Search

Background: Risk biomarkers that are specific to ER subtypes of breast cancer would help developing distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast is a good model for defining subtype specific risk as women with ER- primary tumor are at high risk for subsequent ER- tumor in contralateral breast. Methods: We performed random fine needle aspiration of unaffected breast of cases. RNA samples from 30 subjects (15 ER+ and 15 ER-) were used for Ilumina expression array analysis. Findings were validated by qRT-PCR using independent sample set consisted of 36 subjects (12 ER+, 12 ER-, and 12 standard risk healthy controls). Results: Gene array studies identified 18 genes with significant higher expression in ER- case samples, 8 of which were associated with lipid metabolism. This pattern was confirmed by qRT -PCR in the same samples and in the 24 cases of validation set. When compared to the healthy controls, significant over-expression of 4 genes (DHRS2, HMGCS2, HPGD, ACSL3) was observed in ER- cases, with significant lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes. Conclusion: Differential expression of lipid metabolism genes my be involved in the risk for subtypes of breast cancer, which might be potential biomarkers of ER specific breast cancer risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To test a multimedia patient education program on colorectal cancer (CRC) screening that was designed specifically for the Hispanic/Latino community, and developed with input from community members. METHODS: A total of 270 Hispanic/Latino adults, age 50-80 years, participated in Spanish for all phases of this pretest-posttest design. Patients were randomly assigned to a version of the multimedia program that opened with either a positive or negative introductory appeal. Structured interviews assessed screening relevant knowledge (anatomy and key terms, screening options, and risk information), past screening behavior, willingness to consider screening options, intention to discuss CRC screening with the doctor, and reactions to the multimedia patient education program. RESULTS: The multimedia program significantly increased knowledge of anatomy and key terms (e.g., polyp), primary screening options (FOBT, flexible sigmoidoscopy, colonoscopy), and risk information as well as willingness to consider screening (p<.001 for all). No significant differences emerged between positive and negative introductory appeals on these measures, intention to discuss CRC screening with their doctor, or rating the multimedia program. CONCLUSION: Multimedia tools developed with community input that are designed to present important health messages using graphics and audio can reach Hispanic/Latino adults across literacy levels and ethnic backgrounds. Additional research is needed to determine effects on actual screening behavior. PRACTICE IMPLICATIONS: Despite promising results for engaging a difficult-to-reach audience, the multimedia program should not be considered a stand-alone intervention or a substitute for communication with physicians. Rather, it is a priming mechanism intended to prepare patients for productive discussions of CRC screening. [ABSTRACT FROM AUTHOR]

We examined the association between blood pressure (BP) in the early third trimester and hypertension 10-14 years after delivery per American College of Cardiology and American Heart Association recommendations. We conducted a secondary analysis using the prospective HAPO FUS (Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study) in patients without a chronic hypertension diagnosis. The exposure and outcome were systolic and diastolic BP measured in the early third trimester and 10-14 years after delivery, respectively. Among 4,697 participants in the HAPO FUS, at 10-14 years after delivery (median age 41.6 years), 8.3% had elevated BP, 14.1% had stage 1 hypertension, and 6.1% had stage 2 hypertension. Compared with normal BP, elevated BP in the early third trimester was associated with an increased risk of stage 1 hypertension (adjusted odds ratio [aOR] 2.76; 95% CI, 1.91-4.00) and stage 2 hypertension (aOR 3.76; 95% CI, 2.28-6.19). Stage 1 hypertension was associated with an increased risk of stage 2 hypertension (aOR 6.16; 4.24, 8.94). Pregnant individuals with high BP in the third trimester were at increased risk of developing hypertension 10-14 years after delivery., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain., Objective: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence., Study Design: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up., Results: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure., Conclusion: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 25 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. These data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics statement: Northwestern University and Lurie Children’s Institutional Review Boards reviewed and approved the studies involving human participants (Northwestern STU00201858, Lurie IRB 2018–2145). The patients/participants provided their written informed consent to participate in this study., (© 2024. The Author(s).)

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth. In this study, we comprehensively characterized the cord blood proteome of infants born between 24 to 42 weeks using untargeted mass spectrometry and functional enrichment analysis. We determined that the cord blood proteome at birth varies significantly across gestational development. Proteins that function in structural development and growth (e.g., extracellular matrix organization, lipid particle remodeling, and blood vessel development) are more abundant earlier in gestation. In later gestations, proteins with increased abundance are in immune response and inflammatory pathways, including complements and calcium-binding proteins. Furthermore, these data contribute to the knowledge of the physiologic state of neonates across gestational age, which is crucial to understand as we strive to best support postnatal development in preterm infants, determine mechanisms of pathology causing adverse health outcomes, and develop cord blood biomarkers to help tailor our diagnosis and therapeutics for critical neonatal conditions., Competing Interests: JFH has received research support, paid to Northwestern University, from Gilead Sciences, and is a paid consultant for Merck. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Associations between pregnancy dysglycemia and subsequent maternal cardiometabolic factors 10-14 years postpartum were largely similar across self-identified racial and ethnic groups among birthing people in the U.S. enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-up Study., Competing Interests: Conflict of interest None of the authors report a conflict of interest., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: People with cancer experience symptoms that adversely affect quality of life. Despite existing interventions and clinical guidelines, timely symptom management remains uneven in oncology care. We describe a study to implement and evaluate an electronic health record (EHR)-integrated symptom monitoring and management program in adult outpatient cancer care., Methods: Our cancer patient-reported outcomes (cPRO) symptom monitoring and management program is a customized EHR-integrated installation. We will implement cPRO across all Northwestern Memorial HealthCare (NMHC) hematology/oncology clinics. We will conduct a cluster randomized modified stepped-wedge trial to evaluate patient and clinician engagement with cPRO. Further, we will embed a patient-level randomized clinical trial to evaluate the impact of an additional enhanced care (EC; cPRO plus web-based symptom self-management intervention) relative to usual care (UC; cPRO alone). The project uses a Type 2 hybrid effectiveness-implementation approach. The intervention will be implemented across seven regional clusters within the healthcare system comprising 32 clinic sites. A 6-month prospective pre-implementation enrollment period will be followed by a post-implementation enrollment period, during which newly enrolled, consenting patients will be randomly assigned (1:1) to EC or UC. We will follow patients for 12 months post-enrollment. Patients randomized to EC will receive evidence-based symptom-management content on cancer-related concerns and approaches to enhance quality of life, using a web-based tool ("MyNM Care Corner"). This design allows for within- and between-site evaluation of implementation plus a group-based comparison to demonstrate effectiveness on patient-level outcomes., Discussion: The project has potential to guide implementation of future healthcare system-level cancer symptom management programs. http://ClinicalTrials.gov # NCT03988543., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight., (© 2023. The Author(s).)