Serum Levels of Markers of Endothelial Activation Are Not Associated with a Positive Blood Culture in Surinamese Children with Suspected Severe Infection

Background: Systemic serum levels of markers of endothelial activation are associated with infection. We hypothesize that levels of markers of endothelial activation are associated with the presence of a positive blood culture as a manifestation of a systemic infection in children with a suspected severe infection in Suriname. Methods: In this prospective observational cohort study, children between 1 month and 18 years of age suspected of severe infection as assessed by the threating physician, and in whom laboratory testing and blood culturing was performed before start of intravenous antibiotic treatment, were recruited at the emergency department of the Academic Hospital Paramaribo, Suriname. Serum was collected at blood culturing and after 48-72 h of admission. Serum was stored for measurement of levels of Angiopoietin (Ang)-1, Ang-2, soluble (s)P-selectin, sE-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1 and platelet and endothelial cell adhesion molecule-1. Results: Fifty-one children were included of whom 10 had a positive blood culture. Baseline characteristics were similar between children with and without a positive blood culture. No significant differences in serum levels of the Angiopoietins or soluble cellular adhesion molecules between groups were observed at start of antibiotic treatment nor after 48-72 h. Conclusions: The data from this study indicate that in children with severe infection, serum levels of markers of endothelial cell activation are not associated with a positive blood culture. Thus, having a positive bacterial blood culture may not be the only factor driving endothelial activation in this patient population

Neutrophil-endothelial interactions in respiratory syncytial virus bronchiolitis:An understudied aspect with a potential for prediction of severity of disease

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) causes significant morbidity and mortality among young infants worldwide. It is currently widely accepted that neutrophil influx into the airways is a hallmark of the pathophysiology. However, the exact mechanism of neutrophil migration from the vasculature into the alveolar space in RSV LRTI has received little attention. Data shows that endothelial cells become activated upon RSV infection, driving a 'pro-adhesive state' for circulating neutrophils with upregulation of endothelial intercellular adhesion molecule-1 (ICAM-1). During RSV LRTI different subsets of immature and mature neutrophils are present in the bloodstream, that upregulate integrins lymphocyte-function associated antigen (LFA)-1 and macrophage (Mac)-1, serving as ICAM-1 ligands. An alveolar gradient of interleukin-8 may serve as a potent chemoattractant for circulating neutrophils. Neutrophils from lung aspirates of RSV-infected infants show further signs of inflammatory and migratory activation, while soluble endothelial cell adhesion molecules (sCAMs), such as sICAM-1, have become measurable in the systemic circulation. Whether these mechanisms are solely responsible for neutrophil migration into the alveolar space remains under debate. However, data indicate that the currently postulated neutrophil influx into the lungs should rather be regarded as a neutrophil efflux from the vasculature, involving substantial neutrophil-endothelial interactions. Molecular patterns of these interactions may be clinically useful to predict outcomes of RSV LRTI and deserve further study

Viral causes of severe acute respiratory infection in hospitalized children and association with outcomes:A two-year prospective surveillance study in Suriname

BackgroundViruses are the most frequent cause of severe acute respiratory infection (SARI) in children. It is currently unknown whether presence of a virus, the number of viruses, or type of virus, are associated with clinical outcomes of pediatric SARI in developing countries.MethodsBetween 2012 and 2014 nasopharyngeal swabs and demographic and clinical variables were prospectively collected for surveillance of viral causes of SARI in Surinamese children within 48 hours after hospitalization. These swabs were tested for 18 respiratory viruses using a multiplex polymerase chain reaction (PCR) panel to identify the specific viral causes of SARI, unknown to the treating physicians. In post hoc analyses we evaluated if the PCR results, and demographic and clinical characteristics, were associated with course of disease, duration of respiratory support, and length of stay (LOS).ResultsOf a total of 316 analyzed children, 290 (92%) had one or more viruses. Rhinovirus/enterovirus (43%) and respiratory syncytial virus (34%) were most prevalent. Course of disease was mild in 234 (74%), moderate in 68 (22%), and severe in 14 (4%) children. Neither presence of a single virus, multiple viruses, or the type of virus, were different between groups. Prematurity and lower weight-for-age-z-score were independent predictors of a severe course of disease, longer duration of respiratory support, and longer LOS.ConclusionsViruses are common causes of pediatric SARI in Suriname, yet not necessarily associated with clinical outcomes. In developing countries, demographic and clinical variables can help to identify children at-risk for worse outcome, while PCR testing may be reserved to identify specific viruses, such as influenza, in specific patient groups or during outbreaks

High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

<p>Abstract</p> <p>Background</p> <p>To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses.</p> <p>Methods</p> <p>Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H₂O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured.</p> <p>Results</p> <p>Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed.</p> <p>Conclusions</p> <p>During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators.</p

Association between sepsis calculator and infection parameters for newborns with suspected early onset sepsis

Context: Early-onset sepsis remains an important clinical problem with significant antibiotic overtreatment as a result of poor specificity of clinical and infection parameters. Quantitative risk stratification models such as the early-onset neonatal sepsis (EOS) calculator are promising, but it is unclear how these models relate to infection parameters in the first 72 h of life. Aim: The aim of this study is to evaluate the hypothesis that higher EOS calculator results are associated with (serial) laboratory infection parameters, in particular an increase in C-reactive protein (CRP) within 24-48 h and low leukocyte counts. Subjects and Methods: EOS risk estimates were determined for infants born >= 34 weeks of gestation who were started on antibiotic treatment for suspected EOS within 72 h after birth. EOS risk estimates were retrospectively compared to (changes in) available laboratory infection parameters, including CRP, leukocyte, and thrombocyte count. Statistical Analysis Used: Spearman's rho rank correlations coefficient was used when testing for correlations between continuous parameters. Kruskal-Wallis and Mann-Whitney U-tests were applied to differences between stratified risk groups. Results: EOS risk was not correlated with changes in infection parameters. We found negative correlations between both EOS risk and CRP level and leukocyte count within 6 h of the start of antibiotics, as well as CRP level between 6 and 24 h after start of treatment. Conclusions: In contrast to our hypothesis, high EOS risk at birth was consistently correlated with lower CRP and leukocyte counts within 24 h after the start of antibiotics, but not with infection parameters after 24 h. Further interpretation of infection parameters during sepsis calculator use needs to be elucidated

STRUCTURAL CHANGES OF THE HEART DURING SEVERE SEPSIS OR SEPTIC SHOCK

Cardiovascular dysfunction is common in severe sepsis or septic shock. Although functional alterations are often described, the elevated serum levels of cardiac proteins and autopsy findings of myocardial immune cell infiltration, edema, and damaged mitochondria suggest that structural changes to the heart during severe sepsis and septic shock may occur and may contribute to cardiac dysfunction. We explored the available literature on structural (versus functional) cardiac alterations during experimental and human endotoxemia and/or sepsis. Limited data suggest that the structural changes could be prevented, and myocardial function improved by (pre-)treatment with platelet-activating factor, cyclosporin A, glutamine, caffeine, simvastatin, or caspase inhibitors

Fever during pediatric intensive care unit admission is independently associated with increased morbidity

AIMS: To investigate the occurrence and etiology of fever at anytime during pediatric intensive care unit (PICU) admission, and to study its possible effects on clinical outcome in a heterogeneous population of critically ill children. METHODS: Retrospective, observational single center study, comprising 202 patients aged 0 to 18 years, admitted during a 6-month period between January and June 2004. Demographic and clinical data were collected. Fever was defined by a core temperature >or=38.3 degrees C. Outcomes of interest were duration of mechanical ventilation (MV) and PICU stay. Statistical analyses were done using nonparametric univariate analysis and multivariate Cox's regression analysis. RESULTS: Fever during PICU stay occurred in 82 of 202 children (40.6%). Demographic, clinical, and laboratory data of febrile patients were compared to data of nonfebrile patients. In 76 of the febrile patients (92.7%), fever occurred in the first 48 hours of admission and was associated with primary diagnosis in all cases. Six patients developed fever after 48 hours of admission and 8 patients developed a new febrile period after 48 nonfebrile hours. At least 50% of the late-onset fever was caused by cultured proven nosocomial infections, in the other cases a nosocomial infection was suspected. Fever after 48 hours of PICU admission or a secondary episode of fever was independently associated with prolonged length of ventilatory support and prolonged length of PICU stay. CONCLUSIONS: Fever in critically ill children occurs frequently during PICU stay. Fever after 48 hours of admission or new episodes of fever after 48 nonfebrile hours were mainly caused by nosocomial infections and was independently associated with prolonged length of ventilatory support and PICU stay

Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats

<p>Background: Mechanical ventilation (MV) may cause ventilator-induced lung injury (VILI) and may thereby contribute to fatal multiple organ failure. We tested the hypothesis that injurious MV of lipopolysaccharide (LPS) pre-injured lungs induces myocardial inflammation and further dysfunction ex vivo, through calcium (Ca2+)-dependent mechanism.</p><p>Materials and methods: N = 35 male anesthetized and paralyzed male Wistar rats were randomized to intratracheal instillation of 2 mg/kg LPS or nothing and subsequent MV with lung-protective settings (low tidal volume (V-t) of 6 mL/kg and 5 cmH(2)O positive end-expiratory pressure (PEEP)) or injurious ventilation (high V-t of 19 mL/kg and 1 cmH(2)O PEEP) for 4 hours. Myocardial function ex vivo was evaluated in a Langendorff setup and Ca2+ exposure. Key mediators were determined in lung and heart at the mRNA level.</p><p>Results: Instillation of LPS and high V-t MV impaired gas exchange and, particularly when combined, increased pulmonary wet/dry ratio; heat shock protein (HSP)70 mRNA expression also increased by the interaction between LPS and high V-t MV. For the heart, C-X-C motif ligand (CXCL)1 and Toll-like receptor (TLR)2 mRNA expression increased, and ventricular (LV) systolic pressure, LV developed pressure, LV +dP/dt(max) and contractile responses to increasing Ca2+ exposure ex vivo decreased by LPS. High V-t ventilation aggravated the effects of LPS on myocardial inflammation and dysfunction but not on Ca2+ responses.</p><p>Conclusions: Injurious MV by high V-t aggravates the effects of intratracheal instillation of LPS on myocardial dysfunction, possibly through enhancing myocardial inflammation via pulmonary release of HSP70 stimulating cardiac TLR2, not involving Ca2+ handling and sensitivity.</p>

Markers of endothelial cell activation in suspected late onset neonatal sepsis in Surinamese newborns:a pilot study

Background: Serum levels of markers of endothelial cell activation are associated with bacteremia and mortality in sepsis in adults, children, and newborns with early onset sepsis. We hypothesize that levels of these markers are associated with these outcomes in hospitalized newborns with suspected late onset neonatal sepsis (LONS). Methods: In this prospective cohort study, newborns admitted to the tertiary neonatal care facility of Suriname were included upon clinical suspicion of LONS and before start of antibiotic treatment, between April 1, 2015 and May 31, 2016. Serum concentrations of angiopoietin-1, angiopoietin-2, and soluble isoforms of P-selectin, E-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), platelet and endothelial cell adhesion molecule-1 (sPECAM-1), matrix metalloproteinase-9 (MMP-9), neutrophil elastase, and tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured. Results: Twenty-thee newborns were included. Baseline characteristics were similar between newborns with and without bacteremia and between non-survivors and survivors. Only soluble E-selectin (sE-selectin) was higher in newborns with bacteremia versus non-bacteremia (P=0.04) and lower in non-survivors (P=0.04). No conclusions could be made for sVCAM-1 due to high serum concentrations. Conclusions: In conclusion, the data from this pilot study indicate that serum levels of markers of endothelial cell activation are poorly associated with bacteremia and mortality