Pediatric sepsis diagnostic and prognostic biomarkers: pancreatic stone protein, copeptin, and apolipoprotein A-V.

BACKGROUND: We assessed serum concentrations of pancreatic stone protein (PSP), copeptin, and apolipoprotein A-V (APOA5) biomarkers for the diagnosis and prognosis of pediatric sepsis, a condition associated with high mortality. METHODS: This prospective study included 180 children admitted to the Pediatric Intensive Care Unit and 100 healthy controls at Menoufia University Hospital. Pediatric Risk of Mortality (PRISM), Pediatric Index of Mortality-2 (PIM2), and Pediatric Sequential Organ Failure Assessment (pSOFA) scores were calculated. Serum PSP, copeptin and APOA5 were measured once within 24 h of admission. RESULTS: PSP, copeptin, and APOA5 were significantly higher in the patients than in the controls (p < 0.001). PSP and copeptin were increased among children who required mechanical ventilation (MV), had multiple organ dysfunctions, and were non-survivors, but APOA5 was decreased in those children. Logistic regression analyses showed that high pSOFA, high PSP and copeptin, low APOA5, and use of MV were associated with mortality. The receiver operating characteristic revealed that the area under the curve (AUC) for APOA5, copeptin, and PSP (0.965, 0.960, and 0.868, respectively) demonstrated high sensitivity (96%, 94%, and 80%) for sepsis diagnosis. The AUC values for PSP, copeptin, and APOA5 were 0.709, 0.705, and 0.571, respectively, with sensitivities of 74%, 58%, and 58% for mortality prediction. CONCLUSIONS: PSP, copeptin, and APOA5 are promising diagnostic biomarkers for pediatric sepsis but inadequate predictors of mortality. IMPACT: Apolipoprotein A-V (APOA5), copeptin, and pancreatic stone protein (PSP) are acute-phase proteins with diagnostic value in evaluating critically ill pediatric patients with sepsis and detecting sepsis severity. PSP and copeptin had the power to discriminate non-survivors from survivors. APOA5 was less powerful than the other biomarkers in discriminating between survivors and non-survivors.

Assessment of asymmetric dimethylarginine and homocysteine in epileptic children receiving antiepileptic drugs.

BACKGROUND: Epilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children. METHODS: This study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children. RESULTS: Low-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001). CONCLUSIONS: Long-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs. IMPACT: The long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation. A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.

The severity and atypical presentations of COVID-19 infection in pediatrics.

BACKGROUND: Emergence of 2019-nCoV attracted global attention and WHO declared COVID-19 a public health emergency of international concern. Therefore we aimed to explore the severity and atypical manifestations of COVID-19 among children. METHODS: This is an observational cohort study conducted on 398 children with confirmed COVID-19 by using real-time reverse transcriptase polymerase chain reaction assay for detection of 2019-nCoV nucleic acid during the period from March to November 2020. Patients were subdivided regarding the severity of COVID-19 presentation into Group I (Non-severe COVID-19) was admitted into wards and Group II (Severe COVID-19) admitted into the PICU. RESULTS: Non- severe cases were 295cases (74.1%) and 103cases (25.9%) of severe cases. There was a significant difference between age groups of the affected children (P < 0.001) with a median (0-15 years). Boys (52%) are more affected than girls (48%) with significant differences (P < 0.001). 68.6%of confirmed cases had contact history to family members infected with COVID-19. 41.7% of severe patients needed mechanical ventilation. Death of 20.4% of severe cases. In COVID-19 patients, fever, headache, fatigue and shock were the most prominent presentations (95, 60.3, 57.8, and 21.8% respectively). 3.5% of children were manifested with atypical presentations; 1.25% manifested by pictures of acute pancreatitis, 1.25% presented by manifestations of deep venous thrombosis and 1.0% had multisystem inflammatory syndrome (MIS-C). Multivariate regression analysis showed that COVID-19 severity in children was significantly higher among children with higher levels of D-dimer, hypoxia, shock and mechanical ventilation. CONCLUSION: Most children had a non-severe type of COVID-19 and children with severe type had higher levels of D-dimer, hypoxia, shock and mechanical ventilation.

Timing of parenteral nutrition initiation in critically ill children: a randomized clinical trial.

BACKGROUND: The optimal timing of parenteral nutrition (PN) initiation in critically ill children remains controversial. PURPOSE: To identify the optimal timing of PN initiation in critically ill children. METHODS: This randomized clinical trial was conducted in the pediatric intensive care unit (PICU) of Menoufia University Hospital. A total of 140 patients were randomized to receive early or late PN. The early PN group consisted of 71 well-nourished and malnourished patients who received PN on the first day of PICU admission. Malnourished (42%) and well-nourished children randomized to the late PN group (42%) started PN on the fourth versus seventh day after admission, respectively. Mechanical ventilation (MV) was the primary outcome, while PICU length of stay and mortality were secondary outcomes. RESULTS: Patients who received early PN started enteral feeding significantly earlier (median, 6 days; interquartile range, 2-20 days) than those not provided early PN (median, 12 days; interquartile range, 3-30 days; P<0.001) and had a significantly lower risk of feeding intolerance (5.6% vs.18.8%, P=0.035). The median time required to obtain full calories enterally was shorter in the early versus late PN group (P=0.004). Furthermore, patients in the early versus late PN group had a significantly shorter median PICU stay (P<0.001) and were less likely to require MV (P=0.018). CONCLUSION: Patients who received early PN had a lower MV need and duration than those who received later PN and had more favorable clinical outcomes in terms of morbidity.

Relation of Procollagen Type III Amino Terminal Propeptide Level to Sepsis Severity in Pediatrics.

BACKGROUND: Sepsis is still the main etiology of mortality in pediatric intensive care units (PICUs). Therefore, we performed this study to evaluate the value of procollagen Type III amino-terminal propeptide (PIIINP) as a biomarker for sepsis severity diagnosis and mortality. METHOD: A prospective study was carried out on 170 critically ill children admitted into the PICU and 100 controls. The performed clinical examinations included calculation of the pediatric risk of mortality. Serum PIIINP was withdrawn from patients at admission and from the controls. RESULTS: PIIINP level was significantly more increased in sepsis, severe sepsis, and septic shock than among the controls (p < 0.001). PIIINP was significantly higher in severe sepsis and septic shock (568.3 (32.5-1304.7) and 926.2 (460.6-1370), respectively) versus sepsis (149.5 (29.6-272.9)) (p < 0.001). PIIINP was significantly increased in non-survivors (935.4 (104.6-1370)) compared to survivors (586.5 (29.6-1169)) (p < 0.016). ROC curve analysis exhibited an area under the curve (AUC) of 0.833 for PIIINP, which is predictive for sepsis, while the cut-off point of 103.3 ng/mL had a sensitivity of 88% and specificity of 82%. The prognosis of the AUC curve for PIIINP to predict mortality was 0.651; the cut-off of 490.4 ng/mL had a sensitivity of 87.5% and specificity of 51.6%. CONCLUSIONS: PIIINP levels are increased in sepsis, with significantly higher levels in severe sepsis, septic shock, and non-survivors, thus representing a promising biomarker for pediatric sepsis severity and mortality.