Rendimiento de ecuaciones para predecir riesgo cardiovascular en una población de Argentina / Performance of equations to predict cardiovascular risk in an Argentine population

Resumen El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la saludregión América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Abstract The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health OrganizationAmerican B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

[Performance of equations to predict cardiovascular risk in an Argentine population]. / Rendimiento de ecuaciones para predecir riesgo cardiovascular en una población argentina.

The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health Organization- American B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la salud- región América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Programmed cell death-1, PD-1, is dysregulated in T cells from children with new onset type 1 diabetes.

BACKGROUND: Programmed death cell 1 (PD-1) is an inhibitor of T cell activation and is also functionally linked to glycolysis. We hypothesized that PD-1 expression is defective in activated T cells from children with type 1 diabetes (T1D), resulting in abnormal T cell glucose metabolism. METHODS: In this pilot study, we enrolled children with new onset T1D within 2 weeks of diagnosis (T1D), unaffected siblings of T1D (SIBS), unaffected, unrelated children (CTRL), children with new onset, and untreated Crohn disease (CD). We repeated the assays 4-6 months post-diagnosis in T1D (T1D follow up). We analyzed anti-CD3/-CD28-stimulated peripheral blood mononuclear cells (PBMC) subsets for PD-1 expression by flow cytometry at baseline and after 24 h in culture. We measured cytokines in the culture medium by multiplex ELISA and glycolytic capacity with a flux analyzer. RESULTS: We enrolled 37 children. T cells derived from subjects with T1D had decreased PD-1 expression compared to the other study groups. However, in T1D follow-up T cells expressed PD-1 similarly to controls, but had no differences in PBMC cytokine production. Nonetheless, T1D follow up PBMCs had enhanced glycolytic capacity compared to T1D. CONCLUSIONS: Activated T cells from T1D fail to upregulate PD-1 upon T-cell receptor stimulation, which may contribute to the pathogenesis of T1D. T1D follow up PBMC expression of PD-1 normalizes, together with a significant increase in glycolysis compared to T1D. Thus, insulin therapy in T1D children is associated with normal PD1 expression and heightened glycolytic capacity in PBMC.

Distinctive colonic mucosal cytokine signature in new-onset, untreated pediatric Crohn disease.

OBJECTIVE: The aim of the study was to compare the colonic mucosal immune response in children with new, untreated Crohn disease (CD-New), CD in remission (CD-Remission), and unaffected children (CTRL [controls]). METHODS: We performed flow cytometry of mitogen-stimulated colonic lamina propria mononuclear cells isolated from colonic biopsies and 72-hour biopsy explant cultures, and analyzed the supernatant by an unbiased multiplex cytokine array of 45 analytes. RESULTS: Thirty-six children were studied (mean age 14 ± 3 years, 14 girls): 12 CD-New, 11 CD-Remission, and 13 CTRL. We found that stimulation of lamina propria mononuclear cells isolated from colonic biopsies induced comparable intracellular cytokine levels of interferon (IFN-γ), interleukin (IL)-17, and tumor necrosis factor (TNF)-α in T cells from CD-New, CD-Remission, and CTRL, suggesting that mucosal innate inflammation plays a larger role than activated T cells in CD-New. To measure factors released during the ongoing inflammatory response in CD-New, we cultured colonic biopsy explants and uncovered 13/45 factors that were significantly higher in CD-New versus CD-Remission, whereas 10 were increased in CD-New over CTRL. Ingenuity Pathway Analysis software revealed the anticipated interconnectivity of TNF-α, IL-6, and CSF-2 in CD-New of the colon. A novel subnetwork of chemokines was, however, evident, whereas IL-17a appeared as a peripheral factor. Principal component analysis and hierarchal clustering showed that CD-New and CD-Remission separated into distinct subgroups based on the 13 factors. CONCLUSIONS: At diagnosis of inflammatory bowel disease, the colonic cytokine response contains a predominance of innate immune factors, with chemoattractants and vascular adhesion molecules playing a central role.

Norovirus infectivity in humans and persistence in water.

To examine the long-term infectivity of human norovirus in water, 13 study subjects were challenged at different time points with groundwater spiked with the prototype human norovirus, Norwalk virus. Norwalk virus spiked in groundwater remained infectious after storage at room temperature in the dark for 61 days (the last time point tested). The Norwalk virus-seeded groundwater was stored for 1,266 days and analyzed, after RNase treatment, by reverse transcription-quantitative PCR (RT-qPCR) to detect Norwalk virus RNA contained within intact capsids. Norwalk virus RNA within intact capsids was detected in groundwater for 1,266 days, with no significant log(10) reduction throughout 427 days and a significant 1.10-log(10) reduction by day 1266. Purified Norwalk virus RNA (extracted from Norwalk virus virions) persisted for 14 days in groundwater, tap water, and reagent-grade water. This study demonstrates that Norwalk virus in groundwater can remain detectable for over 3 years and can remain infectious for at least 61 days. (ClinicalTrials.gov identifier NCT00313404.).

Randomized, double-blinded clinical trial for human norovirus inactivation in oysters by high hydrostatic pressure processing.

Contamination of oysters with human noroviruses (HuNoV) constitutes a human health risk and may lead to severe economic losses in the shellfish industry. There is a need to identify a technology that can inactivate HuNoV in oysters. In this study, we conducted a randomized, double-blinded clinical trial to assess the effect of high hydrostatic pressure processing (HPP) on Norwalk virus (HuNoV genogroup I.1) inactivation in virus-seeded oysters ingested by subjects. Forty-four healthy, positive-secretor adults were divided into three study phases. Subjects in each phase were randomized into control and intervention groups. Subjects received Norwalk virus (8FIIb, 1.0 × 10(4) genomic equivalent copies) in artificially seeded oysters with or without HPP treatment (400 MPa at 25°C, 600 MPa at 6°C, or 400 MPa at 6°C for 5 min). HPP at 600 MPa, but not 400 MPa (at 6° or 25°C), completely inactivated HuNoV in seeded oysters and resulted in no HuNoV infection among these subjects, as determined by reverse transcription-PCR detection of HuNoV RNA in subjects' stool or vomitus samples. Interestingly, a white blood cell (granulocyte) shift was identified in 92% of the infected subjects and was significantly associated with infection (P = 0.0014). In summary, these data suggest that HPP is effective at inactivating HuNoV in contaminated whole oysters and suggest a potential intervention to inactivate infectious HuNoV in oysters for the commercial shellfish industry.

Comparison of the Activity of Alcohol-Based Handrubs Against Human Noroviruses Using the Fingerpad Method and Quantitative Real-Time PCR.

Noroviruses (NoV) are the most common cause of acute nonbacterial gastroenteritis in the United States, and human hands play an important role in their transmission. Little is known about the efficacy of hand hygiene agents against these highly infectious pathogens. We investigated the activity of seven commercially available hand hygiene products against human noroviruses by in vivo fingerpad tests. The in vivo activity of alcohol-based handrubs ranged from 0.10 to 3.74 log reduction and was not solely dependent on alcohol concentration. A handrub (VF481) based on 70% ethanol and a blend of other skin care ingredients reduced Norwalk virus (NV) by 3.74 log in 15 s and provided significantly greater NV reduction than all the other products tested (P < 0.001). Furthermore, VF481 was the most effective product tested against the NoV genogroup II strains Snow Mountain virus (GII.2) and a GII.4 strain. These results demonstrate that alcohol by itself is not effective against NoV, but effective formulation of alcohol-based handrubs can achieve significant reduction of norovirus RNA on fingers.

Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression.

The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8+ T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.