Prognostic Value of Red Blood Cell Distribution Width in Non-Cardiovascular Critically or Acutely Patients: A Systematic Review

<div><p>Background</p><p>RDW (red cell distribution width) has been reported to been associated with the prognosis of patients with cardiovascular diseases. However, RDW is often overlooked by clinicians in treating patients with non-cardiovascular diseases, especially in an emergency. The objective of this systematic review is to explore the prognostic value of RDW in non-cardiovascular emergencies.</p><p>Methods</p><p>PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched from their inception to December 31, 2015. We included studies examining the relationship between RDW and mortality rate by adjusting important covariables in non-cardiovascular emergencies. All included studies were divided into three groups. Group A: general critically ill patients; Group B: patients with infectious disease; Group C: other conditions. We extracted each study’ characteristics, outcomes, covariables, and other items independently.</p><p>Results</p><p>A total of 32 studies were eligible for inclusion in our meta-analysis. Six studies belonged to Group A, 9 studies belonged to Group B and 17 studies belonged to Group C. Among these included studies, RDW was assessed as a continuous variable (per 1% increase) in 16 studies, as a binary variable in 8 studies, and as a categorical variable in 8 studies. In addition, AUCs (area under the receiver operating characteristic curve) of RDW for predicting mortality were reported in 25 studies. All studies were published between 2011–2015. The qualities of included 32 studies were moderate or high.</p><p>Conclusion</p><p>The present systematic review indicates that the increased RDW is significantly associated with a higher mortality rate in an non-cardiovascular emergency. The low cost and readily accessible of this laboratory variable may strengthen its usefulness in daily practice in the future.</p></div

Study Quality as Assessed by The Newcastle-Ottawa Scale.

<p>Study Quality as Assessed by The Newcastle-Ottawa Scale.</p

The Effect of RDW on Mortality.

<p>The Effect of RDW on Mortality.</p

Characteristics of Included Studies.

<p>Characteristics of Included Studies.</p

Flowchart of study selection.

<p>Flowchart of study selection.</p

Healing in Holy Scripture and today

Forest plot showing the effects of early goal-direced therapy on vasopressor use rate. (TIF 968 kb

Trial sequential analysis of all-cause mortality in patients with septic shock.

<p>Trial sequential analyses assessing the effect of albumin on all-cause mortality in 3 studies. The diversity-adjusted required information size (4586 participants) was based on a relative risk reduction of 10%; an alpha of 5%; a beta of 2% and an event proportion of 40.3% in the control arm. The blue cumulative z curve was constructed using a random effects model.</p

PIAS1 Is a GATA4 SUMO Ligase That Regulates GATA4-Dependent Intestinal Promoters Independent of SUMO Ligase Activity and GATA4 Sumoylation

<div><p>GATA4 confers cell type-specific gene expression on genes expressed in cardiovascular, gastro-intestinal, endocrine and neuronal tissues by interacting with various ubiquitous and cell-type-restricted transcriptional regulators. By using yeast two-hybrid screening approach, we have identified PIAS1 as an intestine-expressed GATA4 interacting protein. The physical interaction between GATA4 and PIAS1 was confirmed in mammalian cells by coimmunoprecipitation and two-hybrid analysis. The interacting domains were mapped to the second zinc finger and the adjacent C-terminal basic region of GATA4 and the RING finger and the adjoining C-terminal 60 amino acids of PIAS1. PIAS1 and GATA4 synergistically activated IFABP and SI promoters but not LPH promoters suggesting that PIAS1 differentially activates GATA4 targeted promoters. In primary murine enterocytes PIAS1 was recruited to the GATA4-regulated IFABP promoter. PIAS1 promoted SUMO-1 modification of GATA4 on lysine 366. However, sumoylation was not required for the nuclear localization and stability of GATA4. Further, neither GATA4 sumoylation nor the SUMO ligase activity of PIAS1 was required for coactivation of IFABP promoter by GATA4 and PIAS1. Together, our results demonstrate that PIAS1 is a SUMO ligase for GATA4 that differentially regulates GATA4 transcriptional activity independent of SUMO ligase activity and GATA4 sumoylation.</p> </div

Mapping of GATA4 and PIAS1 domains required for IFABP coactivation.

<p>Transient cotransfections were performed in subconfluent HCT116 cells using wild-type and deletion mutants of GATA4 and wild-type PIAS1 (<b>panel A</b>). In <b>panel B</b>, wild-type and deletion mutants of PIAS1 and wild-type GATA4 were used for cotransfections. Lysates were assayed for luciferase activity 48 hours post-transfection. Results from 3 experiments done in triplicates are shown as mean±SEM.</p

Forkhead Box Protein A2 (FOXA2) Protein Stability and Activity Are Regulated by Sumoylation

<div><p>The forkhead box protein A2 (FOXA2) is an important regulator of glucose and lipid metabolism and organismal energy balance. Little is known about how FOXA2 protein expression and activity are regulated by post-translational modifications. We have identified that FOXA2 is post-translationally modified by covalent attachment of a small ubiquitin related modifier-1 (SUMO-1) and mapped the sumoylation site to the amino acid lysine 6 (K6). Preventing sumoylation by mutating the SUMO acceptor K6 to arginine resulted in downregulation of FOXA2 protein but not RNA expression in INS-1E insulinoma cells. K6R mutation also downregulated FOXA2 protein levels in HepG2 hepatocellular carcinoma cells, HCT116 colon cancer cells and LNCaP and DU145 prostate cancer cells. Further, interfering with FOXA2 sumoylation through siRNA mediated knockdown of UBC9, an essential SUMO E2 conjugase, resulted in downregulation of FOXA2 protein levels. Stability of sumoylation deficient FOXA2K6R mutant protein was restored when SUMO-1 was fused in-frame. FOXA2 sumoylation and FOXA2 protein levels were increased by PIAS1 SUMO ligase but not a SUMO ligase activity deficient PIAS1 mutant. Although expressed at lower levels, sumoylation deficient FOXA2K6R mutant protein was detectable in the nucleus indicating that FOXA2 nuclear localization is independent of sumoylation. Sumoylation increased the transcriptional activity of FOXA2 on <em>Pdx-1</em> area I enhancer. Together, our results show that sumoylation regulates FOXA2 protein expression and activity.</p> </div