-CM, of whom 9 had hereditary ATTR-CM. The Mayo 3D Score showed excellent discrimination against pathology (area under the receiver operating characteristic curve, 0.92 [0.88–0.96]), exceeding planar Perugini (0.87 [0.83–0.92]; P =0.006), and heart-to-contralateral lung ratio (0.86 [0.81–0.91]; P =0.004) and comparable to SPECT Perugini (0.90 [0.86–0.94]; P =0.12). A cutoff ≥1.0 yielded 86.0% sensitivity, 92.7% specificity, 91.1% positive predictive value, and 88.4% negative predictive value. Among ATTR-positive cases, the Mayo 3D Score correlated strongly with semiquantitative amyloid burden (Spearman ρ=0.69), was higher in pericellular than nodular deposition patterns ( P <0.001), and was not associated with vascular involvement ( P =0.42). CONCLUSIONS: In patients with suspected ATTR-CM undergoing 99m Tc-pyrophosphate SPECT/CT, the Mayo 3D Score demonstrated superior diagnostic performance compared with planar metrics and comparable to SPECT Perugini, while correlating with myocardial ATTR burden and deposition patterns on pathology. These findings support its integration as a quantitative adjunct within clinical diagnostic ATTR-CM workflows.

Introduction: Limited research explores dermoscopy use among physician associates (PAs), outside of one prior study examining dermoscopy in PA student education. This study sought to investigate dermoscopy use among practicing PAs and its impact on their overall diagnostic confidence, including in darker skin tones, when differentiating between benign and malignant skin lesions. Methods: An anonymous survey was developed in 2023 with input from experts in dermoscopy and survey creation to assess PA confidence in skin lesion evaluation as well as PA dermoscopy knowledge and use, perceptions, barriers to use, and prior education. The dermoscopy survey was included as an optional module in the 2024 American Academy of Physician Associates (AAPA) Salary Survey. Results: Of 3,174 invited PAs, 995 (31.4%) responded. Most had never used dermoscopy in practice (81%) but knew or recognized the term (71%). A majority (53%) believed PAs should be trained in dermoscopy during PA school, and 26% reported no interest in future dermoscopy use. Dermatology PAs reported more frequent dermoscopy use and generally greater confidence in evaluating skin lesions, both overall and in darker skin tones, than PAs in other specialties. PAs in surgical (OR=0.2, 95% CI 0.1-0.6) and medical (OR=0.3, 95% CI 0.2-0.5) subspecialties were less likely to use dermoscopy at least annually compared with PAs in primary care. PAs in rural areas were more likely to feel confident in differentiating skin lesions than those in urban areas (OR 2.9, 95% CI 1.7-5.0). Conclusion: Dermoscopy use is associated with higher overall skin lesion assessment confidence. Wider adoption, especially outside dermatology, requires training, increased advocacy, and expanded education.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.

Objective Respiratory syncytial virus (RSV) is an important viral pathogen in children, older adults and adults with certain high-risk conditions. In our prospective community-based cohort study of adults 50 years and older before the COVID-19 pandemic, the incidence of RSV acute respiratory infection (ARI) was 48.6 cases/1000 person-years (PY), which decreased to near zero during the COVID-19 pandemic. Our objective was to determine the incidence of RSV-ARI during the 2 years following the initial phase of the pandemic (2021–2022 and 2022–2023). Design This is a community-based prospective cohort study. Setting Adults living in southeast Minnesota from October 2021 to September 2022 (year 3) and October 2022 to September 2023 (year 4). Participants Adults≥50 years (n=2500). Primary and secondary outcomes We calculated incidence and attack rates for RSV-ARI as primary outcome and reported hospitalisations, pneumonia and death following ARI as secondary outcome. Results There were 2500 participants in the study with a mean age of 68.2 years (SD 9.3) at the start of year 3. Participants were predominantly female (60%), non-Hispanic white (96%) and residing in urban areas (76%). The incidence rate of RSV-ARI was 6.12/1000 PY (95% CI 3.42 to 10.09) in 2021–2022 and 16.40/1000 PY (95% CI 11.66 to 22.42) in 2022–2023. We noted higher attack rates of RSV-ARI during the winter months. There were no hospitalisations, pneumonia or deaths within 30 days of RSV-ARI. Conclusions Compared with the period before the COVID-19 pandemic, RSV-ARI incidence was lower in both 2021–2022 and 2022–2023 periods. In 2022–2023, the incidence increased 2.7-fold compared with the 2021–2022 period. The observed incidence rates, particularly the significant increase in the most recent season, underscore the continued public health relevance of RSV-ARI and support the rationale for ongoing RSV vaccination efforts to mitigate its overall burden in the population.

ABSTRACT Objective Weight loss is frequently considered a cardinal presenting symptom for patients with Zenker diverticulum (ZD). We hypothesized that weight loss in patients with cricopharyngeal muscle dysfunction (CPMD), with or without diverticula, was associated with the length of symptoms and size of diverticulum. Methods Prospective, multicenter observational study of CPMD patients with and without diverticula reporting unintentional weight loss (+WL) or no weight loss (−WL) prior to enrollment in the Prospective Outcomes of Cricopharyngeal Hypertonicity (POuCH) database. Complications and symptom response using a patient reported outcome measure, the Eating Assessment Tool (EAT‐10), were compared. Results Of 427 patients, 101 (23.6%) were +WL. Median weight loss was 14 pounds (interquartile range [IQR] 10–25). +WL cohort had a mean age of 71.5 (standard deviation [SD] 11.5) vs. 67.9 in −WL (SD 11.6, p = 0.007). Mean preoperative EAT‐10 score was 24.7 in +WL (SD 9.7) and 14.8 in −WL (SD 8.8, p < 0.0001). Higher preoperative weight loss was associated with higher preoperative EAT‐10 ( p < 0.0001, Spearman's ρ = 0.43). Size of diverticulum was associated with WL ( p = 0.003), but weight loss was highest in both large diverticula and CP bars. Duration of symptoms was not associated with weight loss ( p = 0.30). Postoperative complications in +WL and −WL patients were similar ( p = 0.78). Conclusion Unintentional weight loss is common with ZD. Patients with worse dysphagia are more likely to have more weight loss. Weight loss does not increase with the size of the diverticulum or length of symptoms. Surgery has a similar safety profile with greater improvement in dysphagia in patients reporting weight loss. Level of Evidence 3.

Abstract Background Breast cancer is etiologically heterogeneous, but which risk factors differ in their associations across tumor subtypes remains unclear. We conducted a large, pooled analysis to evaluate independent, dose-response associations between breast cancer risk factors and quantitative tumor features. Methods Analyses of 15,731 invasive breast cancers from 24 studies evaluated associations (p-trend) between reproductive and hormonal factors, body mass index (BMI), alcohol, smoking, and family history in relation to quantitative immunohistochemistry measures on tissue microarrays (ER, PR, HER2, KI67, TP53) and tumor grade. Analyses in a subset of 10 population-based studies estimated subtype-specific odds ratios (ORs) comparing cases to controls. A Bayesian False Discovery Probability (BFDP) &lt;0.2 was used to identify associations with strong statistical evidence. Results Nulliparity and later age at menopause were associated with higher ER-positivity (p-trend=0.021 and 0.001, respectively), with corresponding OR[ER+] (95% CI) = 1.49 (1.16-1.90) for nulliparous vs. parous and 1.07 (1.03-1.11) per 5 years. Current combined menopausal hormone therapy (MHT) use was associated with lower grade (p-trend&lt;0.001), with OR [grade1] = 3.37 (2.69-4.21) for current vs. never users. Higher BMI was associated with lower ER-positivity and higher grade in premenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[ER+] = 0.80 (0.74-0.87) and OR[grade1] = 0.75 (0.63-0.88) per 5 units, and with higher PR-positivity and higher grade in postmenopausal women (p-trend&lt;0.001 and &lt;0.001), with OR[PR+] = 1.08 (1.03-1.14) and OR[grade 3] = 1.10 (1.04-1.17) per 5 units. Conclusion This pooled analysis of 15,731 cases showed that nulliparity, age at menopause, MHT, and BMI have independent, dose-response associations with ER, PR, and grade, clarifying patterns of etiologic heterogeneity. Associations with HER2, KI67 and TP53, or other risk factors did not meet our threshold for strong evidence.