Macroloides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains

Producción CientíficaThe current outburst of a new H1N1 swine influenza strain(s) in México and the United States is causing great concern in health authorities and in the general population [1]. With the World Health Organization (WHO) reporting the pandemic potential of the new strain, it is necessary to determine which therapeutic options are available until a specific vaccine is available. Based on information from the Centre for Disease Control (CDC), the virus is sensitive to oseltamivir and zanamivir. Antivirals are strongly affected by viral mutations; thus their efficiency could be lost as the virus changes

Ventilator-associated pneumonia is an important risk factor for mortality after major cardiac surgery

Producción CientíficaVentilator-associated pneumonia (VAP) is the main infectious complication in cardiac surgery patients and is associated with an important increase in morbidity and mortality. The aim of our study was to analyze the impact of VAP on mortality excluding other comorbidities and to study its etiology and the risk factors for its development. MATERIALS AND METHODS: This prospective cohort study included 1610 postoperative cardiac surgery patients' status post cardiopulmonary bypass (CPB) between July 2004 and January 2008. The primary outcome measures were the development of VAP and in-hospital mortality. RESULTS: Ventilator-associated pneumonia was observed in 124 patients (7.7%). Patients with VAP had a longer length of hospitalization (40.7 ± 35.1 vs 16.1 ± 30.1 days, P <.0001) and greater in-hospital mortality (49.2% [61/124] vs 2.0% [30/1486], P =.0001) in comparison with patients without VAP. After performing the Cox multivariant analysis adjustment, VAP was identified as the most important independent mortality risk factor (adjusted hazard ratio [HR], 8.53; 95% confidence interval, 4.21-17.30; P =.0001). Other independent risk factors of in-hospital mortality were chronic renal failure (HR, 2.56), diabetes mellitus (HR, 1.90), CPB time (HR, 1.51), respiratory failure (HR, 2.13), acute renal failure (HR, 2.39), and mediastinal bleeding of at least 1000 mL (HR, 1.81)

Genetic polymorphisms located in TGFB1, AGTR1, and VEGFA genes are associated to chronic renal allograft dysfunction

Background: Persistent inflammation and fibrosis have been related to active progression of renal deterioration and reduced survival of kidney transplant. The aim of this study was to determine the impact of single-nucleotide polymorphisms (SNPs) located in regions related to inflammatory and immune processes on the development of chronic renal allograft dysfunction (CRAD). Methods: A retrospective study was carried out on 276 patients who received kidney transplant (KT). SNPs were genotyped via the SNPlex platform. Statistical analysis was performed with SNPstat and regression logistic analyses were adjusted by age and gender of recipients and donors, cold ischemia time and the number of human leukocyte antigen (HLA) mismatches. Results: From 276 patients with KT, 118 were non-CRAD and 158 were CRAD. Three SNPs showed significant associations with CRAD development: rs1800471 in transforming growth factor beta 1 (TGFB1), rs5186 in angiotensin II receptor type 1 (AGTR1), and rs699947 in vascular endothelial growth factor A (VEGFA). GC genotype of rs1800471 was associated with increased odds of CRAD compared to GG genotype (OR=2.65 (95% confidence interval (CI)=1.09; 6.47), p=0.025), as well as AC and AA genotype of rs699947 assuming a dominant model (OR=1.80 (95% CI=1.02; 3.20), p=0.044). Besides, AC and CC genotypes of rs5186 were associated with reduced odds of CRAD assuming a dominant model (OR=0.56 (95% CI=0.33; 0.96), p=0.033). Conclusion: Our findings suggest that three genes related to immunity and inflammation (rs1800471, rs5186 and rs699947) are associated to susceptibility or protection to CRAD, and might have diagnostic utility in predicting the likelihood of developing CRAD.This work was supported by two Grants from Instituto de Salud Carlos III (Ref: PI08/0738 and PI11/00245) and from Junta de Castilla y León (Ref: GRS 234/A/08). MAJs, AFR and MGF are supported by Grants from Instituto de Salud Carlos III, CM10/00105, UIPY-1377/08 and CM09/00031, respectively.S

Circulating neutrophil counts and mortality in septic shock

Producción CientíficaPolynuclear neutrophils can play dual roles in sepsis: on the one hand they mediate major antimicrobial activities and on the other hand they can contribute to the development of multiple organ failure [1]. Nonetheless, in spite of the importance of these cells in sepsis, the influence of the circulating neutrophil count (CNC) on the prognosis of septic patients with this pathology has not been properly evaluated. We analyzed the association between CNC and outcome in two cohorts of patients with diagnostic criteria of septic shock (SS) [2]: the first was recruited in the context of a single center study (EXPRESS study, discovery cohort, n = 195; Table 1), and the second in the context of a multi-centric study (GRECIA study, validation cohort, n = 194; Table 2). Written informed consent was obtained from each patient or their legal representative. The two studies were approved by the Research Ethics Committee of the Hospital Clínico Universitario, Valladolid, Spain (for the EXPRESS study) and Hospital Universitario Río Hortega, Valladolid, Spain (coordinating center for the GRECIA study).Instituto de Salud Carlos III (grant PI 10/01362)Junta de Castilla y León (grant BOCYL-D-26072010

Biological differences between in vitro produced bovine embryos and parthenotes

Parthenotes may represent an alternate ethical source of stem cells, once biological differences between parthenotes and embryos can be understood. In this study, we analyzed development, trophectoderm (TE) differentiation, apoptosis/necrosis, and ploidy in parthenotes and in vitro produced bovine embryos. Subsequently, using real-time PCR, we analyzed the expression of genes expected to underlie the observed differences at the blastocyst stage. In vitro matured oocytes were either fertilized or activated with ionomycin C6-DMAP and cultured in simple medium. Parthenotes showed enhanced blastocyst development and diploidy and reduced TE cell counts. Apoptotic and necrotic indexes did not vary, but parthenotes evidenced a higher relative proportion of apoptotic cells between inner cell mass and TE. The pluripotence-related POU5F1 and the methylation DNMT3A genes were downregulated in parthenotes. Among pregnancy recognition genes, TP-1 was upregulated in parthenotes, while PGRMC1 and PLAC8 did not change. Expression of p66shc and BAX/BCL2 ratio were higher, and p53 lower, in parthenotes. Among metabolism genes, SLC2A1 was downregulated, while AKR1B1, PTGS2, H6PD, and TXN were upregulated in parthenotes, and SLC2A5 did not differ. Among genes involved in compaction/blastulation, GJA1 was downregulated in parthenotes, but no differences were detected within ATP1A1 and CDH1.Within parthenotes, the expression levels of SLC2A1, TP-1, and H6PD, and possibly AKR1B1, resemble patterns described in female embryos. The pro-apoptotic profile is more pronounced in parthenotes than in embryos, which may differ in their way to channel apoptotic stimuli, through p66shc and p53 respectively, and in their mechanisms to control pluripotency and de novo methylation

Validación del código subcanal CTF por medio de los resultados experimentales de Benchmarck PSBT de la OECD/NEA

El análisis de seguridad en reactores se ha incrementado rápidamente en las últimas décadas. Debido a esto se han visto desarrollados métodos avanzados para la predicción de la fenomenología que tiene lugar en el núcleo del reactor. Este desarrollo se hace significativo en el campo termohidráulico centrado en la escala subcanal. CTF es una versión del código subcanal COBRA-TF mejorada por el ISIRYM. El código ha de ser validado comparando datos de experimentales y los resultados obtenidos al modelar el evento correspondiente, dentro la variedad de transitorios posibles. El benchmark PWR Subchannel and Bundle Test (PSBT) de la OECD/NEA se ha modelado y sus resultados se han comparado con los datos experimentales para validar las funciones de modelado de CTF tanto para estados estacionarios como transitorios en reactores de agua ligera (LWR). El objetivo de este benchmark es analizar la predicción de fracción de huecos obtenida con CTF en 4 casos distintos para estacionario y transitorio. Estos casos se realizan empleando 3 tipos distintos de elemento combustible.Hidalga García-Bermejo, P.; Abarca Giménez, A.; Miró Herrero, R.; Barrachina Celda, TM.; Verdú Martín, GJ. (2014). Validación del código subcanal CTF por medio de los resultados experimentales de Benchmarck PSBT de la OECD/NEA. Grupo Senda. http://hdl.handle.net/10251/61032

Development of the Post Cardiac Surgery (POCAS) prognostic score

Producción CientíficaThe risk of mortality in cardiac surgery is generally evaluated using preoperative risk-scale models. However, intraoperative factors may change the risk factors of patients, and the organism functionality parameters determined upon ICU admittance could therefore be more relevant in deciding operative mortality. The goals of this study were to find associations between the general parameters of organism functionality upon ICU admission and the operative mortality following cardiac operations, to develop a Post Cardiac Surgery (POCAS) Scale to define operative risk categories and to validate an operative mortality risk score. Methods: We conducted a prospective study, including 920 patients who had undergone cardiac surgery with cardiopulmonary bypass. Several parameters recorded on their ICU admission were explored, looking for a univariate and multivariate association with in-hospital mortality (90 days). In-hospital mortality was 9%. Four independent factors were included in the POCAS mortality risk model: mean arterial pressure, bicarbonate, lactate and the International Normalized Ratio (INR). The POCAS scale was compared with four other risk scores in the validation series. Results: In-hospital mortality (90 days) was 9%. Four independent factors were included in the POCAS mortality risk model: mean arterial pressure, bicarbonate ratio, lactate ratio and the INR. The POCAS scale was compared with four other risk scores in the validation series. Discriminatory power (accuracy) was defined with a receiver-operating characteristics (ROC) analysis. The best accuracy in predicting in-hospital mortality (90 days) was achieved by POCAS. The areas under the ROC curves of the different systems analyzed were 0.890 (POCAS), followed by 0.847 (Simplified Acute Physiology Score (SAP II)), 0.825 (Sepsis-related Organ Failure Assessment (SOFA)), 0.768 (Acute Physiology and Chronic Health Evaluation (APACHE II)), 0.754 (logistic EuroSCORE), 0.714 (standard EuroSCORE) and 0.699 (Age, Creatinine, Ejection Fraction (ACEF) score). Conclusions: Our new system to predict the operative mortality risk of patients undergoing cardiac surgery is better than others used for this purpose (SAP II, SOFA, APACHE II, logistic EuroSCORE, standard EuroSCORE, and ACEF score). Moreover, it is an easy-to-use tool since it only requires four risk factors for its calculation.Junta de Castilla y León (grant GRS 463/A/10)Ministerio de Sanidad, Consumo y Bienestar Social (grant RD06/0001/0020

Importancia de los parámetros clínicos analíticos de la sepsis grave en la uropatía obstructiva

INTRODUCTION. Obstructive uropathy (OU) is very prevalent. Its level of bacteremia is high, complicating up to 40% of cases with severe sepsis. &nbsp; OBJECTIVE The purpose of this clinical case report is to describe medical profiles of patients with Obstructive Uropathy at the HCU of Valladolid. MATERIALS AND METHODS All patients of legal age urgently admitted with the diagnosis of UO were included. An observational and descriptive prospective study was designed to classify patients into two groups: severe sepsis patients and non-severe sepsis patients. A descriptive and inferential statistical analysis was carried out, considering a p &lt;0.05 as significant. The quantitative variables were expressed in an interquartile range; medians and the qualitative ones in percentages and absolute numbers. Demographic and clinical data were analysed using Pearson's Chi-square test (Ӽ2) for categorical variables, and the U - Mann - Whitney test was used for continuous variables. OUTCOMES: Our series consists of 65 patients. UO occurred preferentially in men (63.07%).&nbsp; The most frequent comorbidities were HBP and obesity. In the majority of patients, OU was incomplete and secondary to lithiasis. 64.61% of them developed severe sepsis. The urine culture was positive in 20.63% of the cases, being Escherichia coli the most frequent microorganism. Urinary diversion was urgently performed in 40% of the patients. CONCLUSION: There is an analytical profile characteristic of severe sepsis maintained over time, consisting of an increased percentage of neutrophils and procalcitonin and decreased amount of bicarbonate in the bloodINTRODUCCIÓN: La uropatía obstructiva (UO) es muy prevalente. Su nivel de bacteriemia es elevado complicándose hasta en el 40% de los casos con una sepsis grave. OBJETIVO: Describir el perfil clínico del paciente con UO del HCU de Valladolid. MATERIAL Y MÉTODOS: Se diseña un estudio observacional y descriptivo prospectivo. Se incluyó a todo paciente mayor de edad ingresado con carácter de urgencia con el diagnóstico de UO. Los pacientes fueron clasificados en dos grupos en función de si desarrollando sepsis grave (SG) o no (NSG). Se realizó un análisis estadístico descriptivo e inferencial considerándose una p &lt; 0,05 como significativa.&nbsp; Las variables cuantitativas se expresaron en rango intercuartílico y medianas y las cualitativas en porcentajes y números absolutos. Los datos demográficos y clínicos se analizaron mediante el test Chi - cuadrado de Pearson (Ӽ2) para las variables categóricas, y para las variables continuas el test U - Mann - Whitney. RESULTADOS: Nuestra serie consta de 65 pacientes. La UO ocurrió preferentemente en varones (63,07%). La HTA y la obesidad fueron las comorbilidades más frecuentes. La mayoría de la UO eran incompletas y secundarias a litiasis. El 64,61% desarrolló una SG. El Cultivo de orina fue positivo en el 20,63% de los casos siendo el microorganismo más frecuente la E. coli. En el 40% de los pacientes se realizó una derivación urinaria urgente. CONCLUSIÓN: Existe un perfil analítico característico de SG mantenido en el tiempo que consiste en la elevación en sangre del porcentaje de neutrófilos, de procalcitonina y disminución de bicarbonato

Impact of ventilator-associated pneumonia on mortality and epidemiological features of patients with secondary peritonitis

Producción CientíficaBackground: Despite the significant impact of nosocomial infections on the morbidity and mortality of patients staying in the intensive care unit (ICU), no study over the past 20 years has focused specifically on VAP following secondary peritonitis. The objective of the present study was to determine in-hospital mortality and epidemiological features attributed to ventilator-associated pneumonia (VAP) following secondary peritonitis. Methods: Prospective observational study involved 418 consecutive patients admitted in the ICU. Univariate and multivariate analyses were performed to identify risk factors associated with mortality and development of VAP. Results: The incidence of VAP following secondary peritonitis was 9.6 %. Risk factors associated with the development of VAP were hospital-acquired peritonitis, requiring >48 h of mechanical ventilation, and SOFA score. The onset of VAP was late in majority of patients. VAP was developed about 16.8 days after the initiation of the peritonitis. Etiological microorganisms responsible for the peritonitis were different than for VAP. The 90-day in-hospital mortality rate was 47.5 % of VAP patients. Independent factors associated with 30- to 90-day in-hospital mortality were VAP and SOFA. Conclusions: In light of the impact on morbidity and mortality in the ICU, more attention should be given to the concurrent features among VAP and secondary peritonitis.Junta de Castilla y León (grant (GRS773/A/13)Instituto de Salud Carlos III (grant PI15/01451