Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis.

Background: One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.

Machine learning derivation of four computable 24-h pediatric sepsis phenotypes to facilitate enrollment in early personalized anti-inflammatory clinical trials.

Background: Thrombotic microangiopathy-induced thrombocytopenia-associated multiple organ failure and hyperinflammatory macrophage activation syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. The National Institutes of General Medical Science sepsis research working group recommendations call for application of new research approaches in extant clinical data sets to improve efficiency of early trials of new sepsis therapies. Our objective is to apply machine learning approaches to derive computable 24-h sepsis phenotypes to facilitate personalized enrollment in early anti-inflammatory trials targeting these conditions.

Automated versus manual urine output monitoring in the intensive care unit.

Acute kidney injury (AKI) is defined by changes in serum creatinine and urine output (UO). Significant limitations exist regarding accurate ascertainment of urine output even within the intensive care unit. We sought to evaluate an automated urine output collections system and compare it to nursing measurements.

Comparison of Anticoagulation Strategies in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: Heparin Versus Bivalirudin.

Objectives: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used.

Serial Measurement of Cell-Cycle Arrest Biomarkers [TIMP-2] · [IGFBP7] and Risk for Progression to Death, Dialysis, or Severe Acute Kidney Injury in Patients with Septic Shock.

Urinary TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor-binding protein 7) can predict acute kidney injury (AKI) in patients with sepsis. To address critical questions about whether biomarkers can inform the response to treatment and whether they might be used to guide therapy, as most sepsis patients present with AKI. We measured [TIMP-2] · [IGFBP7] before and after a 6-hour resuscitation in 688 patients with septic shock enrolled in the ProCESS (Protocol-based Care for Early Septic Shock) trial.

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.

Objectives: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis.

Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival.

Objective: We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes.

Design: We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids.

Targeting Endogenous Repair Pathways after AKI.

AKI remains a highly prevalent disease associated with poor short- and long-term outcomes and high costs. Although significant advances in our understanding of repair after AKI have been made over the last 5 years, this knowledge has not yet been translated into new AKI therapies. A consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 and reviewed new evidence on successful kidney repair to identify the most promising pathways that could be translated into new treatments.

Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps.

Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation.

Therapeutic Targets of Human AKI: Harmonizing Human and Animal AKI.

The opportunity to make advances in the prevention and treatment of AKI has never been greater than it is today. Major advances have been made in the understanding of the biology of AKI, the design of clinical trials, and the use of diagnostic and prognostic biomarkers. These advances have been supplemented by the coordinated effort of societies, federal agencies, and industry, such that we are poised in the ensuing years to positively address the unrelenting harm that this disorder has created.

Renal Hemodynamics in AKI: In Search of New Treatment Targets.

Novel therapeutic interventions are required to prevent or treat AKI. To expedite progress in this regard, a consensus conference held by the Acute Dialysis Quality Initiative was convened in April of 2014 to develop recommendations for research priorities and future directions. Here, we highlight the concepts related to renal hemodynamics in AKI that are likely to reveal new treatment targets on investigation.

Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes.

Background And Objectives: Critically ill patients requiring RRT have higher circulating plasma concentrations of inflammatory and apoptosis markers that are associated with subsequent RRT dependence and death. Whether intensive dosing of RRT is associated with changes in specific mediators is unknown.

Design, Setting, Participants, & Measurements: A multicenter, prospective, cohort study of 817 critically ill patients receiving RRT ancillary to the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study was conducted between November 2003 and July 2007.

Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.

Objective: To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7) and TIMP-2 (tissue inhibitor of metalloproteinase 2) to early predict acute kidney injury (AKI) in high-risk surgical patients.

Introduction: Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.

Classifying AKI by Urine Output versus Serum Creatinine Level.

Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients.

AKI in low-risk versus high-risk patients in intensive care.

Background And Objectives: AKI in critically ill patients is usually part of multiorgan failure. However, nonrenal organ failure may not always precede AKI and patients without evidence of these organ failures may not be at low risk for AKI. This study examined the risk and outcomes associated with AKI in critically ill patients with and without cardiovascular or respiratory organ failures at presentation to the intensive care unit (ICU).

A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury.

Given that the leading clinical conditions associated with acute kidney injury (AKI), namely, sepsis, major surgery, heart failure, and hypovolemia, are all associated with shock, it is tempting to attribute all AKI to ischemia on the basis of macrohemodynamic changes. However, an increasing body of evidence has suggested that in many patients, AKI can occur in the absence of overt signs of global renal hypoperfusion. Indeed, sepsis-induced AKI can occur in the setting of normal or even increased renal blood flow.