Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Are citations from clinical trials evidence of higher impact research? An analysis of ClinicalTrials.gov

An important way in which medical research can translate into improved health outcomes is by motivating or influencing clinical trials that eventually lead to changes in clinical practice. Citations from clinical trials records to academic research may therefore serve as an early warning of the likely future influence of the cited articles. This paper partially assesses this hypothesis by testing whether prior articles referenced in ClinicalTrials.gov records are more highly cited than average for the publishing journal. The results from four high profile general medical journals support the hypothesis, although there may not be a cause-and effect relationship. Nevertheless, it is reasonable for researchers to use citations to their work from clinical trials records as partial evidence of the possible long-term impact of their research

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

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Urine Complement Factor Ba is Associated with AKI in Critically Ill Children

KEY POINTS: Complement activation, specifically factor B, is implicated in AKI pathogenesis in animal models. Urine Ba (an activation fragment of factor B) was significantly higher in critically ill children with stage 3 AKI and sepsis-AKI. If larger studies show similar association between urine Ba and AKI severity, clinical trials of factor B inhibition are warranted. BACKGROUND:: Critically ill children with AKI have high morbidity and mortality rates and lack treatment options. Complement activation is implicated in AKI pathogenesis, which could be treated with complement-targeted therapeutics. We assessed for an association between urine Ba, an activation fragment of the alternative complement pathway, and AKI in a large cohort of critically ill children. METHODS:: A biorepository of children requiring mechanical ventilation was leveraged. AKI was based on pediatric version of the RIFLE criteria—stage 1: 25% decreased eGFR or urine output (UOP) \u3c0.5ml/kg per hour for 8 hours; stage 2: 50% decreased eGFR or UOP RESULTS:: Seventy-three patients were included, of which 56 had AKI: 26 (46%) stage 1, 16 (29%) stage 2, and 14 (25%) stage 3. Ba was significantly higher in patients with stage 3 AKI compared with all other stages. Ba was higher in sepsis-associated AKI compared with non–sepsis-associated AKI. Multivariate analysis included urine Ba, urine IL-18, urine NGAL, sepsis, and Pediatric Risk of Mortality Scores-II (an estimate of illness severity) and showed a significant association between urine Ba and AKI (odds ratio 1.57, 95% confidence interval, 1.13 to 2.20; CONCLUSION:: Urine Ba is significantly increased in patients with AKI compared with patients without AKI. In patients with similar illness severity, a doubling of urine Ba level was associated with a 57% increase in AKI diagnosis of any stage. Further studies are needed to study complement inhibition in treatment or prevention of AKI in critically ill children

Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis

Introduction: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. Methods: We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. Results: The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuronspecific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p \u3c 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brainbarrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p \u3c 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain

Fluid Assessment, Fluid Balance, and Fluid Overload in Sick Children: A Report From the Pediatric Acute Disease Quality Initiative (ADQI) Conference

BACKGROUND: The impact of disorders of fluid balance, including the pathologic state of fluid overload in sick children has become increasingly apparent. With this understanding, there has been a shift from application of absolute thresholds of fluid accumulation to an appreciation of the intricacies of fluid balance, including the impact of timing, trajectory, and disease pathophysiology. METHODS: The 26th Acute Disease Quality Initiative was the first to be exclusively dedicated to pediatric and neonatal acute kidney injury (pADQI). As part of the consensus panel, a multidisciplinary working group dedicated to fluid balance, fluid accumulation, and fluid overload was created. Through a search, review, and appraisal of the literature, summative consensus statements, along with identification of knowledge gaps and recommendations for clinical practice and research were developed. CONCLUSIONS: The 26th pADQI conference proposed harmonized terminology for fluid balance and for describing a pathologic state of fluid overload for clinical practice and research. Recommendations include that the terms daily fluid balance, cumulative fluid balance, and percent cumulative fluid balance be utilized to describe the fluid status of sick children. The term fluid overload is to be preserved for describing a pathologic state of positive fluid balance associated with adverse events. Several recommendations for research were proposed including focused validation of the definition of fluid balance, fluid overload, and proposed methodologic approaches and endpoints for clinical trials

Programs and processes for advancing pediatric acute kidney support therapy in hospitalized and critically ill children: A report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference

Pediatric acute kidney support therapy (paKST) programs aim to reliably provide safe, effective, and timely extracorporeal supportive care for acutely and critically ill pediatric patients with acute kidney injury (AKI), fluid and electrolyte derangements, and/or toxin accumulation with a goal of improving both hospital-based and lifelong outcomes. Little is known about optimal ways to configure paKST teams and programs, pediatric-specific aspects of delivering high-quality paKST, strategies for transitioning from acute continuous modes of paKST to facilitate rehabilitation, or providing effective short- and long-term follow-up. As part of the 26th Acute Disease Quality Initiative Conference, the first to focus on a pediatric population, we summarize here the current state of knowledge in paKST programs and technology, identify key knowledge gaps in the field, and propose a framework for current best practices and future research in paKST

Renal Dysfunction Criteria in Critically Ill Children: The PODIUM Consensus Conference

CONTEXT Renal dysfunction is associated with poor outcomes in critically ill children. OBJECTIVE To evaluate the current evidence for criteria defining renal dysfunction in critically ill children and association with adverse outcomes. To develop contemporary consensus criteria for renal dysfunction in critically ill children. DATA SOURCES PubMed and Embase were searched from January 1992 to January 2020. STUDY SELECTION Included studies evaluated critically ill children with renal dysfunction, performance characteristics of assessment tools for renal dysfunction, and outcomes related to mortality, functional status, or organ-specific or other patient-centered outcomes. Studies with adults or premature infants (≤36 weeks' gestational age), animal studies, reviews, case series, and studies not published in English with inability to determine eligibility criteria were excluded. DATA EXTRACTION Data were extracted from included studies into a standard data extraction form by task force members. RESULTS The systematic review supported the following criteria for renal dysfunction: (1) urine output <0.5 mL/kg per hour for ≥6 hours and serum creatinine increase of 1.5 to 1.9 times baseline or ≥0.3 mg/dL, or (2) urine output <0.5 mL/kg per hour for ≥12 hours, or (3) serum creatinine increase ≥2 times baseline, or (4) estimated glomerular filtration rate <35 mL/minute/1.73 m2, or (5) initiation of renal replacement therapy, or (6) fluid overload ≥20%. Data also support criteria for persistent renal dysfunction and for high risk of renal dysfunction. LIMITATIONS All included studies were observational and many were retrospective. CONCLUSIONS We present consensus criteria for renal dysfunction in critically ill children