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ImportanceUptake of human papillomavirus (HPV) vaccination varies by characteristics, exposing some children to higher HPV cancer risks than others.ObjectiveTo examine whether the effectiveness of a multilevel intervention on HPV vaccination differed by race and ethnicity, rurality, and Area Deprivation Index (ADI) in children ages 11 to 12 years.Design, Setting, and ParticipantsA stepped-wedge cluster randomized trial was conducted from April 2018 to August 2022 among children at 6 Mayo Clinic primary care practices in Minnesota to improve HPV vaccination. This secondary analysis was performed from March to June 2024.InterventionA multilevel intervention that included parent reminder/recall letters, which alerted parents of children due or past due for vaccination, and health care professional audit/feedback reports, which alerted health care professionals of their own vaccination rates.Main Outcome and MeasureVaccine initiation (first dose of the 2-dose HPV vaccine) and vaccine completion (second dose) were the primary study outcomes. In this secondary analysis, the effect of the intervention on HPV vaccine initiation and completion by race and ethnicity, rurality, and ADI quartiles (Qs) was assessed.ResultsA total of 6232 children aged 11 to 12 years (3285 [52.7%] male; 3481 [55.9%] aged 11 years and 2751 [44.1%] aged 12 years) were included in the analysis. Of the study participants, 304 (4.9%) were Asian, 561 (9.0%) Black, 146 (2.3%) Hispanic, 4501 (72.2%) White, and 720 (11.6%) other, including American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, Other Pacific Islander, Samoan, unable to provide, unknown, chose not to disclose, or other unspecified. A total of 5434 participants (87.2%) were urban residents, and 2794 (44.8%) resided in ADI Q2 areas. With usual care, HPV vaccine initiation and completion rates were significantly lower with each increasing ADI quartile (initiation: Cochran-Armitage test for trend [SE], −0.02 [0.01]; P < .001; completion: Cochran-Armitage test for trend [SE], −0.05 [0.01]; P < .001) but did not differ by children’s race and ethnicity or rurality. With the intervention, vaccine initiation increased significantly for most children (range of rates, 9.2% [95% CI, 5.2%-13.3%] to 24.0% [95% CI, 7.5%-40.6%]) except those with Black race, in rural settings, and in ADI Q4 (highest area deprivation); vaccine completion increased significantly for most children (range of rates, 19.4% [95% CI, 5.5%-33.3%] to 31.2% [95% CI, 12.1%-50.3%]) except for those in ADI Q4.Conclusions and RelevanceIn this secondary analysis of a cluster randomized trial, a multilevel intervention was associated with increased HPV vaccination for most children but had limited effect for those residing in areas of highest deprivation. Future research should explore other intervention strategies that would effectively promote HPV vaccination among families in socioeconomically disadvantaged areas to reduce HPV vaccination disparities.Trial RegistrationClinicalTrials.gov Identifier: NCT03501992

ImportanceEtiologic heterogeneity in breast carcinogenesis needs to be well characterized for targeted prevention. Associations between menopausal hormonal therapy (MHT) and oral contraceptive (OC) use and breast cancer intrinsic-like subtypes are not well understood.ObjectiveTo examine whether exogenous hormone use is differentially associated with breast cancer subtypes and to evaluate heterogeneity by intrinsic-like subtypes.Design, Setting, and ParticipantsThis study pooled data from 31 nested and population-based case-control studies involved in the Breast Cancer Association Consortium. The study population included individuals with breast cancer and control participants from 13 case-control studies nested in prospective cohorts (recruited between 1982 and 2011) and 18 population-based case-control studies (recruited between 1990 and 2013). Data analysis was performed in June 2024.ExposureMHT use (estrogen-progestin therapy [EPT] or estrogen-only therapy [ET]) in postmenopausal women and OC use in premenopausal women (never, past use, or current use).Main Outcomes and MeasuresBreast cancer intrinsic-like subtypes (luminal A–like, luminal B–like, luminal B–ERBB2 [formerly HER2 or HER2/neu]-like, ERBB2 enriched–like, or triple-negative) were determined by immunohistochemistry of tumor sections. Polytomous logistic regression was performed to estimate the association between exogenous hormones and risk of breast cancer by intrinsic-like subtypes. Analyses by subtypes were stratified by body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]; healthy weight, 18.5-<25; overweight, 25-<30; or obesity, ≥30).ResultsThis study included 42 269 individuals with breast cancer (11 901 [28.2%] premenopausal and 30 368 [71.8%] postmenopausal; 23 353 [55.2%] had a known intrinsic-like subtype) and 71 072 control participants. The mean (SD) age of all participants was 57.9 (10.9) years. In postmenopausal women, associations between current MHT use (EPT or ET) and breast cancer differed by subtype. Current EPT users with healthy weight were more likely to be diagnosed with luminal A–like (odds ratio [OR], 2.51 [95% CI, 2.26-2.80]) or luminal B–ERBB2-like (OR, 1.95 [95% CI, 1.61-2.37]) subtypes. These associations were attenuated but remained for individuals with overweight (OR, 1.40 [95% CI, 1.02-1.92]) or obesity (OR, 1.68 [95% CI, 1.01-2.78]). EPT use increased the odds of being diagnosed with luminal B–like tumors solely in women with healthy weight (OR, 1.47 [95% CI, 1.17-1.86]). Current ET use was positively associated with luminal A–like disease in women with healthy weight only (OR, 1.16 [95% CI, 1.01-1.32]), showing inverse associations with higher BMI (obesity: OR, 0.65 [95% CI, 0.50-0.85]). In premenopausal women, recent OC use was associated with luminal B–ERBB2-like (OR, 1.50 [95% CI, 1.09-2.08]), ERBB2 enriched–like (OR, 2.33 [95% CI, 1.55-3.51]), and triple-negative (OR, 1.75 [95% CI, 1.33-2.29]; P < .04 for heterogeneity) tumors.Conclusions and RelevanceIn this study, clear differences were observed in associations between current EPT use and luminal-like breast cancer subtypes and other subtypes. EPT users with healthy weight were more likely to be diagnosed with luminal-like breast cancer compared with nonusers. Subtype heterogeneity was less apparent in associations of OC and ET use. Future studies on contemporary formulations, patterns of use, and routes of administration of exogenous hormone usage are warranted.

BACKGROUND AND OBJECTIVES: Gynecological cancers represent 10% to 15% of cancers in women, but brain metastases (BM) are uncommon, with limited evidence regarding their management. This study investigates the role of stereotactic radiosurgery (SRS) for BM from primary gynecological cancers. METHODS: Institutions of the International Radiosurgery Research Foundation participated in this study. Inclusion criteria required histological diagnosis of epithelial ovarian, cervical, or endometrial cancer, SRS between 2000 and 2020, and at least 1 imaging or clinical follow-up. RESULTS: A total of 276 patients having SRS for 977 BM were included. Median age at SRS was 62 years (IQR, 55-70). Primary cancer origin was ovarian in 128 (46%), cervical in 43 (16%), and endometrial in 105 patients (38%). Median Karnofsky Performance Scale was 80%, and systemic disease was active in 124 (45%) of patients. A median of 1 metastasis was treated (IQR, 1-3) per patient. Median individual metastasis volume was 0.27 cc (IQR, 0.05-1.59 cc). The majority (91%) received single-fraction SRS, using a median margin dose of 18 Gy (IQR, 16-20 Gy). Actuarial overall survival was 77%, 65%, and 44% at 6, 12, and 24 months, respectively. Predictors of worsened survival included older age, cervical and endometrial primary, previous whole-brain radiation therapy (WBRT), active systemic disease, worsened Karnofsky Performance Scale, absence of subsequent surgery, and increasing number of BM. Actuarial local control was 94% at 6 months, 89% at 12 months, and 78% at 24 months. Previous SRS or WBRT, tumor bed treatment, and cervical histology increased the risk of local failure. New remote BM and leptomeningeal dissemination occurred in 44% and 11% of patients, respectively. Adverse radiation effects (ARE) occurred in 13% of cases but were symptomatic in only 3%. Previous WBRT or SRS and increased tumor diameter increased the risk of ARE. CONCLUSION: SRS is an effective management for BM from gynecological cancers with low risks of symptomatic ARE.

Objectives Periodic quality control (QC) testing of ultrasound (US) imaging systems is essential to ensure and maintain image quality and safety. The study aims to analyze QC findings from medical physics annual surveys of modern clinical US systems in a multi‐institutional survey. Methods QC results from annual surveys between 2018 and 2021 were retrospectively collected from 12 medical physicists from 11 institutions or consulting companies (hereafter referred to as sites). QC tests were classified as scanner‐ and transducer‐related tests, where scanner‐related tests also included evaluation of diagnostic workstation display monitors and routine QC programs if applicable. Test methodology and pass/fail criteria were established by each site. QC findings were defined as results requiring follow‐up action by service engineers, vendors, or other personnel. The percentage of annual findings was calculated for each site and averaged across the years of data contributed. Furthermore, findings across all sites were aggregated for an overall analysis. Results QC data from a total of 1069 scanner tests and 4542 transducer tests were collected. The average annual percentage of scanner‐related findings varied from 0 to 40.8% among all sites (first quartile 8.7%, median 18.2%, and third quartile 34.1%), while that of transducer‐related findings ranged between 0.5% and 19.9% (first quartile 3.9%, median 7.2%, and third quartile 14.5%). For scanner‐related tests, the top 3 categories of findings were associated with physical and mechanical integrity (171 findings, 74.7%), quantitative testing of the scanner display monitor (40 findings, 17.5%), and scanner port creating artifacts (10 findings, 4.4%). The top 3 findings for transducers related to uniformity and artifact (227 findings, 79.9%), physical and mechanical integrity (44 findings, 15.5%), and sensitivity in fundamental mode (9 findings, 3.2%). Conclusions Medical physics annual surveys revealed considerable actionable findings of modern US systems, which inform the status of current US QC practices in the United States and may guide future standardization and recommendation of QC tests.

AbstractDespite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (MRD) is a promising surrogate end point candidate, providing a sensitive and quantitative assessment of disease burden. Numerous studies have demonstrated that negative MRD status—across diverse methodologies, assessment timepoints and thresholds, patient subgroups, and clinical settings—independently predicts improved survival. Although MRD can inform therapeutic decisions at the patient level, its formal integration as a primary surrogate end point in regulatory frameworks for clinical trials requires rigorous validation. MRD Partnership and Alliance in AML Clinical Treatment (MPAACT) is a research consortium among industry and academic leaders. MPAACT actively engages with regulatory agencies, health technology assessment bodies, technology vendors, and patient groups to establish a pathway for validating MRD as a surrogate end point in AML clinical trials. For the current article, the authors reviewed the status of MRD assessment, its use in recent clinical trials, current MRD assessment methodologies, standardization, regulatory guidance, statistical approaches, and patient access considerations necessary for MRD to become a surrogate clinical trial end point. The extensive collaboration between MPAACT, global industry, and academic partners—including data sharing and resource integration—underscores the collective commitment to advancing AML therapies. Establishing MRD as a surrogate end point could accelerate the development and approval of innovative treatments, ultimately improving patient outcomes.

Multidisciplinary case conferences have been shown to improve patient outcomes. However, such case conferences may be unavailable in some settings. This multidisciplinary discussion of 4 challenging hepatobiliary cases was presented at the 2023 Society of Advanced Body Imaging Annual Meeting in Dallas, TX. The cases include an “imaging occult” pancreatic tumor, a large pancreatic mass, an intraductal biliary mass, and a polypoid intraluminal gallbladder mass.

Abstract Objectives In 2023, AMIA’s Inclusive Language and Context Style Guidelines (the “Guidelines”) were approved by the Board of Directors and made a publicly available resource. This work began in 2021 through AMIA’s DEI Task Force and subsequent DEI Committee; many members provided input, feedback, and time to create the Guidelines. In this paper, the authors provide a transparent account of the origin, development, contents, and dissemination of the Guidelines and share plans for their future development and use. Materials and Methods Our approach to drafting, refining, and distributing the Guidelines included consulting existing language guides, AMIA member reviews, external expert reviews, webinars, and workshops. Through an iterative approach to drafting and refining the Guidelines, the authors consulted relevant language guidelines and many experts throughout and beyond the AMIA community. Results The Inclusive Language Context Guidelines were formally approved by the AMIA Board of Directors on February 15, 2023. The Guidelines included four principles to be considered in scientific communications: Plurality, Precision, Transparency, and Destigmatization. Discussion A moment of vulnerability where an AMIA member raised concerns about the use of harmful language during a presentation resulted in the creation of a principled approach to support inclusive language within biomedical and health informatics communications. We envision that the Guidelines will support health equity by challenging dominant public narratives around health, fostering stronger interdisciplinary collaboration and critical thinking about the impact of language, and creating a more welcoming environment for the broader AMIA community. This work could not have been completed without the support of many AMIA members and other researchers in biomedical and health informatics. The Guidelines are a living document that will continue to be updated with input and feedback from the AMIA community into the future.

Background: The use of validated risk stratification tools for the workup of suspected pulmonary embolism (PE) is a recommendation of the American Society of Hematology and the American College of Emergency Physicians. Methods: We designed and implemented electronic clinical pretest probability (PTP) tools for use in emergency departments (ED). Overall, 38 EDs (tertiary and regional EDs) in the United States were involved across three health systems. PTP use was analyzed between September 12, 2022 and January 11, 2023 in 270,247 ED visits. PTP use was examined in terms of the percentage of visits for which patients underwent computed tomography pulmonary angiography (CTPA). Each site chose the 3-tier Wells’ score for implementation and Site 2 designed a combined Wells’, pulmonary embolism rule-out criteria (PERC), and YEARS score. Results: At Site 3, forced use resulted in documented PTP scores in 49–53% of ordered CTPAs. At Sites 1 and 2, where PTP scores were optional, documented PTP scores occurred in 2–3% and 1–3% of CTPA orders, respectively. At Site 1, the use of PTP increased slightly over the study period, with signs that PE yield on imaging was also increasing (3.4–5.9%). At Site 2, PE yield on imaging was 9–10%, and it remained similar, with similar use of PTP tools over the study period. PE yield (6–8%) on imaging also remained similar throughout the study at Site 3. Conclusions: Guideline-endorsed PTP scores for PE at three independent health systems in the United States did not increase PE yield on imaging. Novel implementation strategies involving interdisciplinary teams are urgently needed.

ABSTRACT Peritoneal fibrosis is one of the main causes of peritoneal dysfunction and withdrawal of patients from peritoneal dialysis (PD). Our previous study has shown that high‐glucose dialysis solution promotes glycolysis in peritoneal mesothelial cells, leading to mesothelial‐to‐mesenchymal transition (MMT) and peritoneal fibrosis. However, the molecular mechanisms remain unclear. Using single‐cell RNA sequencing (scRNA‐seq) analysis of cells from the effluent of patients undergoing PD from our previous study, we found that pyruvate kinase isozymes M2 (PKM2), a key rate‐limiting enzyme of glucose metabolism, was significantly upregulated in the mesothelial cells of patients with long‐term peritoneal dialysis (LPD). Using co‐immunoprecipitation, chromatin immunoprecipitation assay, and gene silencing techniques, we revealed that PKM2 promotes the expression of transcription factor SNAI2 by acetylating histone H3K9 (H3K9ac), thereby promoting the occurrence of MMT and hence peritoneal fibrosis. l ‐cysteine, a known PKM2 inhibitor, blocked these responses and prevented PD‐induced peritoneal fibrosis. These results could provide a novel therapeutic strategy for treating peritoneal fibrosis.