Liver Transplant Listing in Pediatric Acute Liver Failure: Practices and Participant Characteristics.

Liver transplant (LT) decisions in pediatric acute liver failure (PALF) are complex. Three phases of the PALF registry, containing data on 1,144 participants over 15 years, were interrogated to characterize clinical features associated with listing status. A decrease in the cumulative incidence of listing (P < 0.

A Learning Collaborative Approach Increases Specificity of Diagnosis of Acute Liver Failure in Pediatric Patients.

Background & Aims: Many pediatric patients with acute liver failure (PALF) do not receive a specific diagnosis (such as herpes simplex virus or Wilson disease or fatty acid oxidation defects)-they are left with an indeterminate diagnosis and are more likely to undergo liver transplantation, which is contraindicated for some disorders. Strategies to facilitate complete diagnostic testing should increase identification of specific liver diseases and might reduce liver transplantation. We investigated whether performing recommended age-specific diagnostic tests (AS-DTs) at the time of hospital admission reduces the percentage PALFs with an indeterminate diagnosis.

Health Related Quality of Life and Neurocognitive Outcomes in the First Year after Pediatric Acute Liver Failure.

Objective: To determine health-related quality of life (HRQoL) and neurocognitive impairment in survivors of pediatric acute liver failure (PALF).

Study Design: A longitudinal prospective study was conducted. At 6 and 12 months after PALF presentation, surveys of HRQoL were completed for 2- to 19-year-olds and executive functioning for ages 2-16 years.

Cognitive decline and brain amyloid-β accumulation across 3 years in adults with Down syndrome.

Adults with Down syndrome (DS) have a high incidence of Alzheimer's disease (AD), providing a unique opportunity to explore the early, preclinical stages of AD neuropathology. We examined change in brain amyloid-β accumulation via the positron emission tomography tracer [11C] Pittsburgh compound B (PiB) across 2 data collection cycles, spaced 3 years apart, and decline in cognitive functioning in 58 adults with DS without clinical AD. PiB retention increased in the anterior cingulate gyrus, precuneus cortex, parietal cortex, and anterior ventral striatum.

An Aggregate Biomarker Risk Score Predicts High Risk of Near-Term Myocardial Infarction and Death: Findings From BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes).

Background: In a previous study, we found that a biomarker risk score (BRS) comprised of C-reactive protein, fibrin-degradation products, and heat shock protein-70 predicts risk of myocardial infarction and death in coronary artery disease patients. We sought to: (1) validate the BRS in the independent BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) cohort, (2) investigate whether 1 year of intensive medical therapy is associated with improved BRS, and (3) elucidate whether an altered BRS parallels altered risk.

Methods And Results: Two thousand thirty-two subjects with coronary artery disease were followed for 5.

Lactate and Lactate: Pyruvate Ratio in the Diagnosis and Outcomes of Pediatric Acute Liver Failure.

Objectives: To assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P  ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days.

Study Design: Retrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day.

Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure.

Objectives: The purpose of the present study is to estimate autoantibody (auto-AB) frequency, clinical characteristics, and 21-day outcome of participants in the Pediatric Acute Liver Failure Study Group (PALFSG) by antinuclear antibody, smooth muscle antibody, and liver-kidney microsomal (LKM) antibody status.

Methods: Auto-ABs were determined at local and/or central laboratories. Subjects were assigned to autoimmune hepatitis (AIH), indeterminate, and other diagnoses groups.

The effects of normal aging on amyloid-β deposition in nondemented adults with Down syndrome as imaged by carbon 11-labeled Pittsburgh compound B.

Introduction: In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology.

Methods: PET imaging with carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellar gray matter as the reference region.

Analysis of the bypass angioplasty revascularization investigation trial using a multistate model of clinical outcomes.

Current cardiovascular randomized trials typically use composite outcomes. We hypothesized that the Bypass Angioplasty Revascularization Investigation (BARI) outcomes and conclusions would differ using a multistate model relative to the intervention for the composite outcome of death (D) and nonfatal Q-wave myocardial infarction (MI). We used a multistate model which uses transition paths to simultaneously assess multiple end points.

Extubating in the operating room after adult cardiac surgery safely improves outcomes and lowers costs.

Objective: Prolonged intubation has been implicated in the poor outcomes after adult cardiac surgery. Accelerated postoperative extubation has been a quality focus, but operating room (OR) extubation after cardiopulmonary bypass is rare. We examined the outcomes and direct costs of protocolized OR extubation versus early postoperative intensive care unit (ICU) extubation after nonemergency open cardiac surgery.

Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.

Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels.

Coronary artery bypass in patients with type 2 diabetes: experience from the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.

Objective: Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) was a study of management strategies for diabetic patients with myocardial ischemia and coronary artery disease. In a 2×2 design, early revascularization versus medical management with or without late revascularization and insulin sensitization versus insulin provision were examined. No advantage for either strategy was seen, except in the group undergoing early coronary artery bypass grafting (CABG).

Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: a collaborative meta-analysis of contemporary randomized clinical trials.

Importance: Myocardial ischemia in patients with stable coronary artery disease (CAD) has been repeatedly associated with impaired survival. However, it is unclear if revascularization with percutaneous coronary intervention (PCI) to relieve ischemia improves outcomes compared with medical therapy (MT).

Objective: The objective of this study was to compare the effect of PCI and MT with MT alone exclusively in patients with stable CAD and objectively documented myocardial ischemia on clinical outcomes.

Change in albuminuria and eGFR following insulin sensitization therapy versus insulin provision therapy in the BARI 2D study.

Background And Objectives: In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin-sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years.

Design, Setting, Participants & Measurements: In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included.

Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease.

Background: Prior trials suggest it is safe to defer transfusion at hemoglobin levels above 7 to 8 g/dL in most patients. Patients with acute coronary syndrome may benefit from higher hemoglobin levels.

Methods: We performed a pilot trial in 110 patients with acute coronary syndrome or stable angina undergoing cardiac catheterization and a hemoglobin <10 g/dL.

Clinical and angiographic risk stratification and differential impact on treatment outcomes in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

Background: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial assigned patients with type 2 diabetes mellitus to prompt coronary revascularization plus intensive medical therapy versus intensive medical therapy alone and reported no significant difference in mortality. Among patients selected for coronary artery bypass graft surgery, prompt coronary revascularization was associated with a significant reduction in death/myocardial infarction/stroke compared with intensive medical therapy. We hypothesized that clinical and angiographic risk stratification would affect the effectiveness of the treatments overall and within revascularization strata.

Presentation in patients with angiographically documented coronary artery disease and type II diabetes mellitus (from the BARI 2D Clinical Trial).

Clinically stable patients with type 2 diabetes mellitus and coronary artery disease are not often thought to present with the symptom of typical angina. The aims of this study were to enumerate the proportion of patients presenting with typical angina or other cardiac symptoms and to elucidate what important clinical variables are associated with the presence of typical angina in patients with type 2 diabetes mellitus and angiographically documented coronary artery disease. Symptoms of angina, anginal equivalents, or an absence of symptoms were obtained using baseline data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial (n = 2,319).

Profibrinolytic, antithrombotic, and antiinflammatory effects of an insulin-sensitizing strategy in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

Background: Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy.

Methods And Results: A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A(1c) were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval.

Resting heart rate and metabolic syndrome in patients with diabetes and coronary artery disease in bypass angioplasty revascularization investigation 2 diabetes (BARI 2D) trial.

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.

High prevalence and diversity of kidney dysfunction in patients with type 2 diabetes mellitus and coronary artery disease: the BARI 2D baseline data.

Background: We describe baseline renal function and albumin excretion rate in patients enrolled in Bypass Angioplasty Revascularization Investigation 2 Diabetes, a randomized clinical trial comparing the impact of revascularization and medical therapy with medical therapy alone and deferred or no revascularization and the impact of glycemic control with either insulin-providing or insulin-sensitizing drugs, on 5-year mortality.

Methods: Study participants had type 2 diabetes mellitus, documented coronary artery disease, and creatinine <2 mg/dL. Albuminuria status (albumin/creatinine ratio [ACR]) and estimated glomerular filtration rate (eGFR), using the abbreviated Modified Diet in Renal Disease equation, were determined at baseline.

Comparison of plasminogen activator inhibitor-1, tissue type plasminogen activator antigen, fibrinogen, and D-dimer levels in various age decades in patients with type 2 diabetes mellitus and stable coronary artery disease (from the BARI 2D trial).

Advancing age is associated with downregulation of fibrinolysis in normal subjects. This is reflected by high concentrations of plasminogen activator inhibitor-1 (PAI-1) in the blood, which has been implicated in the increasing cardiovascular morbidity and mortality with age. We sought to delineate the relation of PAI-1 to several factors, including age, gender, and ethnicity in patients with type 2 diabetes mellitus (DM) and stable coronary artery disease enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.

The Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: impact of treatment strategy on cardiac mortality and myocardial infarction.

Background: The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI).

Methods And Results: Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates.

A randomized trial of therapies for type 2 diabetes and coronary artery disease.

Background: Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.

Methods: We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events).

Association between increased platelet P-selectin expression and obesity in patients with type 2 diabetes: a BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) substudy.

Objective: To determine whether obesity increases platelet reactivity and thrombin activity in patients with type 2 diabetes plus stable coronary artery disease.

Research Design And Methods: We assessed platelet reactivity and markers of thrombin generation and activity in 193 patients from nine clinical sites of the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D). Blood taken at the time of enrollment was used for assay of the concentration of prothrombin fragment 1.