Lower serum endocan levels are associated with the development of acute lung injury after major trauma.

Purpose: Endocan is a proteoglycan expressed by endothelial cells in the lung that may inhibit leukocyte recruitment and thus prevent the development of acute lung injury (ALI). We tested the association of serum endocan levels with subsequent development of ALI after major trauma.

Materials And Methods: This was a single-center nested case-control study within a prospective cohort study of major trauma patients.

Clinical protocols and trainee knowledge about mechanical ventilation.

Context: Clinical protocols are associated with improved patient outcomes; however, they may negatively affect medical education by removing trainees from clinical decision making.

Objective: To study the relationship between critical care training with mechanical ventilation protocols and subsequent knowledge about ventilator management.

Design, Setting, And Participants: A retrospective cohort equivalence study, linking a national survey of mechanical ventilation protocol availability in accredited US pulmonary and critical care fellowship programs with knowledge about mechanical ventilation among first-time examinees of the American Board of Internal Medicine (ABIM) Critical Care Medicine Certification Examination in 2008 and 2009.

The societal impact of single versus bilateral lung transplantation for chronic obstructive pulmonary disease.

Rationale: Bilateral lung transplantation (BLT) improves survival compared with single lung transplantation (SLT) for some individuals with chronic obstructive pulmonary disease (COPD). However, it is unclear which strategy optimally uses this scarce societal resource.

Objectives: To compare the effect of SLT versus BLT strategies for COPD on waitlist outcomes among the broader population of patients listed for lung transplantation.

Obesity and primary graft dysfunction after lung transplantation: the Lung Transplant Outcomes Group Obesity Study.

Rationale: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation.

Objectives: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation.

Methods: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study.

The state of genome-wide association studies in pulmonary disease: a new perspective.

With rapid advances in our knowledge of the human genome and increasing availability of high-throughput investigative technology, genome-wide association (GWA) studies have recently gained marked popularity. As an unbiased approach to identifying genomic regions of importance in complex human disease, the results of such studies have the potential to illuminate novel causal pathways, guide mechanistic research, and aid in prediction of disease risk. The use of a genome-wide approach presents considerable methodological and statistical challenges, and properly conducted studies are essential to avoid false-positive results.

Novel variants in the PRDX6 Gene and the risk of Acute Lung Injury following major trauma.

Background: Peroxiredoxin 6 (PRDX6) is involved in redox regulation of the cell and is thought to be protective against oxidant injury. Little is known about genetic variation within the PRDX6 gene and its association with acute lung injury (ALI). In this study we sequenced the PRDX6 gene to uncover common variants, and tested association with ALI following major trauma.

Primary graft dysfunction.

Primary graft dysfunction (PGD) is the most important cause of early morbidity and mortality following lung transplantation. PGD affects up to 25% of all lung transplant procedures and currently has no proven preventive therapy. Lung transplant recipients who recover from PGD may have impaired long-term function and an increased risk of bronchiolitis obliterans syndrome.

Effect of single vs bilateral lung transplantation on plasma surfactant protein D levels in idiopathic pulmonary fibrosis.

Background: Serum levels of surfactant protein D (SP-D) have been suggested as reflecting epithelial damage in acute lung injury, COPD, and idiopathic pulmonary fibrosis (IPF). However, little is known about SP-D levels in the setting of lung transplantation.

Methods: We examined plasma SP-D levels in 104 subjects from a prospective, multicenter cohort study of lung allograft recipients.

ANGPT2 genetic variant is associated with trauma-associated acute lung injury and altered plasma angiopoietin-2 isoform ratio.

Rationale: Acute lung injury (ALI) acts as a complex genetic trait, yet its genetic risk factors remain incompletely understood. Large-scale genotyping has not previously been reported for ALI.

Objectives: To identify ALI risk variants after major trauma using a large-scale candidate gene approach.

Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height.

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.

Ca(2+)-dependent enhancement of release by subthreshold somatic depolarization.

In many neurons, subthreshold somatic depolarization can spread electrotonically into the axon and modulate subsequent spike-evoked transmission. Although release probability is regulated by intracellular Ca(2+), the Ca(2+) dependence of this modulatory mechanism has been debated. Using paired recordings from synaptically connected molecular layer interneurons (MLIs) of the rat cerebellum, we observed Ca(2+)-mediated strengthening of release following brief subthreshold depolarization of the soma.

Elevated pulmonary artery pressure is a risk factor for primary graft dysfunction following lung transplantation for idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is often associated with elevations in pulmonary artery pressures. Although primary pulmonary arterial hypertension (PAH) has been associated with primary graft dysfunction (PGD), the role of secondary PAH in mediating PGD risk in patients with IPF is incompletely understood. The purpose of this study was to evaluate the relationship between mean pulmonary artery pressure (mPAP) and PGD among patients with IPF.

The contribution of airway and lung tissue ischemia to primary graft dysfunction.

Purpose Of Review: Primary graft dysfunction (PGD) is the primary obstacle to short-term survival for post-lung transplant patients. PGD is a form of acute lung injury secondary to donor brain death and ischemia-reperfusion damage to the allograft affecting 10-25% of all lung transplant recipients. This article reviews the significant role of allograft ischemia in the phenotypic presentation of PGD and the evidence for activation and disruption of normal cellular pathways for the development and long-term sequelae.

Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors.

Translational studies in liver transplantation often require an endpoint of graft function or dysfunction beyond graft loss. Prior definitions of early allograft dysfunction (EAD) vary, and none have been validated in a large multicenter population in the Model for End-Stage Liver Disease (MELD) era. We examined an updated definition of EAD to validate previously used criteria, and correlated this definition with graft and patient outcome.

Construct validity of the definition of primary graft dysfunction after lung transplantation.

Background: This study tested the discriminant validity of International Society for Heart and Lung Transplantation (ISHLT) primary graft dysfunction (PGD) grades with lung injury biomarker profiles and survival.

Methods: The study samples consisted of a multicenter prospective cohort study for the biomarker analysis and a cohort study of 450 patients for the mortality analyses. PGD was defined according to ISHLT consensus at 24, 48, and 72 hours after transplantation.