The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

Introduction: Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study. Methods: This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFa, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman’s rank correlation coefficient or Spearman’s rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission. Results: Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (c2 = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (r = -0.19; P = 0.002), MMP-10 (r = 0.55; P <0.001), TNFa (r = 0.56; P <0.001), IL-10 (r = 0.48; P <0.001) and PAI-1 (r = 0.49; P <0.001). Conclusion: The novel findings of our study are that septic patients with the T allele in the 372 T/C genetic polymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic implications and could help in the selection of patients who may benefit from modulation of the MMP/TIMP balance

Percutaneous mitral valve repair : Outcome improvement with operator experience and a second-generation device

Background and aim: Recent randomized data comparing percutaneous mitral valve repair (PMVR) versus optimal medical treatment in patients with functional MR (FMR) seemed to highlight the importance of the learning curve not only for procedural outcomes but also for patient selection. The aim of the study was to compare a contemporary series of patients undergoing PMVR using a second-generation Mitraclip device (Mitraclip NT) with previous cohorts treated with a first-generation system. Methods: This multicenter study collected individual data from 18 centers between 2012 and 2017. The cohort was divided into three groups according to the use of the first-generation Mitraclip during the first (control-1) or second half (control-2) or the Mitraclip NT sys-tem. Results: A total of 545 consecutive patients were included in the study. Among all, 182 (33.3%), 183 (33.3%), and 180 (33.3%) patients underwent mitral repair in the control-1, control-2, and NT cohorts, respectively. Procedural success was achieved in 93.3% of patients without differences between groups. Major adverse events did not statistically differ among groups, but there was a higher rate of pericardial effusion in the control-1 group (4.3%, 0.6%, and 2.6%, respectively; p = 0.025). The composite endpoint of death, surgery, and admission for congestive heart failure (CHF) at 12 months was lower in the NT group (23.5% in control-1, 22.5% in control-2, and 8.3% in the NT group; p = 0.032). Conclusions: The present paper shows that contemporary clinical outcomes of patients undergoing PMVR with the Mitraclip system have improved over time

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Efectos secretagogos de la cimetidina sobre la secreción pancreática exocrina del conejo

El efecto de la cimetidina sobre la secreción exocrina pancreática se estudió en conejos anestesiados con fístulas pancreáticas agudas. La administración del antagonista H2 aumenta significativamente en función de la dosis el flujo de secreción pancreática. Además, la cimetidina disminuye la concentración de bicarbonato, proteína total, lipasa, amilasa y tripsina. Por el contrario, el contenido de quimotripsina no cambió. Estos resultados sugieren que la cimetidina es un leve secretagogo en el páncreas exocrino del conejo. Se discute el posible mecanismo a través de los efectos de la cimetidina en el tejido pancreático.The effect of cimetidine on pancreatic exocrine secretion was studied in anesthetized rabbits witlt acute pancreatic fistulas. The administration of the H2-antagonist increases significantly in a dose-dependent manner the flow ofpancreatic secretion. Moreover, cimetidine decreases bicarbonate, total protein, lipase, amylase and tripsin concentration. On tite contrary tite content of chymotripsin did not change. These results suggest tltat cimetidine is a slight secretagoge on the rabbit exocrine pancreas. The posible mechanism through cimetidine effects tite pancreatic tissue are discussed.peerReviewe

Effects offeeding fluorine onlamb growing

Se estudiaron los efectos del fluoruro en la dieta sobre el peso corporal y la ingesta diaria de alimentos en corderos. Tres grupos de dieciocho corderos machos de raza «entrefina» se mantuvieron ad libitum durante 60 días con diferente dieta: C = pienso mixto comercial (29,0 ± 0,8 ppm F-) S = pienso mixto comercial + 2% de sepiolita (2 12,3 ± 2,1 ppm F"), F = alimentación mixta comercial + 0,044 % NaF (213,9 ± 2,7 ppm F"). La dieta F indujo una disminución significativa en la ingesta diaria total de alimentos y redujo drásticamente el desarrollo. de corderos Estos dala sugieren que la fluoroscopia crónica depende no solo de la cantidad del lago de fin, sino también de la naturaleza química del suplemento mineral.Dietary fluoride effecls on bodyweight and daily food intake were studied in lamb. Three groups of eighteen mal e lambs of «entrefina» breed were maintained ad libitumfor 60 days with different diet: C = commercial mixed feed (29.0 ± 0.8 ppm F-) S = commercial mixed feed + 2% sepiolite (2 12.3 ± 2.1 ppm F"), F = commercialmixed feed + 0.044% NaF (213.9 ± 2.7 ppm F"). Diet Finduced a significant decrease in total daily food intake and reduced drasticallythe development. oflambs. These dala suggest thal chronic fluoros is depends not only (on) the amount of t.he F inlake, but also, on t.he chemical nature of the mineral supplement.peerReviewe

Actividad de la GGT en el proceso ulcerativo duodenal inducido por indometacina

Actividad de la GGT en el proceso ulcerativo duodenal inducido por indometacina Utilizando un modelo de úlcera duodenal aguda en ratas, observamos que los cambios en la actividad de la y-glutamil transpeptidasa (GGT) parecen estar en estrecha relación con la ulceración. Hemos encontrado una actividad GGT significativamente más baja en la mucosa duodenal cuatro y ocho horas antes de la administración de indometacina en comparación con la actividad GGT duodenal de animales no tratados. Al mismo tiempo, las microvellosidades en el epitelio duodenal se acortan aunque el glicocalix todavía está presente. En algunas zonas se puede apreciar una ausencia total de microvellosidades.Actividad de la GGT en el proceso ulcerativo duodenal inducido por indometacina Using an acute duodenal ulcer model in rats, we observed that changes in y-glutamil transpeptidase (GGT) activity seem to be in clase connection with ulceration. We have found a significantly lower GGT activity in the duodenal mucosa four and eight hours befare administration of indomethacin compared to the duodenal GGT activity of untreated animals. At the same time microvilli in the duodenal cpithelium are shortened altough the glicocalix is still present. In sorne areas a total absence of microvilli can be apreciated.peerReviewe

Tobin's imperfect asset substitution in optimizing general equilibrium

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Volume under the ROC surface for multi-class problems

Abstract. Receiver Operating Characteristic (ROC) analysis has been successfully applied to classifier problems with two classes. The Area Under the ROC Curve (AUC) has been elected as a better way to evaluate classifiers than predictive accuracy or error and has also recently used for evaluating probability estimators. However, the extension of the Area Under the ROC Curve for more than two classes has not been addressed to date, because of the complexity and elusiveness of its precise definition. Some approximations to the real AUC are used without an exact appraisal of their quality. In this paper, we present the real extension to the Area Under the ROC Curve in the form of the Volume Under the ROC Surface (VUS), showing how to compute the polytope that corresponds to the absence of classifiers (given only by the trivial classifiers), to the best classifier and to whatever set of classifiers. We compare the real VUS with “approximations ” or “extensions ” of the AUC for more than two classes.