Jenkins, Sarah M.

Background: Latinas with mammographic dense breasts are at increased risk of breast cancer. This randomized controlled trial tests the effectiveness of three breast density (BD) educational approaches on adherence to subsequent mammography screening among Latinas receiving care at a Federally Qualified Health Center (FQHC). Measure(s): Adherence was ascertained using electronic health record and survey responses. Kaplan–Meier estimates of the time to subsequent mammogram were used to obtain adherence rates at 1- and 2-years post baseline mammogram. Cox modeling assessed whether adherence differed by patient characteristics or group assignment. Results: This analysis was limited to Latinas enrolled between October 27, 2016, and December 21, 2018 ( n = 946; 66.1% <50 years of age, 53.5% with dense breasts). Adherence rates at 1 year was 24.8% increasing to 51.7% by year 2. Latinas randomized to the Promotora + brochure + letter arm (hazard ratio [HR]: 1.09 [95% confidence interval [95% CI] 0.87 to 1.36]) or brochure + letter (HR: 1.03 [95% CI 0.82 to 1.29]) arm were not more likely to be adherent to subsequent mammography compared to the letter only arm ( p = 0.76) . Adjusting for age and study group, having more prior mammograms, being “extremely likely” to get an annual mammogram, and having more confidence to get an annual mammogram at baseline were significant drivers of subsequent adherence. Conclusion: Informational interventions targeting BD education alone are unlikely to significantly improve adherence to subsequent mammography among Latinas receiving care in FQHCs.

AimsWe compiled two cohorts of colorectal adenosquamous carcinoma (ASC) to describe its histologic and molecular aspects using modern parameters to compare them with literature reports using meta‐analysis of cohorts and individual case series.Methods and ResultsWe identified 53 colorectal ASC from 19 North American academic medical centres, in addition to national database reports on 94 Dutch cases. We analysed available clinical, histologic, and immunohistochemical features and patient outcome. ASC comprised 0.02% of colorectal cancers in the Dutch database. The median cohort patient ages at resection were 65 and 69 years (North American and Dutch cohorts, respectively), with a roughly equal male:female ratio. The squamous component represented between 5% and 95% of each tumour, with a median of 50%. Tumour‐infiltrating lymphocytes (TILs) were generally low (66%), and tumour budding was often Bd1 (64%). Most cases were pT3 (55%) or pT4 (40%), with nodal metastases in more than half (58%). Twenty‐three cases (43%) metastasized distantly, most commonly to the liver. Mismatch repair (MMR) deficiency was identified in 34% of the cases. Follow‐up was available for 48 patients; 13 (27%) had recurrent disease and 29 (60%) died. A total of 31 patients progressed, with median time to progression of 18 months. Available data for the Dutch cohort revealed largely similar findings, as did review of cases in the literature.ConclusionColorectal ASC usually presents at an advanced stage. Despite high rates of MMR deficiency and low tumour budding, TILs were generally low, and there is a high recurrence rate and poor prognosis.

Background African Americans have a higher prevalence of cardiovascular risk factors, leading to higher cardiovascular disease mortality than White adults. Our culturally tailored mobile health (mHealth) lifestyle intervention ( FAITH! App) has previously demonstrated efficacy in promoting ideal cardiovascular health in African Americans. Methods We conducted a secondary analysis from a cluster randomized controlled trial among African-Americans from 16 churches in Minnesota that compared the FAITH! App to a delayed intervention control group. A subgroup of participants with ≥ 1 diagnosis of overweight/obesity, hyperlipidemia, hypertension, or diabetes was examined. The primary outcome was a change in LS7 score—a measure of cardiovascular health ranging from poor to ideal (range 0–14 points)—at 6-months post-intervention. Results The analysis included 49 participants (intervention group: n = 20; mean age 58.8 years, 75% female; control group: n = 29, mean age 52.5 years, 76% female) with no significant baseline differences in cardiovascular risk factors. Compared to the control group, the intervention group showed a greater increase in LS7 score across all cardiovascular risk factors at 6-months post-intervention, with statistically significant differences among those with overweight/obesity (intervention effect 1.77, p < 0.0001) and 2+ or 3+ cardiovascular risk factors (1.00, p = 0.03; 1.09, p = 0.04). The intervention group demonstrated a higher increase in the percentage of participants with intermediate or ideal LS7 scores than the control group, although these differences were not statistically significant. Conclusions Our culturally tailored mHealth lifestyle intervention was associated with significant increases in LS7 scores among African Americans with preexisting cardiovascular risk factors, suggesting its efficacy in improving cardiovascular health among this population.

AbstractObjectiveThis study aimed to evaluate the diagnostic accuracy of dried blood spot (DBS) compared with conventional serum Aquaporin‐4‐IgG (AQP4‐IgG) testing.MethodsProspective multicenter diagnostic study was conducted between April 2018 and October 2023 across medical centers in the United States, Uganda, and the Republic of Guinea. Neuromyelitis optica spectrum disorder (NMOSD) patients and controls collected blood on filter paper cards along with concurrent serum samples. These samples underwent analysis using flow cytometric live‐cell‐based assays (CBA) and enzyme‐linked immunosorbent assay (ELISA) to determine AQP4 serostatus. The accuracy of AQP4‐IgG detection between DBS and serum (gold standard) was compared.ResultsAmong 150 participants (47 cases, 103 controls), there was a strong correlation between DBS and serum samples (Spearman's correlation coefficient of 0.82). The AUC was 0.97 (95% CI: 0.92–0.99). AQP4‐IgG detection through DBS showed 87.0% sensitivity (95% CI: 0.74–0.95) and 100% specificity (95% CI: 0.96–1.00) using CBA, and 65.2% sensitivity (95% CI: 0.43–0.84) and 95.2% specificity (95% CI: 0.76–0.99) using ELISA. Serum ELISA demonstrated 69.6% sensitivity (95% CI: 0.47–0.87) and 98.4% specificity (95% CI: 0.91–0.99). The stability of DBS in detecting AQP4‐IgG persisted over 24 months for most cases.InterpretationThe DBS represents a viable alternative for detecting AQP4‐IgG in resource‐limited settings to diagnose NMOSD, offering high sensitivity and specificity comparable to serum testing. Moreover, DBS has low shipping costs, is easy to administer, and is suitable for point‐of‐care testing.

Abstract Pleomorphic xanthoastrocytomas (PXAs) harbor CDKN2A homozygous deletion in &gt;90% of cases, resulting in loss of p16 expression by immunohistochemistry. Considering the proximity of MTAP to CDKN2A and their frequent concurrent deletions, loss of MTAP expression may be a surrogate for CDKN2A homozygous deletion. We evaluated p16 and MTAP expression in 38 patient PXAs (CNS WHO grade 2: n = 23, 60.5%; grade 3: n = 15, 39.5%) with available chromosomal microarray data to determine whether MTAP can be utilized independently or in combination with p16 to predict CDKN2A status. CDKN2A, CDKN2B, and MTAP homozygous deletion were present in 37 (97.4%), 36 (94.7%), and 25 (65.8%) cases, respectively. Expression of p16 was lost in 35 (92.1%) cases, equivocal in one (2.6%), and failed in 2 (5.3%), while MTAP expression was lost in 27 (71.1%) cases, retained in 10 (26.3%), and equivocal in one (2.6%). This yielded a sensitivity of 94.6% for p16 and 73.0% for MTAP in detecting CDKN2A homozygous deletion through immunohistochemistry. MTAP expression was lost in the 2 cases with failed p16 staining (combined sensitivity of 100%). Our findings demonstrate that combined p16 and MTAP immunostains correctly detect CDKN2A homozygous deletion in PXA, while MTAP expression alone shows reduced sensitivity.

Background and Aims: Early identification of malignant biliary strictures (MBSs) is challenging, with up to 20% classified as indeterminants after preliminary testing and tissue sampling with endoscopic retrograde cholangiopancreatography. We aimed to evaluate the use of methylated DNA markers (MDMs) from biliary brushings to enhance MBS detection in a prospective cohort. Approach: Candidate MDMs were evaluated for their utility in MBS diagnosis through a series of discovery and validation phases. DNA was extracted from biliary brushing samples, quantified, bisulfite-converted, and then subjected to methylation-specific droplet digital polymerase chain reaction. Patients were considered to have no malignancy if the sampling was negative and there was no evidence of malignancy after 1 year or definitive negative surgical histopathology. Results: Fourteen candidate MDMs were evaluated in the discovery phase, with top-performing and new markers evaluated in the technical validation phase. The top 4 MDMs were TWIST1, HOXA1, VSTM2B, and CLEC11A, which individually achieved AUC values of 0.82, 0.81, 0.83, and 0.78, respectively, with sensitivities of 59.4%, 53.1%, 62.5%, and 50.0%, respectively, at high specificities for malignancy of 95.2%–95.3% for the final biologic validation phase. When combined as a panel, the AUC was 0.86, achieving 73.4% sensitivity and 92.9% specificity, which outperformed cytology and fluorescence in situ hybridization (FISH). Conclusions: The selected MDMs demonstrated improved performance characteristics for the detection of MBS compared to cytology and FISH. Therefore, MDMs should be considered viable candidates for inclusion in diagnostic testing algorithms.

AbstractSinonasal mucosal melanoma (SNMM) is a rare malignancy with poor prognosis and high recurrence rate. In those with recurrence, survival is dismal. Immunotherapy is an emerging area of investigation; however, there is a scarcity of data on immunotherapy outcomes in SNMM patients with recurrence. We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty‐four patients with recurrent SNMM were identified, and 31 (57.4%) had distant recurrence. One‐year overall survival (OS) following recurrence was 47.5% (95% confidence interval [CI]: 34.0%‐60.9%), with a median survival of 2.8 years (95% CI: 2.0‐5.3). In those with distant recurrence, receipt of immunotherapy was associated with better OS compared to those without immunotherapy (hazard ratio [HR] = 0.29 [95% CI: 0.12‐0.68], P = .004). While patients with nondistant recurrence (n = 23), who received immunotherapy (n = 6) had worse OS compared to those who did not receive immunotherapy (HR = 4.76 [95% CI: 1.36, 15.89], P = .02).Level of EvidenceLevel IV.

Background: Physical inactivity and poor adherence to healthy eating guidelines impact cardiovascular health (CVH) outcomes in African American (AAs). Our randomized controlled trial (RCT) testing the FAITH! App, an mHealth lifestyle intervention, showed efficacy in promoting ideal CVH, particularly diet and physical activity (PA) among AAs, warranting exploration of underlying factors. Psychosocial factors (e.g., self-regulation, self-efficacy, social support) are key to healthy behavior adoption. Hypothesis: The intervention group would have greater improvements in diet and PA-related psychosocial factors than the control group after using the FAITH! App. Methods: A 2-arm cluster RCT was conducted among AAs from 16 churches in Minnesota comparing the FAITH! App intervention to a delayed intervention control group. The FAITH! App included culturally relevant, CVH-focused education modules, diet/PA self-monitoring and a sharing board. The outcomes were change in diet and PA self-regulation and self-efficacy (primary) and social support and barriers (secondary) at 6 months post-intervention. The intervention effect was assessed using linear regression. Results: Sixty-eight participants were included (71% female; mean age [SD]: 54.7 [12.6] years) ( Table 1 ). The intervention group showed a significantly greater increase in diet self-regulation [planning/tracking nutrition] (+0.66, p<.03) and PA self-regulation [step count strategies] (+0.47, p=.003) than the control group. Within groups, the intervention group demonstrated significant improvements across diet and PA self-regulation measures, while the control group showed an improvement only in fruit/vegetable and grain intake. No effect was observed in self-efficacy, social support, or barriers. Conclusions: Our culturally tailored mHealth lifestyle intervention was associated with notable increases in diet and PA self-regulation, suggesting a potential mechanism by which the FAITH! App improves healthy eating and PA among AAs.

Prognostic stratification of pulmonary carcinoids into “typical” and “atypical” categories requires examination of large tissue volume. However, there is a need for tools that provide similar prognostic information on small biopsy samples. Ki-67 and OTP immunohistochemistry have shown promising prognostic value in studies of resected pulmonary carcinoids, but prognostic value when using biopsy/cytology specimens is unclear. Ki-67 immunohistochemistry was performed on small biopsy/cytology specimens from pulmonary carcinoid tumors (n=139), and labeling index was scored via automated image analysis of at least 500 cells. OTP immunohistochemistry was performed on 70 cases with sufficient tissue and scored as positive or negative (<20% tumor nuclei staining). Higher Ki-67 index was associated with worse disease-specific progression-free survival (ds-PFS), with 3% and 4% thresholds having similarly strong associations with ds-PFS ( P <0.001, hazard ratio ≥11). Three-year ds-PFS was 98% for patients with Ki-67 <3% and 89% for patients with Ki-67≥3% ( P =0.0006). The optimal Ki-67 threshold for prediction of typical versus atypical carcinoid histology on subsequent resection was 3.21 (AUC 0.68). Negative OTP staining approached significance with atypical carcinoid histology ( P =0.06) but not with ds-PFS ( P =0.24, hazard ratio=3.45), although sample size was limited. We propose that Ki-67 immunohistochemistry may contribute to risk stratification for carcinoid tumor patients based on small biopsy samples. Identification of a 3% hot-spot Ki-67 threshold as optimal for prediction of ds-PFS is notable as a 3% Ki-67 threshold is currently used for gastrointestinal neuroendocrine tumor stratification, allowing consideration of a unified classification system across organ systems.

Background Extended sedentary behavior is a risk factor for chronic disease and mortality, even among those who exercise regularly. Given the time constraints of incorporating physical activity into daily schedules, and the high likelihood of sitting during office work, this environment may serve as a potentially feasible setting for interventions to reduce sedentary behavior. Methods and Results A randomized cross‐over clinical trial was conducted at an employee wellness center. Four office settings were evaluated on 4 consecutive days: stationary or sitting station on day 1 (referent), and 3 subsequent active workstations (standing, walking, or stepper) in randomized order. Neurocognitive function (Selective Attention, Grammatical Reasoning, Odd One Out, Object Reasoning, Visuospatial Intelligence, Limited‐Hold Memory, Paired Associates Learning, and Digit Span) and fine motor skills (typing speed and accuracy) were tested using validated tools. Average scores were compared among stations using linear regression with generalized estimating equations to adjust standard errors. Bonferroni method adjusted for multiple comparisons. Healthy subjects were enrolled (n=44), 28 (64%) women, mean±SD age 35±11 years, weight 75.5±17.1 kg, height 168.5±10.0 cm, and body mass index 26.5±5.2 kg/m 2 . When comparing active stations to sitting, neurocognitive test either improved or remained unchanged, while typing speed decreased without affecting typing errors. Overall results improved after day 1, suggesting habituation. We observed no major differences across active stations, except decrease in average typing speed 42.5 versus 39.7 words per minute with standing versus stepping ( P =0.003). Conclusions Active workstations improved cognitive performance, suggesting that these workstations can help decrease sedentary time without work performance impairment. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06240286.