Purpose Prone positioning for ARDS has been performed for decades without definitive evidence of clinical benefit. A recent multicenter trial demonstrated for the first time significantly reduced mortality with prone positioning. This meta-analysis was performed to integrate these findings with existing literature and test whether differences in tidal volume explain conflicting results among randomized trials. Methods Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review. Included were randomized trials evaluating the effect on mortality of prone versus supine positioning during conventional ventilation for ARDS. The primary outcome was risk ratio of death at 60 days meta-analyzed using random effects models. Analysis stratified by high (>8 ml/kg predicted body weight) or low (≤8 ml/kg PBW) mean baseline tidal volume was planned a priori. Results Seven trials were identified including 2,119 patients, of whom 1,088 received prone positioning. Overall, prone positioning was not significantly associated with the risk ratio of death (RR 0.83; 95 % CI 0.68–1.02; p = 0.073; I2 = 64 %). When stratified by high or low tidal volume, prone positioning was associated with a significant decrease in RR of death only among studies with low baseline tidal volume (RR 0.66; 95 % CI 0.50–0.86; p = 0.002; I2 = 25 %). Stratification by tidal volume explained over half the between-study heterogeneity observed in the unstratified analysis. Conclusions Prone positioning is associated with significantly reduced mortality from ARDS in the low tidal volume era. Substantial heterogeneity across studies can be explained by differences in tidal volume.

Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk is being considered as a therapeutic target we asked whether Syk is central to the multiple aberrantly modulated molecules in SLE T cells. Using a gene expression array, we demonstrate that forced expression of Syk in normal T cells reproduces most of the aberrantly expressed molecules whereas silencing of Syk in SLE T cells normalizes the expression of most abnormally expressed molecules. Protein along with gene expression modulation for select molecules was confirmed. Specifically, levels of cytokine IL-21, cell surface receptor CD44, and intracellular molecules PP2A and OAS2 increased following Syk overexpression in normal T cells and decreased after Syk silencing in SLE T cells. Our results demonstrate that levels of Syk affect the expression of a number of enzymes, cytokines and receptors that play a key role in the development of disease pathogenesis in SLE and provide support for therapeutic targeting in SLE patients.

Objective Little is known about patterns of use of initial kidney replacement therapies among patients with LN end-stage renal disease (LN ESRD). We aimed to identify sociodemographic and clinical factors associated with variation in initial kidney replacement therapies among LN ESRD patients. Methods Patients with incident LN ESRD (1995–2006) were identified in the US Renal Data System. Age, sex, race, ethnicity, medical insurance, employment status, residential region, clinical factors and comorbidities were considered as potential predictors of ESRD treatment choice -- peritoneal dialysis (PD), hemodialysis (HD) or pre-emptive kidney transplantation -- in age-adjusted and multivariable-adjusted logistic regression analyses. Results Of 11,317 individuals with incident LN ESRD, 82.0% initiated HD; 12.2% PD, and 2.8% underwent pre-emptive kidney transplantation. Receiving initial PD was significantly associated with earlier calendar year, female sex, higher albumin and hemoglobin, and lower serum creatinine levels. African Americans (vs. Whites), Medicaid beneficiaries and those with no health insurance (vs. private insurance), and those unemployed (vs. employed) had significantly reduced PD initiation. Comorbidities including congestive heart failure, peripheral vascular disease and inability to ambulate were also associated with decreased PD. Many sociodemographic and clinical factors favoring PD were associated with pre-emptive kidney transplant (vs. dialysis) as well. Conclusion Few patients with LN ESRD receive initial PD or pre-emptive kidney transplantation. Race, ethnicity, employment and medical insurance type are strongly associated with initial kidney replacement therapy choice. Future studies need to investigate the appropriateness of sociodemographic and clinical variation and the comparative effectiveness of kidney replacement therapies for LN ESRD.

Systemic Lupus Erythematosus (SLE) remains a challenging disease to diagnose and follow, as no reliable biomarkers are known to date. We designed a gene expression panel with 40 genes known to play a role in SLE pathogenesis. We found that the combined expression of these genes in SLE T cells can accurately differentiate SLE from healthy individuals and patients with other autoimmune diseases. The accuracy of the test increased further (83%) when only three out of the initial genes (OAS2, CD70 and IL10) were used. A T cell score, calculated from the combined expression levels of these genes, correlated positively with various SLE activity markers in a cross-sectional cohort and in a few patients that were followed prospectively. These data showcase the usefulness of measuring mRNA levels of key molecules in diagnosing and following patients with SLE.