Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study.

PURPOSE: Over 170 biomarkers are being investigated regarding their prognostic and diagnostic accuracy in sepsis in order to find new tools to reduce morbidity and mortality. Matrix metalloproteinases (MMPs) and their inhibitors have been recently studied as promising new prognostic biomarkers in patients with sepsis. This study is aimed at determining the utility of several cutoff points of these biomarkers to predict mortality in patients with sepsis. MATERIALS AND METHODS: A multicenter, prospective, analytic cohort study was performed in the metropolitan area of Bucaramanga, Colombia. A total of 289 patients with sepsis and septic shock were included. MMP-9, MMP-2, tissue inhibitor of metalloproteinase 1 (TIMP-1), TIMP-2, TIMP-1/MMP-9 ratio, and TIMP-2/MMP-2 ratio were determined in blood samples. Value ranges were correlated with mortality to estimate sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiving operating characteristic curve. RESULTS: Sensitivity ranged from 33.3% (MMP-9/TIMP-1 ratio) to 60.6% (TIMP-1) and specificity varied from 38.8% (MMP-2/TIMP-2 ratio) to 58.5% (TIMP-1). As for predictive values, positive predictive value range was from 17.5% (MMP-9/TIMP-1 ratio) to 70.4% (MMP-2/TIMP-2 ratio), whereas negative predictive values were between 23.2% (MMP-2/TIMP-2 ratio) and 80.9% (TIMP-1). Finally, area under the curve scores ranged from 0.31 (MMP-9/TIMP-1 ratio) to 0.623 (TIMP-1). CONCLUSION: Although TIMP-1 showed higher sensitivity, specificity, and negative predictive value, with a representative population sample, we conclude that none of the evaluated biomarkers had significant predictive value for mortality.

Prognostic Value of MMP-9 -1562 C/T Gene Polymorphism in Patients With Sepsis.

INTRODUCTION: Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected. MATERIALS AND METHODS: A case-control study exploratory was carried out in a cohort of infected patients. 540 individuals were selected in total, 270 patients with sepsis and 270 controls (infected but non-septic), classified according to the 2016 consensus (Sepsis-3). The presence of the single-nucleotide polymorphism (SNP; allele T and/or allele C) was determined through analyses of restriction fragment length polymorphism and plasma levels of MMP-9 were determined through enzyme-linked immunosorbent assay immunoassay. RESULTS: SNP MMP-9 -1562 has two known alleles (T and C), with predominance of the C over the T allele; in the group of patients with sepsis, T allele was found in 7.2% of cases, while C allele in the rest (92.8%); in comparison, in the group of infected but non-septic patients, frequencies were 9.4% for T allele and 90.6% for the C allele (P = .33). Also, the presence of the polymorphic T allele was not related to the levels of MMP-9 in patients with sepsis in comparison with infected but non-septic patients 780 (397-1375) ng/mL vs 646 (172-1249) ng/mL (P = .64). There was also no association between the SNP and sepsis mortality (P = .78). CONCLUSIONS: We concluded that there was no association between the SNP MMP9 -1562 C/T and sepsis or between the SNP MMP9 -1562 C/T and sepsis mortality in the Northeastern Colombian septic patient cohort. Further research is needed to clarify the correlation among sepsis, genetic factors with allele T and MMP-9 plasma concentration.

TIMP1 and MMP9 are predictors of mortality in septic patients in the emergency department and intensive care unit unlike MMP9/TIMP1 ratio: Multivariate model.

INTRODUCTION: Matrix metalloproteinases and tissue inhibitors of metalloproteinases could be promising biomarkers for establishing prognosis during the development of sepsis. It is necessary to clarify the relationship between matrix metalloproteinases and their tissue inhibitors. We conducted a cohort study with 563 septic patients, in order to elucidate the biological role and significance of these inflammatory biomarkers and their relationship to the severity and mortality of patients with sepsis. MATERIALS AND METHODS: A multicentric prospective cohort was performed. The sample was composed of patients who had sepsis as defined by the International Conference 2001. Serum procalcitonin, creatinine, urea nitrogen, C-Reactive protein, TIMP1, TIMP2, MMP2 and MMP9 were quantified; each patient was followed until death or up to 30 days. A descriptive analysis was performed by calculating the mean and the 95% confidence interval for continuous variables and proportions for categorical variables. A multivariate logistic regression model was constructed by the method of intentional selection of covariates with mortality at 30 days as dependent variable and all the other variables as predictors. RESULTS: Of the 563 patients, 68 patients (12.1%) died within the first 30 days of hospitalization in the ICU. The mean values for TIMP1, TIMP2 and MMP2 were lower in survivors, MMP9 was higher in survivors. Multivariate logistic regression showed that age, SOFA and Charlson scores, along with TIMP1 concentration, were statistically associated with mortality at 30 days of septic patients; serum MMP9 was not statistically associated with mortality of patients, but was a confounder of the TIMP1 variable. CONCLUSION: It could be argued that plasma levels of TIMP1 should be considered as a promising prognostic biomarker in the setting of sepsis. Additionally, this study, like other studies with large numbers of septic patients does not support the predictive value of TIMP1 / MMP9.

The L-Arginine-Nitric Oxide-Peroxynitrite pathway (LANOP pathway): does it protect or worsen the course of Chagas disease? / Vía L-Arginina-Óxido Nítrico-Peroxinitrito (Vía-LAONP): ¿protege o empeora el curso de la enfermedad de Chagas?

Many different immunological processes have been described in the Chagas infection, some of them associated with the Chagas disease. In this scenario, the L-Arginine-Nitric oxide (NO) – Peroxynitrite (NOOO-) pathway (LANOP pathway) appears as an essential component of that process. The relationship is well known between cytokines that can induce Oxide Nitric Synthase (iNOS) genes, such as TNF-a and IFN-g, and other molecules that can inhibit their expression (TGF-b, IL-10 and others), which are involved in both acute and chronic stages of the disease pathogenesis. However the participation of the LANOP pathway seems complex, given that evidence shows different roles for it during the course of the infection. In this article, the authors review the immunological and inflammatory response leading to the activation of the LANOP pathway during the Chagas infection, and the role this via plays, including different effects, protector or deleterious, observed in parallel during the development of the infection.

En la infección chagásica se han descrito diversos procesos inmunológicos, algunos de los cuales se han asociado con la enfermedad. En este escenario, aparece la vía L-Arginina-Óxido Nítrico (NO) - Peroxinitrito (ONOO-) (Vía-LAONP) como un componente esencial de estos procesos. Se conoce la asociación entre citocinas inductoras de los genes de la Sintasa del Óxido Nítrico (iNOS) tales como TNF-a e IFN-g, así como moléculas que inhiben su expresión (TGF-b e IL-10 entre otras), involucradas en la patogénesis tanto de la fase aguda como crónica de la enfermedad. No obstante, la participación de la vía-LAONP parece ser compleja, una vez que las evidencias señalan papeles diferentes de ésta durante el curso de la infección. Por tanto, los autores revisan la respuesta inmunológica e inflamatoria que da lugar a la activación de la vía-LAONP durante la infección chagásica, y el papel que ésta desempeña, incluyendo efectos diversos, tanto protectores como deletéreos, que han sido observados en paralelo durante el curso de la misma.

Estado actual del diagnóstico de la toxoplasmosis en la mujer embarazada y su feto / Present state of toxoplasmosis diagnosis on pregnant women and in her fetus

La toxoplasmosis adquirida por la mujer embarazada tiene la mayoría de las veces una presentación subclínica, y su diagnóstico se basa en exámenes serológicos sistemáticos, para verificar sí la gestante está inmunizada, o si es susceptible al Toxoplasma. Las gestantes no inmunizadas (seronegativas), conforman un grupo de especial cuidado, en las cuales la repetición de las pruebas serológicas debe permitir un diagnóstico precoz y un manejo apropiado de las primoinfecciones. Por otro lado la infección congénita con Toxoplasma gondii puede producir alteraciones serias del desarrollo fetal; con el fin de reducir las graves secuelas mediante tratamiento antiparasitario oportuno, se hace necesario la implementación de herramientas que permitan realizar un diagnóstico temprano de la infección fetal, con técnicas que sean altamente específicas y de gran sensibilidad y además, que en lo posible sean inocuas para el feto. La presente revisión describe las principales secuencias metodológicas desarrolladas, y actualmente utilizadas en diversos países para la detección serológica de la seroconversión de las madres gestantes, y la manera de descartar la transmisión congénita del parásito