Role of soluble urokinase plasminogen activator receptor in critically ill children with hospital-acquired pneumonia: an observational study in hospital with controls.

BACKGROUND: Diagnosing hospital-acquired pneumonia (HAP) (ventilator-associated pneumonia (VAP) and non-ventilator associated pneumonia (Non-VAP)) is still a hot issue. Soluble urokinase plasminogen activator receptor (suPAR) is prognostic in critically ill children with sepsis regarding mortality prediction. Our aim was to evaluate suPAR levels in children with HAP. METHODS: An observational, prospective study was conducted on 45 children diagnosed HAP (VAP and Non-VAP) and 40 healthy controls. Paediatric Sequential Organ Failure assessment Score (pSOFA) was assessed for each patient. Plasma suPAR levels were measured with ELISA on the day of diagnosis. RESULTS: On comparison levels of plasma suPAR for the children with HAP with the healthy control group, no statistically significant difference was observed (148 pg/mL (22.4-1939.7) and 184.4 pg/mL (31.6-1311.7), respectively, (p=0.32). suPAR was significantly increased in children with elevated pSOFA score on the day of diagnosis of pneumonia (p=0.034). suPAR was significantly increased in children with shock (p=0.005). suPAR levels was negatively correlated with oxygen saturation (rs=0.31,p=0.048). suPAR was not significantly correlated with C reactive protein. CONCLUSIONS: suPAR can be used as a predictor for severity of illness in children with HAP. We firmly know that plasma suPAR, a novel marker, could indicate the disease if carried out on larger patient groups.

Soluble urokinase plasminogen activator receptor: a novel biomarker of pediatric community-acquired and hospitalacquired pneumonia.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker in different clinical disorders but data in pediatric pneumonia is scarce. Our objective was to assess utility of suPAR in pediatric community-acquired and hospital-acquired pneumonia. METHODS: A prospective observational study including 120 hospitalized pneumonia patients and 55 healthy controls. Patients fell into two groups: community-acquired pneumonia (CAP) group (75 patients) and hospitalacquired pneumonia (HAP) group (45 patients). CAP severity scores were calculated, including Predisposition, Insult, Response, Organ dysfunction modified (PIROm) score and Pediatric Respiratory Severity (PRESS) Score. suPAR was measured to CAP patients on admission and to HAP patients on the day of pneumonia diagnosis. suPAR was also measured to controls. RESULTS: suPAR was higher among the whole patient cohort compared with controls (p < 0.001) and higher among CAP group compared with both controls (p < 0.001) and HAP group (p < 0.001). No significant difference was found between HAP and control groups. suPAR was higher among CAP patients with shock, PICU admission, mechanical ventilation, and death (p=0.013, 0.044, 0.019, 0.049 respectively). Among CAP patients, suPAR correlated with oxygen saturation, pulse rate, respiratory rate, PRESS, and PIROm. suPAR had area under Receiver Operating Characteristic Curve=0.68 for prediction of severe CAP. Among HAP group, suPAR was negatively correlated with oxygen saturation (rs=-0.31; p=0.048) and was higher among patients with shock (p=0.005) and among those with increased pediatric Sequential Organ Failure Assessment (pSOFA) score (p=0.034). CONCLUSIONS: suPAR is promising for diagnosing pediatric CAP but not HAP. suPAR predicted illness severity in both CAP and HAP but performed better in the former.

Surfactant protein D: a predictor for severity of community-acquired pneumonia in children.

BACKGROUND: Surfactant protein D (SP-D) is a promising biomarker proposed for the prediction of community-acquired pneumonia (CAP) severity. Therefore, we aimed to assess the role of SP-D in the prediction of CAP severity in pediatric patients. METHODS: A prospective cohort study was carried out at the Pediatric Intensive Care Unit (PICU) and wards of Menoufia University Hospital. We recruited 112 children admitted into wards with pneumonia (simple pneumonia) and 68 children admitted into PICU with severe pneumonia (PICU admitted). World Health Organization (WHO) classification and mortality predictive scores were calculated to determine the severity of pneumonia for the two groups, including the Pediatric Respiratory Severity Score (PRESS) and the Predisposition, Insult, Response, and Organ dysfunction modified Score (PIROm). SP-D was measured at admission. RESULTS: The SP-D level was significantly lower in patients with simple pneumonia than in patients with severe pneumonia (P < 0.001). SP-D was significantly higher among children with severe pneumonia, as determined by WHO, PRESS, and PIROm (P = 0.001). SP-D was significantly higher among children with mechanical ventilation, shock, hypoxia, sepsis, and mortality. Receiver operating characteristic curve analysis for SP-D showed that the area under the curve was 0.741 (P value < 0.001), with a sensitivity of 85.3% and a specificity of 44.6%. CONCLUSIONS: Serum SP-D level has a predictive value for the detection of community-acquired pneumonia severity in children. IMPACT: SP-D is a good predictor for the detection of CAP severity in hospitalized children. SP-D was correlated with severity scores and was associated with indicators of CAP severity, including mechanical ventilation, shock, hypoxia, sepsis, and mortality.

Value of Thrombomodulin as a Marker for Sepsis in Critically Ill Children.

OBJECTIVE: Pediatric sepsis is altered organ function in critically ill children and a main etiology of mortality for children. Therefore, the authors aimed to assess the role of serum thrombomodulin as valuable biomarker in the diagnosis and prognosis of sepsis in acutely ill pediatrics in the intensive unit. METHODS: This prospective clinical study conducted on 140 acutely ill patients admitted to the Pediatric Intensive Care Unit (PICU) of Menoufia University Hospital and 50 apparently healthy controls from October 2018 through September 2019. All included children were subjected to clinical examination and the Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality II (PIM II) scores were calculated. Serum thrombomodulin was measured for both patients and the control group upon admission. The children were followed for a period of 30 d. RESULTS: Serum thrombomodulin level was increased among all the patients and those with systemic inflammatory response syndrome (SIRS), sepsis and severe sepsis compared with controls (p < 0.001). Furthermore, serum thrombomodulin was higher in patients who died than who survived (p = 0.005). Thrombomodulin had area under Receiver Operating Characteristic Curve (AUC) =0.915 for predicting sepsis, whereas C-reactive protein had AUC = 0.789. According to the prognosis, thrombomodulin had AUC = 0.711 for predicting mortality whereas PRISM and PIM scores had AUC = (0.918, 0.960) respectively. CONCLUSIONS: Serum thrombomodulin is a promising marker for pediatric sepsis. The data showed that serum thrombomodulin had a valuable role in diagnosis of sepsis early in critically ill pediatrics.

Low serum zinc level: The relationship with severe pneumonia and survival in critically ill children.

BACKGROUND: Zinc deficiency is common among children in developing countries; but, there is still conflicting evidence on whether the alteration in zinc metabolism is the predictive of disease severity in the setting of critical illness. OBJECTIVES: To assess serum zinc levels in children admitted with pneumonia, and also to study the relationship between zinc levels and severity and mortality from pneumonia. METHODS: In a prospective cohort study, we enrolled 320 critically ill children admitted to the paediatric intensive care unit (PICU) with severe pneumonia (group 1) in addition to 160 children admitted into wards with pneumonia (group 2). Serum zinc measured in all patients on admission. RESULTS: Serum zinc level was significantly lower among patients admitted to PICU (group 1) compared with patients admitted to wards (group 2) (P < .001). There was a highly statistically significant decrease in zinc level in critically ill children complicated by sepsis, mechanically ventilated cases and those who died. Regarding the diagnosis of sepsis, zinc had an area under the curve (AUC) of 0.81 while C-reactive protein (CRP) had an AUC of 0.83. Regarding the prognosis, zinc had an AUC of 0.649 for prediction of mortality, whereas the AUC for Pediatric risk of mortality (PRISM), Pediatric index of mortality2 (PIM2) and CRP were 0.83, 0.82 and 0.78, respectively. The combined zinc with PRISM and PIM2 has increased the sensitivity of zinc for mortality from 86.5% to 94.9%. CONCLUSION: Zinc has both a diagnostic and a prognostic value for children with pneumonia.

Serum Neutrophil Gelatinase-Associated Lipocalin: A Diagnostic Marker in Pediatric Sepsis.

OBJECTIVES: Sepsis is a life-threatening condition that arises when the response of the body to infection injures its own tissues and organs. The early prediction of sepsis by current clinical and laboratory methods remains inadequate. Serum neutrophil gelatinase-associated lipocalin level is increased in sepsis irrespective of renal dysfunction. Therefore, we aimed to correlate the serum neutrophil gelatinase-associated lipocalin value determined at admission with clinical progression and severity of disease in critically ill children and to declare its role as a potential diagnostic and prognostic marker for sepsis in critically ill children in the emergency department. DESIGN: A prospective cohort study. SETTING: The study carried out at the PICU of Menoufia University Hospital. PATIENTS: We serially enrolled 120 critically ill children admitted to the PICU at 2 fixed days per week in addition to 40 healthy children served as controls. INTERVENTIONS: Clinical examination was performed including calculation of the Pediatric Risk of Mortality and Pediatric Index of Mortality 2. Serum neutrophil gelatinase-associated lipocalin measurement was performed for patients at admission and for the controls. Patients were followed up for 30 days. The discriminatory power of neutrophil gelatinase- associated lipocalin was determined using the receiver-operating characteristic and other predictive likelihood values. MEASUREMENTS AND MAIN RESULTS: Serum neutrophil gelatinase-associated lipocalin level was significantly higher among the total patient cohort and those with sepsis than among the controls (p < 0.001), also in patients with systemic inflammatory response syndrome without sepsis and patients without systemic inflammatory response syndrome (p = 0.04 and <0.001). Furthermore, plasma level of neutrophil gelatinase-associated lipocalin was significantly elevated in nonsurvivors compared with survivors (p < 0. 001). Receiver-operating characteristic curve analysis exhibited an area under the curve of 0.84 for neutrophil gelatinase-associated lipocalin for diagnosis of sepsis, whereas C-reactive protein had an area under the curve of 0.79. Regarding the prognosis, neutrophil gelatinase-associated lipocalin had an area under the curve of 0.74 for prediction of mortality, whereas the area under the curve for Pediatric Risk of Mortality, Pediatric Index of Mortality 2, and C-reactive protein were 0.59, 0.58, and 0.62, respectively. CONCLUSION: Overall, the data support the view that measurement at admission, serum neutrophil gelatinase-associated lipocalin results in substantial added value for early diagnosis and prognostication of sepsis in critically sick children.