Omega-3 LCPUFA supplement: a nutritional strategy to prevent maternal and neonatal oxidative stress.

There is controversy about fish-oil supplementation and oxidative damage. This ambiguity should be explored to elucidate its role as modulator of oxidative stress, especially during gestation and postnatal life. This is the objective of this study. One hundred ten pregnant women were divided in two groups: control group CT (400 mL/day of the control dairy drink); supplemented group FO (400 mL/day of the fish oil-enriched dairy drink (±400-mg EPA-DHA/day)). Different biomarkers of oxidative damage were determined in the mother's at enrolment, at delivery and at 2.5 and 4 months postpartum and newborns at delivery and at 2.5 months postpartum. Omega-3 LC-PUFA supplementation during pregnancy and lactation decreased plasma hydroperoxides especially in newborn at delivery (P = 0.001) and 2.5 months (P = 0.006), increased superoxide dismutase (SOD) and catalase (CAT) in mothers at delivery (P = 0.024 (SOD)) and after 2.5 months (P = 0.040 (CAT)) and in newborns at 2.5 months (P = 0.035 (SOD); P = 0.021 (CAT)). Also, supplementation increased α-tocoferol in mothers at 2.5 months (P = 0.030) and in umbilical cord artery (P = 0.039). Higher levels of CoQ10 were found in mothers at delivery (P = 0.039) as well as in umbilical cord vein (P = 0.024) and artery (P = 0.036). Our supplementation prevents the oxidative stress in the mother and neonate during the first months of postnatal life, being a potential preventive nutritional strategy to prevent functional alterations associated with oxidative stress that have an important repercussion for the neonate development in the early postnatal life.

Effects of Maternal Ω-3 Supplementation on Fatty Acids and on Visual and Cognitive Development.

OBJECTIVES: The aim of the present study was to elucidate whether a dairy drink enriched with ω-3 long-chain polyunsaturated fatty acid (LC-PUFA) could have an impact on the lipid profile of the mother and the newborn, and also whether this intervention could affect the newborns' visual and cognitive development. METHODS: A total of 110 pregnant women were randomly assigned to one of the following intervention groups: control group (n = 54), taking 400 mL/day of the control dairy drink, and supplemented group (fish oil [FO]) (n = 56), taking 400 mL/day of the fish oil-enriched dairy drink (including ∼400 mg eicosapentaenoic acid-docosahexaenoic acid [DHA]/day). During the study, the mothers' diets were supervised by a nutritionist to encourage compliance with present recommendations of FA intake. Blood fatty acid profiles were determined in the mother's (at enrollment, at delivery, and at 2.5 and 4 months) and newborn (at delivery and at 2.5 months) placenta and breast milk (colostrum and at 1, 2, and 4 months). Pattern reversal visual evoked potentials (VEPs) (at 2.5 and 7.5 months) and Bayley test (at 12 months) were recorded. RESULTS: DHA percentage was higher in plasma, erythrocyte membranes, and breast milk samples from the FO group. The ratio of nervonic acid was also higher in plasma and erythrocyte lipids of the mother and newborn's blood samples from the FO group. No differences were observed in the Bayley test. No differences were observed in VEPs between both groups. We observed a shorter latency, however, in the lower visual angle (7.5') in the boys of the supplemented group. CONCLUSIONS: Omega-3 LC-PUFA dietary supplement during pregnancy and lactation influenced the mother and newborn's fatty acid profile and nervonic acid content but did not show effects on visual and cognitive/psychomotor development.

Oral anticoagulation improves the prognosis of octogenarian patients with atrial fibrillation undergoing percutaneous coronary intervention and stenting.

BACKGROUND: a significant proportion of octogenarian patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI) with stenting. Dual antiplatelet therapy is recommended in these patients, requiring a period of triple therapy with dual antiplatelet agent plus oral anticoagulation (OAC). Concerns remain regarding the appropriateness of OAC in octogenarians. METHODS: we reviewed 604 patients (15.7% ≥80 years) with AF undergoing PCI. Clinical follow-up was performed, recording any bleeding episode, thrombo-embolism and major adverse cardiac events (MACE = death, acute myocardial infarction and/or revascularisation of target lesion). We compared octogenarian patients in relation to treatment with OAC at discharge. A secondary aim was to compare octogenarian patients with non-octogenarian patients in terms of their clinical and demographic characteristics, management and clinical outcome. RESULTS: among the 604 patients, 95(15.7%) were aged ≥80 years. Octogenarians had a higher median CHADS2 score (2.78 versus 2.01; P < 0.001) and HAS-BLED score (3.05 versus 2.84; P = 0.028). After a follow-up of 17 ± 14 months, all-cause death occurred in 33%, MACE in 44%, and major bleeding in 21%. OAC was associated with less MACE (28.9 versus 58.3%; P = 0.012) and a similar rate of major bleeding. On multivariable analysis, non-use of OAC at discharge was associated with increased MACE (OR = 4.3; 95% CI = 1.3-14.6; P = 0.02). CONCLUSION: octogenarian AF patients undergoing PCI/stenting have a high mortality rate and MACE, which can be reduced by means of OAC therapy.

Percutaneous coronary intervention with rotational atherectomy for severely calcified unprotected left main: immediate and two-years follow-up results.

INTRODUCTION: According to current practice guidelines, coronary bypass surgery is the standard care option for unprotected left main (ULM) stenosis. However, a group of high surgical risk patients who are not eligible for coronary bypass surgery could benefit from percutaneous coronary intervention (PCI). Severe calcification hampers PCI in this setting, and rotational atherectomy (RA) could be of great help. METHODS: We retrospectively analyzed a cohort of 40 patients with severely calcified ULM stenosis, not eligible for coronary artery bypass grafting, who underwent RA in our center. RESULTS: Forty patients (mean age, 73 ± 8 years; 26 males) with ULM stenosis were treated with RA. Twenty-seven (67%) had distal stenosis. The mean number of treated vessels was 2.38 ± 0.74, with a mean lesion length of 30 ± 18 mm. Abciximab was used in 12 (30%) cases and an intra-aortic balloon pump in three cases. One patient died during the procedure and another two patients died in the first 24 hr after the procedure. The major events registered after the procedure included one significant branch loss, and two minor and one major case of bleeding (the latter requiring transfusion) at the puncture point. After a median of 24.7 (IQR 19.6-34.3) months of follow-up, 12 cardiac deaths were recorded. Survival free of cardiac death was 71 ± 7% and clinical guided target vessel revascularization 19.3 ± 7% at 2 years. CONCLUSION: In a group of high surgical risk patients, RA on severely calcified left main stenosis is feasible and, in spite of high mortality rates, could pose the only possible effective treatment.

Concentrations of perfluoroalkyl substances in donor breast milk in Southern Spain and their potential determinants.

BACKGROUND: Breast milk is considered to offer the best nutrition to infants; however, it may be a source of exposure to environmental chemicals such as perfluoroalkyl compounds (PFAS) for breastfeeding infants. PFAS are a complex group of synthetic chemicals whose high stability has led to their ubiquitous contamination of the environment. OBJECTIVE: To assess the concentrations and profiles of PFAS in breast milk from donors to a human milk bank and explore factors potentially related to this exposure. METHODS: Pooled milk samples were collected from 82 donors to the Human Milk Bank of the Virgen de las Nieves University Hospital (Granada, Spain). Ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was applied to determine milk concentrations of 11 PFAS, including long-chain and short-chain compounds. A questionnaire was used to collect information on donors' socio-demographic characteristics, lifestyle, diet, and use of personal care products (PCPs). Factors related to individual and total PFAS concentrations were evaluated by multivariate regression analysis. RESULTS: PFAS were detected in 24-100% of breast milk samples. PFHpA was detected in 100% of samples, followed by PFOA (84%), PFNA (71%), PFHxA (66%), and PFTrDA (62%). Perfluorooctane sulfonate (PFOS) was detected in only 34% of donors. The median concentrations ranged from <0.66 ng/dL (perfluorohexane sulfonic acid [PFHxS]) to 19.39 ng/L (PFHpA). The median of the sum of PFAS concentrations was 87.67 ng/L and was higher for short-chain than long-chain PFAS. Factors most frequently associated with increased PFAS concentrations included intake of creatin animal food items and use of PCPs such as skin care and makeup products. CONCLUSIONS: Several PFAS, including short-chain compounds, are detected in pooled donor milk samples. Breast milk may be an important pathway for the PFAS exposure of breastfed infants, including preterm infants in NICUs. Despite the reduced sample size, these data suggest that various lifestyle factors influence PFAS concentrations, highlighting the use of PCPs.

Efficacy and safety of drug-eluting stent use in patients with atrial fibrillation.

AIMS: Drug-eluting stents (DES) have never been sufficiently studied in patients with atrial fibrillation (AF). The latter are considered as a high-risk population with uncertainty over the optimal antithrombotic therapy strategy to prevent stroke, stent thrombosis, and recurrent cardiac ischaemia, balanced against the high risk of haemorrhage. The aim of this study was to evaluate the safety and efficacy of the use of DES vs. bare-metal stents (BMS) in a cohort of patients with AF. METHODS AND RESULTS: We reviewed 604 patients with AF who had undergone percutaneous coronary intervention with stent over a period of 7 years (January 2001-January 2008). After a propensity score selection, we identified two matched cohorts who received DES (n = 207) or BMS (n = 207). Clinical follow-up was performed, and all bleeding episodes, thrombo-embolism, and major adverse cardiac events (MACE; i.e. death, acute myocardial infarction, target vessel failure) were recorded. Complete follow-up was achieved in 95.9% of the cohort (mean: 693 +/- 427 days, median: 564). The incidence density of MACE as well as the incidence of all-cause mortality in both groups was similar. There was a higher incidence of major bleeding in DES group (2.26 vs. 1.19 per 10 000 days of exposure; P = 0.03). In a multivariate analysis, age, chronic AF, chronic renal failure, and non-use of dicoumarin were predictors of MACE and of all-cause mortality. The use of DES was not a predictor of reduced events. CONCLUSION: On the basis of this study, the routine use of DES in patients with AF does not seem to be justified. A higher risk of major bleeding with DES in comparison with BMS raises the possibility that DES should be limited to lesions or patients with a high risk of restenosis.

Presence of Bisphenol A and Parabens in a Neonatal Intensive Care Unit: An Exploratory Study of Potential Sources of Exposure.

BACKGROUND: Newborns in neonatal intensive care units (NICUs) are in contact with a variety of medical products whose production might include synthetic chemicals with hormonal activity. OBJECTIVES: Our aim was to assess the content of bisphenol A (BPA) and parabens (PBs) and the hormone-like activities of a subset of medical products commonly used in NICUs in prolonged intimate contact with NICU newborns. METHODS: Fifty-two NICU items were analyzed, determining the concentrations of BPA and PBs [methyl- (MeP), ethyl- (EtP), propyl- (PrP), and butylparaben (BuP)] and using the E-Screen and PALM-luciferase assays to measure the in vitro (anti-)estrogenic and (anti-)androgenic activity, respectively, of the extracts. Items found to have elevated BPA/PB content or hormone-like activities were further extracted using leaching methodologies. RESULTS: BPA was found in three-fifths and PBs in four-fifths of tested NICU items, and ∼25% and ∼10% of extracts evidenced estrogenic and anti-androgenic activity, respectively. The highest BPA content was found in the three-way stopcock (>7.000 ng/g), followed by patterned transparent film dressing, gastro-duodenal feeding tubes, sterile gloves, single-lumen umbilical catheters, and intravenous (IV) infusion extension sets (concentrations ranged from 100 to 700 ng/g BPA). A total PB concentration (∑PBs) >100 ng/g was observed in several items, including light therapy protection glasses, patterned transparent film dressing, winged IV catheters, IV infusion extension sets, and textile tape. The highest estrogenic activity [>450 pM estradiol equivalent (E2eq)] was found in small dummy nipples, three-way stopcocks, and patterned transparent film dressing and the highest anti-androgenic activity [>5 mM procymidone equivalent units per gram (Proceq/g)] in small dummy nipples and three-way stopcocks. DISCUSSION: According to these findings, neonates might be exposed to multiple sources of BPA and PBs in NICUs via inhalation, dermal, oral, and IV/parenteral routes. There is a need to address the future health implications for these extremely vulnerable patients and to adopt precautionary preventive measures as a matter of urgency. https://doi.org/10.1289/EHP5564.

Should we recommend oral anticoagulation therapy in patients with atrial fibrillation undergoing coronary artery stenting with a high HAS-BLED bleeding risk score?

BACKGROUND: Recent European guidelines for the management of atrial fibrillation recommend oral anticoagulation (OAC) in patients with CHA(2)DS(2)-VASc score (congestive heart failure, hypertension, age ≥75 years, diabetes, history of previous stroke, vascular disease, age 65-74 years, and sex category [female]) ≥1. The HAS-BLED score (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [>65 years], Drugs/alcohol concomitantly) has been suggested to assess bleeding risk in patients with atrial fibrillation (score ≥3 indicates high risk of bleeding). Despite the guidelines, this approach has never been tested in a cohort of patients with atrial fibrillation undergoing percutaneous coronary intervention with stent implantation. METHODS AND RESULTS: We studied 590 consecutive patients with atrial fibrillation undergoing percutaneous coronary intervention/stenting and CHA(2)DS(2)-VASC score >1 (ie, OAC recommended). We compared patients with low-intermediate bleeding risk (HAS-BLED 0-2) and high risk (HAS-BLED ≥3), the relation between CHA(2)DS(2)-VASC and HAS-BLED, and the benefit and risks of the use of OAC in patients with high bleeding risk. The development of any bleeding episode, thromboembolism, mortality, cardiac events, and the composite major adverse cardiac events (ie, death, acute myocardial infarction, and/or target lesion revascularization) end point was recorded as well as the composite major adverse events (ie, major adverse cardiac events, major bleeding, or thromboembolism) end point at 1-year follow-up. Of the study cohort, 420 (71%) had a HAS-BLED score ≥3, and patients who were on OAC at discharge had lower mortality rate (9.3% versus 20.1%; P<0.01) and major adverse cardiac events (13.0% versus 26.4%; P<0.01) but with a similar major adverse event (20.5% versus 27.6%; P=0.11) and higher major bleeding rate (11.8% versus 4.0%; P<0.01). In a Cox multivariable analysis in patients with HAS-BLED ≥3, predictors of increased death were chronic renal failure and heart failure (both P<0.05), whereas OAC at discharge was associated with a reduced death rate (P<0.01). Predictors of major bleeding were chronic renal failure and the use of drug-eluting stents (both P<0.05). CONCLUSIONS: Most patients with atrial fibrillation undergoing percutaneous coronary intervention/stenting have a high risk for major bleeding (HAS-BLED score ≥3). Even in these patients, OAC improves prognosis in these patients (reduced mortality and major adverse cardiac events) with an increase in major bleeding.

Influence of CYP2C19 polymorphisms in platelet reactivity and prognosis in an unselected population of non ST elevation acute coronary syndrome.

INTRODUCTION AND OBJECTIVES: CYP2C19*2 and CYP2C19*17 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coronary syndrome. METHODS: Recruitment for the first and second objectives was 40 stable acute coronary syndrome patients under dual antiplatelet therapy at 12 months after coronary stent placement and an unselected population of 493 consecutive patients with non-ST elevation acute coronary syndrome, respectively. Platelet reactivity was assessed by optical aggregometry induced by adenosine diphosphate and thrombin receptor activating peptide, and by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Genotypes were determined with a TaqMan assay. RESULTS: Only the vasodilator-stimulated phosphoprotein phosphorylation measurement detected significant differences in on-clopidogrel platelet reactivity between the wild-type subjects and the CYP2C19*2 (P=.020) and *17 allele carriers (P=.048). No significant difference was found between CYP2C19*2 ([HR (95%CI): 1 (0.94-1.55)], P=.984) or *17 ([HR (95%CI): 0.93 (0.61-1.43)], P=.753) allele carriage and the occurrence of adverse events at 6-month follow-up. CONCLUSIONS: Even though CYP2C19 genotype is associated with variable on-clopidogrel platelet reactivity, it has no significant clinical influence. Prognosis of acute coronary syndromes may be influenced by a myriad of variables.

An evaluation of the CHADS2 stroke risk score in patients with atrial fibrillation who undergo percutaneous coronary revascularization.

BACKGROUND: There are various schemas designed to stratify the risk of thromboembolism (TE) in patients with atrial fibrillation (AF), of which the CHADS(2) (congestive heart failure, hypertension, age ≥ 75 y, diabetes, stroke [doubled]) score is the most widely studied. We evaluated whether the CHADS(2) score was adequate for TE risk stratification while assessing cardiac risk in patients with AF revascularized with coronary artery stents. METHODS: We reviewed 604 consecutive patients with AF treated with at least one stent between 2001 and 2008 in relation to TE risk using CHADS(2) score. We stratified our patients with a CHADS(2) score ≤ 1 as low-moderate thromboembolic risk (group 1: n = 193, 32%) and > 1 as high risk (and, hence, requiring anticoagulation; group 2: n = 411, 68%). We determined the benefits and/or risks of oral anticoagulation (OAC) therapy in both cohorts. RESULTS: Completed follow-up was achieved in 90.4% (mean 642.2 days). Group 1 event-free survival was better than group 2 (major adverse cardiovascular events [MACEs], log-rank test P = .03; and death, log-rank test P = .03). In group 1, event-free survival was better on OAC vs non-OAC use (death 5% vs 15%, P = .04; MACE 10% vs 26%, P < .01) with a trend for more major hemorrhages (12% vs 4%, P = .08). Stroke rate was 4.1% per 100 patient-years in patients without OAC therapy and 1.38% in patients on OAC therapy. Group 2 had a lower incidence of death (20% vs 34%, P < .01) and MACE (26% vs 43%, P < .01) among those on OAC therapy on discharge, with a higher incidence of major hemorrhages (18% vs 8%, P < .01). CONCLUSION: In a population of patients with AF revascularized with stents, even those with CHADS(2) ≤ 1 should be regarded as being at high risk. OAC should be considered as thromboprophylaxis in patients with AF revascularized with coronary stents.

La concentración sérica de adiponectina como biomarcador de calcificación arterial coronaria y lesiones coronarias graves / Serum adiponectin level as a biomarker of coronary artery calcification and severe coronary lesions

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Influencia de los polimorfismos de CYP2C19 en la reactividad plaquetaria y el pronóstico en una población no seleccionada de pacientes con síndrome coronario agudo sin elevación del ST / Influence of CYP2C19 polymorphisms in platelet reactivity and prognosis in an unselected population of non ST elevation acute coronary syndrome

Introducción y objetivos. Los alelos CYP2C19*2 y *17 parecen relacionarse con la variabilidad en el metabolismo del clopidogrel. Los objetivos del presente estudio son valorar la relación fenotipo-genotipo asociada a los polimorfismos CYP2C19*2 y *17 y explorar el impacto clínico de estos polimorfismos durante 6 meses de seguimiento en una población no seleccionada con síndrome coronario agudo sin elevación del segmento ST. Métodos. Se reclutó a 40 pacientes estables doblemente antiagregados, 12 meses después del implante de stent coronario para el primer objetivo, y a 493 pacientes ingresados con síndrome coronario agudo sin elevación del segmento ST para el segundo. La reactividad plaquetaria se evaluó mediante agregometría óptica estimulando las plaquetas con adenosina difosfato o péptido activador del receptor de trombina, y valorando la fosfoproteína estimulada por vasodilatadores fosforilada mediante citometría de flujo. El genotipo para los polimorfismos CYP2C19*2 y *17 se analizó con sondas TaqMan. Resultados. Sólo el test de fosforilación de fosfoproteína estimulada por vasodilatadores mostró diferencias significativas en la reactividad plaquetaria entre los pacientes portadores y no portadores de los alelos CYP2C19*2 (p=0,020) y *17 (p=0,048). No se observó asociación con el pronóstico a 6 meses de los alelos CYP2C19*2 ([HR (IC95%): 1 (0,94-1,55)], p=0,984) y *17 ([HR (IC95%): 0,93 (0,61-1,43)], p=0,753). Conclusiones. Los polimorfismos de CYP2C19 *2 y *17 se relacionaron con la reactividad plaquetaria, pero no con el pronóstico a 6 meses, en el que multitud de variables deben influir (AU)

Introduction and objectives. CYP2C19*2 and CYP2C19*17 alleles appear to contribute to heterogeneous clopidogrel metabolism. The aims of the present study were to assess the phenotype-genotype relationship of CYP2C19*2 and *17 allele carriage and to explore the clinical impact of those polymorphisms at 6-month follow-up of an acute event in an unselected population of non-ST elevation acute coronary syndrome. Methods. Recruitment for the first and second objectives was 40 stable acute coronary syndrome patients under dual antiplatelet therapy at 12 months after coronary stent placement and an unselected population of 493 consecutive patients with non-ST elevation acute coronary syndrome, respectively. Platelet reactivity was assessed by optical aggregometry induced by adenosine diphosphate and thrombin receptor activating peptide, and by vasodilator-stimulated phosphoprotein phosphorylation measurement using flow cytometry. Genotypes were determined with a TaqMan assay. Results. Only the vasodilator-stimulated phosphoprotein phosphorylation measurement detected significant differences in on-clopidogrel platelet reactivity between the wild-type subjects and the CYP2C19*2 (P=.020) and *17 allele carriers (P=.048). No significant difference was found between CYP2C19*2 ([HR (95%CI): 1 (0.94-1.55)], P=.984) or *17 ([HR (95%CI): 0.93 (0.61-1.43)], P=.753) allele carriage and the occurrence of adverse events at 6-month follow-up. Conclusions. Even though CYP2C19 genotype is associated with variable on-clopidogrel platelet reactivity, it has no significant clinical influence. Prognosis of acute coronary syndromes may be influenced by a myriad of variables (AU)

Estratificación del riesgo hemorrágico en el síndrome coronario agudo / Stratification of bleeding risk in acute coronary syndrome

El síndrome coronario agudo es un proceso con una elevada morbimortalidad cuyo tratamiento está bien establecido en las guías clínicas desde hace años, no así todas las complicaciones que se derivan de él. El sangrado es uno de los principales efectos adversos de los fármacos antitrombóticos empleados en la actualidad y su incidencia real es desconocida. Sin embargo, está bien establecido que se trata de una situación que empeora el pronóstico de los pacientes tanto a corto como a largo plazo, y que es parcialmente evitable si se consigue identificar a los pacientes más vulnerables y se lleva a cabo una serie de medidas preventivas (AU)

Acute coronary syndrome is associated with high morbidity and mortality. Its treatment has been clearly defined by clinical practice guidelines for many years, but the various complications resulting from treatment are less well understood. Although bleeding is one of the main side effects of currently used antithrombotic drugs, its actual incidence is unknown. However, it is well recognized that bleeding worsens the patient’s prognosis over both the short and long term and that it could be avoided to some extent by identifying the most vulnerable individuals and by fully implementing a range of preventive measures (AU)