Timing of Surgery and Social Determinants of Health Related to Pathologic Complete Response after Total Neoadjuvant Therapy for Rectal Adenocarcinoma: Retrospective Study of National Cancer Database.

Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to evaluate the relationship between the rest period and pCR. This study utilized the National Cancer Database (NCDB) to retrospectively analyze 5997 stage-appropriate RAC cases treated with TNT from 2016 to 2020. The overall pCR rate was 18.6%, with most patients undergoing induction chemotherapy followed by long-course chemoradiation (81.5%). Multivariable logistic regression models revealed a significant non-linear relationship between the rest period and pCR (p = 0.033), with optimal odds at 14.7-15.9 weeks post radiation (odds ratio: 1.49, 95% confidence interval: 1.13-1.98) when compared to 4.0 weeks. Medicaid, distance to the treatment facility, and community education were associated with decreased odds of pCR. Findings highlight the importance of a 15-16-week post-radiation surgery window for achieving pCR in RAC treated with TNT and socioeconomic factors influencing pCR rates. Findings also emphasize the need for clinical trials to incorporate detailed analyses of the rest period and social determinant of health to better guide clinical practice.

Adipokines and adiposity among postmenopausal women of the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We investigated whether the associations of serum adiponectin, leptin, and resistin with adiposity differ with menopausal age. METHODS: In this cross-sectional study, we included 751 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis (MESA) who reported their menopausal age (<45, 45-49, 50-54 and ≥55 y) and had anthropometrics, serum adipokines, and abdominal computed tomography measures of visceral and subcutaneous adipose tissue (VAT and SAT) obtained at MESA exam 2 or 3. Linear regression models were used for analysis. RESULTS: The mean ± SD age was 65.1 ± 9.0 years for all participants. The median (interquartile range) values for serum adiponectin, leptin and resistin, VAT, and SAT were 21.9 (14.8-31.7) ng/L, 24.3 (12.5-42.4) pg/L, 15.3 (11.8-19.5) pg/L, 183.9 (130.8-251.1) cm2, and 103.7 (65.6-151.5) cm2, respectively. The mean ± SD values for body mass index, waist circumference, and waist-to-hip ratio were 28.3 ± 5.81 kg/m2, 96.6 ± 15.9 cm, and 0.91 ± 0.078, respectively. Adiponectin was inversely associated with all adiposity measures, with similar patterns across menopausal age categories. Leptin was positively associated with all adiposity measures, and the strength of associations varied across menopausal age categories for body mass index, waist circumference, and SAT (Pinteraction ≤ 0.01 for all). The associations of resistin with adiposity measures were mostly nonsignificant except in the 45- to 49-year menopausal age category. CONCLUSIONS: Menopausal age category had no influence on the association of serum adiponectin with adiposity. The association of serum leptin and resistin differed according to menopausal age category for generalized adiposity but was inconsistent for measures of abdominal adiposity.

Listeria-based vaccination against the pericyte antigen RGS5 elicits anti-vascular effects and colon cancer protection.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.

Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression.

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer. Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.

Reduced Risk of All-Cause, Cancer-, and Cardiovascular Disease-Related Mortality among Patients with Primary Malignant Cardiac Tumors Receiving Chemotherapy in the United States.

Primary malignant cardiac tumors (PMCTs) are rare but lethal neoplasms. There are limited evidence-based treatment guidelines for PMCTs. We evaluated the relation of chemotherapy with mortality outcomes in patients with PMCTs in the United States. Data were from patients aged ≥ 20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with PMCTs from 2000 to 2020. Cox regression, competing risk, and propensity score analyses were performed to estimate hazard ratios (HR) and confidence intervals (CI). About 53% of the 563 patients with PMCTs received chemotherapy as the first course of treatment. During a mean follow-up of 24.7 months (median: 10), 458 deaths occurred with 81.7% and 9.4% due to cancer and cardiovascular disease (CVD), respectively. In models adjusted for sociodemographic and clinico-pathophysiological factors including histology, receipt of chemotherapy was associated with low risk for all-cause (HR: 0.56, 95%CI: 0.45-0.69), cancer (HR: 0.63, 95%CI: 0.50-0.80) and CVD mortality (HR: 0.27, 95%CI: 0.12-0.58). Patients who had both chemotherapy and surgery had the lowest risk for all-cause and cancer mortality. This study suggests that the subpopulations of patients with PMCTs who receive chemotherapy may have better prognosis than those who do not receive this therapy regardless of histology.

Global Prevalence of Severe Neonatal Jaundice among Hospital Admissions: A Systematic Review and Meta-Analysis.

Evidence regarding the adverse burden of severe neonatal jaundice (SNJ) in hospitalized neonates in resource-constrained settings is sparse. We attempted to determine the prevalence of SNJ, described using clinical outcome markers, in all World Health Organization (WHO) regions in the world. Data were sourced from Ovid Medline, Ovid Embase, Cochrane Library, African Journals Online, and Global Index Medicus. Hospital-based studies, including the total number of neonatal admissions with at least one clinical outcome marker of SNJ, defined as acute bilirubin encephalopathy (ABE), exchange blood transfusions (EBT), jaundice-related death, or abnormal brainstem audio-evoked response (aBAER), were independently reviewed for inclusion in this meta-analysis. Of 84 articles, 64 (76.19%) were from low- and lower-middle-income countries (LMICs), and 14.26% of the represented neonates with jaundice in these studies had SNJ. The prevelance of SNJ among all admitted neonates varied across WHO regions, ranging from 0.73 to 3.34%. Among all neonatal admissions, SNJ clinical outcome markers for EBT ranged from 0.74 to 3.81%, with the highest percentage observed in the African and South-East Asian regions; ABE ranged from 0.16 to 2.75%, with the highest percentages observed in the African and Eastern Mediterranean regions; and jaundice-related deaths ranged from 0 to 1.49%, with the highest percentage observed in the African and Eastern Mediterranean regions. Among the cohort of neonates with jaundice, the prevalence of SNJ ranged from 8.31 to 31.49%, with the highest percentage observed in the African region; EBT ranged from 9.76 to 28.97%, with the highest percentages reported for the African region; ABE was highest in the Eastern Mediterranean (22.73%) and African regions (14.51%). Jaundice-related deaths were 13.02%, 7.52%, 2.01% and 0.07%, respectively, in the Eastern Mediterranean, African, South-East Asian and European regions, with none reported in the Americas. aBAER numbers were too small, and the Western Pacific region was represented by only one study, limiting the ability to make regional comparisons. The global burden of SNJ in hospitalized neonates remains high, causing substantial, preventable morbidity and mortality especially in LMICs.

Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.

The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women's study.

In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.

Factors Associated with Potentially Inappropriate Screening for Vitamin D Deficiency among Women in Medically Underserved Regions of West Texas.

Testing for vitamin D deficiency (VDD) has been on the increase due to its association with several diseases. However, inappropriate testing for VDD, defined as screening for VDD among individuals with a low risk, has been reported. The aim of this study was to evaluate the prevalence and factors associated with potentially inappropriate screening for VDD among medically underserved populations in West Texas. Data were from 21,407 women who were hospitalized from 2016 to 2018 at a large regional health system. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The median age of patients was 40 years. While the proportion of patients tested for VDD reduced from 8.9% to 7.6% (p = 0.013) from 2016 to 2018, the prevalence of inappropriate testing increased from 32.3% to 46.8% (p < 0.001), with the 3-year prevalence of VDD being 27.6%. White race (OR = 2.71, CI: 1.95-3.78), an age ≥ 65 years (OR = 3.07, CI: 2.05-4.59), the use of public-sponsored insurance (OR = 1.62, CI: 1.20-2.17), cardiovascular disease (OR = 0.75, CI: 0.63-0.90), and vitamin D supplement use (OR = 7.05, CI: 5.82-8.54) were associated with inappropriate testing for VDD. In this study, an increasing prevalence of potentially inappropriate testing for VDD was observed. Sociodemographic and health-related conditions were associated with potentially inappropriate testing for VDD.

Maternal age at birth of last child and cardiovascular disease mortality later in life among a national cohort of postmenopausal women from the United States.

Maternal age at last birth (ALB) of child is increasing in the United States, and it has been reported to influence future chronic diseases. However, the relationship of ALB and cardiovascular disease (CVD) events later in life has not been widely studied. We evaluated the association of ALB with CVD mortality. Data were from 7,971 parous postmenopausal women older than 45 years who participated in the US National Health and Nutritional Examination Survey from 1999 to 2018 and had mortality follow-up data through to December 31, 2019. ALB was self-reported, whereas CVD mortality was assessed using International Classification of Diseases codes. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). The mean age of participants was 63 ± 9.8 years, with 9.5% being non-Hispanic Black, 9.7% being Hispanic women, and 21% reporting ALB ≥35 years. During a median follow-up of 8.1 years, 443 participants died from CVD. In age-adjusted models, CVD mortality was elevated for women with ALB of <25 years (HR, 1.68; 95% CI, 1.23-2.29) and ALB of ≥35 years (HR, 1.37; 95% CI, 1.00-1.88). However, after additional adjustment for race and ethnicity, foreign born, education, marital status, poverty income ratio, parity, smoking status, age at menarche, oral contraceptive pills use and family history of myocardial infarction, these estimates were attenuated resulting in no association between ALB and CVD mortality. In this study of nationally representative sample of postmenopausal women, there was no conclusive association between maternal ALB and CVD mortality later in life.

Women's Reproductive Milestones and Cardiovascular Disease Risk: A Review of Reports and Opportunities From the CARDIA Study.

In 1985 to 1986, the CARDIA (Coronary Artery Risk Development in Young Adults) study enrolled 5115 Black or White participants, including 2788 women, aged 18 to 30 years. Over the following 35 years, the CARDIA study amassed extensive longitudinal data on women's reproductive milestones, spanning menarche to menopause. Although not initially conceived as a study of women's health, >75 CARDIA study publications address relationships between reproductive factors and events with cardiovascular and metabolic risk factors, subclinical and clinical cardiovascular disease, and social determinants of health. The CARDIA study was one of the earliest population-based reports to note Black-White differences in age at menarche and associations with cardiovascular risk factors. Adverse pregnancy outcomes, particularly gestational diabetes and preterm birth, have been assessed along with postpartum behaviors, such as lactation. Existing studies have examined risk factors for adverse pregnancy outcomes and lactation, as well as their relationship to future cardiovascular and metabolic risk factors, diagnoses, and subclinical atherosclerosis. Ancillary studies examining components of polycystic ovary syndrome and ovarian biomarkers, such as anti-Müllerian hormone, have facilitated examination of reproductive health in a population-based cohort of young adult women. As the cohort transitioned through menopause, examination of the importance of premenopausal cardiovascular risk factors along with menopause has improved our understanding of shared mechanisms. The cohort is now aged in the 50s to mid-60s, and women will begin to experience a greater number of cardiovascular events as well as other conditions, such as cognitive impairment. Thus, in the next decade, the CARDIA study will provide a unique resource for understanding how the women's reproductive life course epidemiology informs cardiovascular risk, as well as reproductive and chronological aging.

Racial and ethnic disparities in the association of maternal infection during pregnancy and risk of cyanotic congenital heart defects in the United States, 2011-2020.

PURPOSE: The etiology of cyanotic congenital heart defects (CCHD) is not well understood. There are scarce data on racial/ethnic disparities in maternal infection and CCHD. We evaluated the relation of maternal infections during pregnancy and risk of CCHD in the United States, and to assess if this association varies by race/ethnicity. METHODS: Data were from the National Vital Statistics System comprising 35.3 million singleton livebirths among mothers aged 15-49 years from 2011 to 2020. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: After adjustment for sociodemographic and maternal health factors, including prepregnancy body mass index, diabetes, hypertension, and smoking during pregnancy, time to prenatal care was initiated and pregnancy complications, any maternal infection, was associated with elevated odds of CCHD (OR: 1.25, 95% CI: 1.15-1.37). The odds of CCHD were mainly evident for sexually transmitted infections, namely chlamydia and hepatitis-C viral infection. The association was limited to non-Hispanic Black (OR: 1.22, 95% CI: 1.03-1.45), Hispanic (OR: 1.61, 95% CI: 1.33-1.95), and Asian (OR: 2.03, 95% CI: 1.42-2.91) mothers. CONCLUSIONS: In this population-based study, maternal infection during pregnancy was associated with a modest risk of CCHD in offspring, which was the highest in racial/ethnic minority mothers.

The role of mental health and substance use disorders on the relation of migraine with self-directed violence among women in the United States.

OBJECTIVES: Migraine disproportionately affects women of reproductive age, and is associated with self-directed violence (SDV) which confers substantial risk for suicides. Mental health disorders (MHD) and substance use disorders (SUD) are higher among persons with migraines. However, there's limited information on the influence of these conditions on SDV among women. We evaluated the interplay of MHD and SUD on the relation of migraine with SDV among US women. METHODS: We analyzed data from 96 million hospitalizations among women aged 15-49 years from the National Inpatient Sample (2004-2015). International Classification of Disease codes were used to identify hospitalizations for migraine and other health conditions. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: From 2004 to 2015 the prevalence (per 1000 hospitalizations) of migraine increased from 17.5 to 33.5, while SDV prevalence also increased from 10.5 to 38.9. A greater proportion of women hospitalized with migraine had epilepsy, suicidal ideations, SUD and MHD than women without migraine. In models adjusted for demographic and behavioral/lifestyle factors, menstrual disorders, pregnancy, health conditions and violent assault, hospitalization with migraine was positively associated with SDV (OR = 1.15, CI: 1.12-1.18). Women with migraine and either SUD (OR = 5.17, CI: 4.46-5.97) or MHD (OR = 14.13; CI: 12.1-16.47) had elevated odds of SDV, with the odds varying by type of MHD and SUD. CONCLUSIONS: A significant relation between hospitalization with migraine and SDV was observed especially among reproductive-age women with SUD and MHD. Clinicians should consider monitoring women with these characteristics for suicide risk.

Factors Influencing Racial and Ethnic Differences in Prescription Opioid Misuse Among Young Adolescents in the USA, 2009-2019.

BACKGROUND: Prescription opioid misuse (POM) is an important public health concern. Not many studies have evaluated factors influencing racial and ethnic differences in POM exclusively in young adolescents. We evaluated factors influencing the racial and ethnic differences in POM in a nationally representative sample of 8th- and 10th-grade (12-15 years old) US adolescents. METHODS: Data were from 107,786 adolescents who participated in the 2009-2019 Monitoring the Future survey. Logistic regression and mediation analysis were used to identify risk factors for POM and evaluate mediators of the association of race and ethnicity on the frequency of POM in the past year. RESULTS: From 2009 to 2019, the prevalence of POM in the past year decreased from 3.2% to 1.8% (p = 0.032), with significant differences in POM trends by race and ethnicity. Overall, the prevalence was higher among non-Hispanic White adolescents (3.2%) than Hispanic (2.5%) and non-Hispanic Black adolescents (1.6%), p < 0.001. After adjustment for demographic, substance use, lifestyle, and family-related factors, the odds of POM were lower among Black (odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.66-0.98) and Hispanic adolescents (OR = 0.64, CI: 0.55-0.74) compared to White adolescents. Illicit drug use and misuse of other prescription drugs together explained 77.2% and 47.3% of the racial and ethnic disparities in POM among Black and Hispanic adolescents, respectively. CONCLUSION: In this study, significant racial and ethnic differences in the trends of POM were observed. Illicit drug use and misuse of other prescription drugs substantially explained the racial and ethnic disparities in POM among young adolescents.

A Culturally Sensitive and Theory-Based Intervention on Prevention and Management of Diabetes: A Cluster Randomized Control Trial.

Type 2 diabetes is an emerging concern in Kenya. This clustered-randomized trial of peri-urban communities included a theory-based and culturally sensitive intervention to improve diabetes knowledge, health beliefs, dietary intake, physical activity, and weight status among Kenyan adults. Those in the intervention group (IG) received a culturally sensitive diabetes education intervention which applied the Health Belief Model in changing knowledge, health beliefs and behavior. Participants attended daily education sessions for 5 days, each lasting 3 h and received mobile phone messages for an additional 4 weeks. The control group (CG) received standard education on COVID-19. Data was collected at baseline, post-intervention (1 week), and follow-up assessment (5 weeks). Linear mixed effect analysis was performed to assess within and across group differences. Compared to the control, IG significantly increased diabetes knowledge (p < 0.001), health beliefs including perceived susceptibility (p = 0.05), perceived benefits (p = 0.04) and self-efficacy (p = 0.02). IG decreased consumption of oils (p = 0.03), refined grains (p = 0.01), and increased intake of fruits (p = 0.01). Perceived barriers, physical activity, and weight status were not significantly different between both groups. The findings demonstrate the potential of diabetes education in improving diabetes knowledge, health beliefs, and in changing dietary intake of among adults in Kenya.

Prepregnancy Protein Source and BCAA Intake Are Associated with Gestational Diabetes Mellitus in the CARDIA Study.

Diet quality and protein source are associated with type 2 diabetes, however relationships with GDM are less clear. This study aimed to determine whether prepregnancy diet quality and protein source are associated with gestational diabetes mellitus (GDM). Participants were 1314 Black and White women without diabetes, who had at least one birth during 25 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort study. The CARDIA A Priori Diet Quality Score (APDQS) was assessed in the overall cohort at enrollment and again at Year 7. Protein source and branched-chain amino acid (BCAA) intake were assessed only at the Year 7 exam (n = 565). Logistic regression analysis was used to determine associations between prepregnancy dietary factors and GDM. Women who developed GDM (n = 161) were more likely to have prepregnancy obesity and a family history of diabetes (p < 0.05). GDM was not associated with prepregnancy diet quality at enrollment (Year 0) (odds ratio [OR]: 1.01; 95% confidence interval [CI] 0.99, 1.02) or Year 7 (odds ratio [OR]: 0.97; 95% confidence interval [CI] 0.94, 1.00) in an adjusted model. Conversely, BCAA intake (OR:1.59, 95% CI 1.03, 2.43) and animal protein intake (OR: 1.06, 95% CI 1.02, 1.10) as a proportion of total protein intake, were associated with increased odds of GDM, while proportion of plant protein was associated with decreased odds of GDM (OR: 0.95, 95% CI 0.91, 0.99). In conclusion, GDM is strongly associated with source of prepregnancy dietary protein intake but not APDQS in the CARDIA study.

Low endogenous estradiol levels are associated with elevated risk of cardiovascular disease mortality in young and middle-aged men in the United States.

BACKGROUND AND AIMS: Evidence for the association of total estradiol (E2) with cardiovascular disease (CVD) in young men is limited. We investigated the association of total E2 or free estradiol (FE2) and CVD mortality in a nationally representative multiracial sample of young and middle-aged men in the United States. METHODS: Data were from 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids, who participated in the National Health and Nutrition Examination Survey (1988-1991), for whom E2 was measured, and were followed for mortality through to 2015. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from the levels of estradiol, sex hormone binding globulin, and albumin. International Classification of Diseases codes were used to define CVD mortality. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of participants at baseline was 35.7 ± 11.6 years, with 11% and 6% reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded. Controlling for baseline demographic and CVD risk factors, and total testosterone levels, a 1 standard deviation decrement in log E2 (HR: 2.33, 95%CI: 1.11-5.00) or FE2 (HR: 1.89, 95%CI: 1.01-3.57) was associated with elevated risk of CVD mortality. This elevated risk was largely limited to non-Hispanic White men. CONCLUSIONS: In this study, low levels of E2 or FE2 were associated with elevated risk of CVD mortality.

Anti PD-1/Anti PDL-1 Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Meta-Analysis of Phase 2/3 Randomized Controlled Trials.

Importance: Immune checkpoint inhibitors (ICI) have revolutionized the treatment for gastroesophageal cancers (GEC). It is important to investigate the factors that influence the response to anti-PD-1/PD-L1 ICIs. Objective: To assess the benefits of PD-1/PD-L1 ICIs in advanced GEC and perform subgroup analysis to identify patient populations who would benefit from ICI. Data sources: PubMed, Embase, Scopus, and the Cochrane Library databases were systematically searched from database inception to September 2021 for all relevant articles. We also reviewed abstracts and presentations from all major conference proceedings including relevant meetings of the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) during the last four years (2018 to 2021) and reviewed citation lists. Study selection, data extraction, and synthesis: Full articles and presentations were further assessed if the information suggested that the study was a phase 2/3 randomized controlled trial (RCT) comparing PD-1/PD-L1 inhibitor either alone, or in combination with standard therapy vs. standard therapy in advanced GEC. The full text of the resulting studies/presentations and extracted data were reviewed independently according to PRISMA guidelines. Main outcomes and measures: The main outcomes were OS, PFS, and treatment-related adverse events (TRAEs). Results: A total of 168 studies were assessed for eligibility, and 17 RCTs with 12,312 patients met the inclusion criteria. There was an OS benefit in the overall population with ICIs (HR 0.78; 95% CI 0.73−0.83 p < 0.001). Immunotherapy showed better OS benefit in males (HR 0.77 95% CI 0.72−0.83; p < 0.001) than females (HR 0.89; 95% CI 0.80−0.99 p < 0.03), esophageal primary tumors (HR 0.70 95% CI 0.64−0.76 p < 0.001) vs. gastric cancer (HR 0.84 95% CI 0.74−0.94 p 0.002) or GEJ cancer (HR 0.84 95% CI 0.72−0.98 p 0.024) and in squamous cell carcinoma (HR 0.71 95% CI 0.66−0.77 p < 0.001) vs. adenocarcinoma (HR 0.85 95% CI 0.78−0.93 p < 0.001). PD-L1 positive patients seemed to benefit more (HR 0.74 95% CI 0.67−0.82 p < 0.001) compared to PD-L1 negative patients (HR 0.86 95% CI 0.74−1.00 p < 0.043), and Asians showed OS benefit (HR 0.76 95% CI 0.67−0.87 p < 0.001) compared to their White counterparts (HR 0.92 95% CI 0.74−1.14; p 0.424). Conclusions and relevance: ICIs improve survival in advanced GEC without significantly increasing the side effects. However, certain subgroups of patients such as males, Asians, and those with esophageal primary, PD-L1 positive tumors and squamous cell carcinoma benefit more from such treatments. Further translational research is needed to understand the mechanistic links and develop new biomarkers.

Long-term changes in plasma proteomic profiles in premenopausal and postmenopausal Black and White women: the Atherosclerosis Risk in Communities study.

OBJECTIVE: The activity, localization, and turnover of proteins within cells and plasma may contribute to physiologic changes during menopause and may influence disease occurrence. We examined cross-sectional differences and long-term changes in plasma proteins between premenopausal and naturally postmenopausal women. METHODS: We used data from 4,508 (19% Black) women enrolled in the Atherosclerosis Risk in Communities study. SOMAscan multiplexed aptamer technology was used to measure 4,697 plasma proteins. Linear regression models were used to compare differences in proteins at baseline (1993-1995) and 18-year change in proteins from baseline to 2011-2013. RESULTS: At baseline, 472 women reported being premenopausal and 4,036 women reported being postmenopausal, with average ages of 52.3 and 61.4 years, respectively. A greater proportion of postmenopausal women had diabetes (15 vs 9%), used hypertension (38 vs 27%) and lipid-lowering medications (10 vs 3%), and had elevated total cholesterol and waist girth. In multivariable adjusted models, 38 proteins differed significantly between premenopausal and postmenopausal women at baseline, with 29 of the proteins also showing significantly different changes between groups over the 18-year follow-up as the premenopausal women also reached menopause. These proteins were associated with various molecular/cellular functions (cellular development, growth, proliferation and maintenance), physiological system development (skeletal and muscular system development, and cardiovascular system development and function), and diseases/disorders (hematological and metabolic diseases and developmental disorders). CONCLUSIONS: We observed significantly different changes between premenopausal and postmenopausal women in several plasma proteins that reflect many biological processes. These processes may help to understand disease development during the postmenopausal period.

Perceived neighborhood social cohesion and the 10-year risk of cardiovascular disease in low- and middle-income countries: The World Health Organization Study on Global Aging and Adult Health.

Low- and middle-income countries (LMICs) bear the greatest burden of cardiovascular disease (CVD) worldwide. Emerging evidence, mostly from industrialized countries, suggest that neighborhood characteristics influence cardiovascular health. This study presents results from 27,797 participants living in six LMICs on the association of perceived neighborhood social cohesion, the degree of connectedness among neighbors, with 10-year risk of CVD. We observed that greater perceived neighborhood social cohesion was associated with lower odds of high (>20%) 10-year CVD risk (OR = 0.67, 95%CI: 0.53-0.86). These novel findings, suggest that interventions to enhance social cohesion may have beneficial effects on cardiovascular health in LMICs.