Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation

Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 g/L versus 20.81 g/L, = 0.002) and homocysteine (11.36 mol/L versus 8.81 mol/L, < 0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 g/L in the patients with bivascular obstruction and 42.77 ± 31.81 g/L in trivascular coronary obstruction, = 0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients

Association between Stable Coronary Artery Disease and In Vivo Thrombin Generation

Background. Thrombin has been implicated as a key molecule in atherosclerotic progression. Clinical evidence shows that thrombin generation is enhanced in atherosclerosis, but its role as a risk factor for coronary atherosclerotic burden has not been proven in coronary artery disease (CAD) stable patients. Objectives. To evaluate the association between TAT levels and homocysteine levels and the presence of coronary artery disease diagnosed by coronary angiography in patients with stable CAD. Methods and Results. We included 95 stable patients admitted to the Haemodynamics Department, including 63 patients with significant CAD and 32 patients without. We measured the thrombin-antithrombin complex (TAT) and homocysteine concentrations in all the patients. The CAD patients exhibited higher concentrations of TAT (40.76 μg/L versus 20.81 μg/L, p=0.002) and homocysteine (11.36 μmol/L versus 8.81 μmol/L, p<0.01) compared to the patients without significant CAD. Specifically, in patients with CAD+ the level of TAT level was associated with the severity of CAD being 36.17 ± 24.48 μg/L in the patients with bivascular obstruction and 42.77 ± 31.81 μg/L in trivascular coronary obstruction, p=0.002. Conclusions. The level of in vivo thrombin generation, quantified as TAT complexes, is associated with the presence and severity of CAD assessed by coronary angiography in stable CAD patients

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Genética y biología molecular de las cardiopatías congénitas y adquiridas

El corazón es el primer órgano que se forma y funciona en el embrión, de tal suerte que todos los eventos subsecuentes en la vida del organismo dependen de la habilidad de este órgano para atender las demandas de oxígeno y nutrientes que éste requiere. Las anormalidades en la formación del corazón, la forma más común de defectos humanos al nacimiento, afecta al 1 % de los nacidos vivos, y su frecuencia en abortos espontáneos se eleva diez veces más. La patofisiología de este tipo de malformaciones congénitas se ha venido enriqueciendo en los últimos años con el conocimiento del Proyecto Genoma Humano; debido al gran avance que se ha producido en el conocimiento genético y molecular de los diferentes genes y cromosomas que suelen ser afectados y muchas veces heredados para producir una enfermedad congénita en general. Esta revisión trata de enfocar su atención sobre la información extraída de los análisis genéticos y moleculares en el diagnóstico, tratamiento y entendimiento de la patogénesis de las enfermedades cardiovasculares pediátricas, dirigidas tanto por los más comunes defectos cardíacos congénitos o heredados, como por los desórdenes esporádicos o adquiridos

Ethnicity and lipoprotein(a) polymorphism in Native Mexican populations.

International audienceBACKGROUND: Lp(a) is a lipoparticle of unknown function mainly present in primates and humans. It consists of a low-density lipoprotein and apo(a), a polymorphic glycoprotein. Apo(a) shares sequence homology and fibrin binding with plasminogen, inhibiting its fibrinolytic properties. Lp(a) is considered a link between atherosclerosis and thrombosis. Marked inter-ethnic differences in Lp(a) concentration related to the genetic polymorphism of apo(a) have been reported in several populations. AIM: The study examined the structural and functional features of Lp(a) in three Native Mexican populations (Mayos, Mazahuas and Mayas) and in Mestizo subjects. METHODS: We determined the plasma concentration of Lp(a) by immunonephelometry, apo(a) isoforms by Western blot, Lp(a) fibrin binding by immuno-enzymatic assay and short tandem repeat (STR) polymorphic marker genetic analysis by capillary electrophoresis. RESULTS: Mestizos presented the less skewed distribution and the highest median Lp(a) concentration (13.25 mg dL(-1)) relative to Mazahuas (8.2 mg dL(-1)), Mayas (8.25 mg dL(-1)) and Mayos (6.5 mg dL(-1)). Phenotype distribution was different in Mayas and Mazahuas as compared with the Mestizo group. The higher Lp(a) fibrin-binding capacity was found in the Maya population. There was an inverse relationship between the size of apo(a) polymorphs and both Lp(a) levels and Lp(a) fibrin binding. CONCLUSION: There is evidence of significative differences in Lp(a) plasma concentration and phenotype distribution in the Native Mexican and the Mestizo group

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)