Sexually Transmitted Disease and Male Infertility: A Systematic Review

Context Theoretically, sexually transmitted diseases (STDs) have the potential to disrupt male fertility; however, the topic remains controversial. Objective To describe the possible association between STDs and male infertility and to explore possible pathophysiologic mechanisms. Evidence acquisition We performed a systematic literature review in accordance with the PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched for articles published before January 1, 2016, using the MeSH terms for a variety of STDs and infertility. The search was restricted to human studies performed in men and published in English. Studies were included if they contained original data on a possible association or a cause-and-effect relationship between STD and male infertility. Studies were considered only if they included an appropriate control group and/or comprehensive laboratory data. Due to heterogeneity in the literature, a qualitative analysis was performed. Evidence synthesis Relevant studies on Chlamydia trachomatis, genital mycoplasmas, Neisseria gonorrhoeae, Trichomonas vaginalis, and viral infections were identified. For all pathogens, the studies were contradictory and generally of limited quality. In studies confirming an association, there was a tendency for authors to perform multiple analyses without appropriate corrections and to subsequently focus solely on outcomes that seemed to suggest a positive association; however, the body of literature that does not confirm an association between STDs and male infertility is also of inadequate quality. The data regarding possible pathophysiologic mechanisms are inconclusive. Conclusions There may be an association between STDs and male infertility of unknown genesis and possibly with different pathogenic mechanisms for different pathogens. Alternatively, some STDs may cause male infertility, whereas others may not; however, there is hardly a strong correlation. High-quality studies of the subject are needed. Patient summary Sexually transmitted diseases may cause male infertility through unknown mechanisms; however, from the available research, we cannot be sure that there is an association, and more studies are needed

Perinatal Factors Associated with Cardiovascular Disease Risk among Preschool-Age Children in the United States: An Analysis of 1999–2008 NHANES Data

We examined the relationships between selected perinatal and early infancy factors (maternal smoking during pregnancy, infant low birthweight, breastfeeding, and early introduction of solid foods [<6 months of age] and increased BMI [≥85th, ≥95th percentiles for age, sex]), waist circumference (WC), C-reactive protein (CRP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and decreased HDL cholesterol during early childhood. The population-based sample included 3,644 3-to-6-year-old Non-Hispanic White (NHW), Hispanic, and Non-Hispanic Black (NHB) children who participated in the 1999–2008 National Health and Nutrition Examination Surveys. Analysis showed that breastfeeding was significantly protective against early childhood obesity (OR 0.43, 95% CI, 0.27–0.69) and the highest quintile for WC (OR 0.58, 95% CI, 0.37–0.32) among NHW, and against the highest quintile of non-HDL cholesterol among NHB (OR 0.56, 95% CI, 0.32–0.98). Additionally, NHW children were significantly more likely to be obese (OR 2.22, 95% CI 1.30–3.78) and have higher CRP levels (OR 1.63, 95% CI, 1.05–2.51) if their mothers smoked during pregnancy. These results support the observation that breastfeeding may be protective against early childhood obesity while maternal smoking during pregnancy is a risk factor for obesity and increased CRP levels among NHW young children

Late cardiotoxicity after low dose of anthracycline therapy for acute lymphoblastic leukemia in childhood

Introduction Late cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier. Methods Seventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m(2) and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6-18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n=19) or 240 mg/m(2) (n=18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI. Results No clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls. Conclusion and implications for cancer survivors At a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m(2), no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients

Maternal age and other predictors of newborn blood pressure

Objective To investigate perinatal predictors of newborn blood pressure. Study design Among 1059 mothers and their newborn infants participating in Project Viva, a US cohort study of pregnant women and their offspring, we obtained five systolic blood pressure readings on a single occasion in the first few days of life. Using multivariate linear regression models, we examined the extent to which maternal age and other pre- and perinatal factors predicted newborn blood pressure level. Results Mean (SD) maternal age was 32.0 (5.2) years, and mean (SD) newborn systolic blood pressure was 72.6 (9.0) mm Hg. A multivariate model showed that for each 5-year increase in maternal age, newborn systolic blood pressure was 0.8 mm Hg higher (95% CI, 0.2, 1.4). In addition to maternal age, independent predictors of newborn blood pressure included maternal third trimester blood pressure (0.9 mm Hg [95% CI, 0.2, 1.6] for each increment in maternal blood pressure); infant age at which we measured blood pressure (2.4 mm Hg [95% CI 1.7, 3.0] for each additional day of life); and birth weight (2.9 mm Hg [95% CI, 1.6, 4.2] per kg). Conclusions Higher maternal age, maternal blood pressure, and birth weight were associated with higher newborn systolic blood pressure. Whereas blood pressure later in childhood predicts adult hypertension and its consequences, newborn blood pressure may represent different phenomena, such as pre- and perinatal influences on cardiac structure and function. Development of risk for adult cardiovascular disease begins very early in life, even before birth.1 Data are scarce, however, regarding blood pressure in the newborn period, which may reflect pre- and perinatal influences on cardiac structure and function. The few studies that have examined determinants of newborn blood pressure suggest a direct association with birth weight,2.; 3.; 4.; 5.; 6.; 7.; 8.; 9. ; 10. in contrast to the inverse association seen with older infants, children, and adults.11 However, most of these studies have at least one important limitation, such as a relatively small sample size of term newborns, lack of data on potentially confounding variables, and limited data on maternal predictors. Maternal age is of particular interest given the known associations of advanced age with adverse reproductive outcomes, including reduced fertility, preterm birth, impaired fetal growth, multiple birth, and congenital anomalies.12.; 13. ; 14. The additional associations of advanced maternal age with diabetes and hypertension,15. ; 16. with possible diminished uterine vascular and placental function,17. ; 18. and in at least two reports with blood pressure level in childhood and in adolescence19. ; 20. warrant examination of its influence on newborn blood pressure. The purpose of this analysis was to investigate associations of pre- and perinatal factors, including maternal age, with systolic blood pressure level during the first few days of life among members of Project Viva, a cohort study of pregnant women and their children

Valsartan for attenuating disease evolution in early sarcomeric hypertrophic cardiomyopathy: the design of the Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) trial

Background: Hypertrophic cardiomyopathy (HCM) is often caused by sarcomere gene mutations, resulting in left ventricular hypertrophy (LVH), myocardial fibrosis, and increased risk of sudden cardiac death and heart failure. Studies in mouse models of sarcomeric HCM demonstrated that early treatment with an angiotensin receptor blocker (ARB) reduced development of LVH and fibrosis. In contrast, prior human studies using ARBs for HCM have targeted heterogeneous adult cohorts with well-established disease. The VANISH trial is testing the safety and feasibility of disease-modifying therapy with an ARB in genotyped HCM patients with early disease. Methods: A randomized, placebo-controlled, double-blind clinical trial is being conducted in sarcomere mutation carriers, 8 to 45 years old, with HCM and no/minimal symptoms, or those with early phenotypic manifestations but no LVH. Participants are randomly assigned to receive valsartan 80 to 320 mg daily (depending on age and weight) or placebo. The primary endpoint is a composite of 9 z-scores in domains representing myocardial injury/hemodynamic stress, cardiac morphology, and function. Total z-scores reflecting change from baseline to final visits will be compared between treatment groups. Secondary endpoints will assess the impact of treatment on mutation carriers without LVH, and analyze the influence of age, sex, and genotype. Conclusions: The VANISH trial is testing a new strategy of disease modification for treating sarcomere mutation carriers with early HCM, and those at risk for its development. In addition, further insight into disease mechanisms, response to therapy, and phenotypic evolution will be gained

Myocardial Alternative RNA Splicing and Gene Expression Profiling in Early Stage Hypoplastic Left Heart Syndrome

Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome

Cardiovascular Effects in Childhood Cancer Survivors Treated with Anthracyclines

Anthracyclines are commonly used to treat childhood leukemias and lymphomas, as well as other malignancies, leading to a growing population of long-term childhood cancer survivors. However, their use is limited by cardiotoxicity, increasing survivors' vulnerability to treatment-related complications that can markedly affect their quality of life. Survivors are more likely to suffer from heart failure, coronary artery disease, and cerebrovascular accidents compared to the general population. The specific mechanisms of anthracycline cardiotoxicity are complex and remain unclear. Hence, determining the factors that may increase susceptibility to cardiotoxicity is of great importance, as is monitoring patients during and after treatment. Additionally, treatment and prevention options, such as limiting cumulative dosage, liposomal anthracyclines, and dexrazoxane, continue to be explored. Here, we review the cardiovascular complications associated with the use of anthracyclines in treating malignancies in children and discuss methods for preventing, screening, and treating such complications in childhood cancer survivors

Assessing Latent Effects of Prenatal Cocaine Exposure on Growth and Risk of Cardiometabolic Disease in Late Adolescence: Design and Methods

Prenatal cocaine exposure has been linked to neurocognitive and developmental outcomes throughout childhood. The cardiovascular toxicity of cocaine is also markedly increased in pregnancy, but it is unknown whether this toxicity affects anthropometric growth and the development of cardiometabolic disease risk factors in the offspring across the lifespan. During the early 1990s, the Miami Prenatal Cocaine Study enrolled a cohort of 476 African American children (253 cocaine-exposed, 223 non-cocaine-exposed) and their biological mothers at delivery in a prospective, longitudinal study. The MPCS has collected 12 prior waves of multidomain data on over 400 infants and their mothers/alternate caregivers through mid-adolescence and is now embarking on an additional wave of data collection at ages 18-19 years. We describe here the analytical methods for examining the relationship between prenatal cocaine exposure, anthropometric growth, and cardiometabolic disease risk factors in late adolescence in this minority, urban cohort. Findings from this investigation should inform both the fields of substance use and cardiovascular research about subsequent risks of cocaine ingestion during pregnancy in offspring

Markers of Bone Mineral Metabolism and Cardiac Structure and Function in Perinatally HIV-Infected and HIV-Exposed but Uninfected Children and Adolescents

Background: Disordered bone mineral metabolism and low vitamin D concentrations are associated with cardiovascular abnormalities; few studies have evaluated this relationship in HIV-infected youth. Setting: Adolescent Master Protocol (AMP) is a Pediatric HIV/AIDS Cohort Study (PHACS) network study conducted across 14 United States sites. Methods: Among perinatally HIV-infected (PHIV) and HIV-exposed uninfected (PHEU) youth enrolled in AMP, we evaluated associations of vitamin D (measured as 25-hydroxyvitamin D [25OHD]), parathyroid hormone (PTH), calcium, phosphate, and fibroblast growth factor-23 (FGF-23) concentrations with echocardiographic measures of left ventricular (LV) structure, function and concentrations of NT-proBNP, a biomarker of cardiac damage. Results: Among 485 participants (305 PHIV, 180 PHEU) with echocardiograms and bone mineralization measures, low 25OHD ( 65 pg/mL) was identified more often among PHIV than PHEU participants (9% vs 3%, p=0.02). After adjusting for HIV status and demographic covariates, both low 25OHD and elevated PTH were associated with lower mean LV mass z-scores, while elevated PTH was associated with higher mean fractional shortening z-scores. Participants with low 25OHD also had slightly higher mean LV end-systolic wall stress z-scores, but differences were more pronounced in PHEU than in PHIV participants. FGF-23 was inversely related to end-diastolic septal thickness both overall and among PHIV participants. Conclusion: In this cohort of PHIV and PHEU youth, we observed associations of 25OHD, PTH, and FGF-23 with both structural and functional cardiac parameters, supporting links between bone mineral metabolism and cardiac status