Performance of prognostic markers in pediatric sepsis

ObjectiveTo evaluate the prognostic performance of the Pediatric Index of Mortality 2 (PIM2), ferritin, lactate, C-reactive protein (CRP), and leukocytes, alone and in combination, in pediatric patients with sepsis admitted to the pediatric intensive care unit (PICU).MethodsA retrospective study was conducted in a PICU in Brazil. All patients aged 6 months to 18 years admitted with a diagnosis of sepsis were eligible for inclusion. Those with ferritin and C-reactive protein measured within 48 h and lactate and leukocytes within 24 h of admission were included in the prognostic performance analysis.ResultsOf 350 eligible patients with sepsis, 294 had undergone all measurements required for analysis and were included in the study. PIM2, ferritin, lactate, and CRP had good discriminatory power for mortality, with PIM2 and ferritin being superior to CRP. The cutoff values for PIM2 (> 14%), ferritin (> 135 ng/mL), lactate (> 1.7 mmol/L), and CRP (> 6.7 mg/mL) were associated with mortality. The combination of ferritin, lactate, and CRP had a positive predictive value of 43% for mortality, similar to that of PIM2 alone (38.6%). The combined use of the three biomarkers plus PIM2 increased the positive predictive value to 76% and accuracy to 0.945.ConclusionsPIM2, ferritin, lactate, and CRP alone showed good prognostic performance for mortality in pediatric patients older than 6 months with sepsis. When combined, they were able to predict death in three-fourths of the patients with sepsis. Total leukocyte count was not useful as a prognostic marker.     

Cannabidiol administration into the bed nucleus of the stria terminalis alters cardiovascular responses induced by acute restraint stress through 5-HT1A receptor

Systemic administration of cannabidiol (CBD) is able to attenuate cardiovascular responses to acute restraint stress through activation of 5-HT_1A receptors. Previous results from our group suggest that the bed nucleus of the stria terminalis (BNST) is involved in the antiaversive effects of the CBD. Moreover, it has been proposed that synapses within the BNST influence restraint-evoked cardiovascular changes, in particular by an inhibitory influence on the tachycardiac response associated to restraint stress. Thus, the present work investigated the effects of CBD injected into the BNST on cardiovascular changes induced by acute restraint stress and if these effects would involve the local activation of 5-HT_1A receptors. The exposition to restraint stress increased both blood pressure and heart rate (HR). The microinjection of CBD (30 and 60 nmol) into the BNST enhanced the restraint-evoked HR increase, in a dose-dependent manner, without affecting the pressor response. The selective 5-HT_1A receptor antagonist WAY100635 by itself did not change the cardiovascular responses to restraint stress, but blocked the effects of CBD. These results showed that CBD microinjected into the BNST enhanced the HR increase associated with acute restraint stress without affecting the blood pressure response. Although these results are not in agreement with those observed after systemic administration of CBD, they are similar to effects observed after reversible inactivation of the BNST. Moreover, similar to the effects observed after systemic administration, CBD effects in the BNST seem to depend on activation of 5-HT_1A receptors.     

Keratinocyte growth factor and hepatocyte growth factor in bronchoalveolar lavage fluid in acute respiratory distress syndrome patients

OBJECTIVES: To determine bronchoalveolar lavage (BAL) fluid concentrations of keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), two potent growth factors for alveolar type II epithelial cells, in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: An adult trauma/surgical intensive care unit in an urban teaching hospital. PATIENTS: A total of 32 ventilated patients with pulmonary infiltrates prospectively identified with ARDS (n = 17) or without ARDS (n = 15), including eight patients with hydrostatic edema (HE), and ten nonventilated patients serving as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BAL was performed 2.88 days +/- 2.4, 3.5 days +/- 2.4, and 2.3 days +/- 2.2 after the lung insult in ARDS, HE, and other non-ARDS patients respectively (p = .32). KGF was detected in BAL fluid in 13 of the 17 ARDS patients (median, 31.6 pg/mL), in one patient with HE, and in none of other non-ARDS patients. In ARDS patients, detection of KGF in BAL was associated in BAL fluid with the detection of type III procollagen peptide (PIIIP), a biological marker of fibroproliferation. In ARDS patients, detection of KGF in BAL was associated with death (p = .02). HGF was detected in 15 ARDS patients (median, 855 pg/mL), in seven patients with HE (median, 294 pg/mL; p = .05 for the comparison with ARDS group), in six of other non-ARDS patients (median, 849 pg/mL; p = .32 with ARDS group). HGF concentrations were higher in nonsurvivors than in survivors (p = .01). None of the ten BAL of controls contained either KGF or HGF. CONCLUSION: KGF was detected almost exclusively in BAL fluid from ARDS patients and correlated with a poor prognosis in this group. In contrast, HGF was detected in the BAL fluid from a majority of patients with or without ARDS. Elevated HGF concentrations were associated with a poor prognosis in the overall group.     

Parathyroid hormone-related protein in epithelial lining fluid in humans negatively correlates with the severity of lung injury

OBJECTIVE: To determine the concentration of parathyroid hormone-related protein (PTHrP; an autocrine/paracrine regulator of type-2 alveolar epithelial cells proliferation and apoptosis) in the epithelial lining fluid (ELF) from patients without pulmonary disease and from patients with acute lung injury (ALI), and to evaluate whether PTHrP concentrations correlated with the intensity of lung injury. DESIGN: Prospective study. SETTING: An adult trauma/surgical ICU in an urban teaching hospital. PATIENTS: A total of 20 patients with ALI receiving mechanical ventilation (patients), and 10 patients without pulmonary disease not receiving mechanical ventilation (control subjects). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: PTHrP was detected in all BAL fluids, and ELF PTHrP concentrations (median; 25% to 75% percentiles) tended to be higher in patients (52.2 nmol/mL; 20.8 to 65.6 nmol/mL) than in control subjects (25.4 nmol/mL; 20.5 to 35.4 nmol/mL; p = 0.18). In patients, ELF PTHrP concentration correlated positively with the PaO(2)/fraction of inspired oxygen ratio (r = 0.53; p = 0.005), and negatively with lung injury score (r = - 0.44; p = 0.02), radiologic score (r = - 0.40; p = 0.04), and BAL albumin concentration (r = - 0.42; p = 0.02). CONCLUSION: PTHrP is present in biologically significant concentrations in the alveolar milieu in humans. In patients with ALI, the PTHrP concentration correlates negatively with the degree of lung injury.     

Niemann-Pick disease type B identified following an episode of bronchopneumonia

Niemann Pick disease type B (NPD type B) is a rare autosomal recessive lipid storage disorder, characterized by a partial deficiency of sphingomyelinase. We report the case of an adult male patient affected by NPD type B and diagnosed at 39-years-of age. Pulmonary CT scan revealed a cranio-caudal gradient with nodular centrilobular ground glass opacities and thickening of the interlobular septa. Pathological examination of the bronchoalveolar lavage showed foamy alveolar macrophages and vacuolated bronchial epithelial cells on bronchial biopsy. Diagnostic confirmation was achieved by a decrease in cell lysosomal enzyme activity and by the presence of the homozygous DeltaR608 mutation in the acid sphingomyelinase gene (SMPD1).     

Adult asthma exacerbations in questions

In this article a French working party critically review the international literature to revise the definition, pathophysiology, treatment and cost of exacerbations of adult asthma. The various guidelines do not always provide a consistent definition of exacerbations of asthma. An exacerbation can be defined as deterioration of clinical and/or functional parameters lasting more than 24 hours, without return to baseline, requiring a change of treatment. No single clinical or functional criterion can be used as an early marker of an exacerbation. Innate and acquired immune mechanisms, modified by contact with infectious, irritant or allergenic agents, participate in the pathogenesis of exacerbations, which are accompanied by bronchial inflammation. In 2010, mortality is related to progression of exacerbations, often occurring before the patient seeks medical attention. The objective of treatment is to control asthma and prevent exacerbations. However, many factors can trigger exacerbations and often cannot be controlled. The efficacy of inhaled corticosteroids has been demonstrated on reduction of the number of exacerbations and the number of asthma-related deaths. This treatment is cost-effective, especially in terms of reduction of exacerbations.