Modified RIFLE criteria in critically ill children with acute kidney injury

A classification system has been proposed to standardize the definition of acute kidney injury in adults. These criteria of risk, injury, failure, loss, and end-stage renal disease were given the acronym of RIFLE. We have modified the criteria based on 150 critically ill pediatric RIFLE (pRIFLE) patients to assess acute kidney injury incidence and course along with renal and/or non-renal comorbidities. Of these children, 11 required dialysis and 24 died. Patients without acute kidney injury in the first week of intensive care admission were less likely to subsequently develop renal Injury or Failure; however, 82% of acute kidney injury occurred in this initial week. Within this group of 123 children, 60 reached pRIFLEmax for Risk, 32 reached Injury, and 31 reached Failure. Acute kidney injury during admission was an independent predictor of intensive care; hospital length of stay and an increased risk of death independent of the Pediatric Risk of Mortality (PRISM II) score (odds ratio 3.0). Our results show that a majority of critically ill children develop acute kidney injury by pRIFLE criteria and do so early in the course of intensive care. Acute kidney injury is associated with mortality and may lead to increased hospital costs. We suggest that the pRIFLE criteria serves to characterize the pattern of acute kidney injury in critically ill children

Less is more: Design of a highly stable disulfide-deleted mutant of analgesic cyclic alpha-conotoxin Vc1.1

Cyclic alpha-conotoxin Vc1.1 (cVc1.1) is an orally active peptide with analgesic activity in rat models of neuropathic pain. It has two disulfide bonds, which can have three different connectivities, one of which is the native and active form. In this study we used computational modeling and nuclear magnetic resonance to design a disulfide-deleted mutant of cVc1.1, [C2H,C8F]cVc1.1, which has a larger hydrophobic core than cVc1.1 and, potentially, additional surface salt bridge interactions. The new variant, hcVc1.1, has similar structure and serum stability to cVc1.1 and is highly stable at a wide range of pH and temperatures. Remarkably, hcVc1.1 also has similar selectivity to cVc1.1, as it inhibited recombinant human alpha9alpha10 nicotinic acetylcholine receptor-mediated currents with an IC50 of 13μM and rat N-type (Cav2.2) and recombinant human Cav2.3 calcium channels via GABAB receptor activation, with an IC50 of ~900pM. Compared to cVc1.1, the potency of hcVc1.1 is reduced three-fold at both analgesic targets, whereas previous attempts to replace Vc1.1 disulfide bonds by non-reducible dicarba linkages resulted in at least 30-fold decreased activity. Because it has only one disulfide bond, hcVc1.1 is not subject to disulfide bond shuffling and does not form multiple isomers during peptide synthesis

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

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

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.]

The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications

Preclinical models and emerging translational data suggest that acute kidney injury (AKI) has far reaching effects on all other major organ systems in the body. Common in critically ill children and adults, AKI is independently associated with worse short and long term morbidity, as well as mortality, in these vulnerable populations. Evidence exists in adult populations regarding the impact AKI has on life course. Recently, non-renal organ effects of AKI have been highlighted in pediatric AKI survivors. Given the unique pediatric considerations related to somatic growth and neurodevelopmental consequences, pediatric AKI has the potential to fundamentally alter life course outcomes. In this article, we highlight the challenging and complex interplay between AKI and the brain, heart, lungs, immune system, growth, functional status, and longitudinal outcomes. Specifically, we discuss the biologic basis for how AKI may contribute to neurologic injury and neurodevelopment, cardiac dysfunction, acute lung injury, immunoparalysis and increased risk of infections, diminished somatic growth, worsened functional status and health related quality of life, and finally the impact on young adult health and life course outcomes

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

Archaeology, Architecture, and the Postcolonial Critique

Peer reviewe

Sociocultural and psychological determinants in migrants for noncompliance with occlusion therapy for amblyopia

Background: Compliance with occlusion therapy for amblyopia in children is low when their parents have a low level of education, speak Dutch poorly, or originate from another country. We determined how sociocultural and psychological determinants affect compliance. Methods: Included we