A Patient-Level Meta-Analysis of Intensive Glucose Control in Critically Ill Adults.

BACKGROUND: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available. METHODS: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome. RESULTS: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001). CONCLUSIONS: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Sepiolite as a novel polysulfide trapper for energy applications: an electrochemical, X-ray spectroscopic and DFT study.

Capacity retention is a critical property to enhance in electrochemical storage systems applied to renewable energy. In lithium-sulfur (Li-S) batteries, the capacity fade resulting from the shuttle effect of polysulfides is a major obstacle to their practical application. Sepiolite, an eco-friendly earth-abundant clay with suitable surface chemistry for anchoring and retaining various molecules and structures, was studied as a cathode additive to mitigate the shuttle effect using experimental and theoretical approaches. Electrochemical measurements, spectroscopy, and ab initio calculations were performed to describe the mechanism and interfaces involved in polysulfide retention using 2 wt% of sepiolite as an additive in Li-S batteries. The results showed that the addition of sepiolite significantly improved the capacity retention during battery cycling. Spectroscopic analysis revealed that the effective sepiolite-polysulfide interface was governed by oxidized sulfur species. Additionally, ab initio studies showed a highly exothermic adsorption both inside and outside the sepiolite pore. This study demonstrates the potential use of eco-friendly, low-cost, non-toxic, natural, and abundant materials as additives to increase capacity retention.

The effects of vasopressors with and without dobutamine on haemodynamics, metabolism and gut injury during endotoxic shock in rabbits. A controlled study.

INTRODUCTION: Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine. MATERIAL AND METHODS: Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A - sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h. RESULTS: The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups. CONCLUSIONS: Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.

Effects of the Poly(ADP-Ribose) Polymerase Inhibitor Olaparib in Cerulein-Induced Pancreatitis.

OBJECTIVE: Activation of the constitutive nuclear and mitochondrial enzyme poly (ADP-ribose) polymerase (PARP) has been implicated in the pathogenesis of cell dysfunction, inflammation, and organ failure in various forms of critical illness. The objective of our study was to evaluate the efficacy and safety of the clinically approved PARP inhibitor olaparib in an experimental model of pancreatitis in vivo and in a pancreatic cell line subjected to oxidative stress in vitro. The preclinical studies were complemented with analysis of clinical samples to detect PARP activation in pancreatitis. METHODS: Mice were subjected to cerulein-induced pancreatitis; circulating mediators and circulating organ injury markers; pancreatic myeloperoxidase and malondialdehyde levels were measured and histology of the pancreas was assessed. In human pancreatic duct epithelial cells (HPDE) subjected to oxidative stress, PARP activation was measured by PAR Western blotting and cell viability and DNA integrity were quantified. In clinical samples, PARP activation was assessed by PAR (the enzymatic product of PARP) immunohistochemistry. RESULTS: In male mice subjected to pancreatitis, olaparib (3 mg/kg i.p.) improved pancreatic function: it reduced pancreatic myeloperoxidase and malondialdehyde levels, attenuated the plasma amylase levels, and improved the histological picture of the pancreas. It also attenuated the plasma levels of pro-inflammatory mediators (TNF-α, IL-1ß, IL-2, IL-4, IL-6, IL-12, IP-10, KC) but not MCP-1, RANTES, or the anti-inflammatory cytokine IL-10. Finally, it prevented the slight, but significant increase in plasma blood urea nitrogen level, suggesting improved renal function. The protective effect of olaparib was also confirmed in female mice. In HPDE cells subjected to oxidative stress olaparib (1 µM) inhibited PARP activity, protected against the loss of cell viability, and prevented the loss of cellular NAD levels. Olaparib, at 1µM to 30 µM did not have any adverse effects on DNA integrity. In human pancreatic samples from patients who died of pancreatitis, increased accumulation of PAR was demonstrated. CONCLUSION: Olaparib improves organ function and tempers the hyperinflammatory response in pancreatitis. It also protects against pancreatic cell injury in vitro without adversely affecting DNA integrity. Repurposing and eventual clinical introduction of this clinically approved PARP inhibitor may be warranted for the experimental therapy of pancreatitis.

Quality indicators for enteral and parenteral nutrition therapy: application in critically ill patients "at nutritional risk".

INTRODUCTION: Quality Indicators for Nutritional Therapy (QINT) allow a practical assessment of nutritional therapy (NT) quality. OBJECTIVE: To apply and monitor QINT for critically ill patients at nutritional risk. METHODS: Cross sectional study including critically ill patients > 18 years old, at nutritional risk, on exclusive enteral (ENT) or parenteral nutritional therapy (PNT) for > 72 hours. After three consecutive years, 9 QINT were applied and monitored. Statistical analysis was performed with SPSS version 17.0. RESULTS: A total of 145 patients were included, 93 patients were receiving ENT, among then 65% were male and the mean age was 55.7 years (± 17.4); 52 patients were receiving PNT, 67% were male and the mean age was 58.1 years (± 17.4). All patients (ENT and PNT) were nutritionally screened at admission and their energy and protein needs were individually estimated. Only ENT was early initiated, more than 70% of the prescribed ENT volume was infused and there was a reduced withdrawal of enteral feeding tube. The frequency of diarrhea episodes and digestive fasting were not adequate in ENT patients. The proper supply of energy was contemplated only for PNT patients and there was an expressive rate of oral intake recovery in ENT patients. CONCLUSION: After three years of research, the percentage of QINT adequacy varied between 55%-77% for ENT and 60%-80% for PNT. The results were only made possible by the efforts of a multidisciplinary team and the continuous re-evaluation of the procedures in order to maintain the nutritional assistance for patients at nutritional risk.

Quality indicators for enteral and parenteral nutrition therapy: application in critically ill patients «at nutritional risk» / Indicadores de calidad para terapia nutricional enteral y parenteral: aplicación en pacientes críticamente enfermos «con riesgo nutricional»

Introduction: Quality Indicators for Nutritional Therapy (QINT) allow a practical assessment of nutritional therapy (NT) quality. Objective: To apply and monitor QINT for critically ill patients at nutritional risk. Methods: Cross sectional study including critically ill patients > 18 years old, at nutritional risk, on exclusive enteral (ENT) or parenteral nutritional therapy (PNT) for > 72 hours. After three consecutive years, 9 QINT were applied and monitored. Statistical analysis was performed with SPSS version 17.0. Results: A total of 145 patients were included, 93 patients were receiving ENT, among then 65% were male and the mean age was 55.7 years (± 17.4); 52 patients were receiving PNT, 67% were male and the mean age was 58.1 years (± 17.4). All patients (ENT and PNT) were nutritionally screened at admission and their energy and protein needs were individually estimated. Only ENT was early initiated, more than 70% of the prescribed ENT volume was infused and there was a reduced withdrawal of enteral feeding tube. The frequency of diarrhea episodes and digestive fasting were not adequate in ENT patients. The proper supply of energy was contemplated only for PNT patients and there was an expressive rate of oral intake recovery in ENT patients. Conclusion: After three years of research, the percentage of QINT adequacy varied between 55%-77% for ENT and 60%-80% for PNT. The results were only made possible by the efforts of a multidisciplinary team and the continuous re-evaluation of the procedures in order to maintain the nutritional assistance for patients at nutritional risk (AU)

Introducción: los indicadores de calidad en terapia nutricional (ICTN) permiten evaluar la calidad de la terapia nutricional (TN) de forma práctica. Objetivo: implementar y monitorizar los ICTN en pacientes críticos con riesgo nutricional. Métodos: estudio transversal con pacientes críticos > 18 años en riesgo nutricional, en terapia nutricional enteral (TNE) o parenteral (TNP) exclusiva a > 72 horas. Después de 3 años consecutivos, 9 ICTN fueron implementados y monitorizados. El análisis estadístico fue realizado con el software SPSS, versión 17.0. Resultados: fueron incluidos 145 pacientes, siendo 93 en TNE, 65% eran de sexo masculino, con edad promedio de 55,7 años (± 17,4); 52 pacientes que estaban en TNP, 67% eran de sexo masculino, con edad promedio de 58,1 años (± 17,4). Todos los pacientes (TNE y TNP) fueron cribados en la admisión, los cálculos de las necesidades calóricas y proteínicas fueron individualizados. Apenas la TNE fue precoz, > 70% del volumen prescrito fue administrado y fue visto una reducida pérdida de la sonda nasoenteral. Las frecuencias de diarrea y ayuno digestivo no fueron adecuadas en TNE. La administración adecuada de energía fue contemplada apenas en TNP y hubo una significativa tendencia de recuperación en la vía oral en TNE. Conclusión: después de 3 años de estudio, el porcentaje de adecuación de los ICTN varió entre 55%-77% para TNE y 60%-80% para TNP. Los resultados reflejan los esfuerzos del equipo multiprofesional de TN en mantener la calidad de la asistencia nutricional en los pacientes críticos con riesgo nutricional (AU)