Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation.

Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E2, and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death.

Human coronavirus alone or in co-infection with rhinovirus C is a risk factor for severe respiratory disease and admission to the pediatric intensive care unit: A one-year study in Southeast Brazil.

OBJECTIVE: We aimed to assess the profile of respiratory viruses in young children hospitalized for acute lower respiratory tract infection (ALRI) and its association with disease severity, defined as need for pediatric intensive care unit (PICU) admission. DESIGN: Prospective observational cohort study. SETTING: A tertiary-care university hospital in Brazil. PATIENTS: Children younger than three years attending the pediatric emergency room with ALRI who were admitted to the hospital. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal aspirates were collected from patients from June 1st, 2008 to May 31st, 2009within the first 48 hours of hospitalization. Nasopharyngeal aspirates were tested for 17humanrespiratory viruses by molecular and immunofluorescence based assays. Simple and multiple log-binomial regression models were constructed to assess associations of virus type with a need for PICU admission. Age, prematurity, the presence of an underlying disease and congenital heart disease were covariates. Nasopharyngeal aspirates were positive for at least one virus in 236 patients. Rhinoviruses were detected in 85.6% of samples, with a preponderance of rhinovirus C (RV-C) (61.9%). Respiratory syncytial virus was detected in 59.8% and human coronavirus (HCoV) in 11% of the samples. Co-detections of two to five viruses were found in 78% of the patients. The detection of HCoV alone (adjusted relative risk (RR) 2.18; 95% CI 1.15-4.15) or in co-infection with RV-C (adjusted RR 2.37; 95% CI 1.23-4.58) was independently associated with PICU admission. CONCLUSIONS: The detection of HCoV alone or in co-infection with RV-C was independently associated with PICU admission in young children hospitalized for ALRI.

CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1ß Release and Inflammation.

Interleukin (IL)-1ß is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus. In this context, bioactive lipids such as prostaglandin (PG)E2 and leukotriene (LT)B4 modulate the production of IL-1ß by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB4, PGE2, and cyclic adenosine monophosphate (cAMP) production to regulate IL-1ß release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized. Here, we identified that both CD14 and CD36 control the synthesis of bioactive lipids, inflammatory cytokines, and mortality mediated by TsV. CD14 induces PGE2/cAMP/IL-1ß release and inflammation. By contrast, CD36 shunts eicosanoid metabolism toward production of LTB4, which represses the PGE2/cAMP/IL-1ß axis and mortality. Of importance, the molecular mechanisms observed in mice strongly correlate with those of human cell responses to TsV. Overall, this study provides major insights into molecular mechanisms connecting CD14 and CD36 with differential eicosanoid metabolism and inflammation mediated by IL-1ß.

The burden of single virus and viral coinfections on severe lower respiratory tract infections among preterm infants: a prospective birth cohort study in Brazil.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with severe lower respiratory tract infection (LRTI), especially in preterm infants. Other viruses, co-detected with RSV, may play a role in the severity of respiratory outcomes. METHODS: This prospective epidemiologic study of severe LRTI incidence among children born ≤35 weeks gestational age at 3 sites in Brazil (2008-2010) followed a birth cohort for 1 year post-enrollment. Nasal washes from subjects with LRTI were tested for respiratory viruses using polymerase chain reaction. The primary outcome was the incidence of severe LRTI requiring hospitalization associated with RSV infection. Secondary outcomes included identification of viruses associated with LRTI, alone or coinfections, and risk factors associated with severe LRTI. RESULTS: Among 303 subjects, 176 (58.1%) experienced LRTI. Among these subjects, 162 had samples tested using polymerase chain reaction; 27.8% (45/162) experienced severe LRTI. More subjects with severe LRTI were infected with RSV (30/45, 66.7%) than with other viruses. RSV was present in 33.1% (143/432) of LRTI events tested, 57.3% (82/143) were coinfections. RSV was the virus most frequently associated with severe LRTIs (34/56 events, 60.7%); 50% (17/34 events) single and 50% coinfections. Significantly longer hospital stays were associated with LRTI events involving RSV coinfections compared with RSV single infections (P = 0.012). Infants with severe LRTIs had significantly lower mean RSV-IgG levels at study entry compared with those with nonsevere or no LRTIs (P < 0.05). CONCLUSIONS: This study confirms the association of RSV alone or as a coinfection with severe LRTI and reinforces the importance of providing adequate prophylaxis for susceptible infants.

Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing ventilator-associated pneumonia after cardiac surgery: an observational study.

BACKGROUND: The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery. METHODS: This was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1. RESULTS: Thirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29). CONCLUSION: Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.

Effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia in children undergoing cardiac surgery.

OBJECTIVE: To evaluate the effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia and ventilator-associated pneumonia (VAP) in children undergoing cardiac surgery. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Pediatric intensive care unit (PICU) at a tertiary care hospital. PATIENTS: One hundred sixty children undergoing surgery for congenital heart disease, randomized into 2 groups: chlorhexidine (n = 87) and control (n = 73). INTERVENTIONS: Oral hygiene with 0.12% chlorhexidine gluconate or placebo preoperatively and twice a day postoperatively until PICU discharge or death. RESULTS: Patients in experimental and control groups had similar ages (median, 12.2 vs 10.8 months; P = .72) and risk adjustment for congenital heart surgery 1 score distribution (66% in category 1 or 2 in both groups; P = .17). The incidence of nosocomial pneumonia was 29.8% versus 24.6% (P = .46) and the incidence of VAP was 18.3% versus 15% (P = .57) in the chlorhexidine and the control group, respectively. There was no difference in intubation time (P = .34), need for reintubation (P = .37), time interval between hospitalization and nosocomial pneumonia diagnosis (P = .63), time interval between surgery and nosocomial pneumonia diagnosis (P = .10), and time on antibiotics (P = .77) and vasoactive drugs (P = .16) between groups. Median length of PICU stay (3 vs 4 days; P = .53), median length of hospital stay (12 vs 11 days; P = .67), and 28-day mortality (5.7% vs 6.8%; P = .77) were also similar in the chlorhexidine and the control group. CONCLUSIONS: Oral hygiene with 0.12% chlorhexidine gluconate did not reduce the incidence of nosocomial pneumonia and VAP in children undergoing cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00829842 .