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Context.--Hypergastrinemia states such as achlorhydria from gastric mucosal atrophy or a gastrin-producing tumor in humans have been associated with the development of enterochromaffin-like (ECL) cell hyperplasia and gastric neuroendocrine tumors (GNETs). Whether drugs that can elevate serum gastrin levels, such as proton pump inhibitors (PPIs), can produce the same tissue effect is not known, and there is no concrete evidence linking the use of PPIs to GNETs outside animal models and case reports. Objective.--To explore the clinicopathologic association for GNETs of presumed ECL cell origin that cannot be reliably placed into any of the 3 established categories currently recognized by the World Health Organization. Design.--This is a retrospective clinicopathologic study of GNETs in the body/fundus during a period of 15 years (2005-2019). Results.--Of a total of 87 cases, 57 (65.5%) were associated with atrophic gastritis, 2 (2.3%) were associated with Zollinger-Ellison syndrome, and 28 (32.2%) were unclassified. Of the latter, 11 were consistent with true sporadic/type 3 GNETs, while 17 had background mucosal changes of parietal cell and ECL cell hyperplasia but without underlying detectable gastrinoma, and 88.2% (15 of 17) of patients from this group had documented longterm PPI use. This subtype of GNETs was more commonly multifocal and of higher grade (P = .03) than 'true' sporadic GNETs. Conclusions.--A subset of GNETs arises in the background of gastric mucosal changes suggestive of hypergastrinemia, but without underlying gastrinoma, and could be linked to long-term PPI use. (Arch Pathol Lab Med. 2022;146:366-371; doi: 10.5858/arpa.2020-0315-OA), Gastric neuroendocrine tumors (GNETs) are uncommon neoplasms of the gastrointestinal tract. (1) They are currently classified into 3 clinicopathologic categories by the World Health Organization (WHO), (2) with types 1 [...]

PurposeThe long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer.Methods and materialsWe analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ2 or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level.ResultsFor subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively.ConclusionsCompared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT.

ImportanceUnderstanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALSSOD1) will provide key information for optimising clinical trials in this patient population.ObjectiveTo establish an updated natural history of ALSSOD1.Design, setting and participantsRetrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.Main outcomes and measuresAge of onset, survival, ALS Functional Rating Scale (ALS-FRS) scores and respiratory function were analysed. Patients with the A4V (Ala-Val) SOD1 mutation (SOD1A4V), the largest mutation population in North America with an aggressive disease progression, were distinguished from other SOD1 mutation patients (SOD1non-A4V) for analysis.ResultsMean age of disease onset was 49.7±12.3 years (mean±SD) for all SOD1 patients, with no statistical significance between SOD1A4V and SOD1non-A4V (p=0.72, Kruskal-Wallis). Total SOD1 patient median survival was 2.7 years. Mean disease duration for all SOD1 was 4.6±6.0 and 1.4±0.7 years for SOD1A4V. SOD1A4V survival probability (median survival 1.2 years) was significantly decreased compared with SOD1non-A4V (median survival 6.8 years; p

Objective To explore the role and mechanism of serum response factor (SRF) in differentiation of rat bone marrow mesenchymal stem cells (MSCs) into bladder smooth muscle cells (SMCs). Methods Rat MSCs and SMCs were isolated respectively from the bone marrow and bladder of 4-week-old female SD rats by adherent method, and then co-cultured together in a Transwell chamber. After the MSCs were harvested at different time points, real-time PCR and immunofluorescense assay were used to detect the expression of SMCs specific marker genes in co-cultured MSCs. Furthermore, the enrichment of histone acetylation modification, histone deacetylase (HDAC) and SRF in the promoter of these genes were tested by chromatin immunoprecipitation assay (ChIP) q-PCR in co-cultured MSCs. Finally, ChIP-qPCR was used to compare the histone acetylation modification and SRF enrichment in sodium butyrate (NaB) pretreatment group with control cells. Results The expression levels of α-SMA, Calponin and SM-MHC were increased in MSCs co-cultured with SMCs. H3K9ace, H3ace and H4ace in the promoter of these genes were enriched (P

Background: Students with intellectual and developmental disabilities (IDD) were disproportionately impacted by the COVID‐19 pandemic. This study's goal was to assess the effectiveness of 2 messaging strategies on participation in SARS‐CoV‐2 weekly testing. Methods: Cluster randomized trials were conducted at 2 school systems, the special school district (SSD) and Kennedy Krieger Institute (Kennedy) to assess messaging strategies, general versus enhanced, to increase weekly screening for SARS‐CoV‐2. Testing was offered to staff and students from November 23, 2020 to May 26, 2022. The primary outcomes were percentage of students and staff consented weekly and percentage of study participants who had a test performed weekly. Generalized estimating equation models were utilized to evaluate the primary outcomes. Results: Increases in enrollment and testing occurred during study start up, the beginning of school years, and following surges in both systems. No statistical difference was observed in the primary outcomes between schools receiving standard versus enhanced messaging. Implications for School Health Policy, Practice, and Equity: Frequent and consistent communication is vital for families and staff. Weekly screening testing within schools is possible and highlighted the importance of utilizing equitable protocols to provide important testing to students with IDD. Conclusion: Enhanced messaging strategies did not increase the number of participants enrolled or the percentage of enrolled participants being tested on a weekly basis. [ABSTRACT FROM AUTHOR]

PurposeComorbid medical conditions are common among breast cancer survivors, contribute to poorer long-term survival and increased overall mortality, and may be ameliorated by weight loss. This secondary analysis evaluated the impact of a weight loss intervention on comorbid medical conditions immediately following an intervention (12 months) and 1-year postintervention (24 months) using data from the Exercise and Nutrition to Enhance Recovery and Good health for You (ENERGY) trial-a phase III trial which was aimed at and successfully promoted weight loss.MethodsENERGY randomized 692 overweight/obese women who had completed treatment for early stage breast cancer to either a 1-year group-based behavioral intervention designed to achieve and maintain weight loss or to a less intensive control intervention. Minimal support was provided postintervention. New medical conditions, medical conditions in which non-cancer medications were prescribed, hospitalizations, and emergency room visits, were compared at baseline, year 1, and year 2. Changes over time were analyzed using chi-squared tests, Kaplan-Meier, and logistic regression analyses.ResultsAt 12 months, women randomized to the intervention had fewer new medical conditions compared to the control group (19.6 vs. 32.2 %, p

ObjectiveThe purpose of this analysis was to examine the correlates of the physical and psychosocial domains of quality of life (QOL) in a cohort of breast cancer survivors participating in a weight loss intervention trial.MethodsCorrelates of QOL and psychosocial functioning were examined in 692 overweight or obese breast cancer survivors at entry into a weight loss trial. QOL was explored with three measures: Short-form 36 (SF-36), Impact of Cancer scale (IOC), and the Breast Cancer Prevention Trial (BCPT) symptom scales. Available data included information on weight and physical activity, as well as demographic and medical characteristics. Multivariate analyses were used to identify associations adjusted for other characteristics.ResultsIn multivariate analysis, younger age was associated with higher negative impact scores (p