Polycomb repressive complex 1.1 coordinates homeostatic and emergency myelopoiesis

Polycomb repressive complex (PRC) 1 regulates stem cell fate by mediating mono-ubiquitination of histone H2A at lysine 119. While canonical PRC1 is critical for hematopoietic stem and progenitor cell (HSPC) maintenance, the role of non-canonical PRC1 in hematopoiesis remains elusive. PRC1.1, a non-canonical PRC1, consists of PCGF1, RING1B, KDM2B, and BCOR. We recently showed that PRC1.1 insufficiency induced by the loss of PCGF1 or BCOR causes myeloid-biased hematopoiesis and promotes transformation of hematopoietic cells in mice. Here we show that PRC1.1 serves as an epigenetic switch that coordinates homeostatic and emergency hematopoiesis. PRC1.1 maintains balanced output of steady-state hematopoiesis by restricting C/EBPα-dependent precocious myeloid differentiation of HSPCs and the HOXA9- and β-catenin-driven self-renewing network in myeloid progenitors. Upon regeneration, PRC1.1 is transiently inhibited to facilitate formation of granulocyte-macrophage progenitor (GMP) clusters, thereby promoting emergency myelopoiesis. Moreover, constitutive inactivation of PRC1.1 results in unchecked expansion of GMPs and eventual transformation. Collectively, our results define PRC1.1 as a novel critical regulator of emergency myelopoiesis, dysregulation of which leads to myeloid transformation

Bleeding anorectal varices treated by a direct puncture approach through the greater sciatic foramen : The utility of a steerable microcatheter for reverse catheterization

Bleeding is less common from anorectal varices than from esophageal varices, but it is potentially life-threatening. Here, we present a case of a woman in her 70s with critical hemorrhage from anorectal varices. The endoscopic approach could not be performed due to the huge variceal formation and the transhepatic approach was also unsuitable due to the presence of portal vein thrombosis and ascites. A direct puncture to the right superior rectal vein was performed through the greater sciatic foramen under computed tomography fluoroscopic guidance. Using a steerable microcatheter, superior rectal veins were bilaterally embolized with a mixture of n-butyl cyanoacrylate and ethiodized oil, and microcoils. Endoscopy and contrast-enhanced computed tomography performed after the procedure confirmed a marked shrinkage of anorectal varices. When endoscopic or any other approaches are difficult, this technique can be a useful alternative therapeutic option

Comparison of the efficacy of three topical antiseptic solutions for the prevention of catheter colonization: a multicenter randomized controlled study

Abstract Background To compare the efficacy of three antiseptic solutions [0.5%, and 1.0% alcohol/chlorhexidine gluconate (CHG), and 10% aqueous povidone-iodine (PVI)] for the prevention of intravascular catheter colonization, we conducted a randomized controlled trial in patients from 16 intensive care units in Japan. Methods Adult patients undergoing central venous or arterial catheter insertions were randomized to have one of three antiseptic solutions applied during catheter insertion and dressing changes. The primary endpoint was the incidence of catheter colonization, and the secondary endpoint was the incidence of catheter-related bloodstream infections (CRBSI). Results Of 1132 catheters randomized, 796 (70%) were included in the full analysis set. Catheter-tip colonization incidence was 3.7, 3.9, and 10.5 events per 1000 catheter-days in 0.5% CHG, 1% CHG, and PVI groups, respectively (p = 0.03). Pairwise comparisons of catheter colonization between groups showed a significantly higher catheter colonization risk in the PVI group (0.5% CHG vs. PVI: hazard ratio, HR 0.33 [95% confidence interval, CI 0.12–0.95], p = 0.04; 1.0% CHG vs. PVI: HR 0.35 [95% CI 0.13–0.93], p = 0.04). Sensitivity analyses including all patients by multiple imputations showed consistent quantitative conclusions (0.5% CHG vs. PVI: HR 0.34, p = 0.03; 1.0% CHG vs. PVI: HR 0.35, p = 0.04). No significant differences were observed in the incidence of CRBSI between groups. Conclusions Both 0.5% and 1.0% alcohol CHG are superior to 10% aqueous PVI for the prevention of intravascular catheter colonization. Trial registration Japanese Primary Registries Network; No.: UMIN000008725 Registered on 1 September 201

Le Courrier

14 septembre 18211821/09/14 (A0,N251)