Acute kidney injury (AKI) is emerging as a complication of increasing clinical importance associated with substantial morbidity and mortality in African children with severe malaria. Using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define AKI, an estimated 24-59% of African children with severe malaria have AKI with most AKI community-acquired. AKI is a risk factor for mortality in pediatric severe malaria with a stepwise increase in mortality across AKI stages. AKI is also a risk factor for postdischarge mortality and is associated with increased long-term risk of neurocognitive impairment and behavioral problems in survivors. Following injury, the kidney undergoes a process of recovery and repair. AKI is an established risk factor for chronic kidney disease and hypertension in survivors and is associated with an increased risk of chronic kidney disease in severe malaria survivors. The magnitude of the risk and contribution of malaria-associated AKI to chronic kidney disease in malaria-endemic areas remains undetermined. Pathways associated with AKI pathogenesis in the context of pediatric severe malaria are not well understood, but there is emerging evidence that immune activation, endothelial dysfunction, and hemolysis-mediated oxidative stress all directly contribute to kidney injury. In this review, we outline the KDIGO bundle of care and highlight how this could be applied in the context of severe malaria to improve kidney perfusion, reduce AKI progression, and improve survival. With increased recognition that AKI in severe malaria is associated with substantial post-discharge morbidity and long-term risk of chronic kidney disease, there is a need to increase AKI recognition through enhanced access to creatinine-based and nextgeneration biomarker diagnostics. Long-term studies to assess severe malaria-associated AKI's impact on long-term health in malaria-endemic areas are urgently needed.

IntroductionA continued need exists for effective diagnostic biomarkers in bacterial sepsis among critically ill patients, despite increasing use of available biomarkers such as procalcitonin (PCT). Interleukin-27 (IL-27) has shown early promise in a recent preliminary study, exhibiting high specificity and positive predictive values for bacterial infection in critically ill children. This validation study was performed to assess the value of IL-27 in predicting bacterial infection among patients admitted to the pediatric intensive care unit and to compare its performance with that of PCT.MethodsA single-center (n = 702) prospective study was performed comparing both IL-27 and PCT levels between bacterially infected and uninfected cohorts in the pediatric intensive care unit. Infected status was determined by a chart review by an intensivist blinded to biomarker results. Formal performance comparisons included calculations of receiver operating characteristic (ROC) curves for IL-27 and PCT individually in addition to a combination strategy using a decision tree generated by classification and regression tree (CART) methodology. Secondary analysis focusing on subjects with documented bloodstream infections was performed.ResultsThe overall infection rate was 27 %. ROC curves for the primary analysis yielded areas under the curve (AUCs) of 0.64 (0.59 to 0.68) for IL-27 and 0.61 (0.56 to 0.65) for PCT. Secondary analysis defining infected status exclusively through positive blood cultures yielded AUCs of 0.75 (0.68 to 0.81) for IL-27 and 0.64 (0.57 to 0.71) for PCT, with a specificity of 95 % (92 % to 97 %) for the prior established IL-27 cut-point value of at least 5.0 ng/ml. Similar AUCs were found for the subset of immunocompromised patients. In a CART-derived analysis taking immunocompromised status into consideration, a combination of IL-27 and PCT yielded an AUC of 0.81 (0.75 to 0.86), statistically improved from either IL-27 or PCT alone.ConclusionsDespite having a modest predictive value for infection independent of source, IL-27 may serve as a useful biomarker in estimating risk of bacterial infection among critically ill pediatric patients with bloodstream infections. In particular, among immunocompromised subjects, this diagnostic biomarker may be helpful either alone or using a combination strategy with other available biomarkers.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1095-2) contains supplementary material, which is available to authorized users.

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Pediatric sepsis and bacterial infection cause significant morbidity and mortality worldwide, with immunocompromised patients being at particularly high risk of rapid deterioration and death. This study evaluated if PERSEVERE, PERSEVERE-II, or the PERSEVERE biomarkers, can reliably estimate the risk of clinical deterioration and 28-day mortality among immunocompromised pediatric patients. This is a single-center prospective cohort study conducted from July 2016 through September 2017 incorporating 400 episodes of suspected bacterial infection from the inpatient units at Cincinnati Children’s Hospital Medical Center, a large, tertiary care children’s hospital. The primary analysis assessed clinical deterioration within 72 hours of evaluation for infection. Secondarily, we assessed 28-day mortality. Clinical deterioration was seen in 15% of subjects. Twenty-eight day mortality was 5%, but significantly higher among critically ill patients. Neither PERSEVERE nor PERSEVERE-II performed well to predict clinical deterioration or 28-day mortality, thus we derived new stratification models using the PERSEVERE biomarkers with both high sensitivity and negative predictive value. In conclusion, we evaluated previously validated biomarker risk models in a novel population of largely non-critically ill immunocompromised pediatric patients, and attempted to stratify patients based on a new outcome metric, clinical deterioration. The new highly predictive models indicate common physiologic pathways to clinical deterioration or death from bacterial infection.

OBJECTIVE Determine if the addition of clonidine was associated with a decreased incidence of dexmedetomidine withdrawal in patients who received prolonged dexmedetomidine infusions. METHODS This was a retrospective observational cohort study conducted at a single-center PICU in an academic children's hospital. Children 1 month to 18 years of age who received dexmedetomidine infusion for 5 days or longer were included in the study. RESULTS Fifty patients met the inclusion criteria with 15 patients who received clonidine and 35 who received a dexmedetomidine wean alone. Withdrawal criteria included blood pressure changes, heart rate changes, and documented agitation. Overall, there was no difference in change in blood pressure or documented agitation between groups. Patients who did not receive clonidine had a greater number of heart rate readings above normal for age following discontinuation of the infusion, yet this was not statistically significant. Potentially more importantly, the addition of clonidine did not impact the duration of dexmedetomidine wean or the PICU length of stay after dexmedetomidine discontinuation. CONCLUSIONS The addition of clonidine while weaning a long-term dexmedetomidine infusion did not lead to lower blood pressures or agitation, but did lead to decreased percentage of heart rates above the age-appropriate range. The clinical significance of this is unknown, and further investigation is warranted. The addition of clonidine did not decrease time to weaning off dexmedetomidine or shorten PICU length of stay.

To investigate the prevalence of left ventricular systolic dysfunction (LVSD) in Malawian children with severe febrile illness and to explore associations between LVSD and mortality and lactate levels.DESIGN: Prospective observational study. SETTING:Pediatric ward of a tertiary government referral hospital in Malawi. PATIENTS:Children between 60 days and 10 years old with severe febrile illness (fever with at least one sign of impaired perfusion plus altered mentation or respiratory distress) were enrolled at admission from October 2017 to February 2018. INTERVENTIONS:Focused cardiac ultrasound (FoCUS) was performed, and serum lactate was measured for each child at enrollment, with repeat FoCUS the following day. LV systolic function was later categorized as normal, reduced, severely reduced, or hyperdynamic by two pediatric cardiologists blinded to clinical course and outcomes. MEASUREMENTS AND MAIN RESULTS:Fifty-four children were enrolled. LVSD was present in 14 children (25.9%; 95% CI, 15.4-40.3%), of whom three had severely reduced function. Thirty patients (60%) had a lactate greater than 2.5 mmol/L, of which 20 (40%) were markedly elevated (>5 mmol/L). Ten children died during admission (18.5%). Of children who survived, 22.7% had decreased LV systolic function versus 40% of those who died. Dysfunction was not associated with mortality or elevated lactate. CONCLUSIONS:Cardiac dysfunction may be present in one in four Malawian children with severe febrile illness, and mortality in these patients is especially high. Larger studies are needed to further clarify the role cardiac dysfunction plays in mortality and integrate practical bedside assessments for decision support around individualized resuscitation strategies.