Gene sequence variations of the platelet P2Y12 receptor are associated with coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The platelet P2Y₁₂receptor plays a key role in platelet activation. The H2 haplotype of the P2Y₁₂receptor gene (<it>P2RY12</it>) has been found to be associated with maximal aggregation response to adenosine diphosphate (ADP) and with increased risk for peripheral arterial disease. No data are available on its association with coronary artery disease (CAD).</p> <p>Methods </p> <p>The H2 haplotype of the <it>P2RY12 </it>was determined in 1378 unrelated patients of both sexes selected according to the presence of significant coronary artery disease (CAD group) or having normal coronary angiogram at cardiac catheterization (CAD-free group). Significant coronary artery disease was angiographically determined, and was defined as a greater than 50% visually estimated luminal diameter stenosis in at least one major epicardial coronary artery.</p> <p>Results</p> <p>In the studied population 71.9% had CAD (n = 991) and 28.1% had normal coronary angiogram (n = 387). H2 haplotype carriers were more frequent in the CAD group (p = 0.03, OR = 1.36, 95%CI = 1.02–1.82). The H2 haplotype was significantly associated with CAD in non-smokers (p = 0.007, OR = 1.83 95%CI = 1.17–2.87), but not in smokers. The association remained significant after adjustment for other covariates (age, triglycerides, HDL, hypertension, diabetes) by multivariate logistic regression (p = 0.004, OR = 2.32 95%CI = 1.30–4.15).</p> <p>Conclusion</p> <p>Gene sequence variations of the P2Y₁₂receptor gene are associated with the presence of significant CAD, particularly in non-smoking individuals.</p

Combined Effect of Hemostatic Gene Polymorphisms and the Risk of Myocardial Infarction in Patients with Advanced Coronary Atherosclerosis

BACKGROUND: Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI. METHODOLOGY/PRINCIPAL FINDINGS: We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential. CONCLUSIONS: The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

A moderate transfusion regimen may reduce iron loading in beta-thalassemia major without producing excessive expansion of erythropoiesis.

BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is frequently associated with manifestations of transfusion iron overload, despite regular chelation therapy with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a transfusion regimen with a target pretransfusion hemoglobin level between 9 and 10 g per dL can allow a significant reduction in blood consumption, while still effectively suppressing erythropoiesis, the records were reviewed of 32 beta-thalassemia major patients, who were maintained at a pretransfusion hemoglobin of 11.3 +/- 0.5 g per dL between 1981 and 1986. These patients were switched at the beginning of 1987 to a transfusion regimen with pretransfusion hemoglobin of 9.4 +/- 0.4 g per dL. The degree of erythroid marrow activity was evaluated in these patients and in 32 subjects with beta-thalassemia intermedia through the simple measurement of serum transferrin receptor. RESULTS: After the adoption of the moderate transfusion regimen, transfusion requirements ecreased from 137 +/- 26 to 104 +/- 23 mL per kg per year of red cells (p < 0.0001), and mean serum ferritin decreased from 2448 +/- 1515 to 1187 +/- 816 micrograms per L (p < 0.0001), with one-half of patients achieving serum ferritin levels lower than 1000 micrograms per L. The proportion of patients having spontaneous pubertal development increased significantly (p < 0.01), as a result of less iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin, erythroid marrow activity did not exceed two to three times normal levels in most subjects. CONCLUSION: As compared with hypertransfusion, moderate transfusion may allow more effective prevention of iron loading, with higher likelihood of spontaneous pubertal development and without producing excessive expansion of erythropoiesis

The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families.

Abstract OBJECTIVE: The objective of this study was to replicate an association study on a newly collected Italian autism spectrum disorder (ASD) cohort by studying the genetic markers associated with ASDs from recent genome-wide and candidate gene association studies. METHODS: We have genotyped 746 individuals from 227 families of the Italian Autism Network using allelic discrimination TaqMan assays for seven common single-nucleotide polymorphisms: rs2292813 (SLC25A12 gene), rs35678 (ATP2B2 gene), rs4307059 (between CDH9 and CDH10 genes), rs10513025 (between SEMA5A and TAS2R1 genes), rs6872664 (PITX1 gene), rs1861972 (EN2 gene), and rs4141463 (MACROD2 gene). A family-based association study was conducted. RESULTS: A significant association was found for two of seven markers: rs4307059 T allele (odds ratio: 1.758, SE=0.236; P-value=0.017) and rs35678 TC genotype (odds ratio: 0.528, SE=0.199; P-value=0.0013). CONCLUSION: A preferential allele transmission of two markers located at loci previously associated with social and verbal communication skill has been confirmed in patients of a new ASD family sample