Serum MicroRNAs as Biomarkers of Sepsis and Resuscitation

There is a lack of biomarkers of sepsis and the resuscitation status. Our objective was to prove that the serum expression of certain microribonucleic acids (miRNAs) is differentially regulated in sepsis and is sensitive to different resuscitation regimes. Anesthetized pigs (Sus scrofa domesticus) received no treatment (n = 15) or intravenous live E. coli (n = 24). The septic animals received 0.9% saline at 4 mL/kg/h (n = 8) (low resuscitation group (LoR)) or 10–17 mL/kg/h (high resuscitation group (HiR)) (n = 8 each group). Blood samples were obtained at the end of the experiment for measurement of seven different miRNAs (RT-qPCR, Qiagen, Hilden, Germany). The serum expression of miR-146a-5p and miR-34a-5p increased significantly in the septic group, and miR-146a-5p was significantly lower in the HiR group than in the LoR group. The toll-like receptor signaling pathway involving 22 target proteins was significantly (adjusted p = 3.87 × 10−4) regulated by these two microRNAs (KEGG). Highly significant (p value = 2.22 × 10−16) protein–protein interactions (STRING) were revealed for these 22 hits. MiR-146a-5p and miR-34a-5p were identified as biomarkers of sepsis, and miRNA146a-5p seemed to be a biomarker of the intensity of the resuscitation

Efectos de la intensidad de la resucitación sobre la respuesta inflamatoria y la expresión de microRNAs en un modelo animal de sepsis

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Fisiología. Fecha de Lectura: 02-03-202

ISAR Score (Identification of Seniors At Risk) predicts mortality in patients older than 75 years admitted in Intensive Care

Antecedentes y objetivos Actualmente, la situación basal del paciente es un factor pronóstico más importante que la edad. El propósito de este estudio es estimar el valor pronóstico de ISAR score (Identification of Senior at Risk) en pacientes ≥ 75 años ingresados en Cuidados Intensivos (UCI). Pacientes y métodos Estudio multicéntrico prospectivo incluyendo a pacientes ≥ 75 años ingresados en UCI > 24 h. Al ingreso, 28 días y 6 meses después del alta de UCI, se evaluaron la mortalidad y la situación basal utilizando el ISAR score, la escala de Lawton y Brody (LB) y el índice de Barthel (BI), la escala de fragilidad Frail scale (FS), el índice de comorbilidad de Charlson (ICC), Dementia Rating Score (DRC). Resultados Treinta y ocho de 94 pacientes (40%) eran de alto riesgo (ISAR ≥ 3) y se caracterizaron por BI 90 (65-100), LB 4 (3-5) y CDR 1 (0-2), ICC 7,5 (6-10). El 58% tenía FS ≥ 3. A largo plazo, quedaron en una situación de dependencia (BI 50 [2,5-77,5], LB 3 [0-4], CDR 1 [0-1,5]). La mortalidad en UCI, a los 28 días y a los 6 meses fue del 18,4, el 25,7 y el 35,3%, respectivamente, siendo estadísticamente significativos. El área bajo la curva ROC del ISAR score fue 0,749 a 0,797 en todos los periodos de mortalidad estudiados, aunque la diferencia con otras variables predictivas no fue significativa, pero el valor de la p fue el más bajo. Conclusiones El ISAR score predice la mortalidad en pacientes ancianos críticos con una capacidad discriminativa comparable con otras variables predictivas.Background and objectives Currently, the patient's baseline situation is a more important prognostic factor than age. The purpose of this study is to estimate the prognostic value of the ISAR score (Identification of Senior at Risk) in patients ≥75 years admitted to intensive care (ICU). Patients and methods Prospective multicenter study including patients ≥75 years admitted to the ICU > 24hours. On admission, 28 days and 6 months after discharge from the ICU, mortality and baseline were evaluated using the ISAR score, the Lawton and Brody scale (LB) and the Barthel index (BI), the Frail fragility scale. scale (FS), the Charlson comorbidity index (ICC), Dementia rating score (DRC). Results 38 of 94 patients (40%) were high risk (ISAR ≥ 3) and were characterized by BI 90 (65-100), LB 4 (3-5), and CDR 1 (0-2), ICC 7.5 (6-10). 58% had FS ≥ 3. In the long term, they were in a situation of dependency [BI 50 (2.5-77.5), LB 3 (0-4), CDR 1 (0-1.5)]. The ICU mortality at 28 days and 6 months was 18.4%, 25.7% and 35.3%, respectively, being statistically significant. The area under the ISAR score ROC curve was 0.749 to 0.797, in all the mortality periods studied, although the difference with other predictive variables was not significant, but the p value was the lowest. Conclusions The ISAR score predicts mortality in critically elderly patients with a discriminative capacity comparable to other predictive variables.Sin financiaciónNo data JCR 20210.243 SJR (2021) Q4, 32/36 AgingNo data IDR 2021UE

Correlations between physiological parameters related with kidney function and minute-by-minute urine output

Aim: Recently, devices capable of measuring minute-by-minute urine output (UOm) have become available. It is not known how UOm correlates with physiological parameters in normal conditions and in disease states characterized by vascular dysfunction. This paper analyzes correlations between UOm and physiological parameters related to kidney perfusion to provide some insight about UOm pathophysiological interpretation and its relationship with renal blood flow. Methods: We studied 14 male pigs were anesthetized, tracheostomized, and mechanically ventilated. Mean systemic blood pressure (PART ), mean pulmonary artery blood pressure (PPA ), carotid artery blood flow (QCA ), as well as total (QREN ), cortical (QCOR ) and medullary (QMED ) renal blood flows, and the renal resistive index (RRI) were measured or calculated. Animals received an intravenous dose of live E. coli for the induction of sepsis (septic group), or an equivalent amount of normal saline (nonseptic group). Three groups were studied: nonseptic (n = 6) and septic (n = 4), both receiving for resuscitation NaCl 0.9% at 4 mL/kg per h; and septic (n = 4), receiving for resuscitation NaCl 0.9% at 17 mL/kg per h. Animals were monitored for 5 h after the induction of sepsis. Results: In septic animals, UOm was strongly positively correlated with QREN (Kendall's τ = 0.770, P < 0.05), QCOR (τ = -0.566, P < 0.05) and QMED (τ = 0.632, P < 0.05); and negatively correlated with PPA (τ = -0.524, P < 0.05) and RRI (τ = -0.672, P < 0.05). Control animals exhibited weaker correlations. Conclusion: UOm is a good physiological surrogate marker of total and regional renal blood flows and vascular resistance, particularly under septic conditions, probably reflecting glomerulo-tubular dysfunction in sepsis.Sin financiación0.716 SJR (2016) Q2, 999/2886 Medicine (miscellaneous), 27/66 NephrologyUE

Microcystis aeruginos strain [D-Leu1] Mcyst-LR producer, from Buenos Aires province, Argentina

Objective: To show the toxicological and phylogenetic characterization of a native Microcystis aeruginosa (M. aeruginosa) strain (named CAAT 2005-3) isolated from a water body of Buenos Aires province, Argentine. Methods: A M. aeruginosa strain was isolated from the drainage canal of the sewage treatment in the town of Pila, Buenos Aires province, Argentina and acclimated to laboratory conditions. The amplification of cpcBA-IGS Phcocyanin (PC, intergenic spacer and flanking regions) was carried out in order to build a phylogenetic tree. An exactive/orbitrap mass spectrometer equipped with an electrospray ionization source (Thermo Fisher Scientific, Bremen, Germany) was used for the LC/ESI-HRMS microcystins analysis. The number of cell/mL and [D-Leu1] Mcyst-LR production obtained as a function of time was modelled using the Gompertz equation. Results: The phylogenetic analysis showed that the sequence clustered with others M. aeruginosa sequences obtained from NCBI. The first Argentinian strain of M. aeruginosa (CAAT 2005-3) growing under culture conditions maintains the typical colonial architecture of M. aeruginosa with profuse mucilage. M. aeruginosa CAAT 2005-3 expresses a toxin variant, that was identified by LC-HRMS/Orbitrapas as [D-Leu1] microcystin-LR ([M+H]+=1 037.8 m/z). Conclusions: [D-Leu1] microcystin-LR has been also detected in M. aeruginosa samples from Canada, Brazil and Argentina. This work provides the basis for technological development and production of analytical standards of toxins present in our region

<i>Microcystis aeruginos</i> strain [D-Leu1] Mcyst-LR producer, from Buenos Aires province, Argentina

Objective: To show the toxicological and phylogenetic characterization of a native Microcystis aeruginosa (M. aeruginosa) strain (named CAAT 2005-3) isolated from a water body of Buenos Aires province, Argentine. Methods: A M. aeruginosa strain was isolated from the drainage canal of the sewage treatment in the town of Pila, Buenos Aires province, Argentina and acclimated to laboratory conditions. The amplification of cpcBA-IGS Phcocyanin (PC, intergenic spacer and flanking regions) was carried out in order to build a phylogenetic tree. An exactive/orbitrap mass spectrometer equipped with an electrospray ionization source (Thermo Fisher Scientific, Bremen, Germany) was used for the LC/ESI-HRMS microcystins analysis. The number of cell/mL and [D-Leu1 ] Mcyst-LR production obtained as a function of time was modelled using the Gompertz equation. Results: The phylogenetic analysis showed that the sequence clustered with others M. aeruginosa sequences obtained from NCBI. The first Argentinian strain of M. aeruginosa (CAAT 2005-3) growing under culture conditions maintains the typical colonial architecture of M. aeruginosa with profuse mucilage. M. aeruginosa CAAT 2005-3 expresses a toxin variant, that was identified by LC-HRMS/Orbitrapas as [D-Leu1 ] microcystin-LR ([M+H]+=1037.8 m/z). Conclusions: [D-Leu1 ] microcystin-LR has been also detected in M. aeruginosa samples from Canada, Brazil and Argentina. This work provides the basis for technological development and production of analytical standards of toxins present in our region.Facultad de Ciencias ExactasFacultad de Ciencias Naturales y Muse

Serum MicroRNAs as Biomarkers of Sepsis and Resuscitation

There is a lack of biomarkers of sepsis and the resuscitation status. Our objective was to prove that the serum expression of certain microribonucleic acids (miRNAs) is differentially regulated in sepsis and is sensitive to different resuscitation regimes. Anesthetized pigs (Sus scrofa domesticus) received no treatment (n = 15) or intravenous live E. coli (n = 24). The septic animals received 0.9% saline at 4 mL/kg/h (n = 8) (low resuscitation group (LoR)) or 10–17 mL/kg/h (high resuscitation group (HiR)) (n = 8 each group). Blood samples were obtained at the end of the experiment for measurement of seven different miRNAs (RT-qPCR, Qiagen, Hilden, Germany). The serum expression of miR-146a-5p and miR-34a-5p increased significantly in the septic group, and miR-146a-5p was significantly lower in the HiR group than in the LoR group. The toll-like receptor signaling pathway involving 22 target proteins was significantly (adjusted p = 3.87 × 10−4 ) regulated by these two microRNAs (KEGG). Highly significant (p value = 2.22 × 10−16) protein–protein interactions (STRING) were revealed for these 22 hits. MiR-146a-5p and miR-34a-5p were identified as biomarkers of sepsis, and miRNA146a-5p seemed to be a biomarker of the intensity of the resuscitation.Sin financiación2.838 JCR (2021) Q2, 39/92 Engineering, Multidisciplinary0.507 SJR (2021) Q2, 33/81 Fluid Flow and Transfer ProcessesNo data IDR 2021UE