The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

A randomized trial of multivitamin supplements and HIV disease progression and mortality.

BACKGROUND: Results from observational studies suggest that micronutrient status is a determinant of the progression of human immunodeficiency virus (HIV) disease. METHODS: We enrolled 1078 pregnant women infected with HIV in a double-blind, placebo-controlled trial in Dar es Salaam, Tanzania, to examine the effects of daily supplements of vitamin A (preformed vitamin A and beta carotene), multivitamins (vitamins B, C, and E), or both on progression of HIV disease, using survival models. The median follow-up with respect to survival was 71 months (interquartile range, 46 to 80). RESULTS: Of 271 women who received multivitamins, 67 had progression to World Health Organization (WHO) stage 4 disease or died--the primary outcome--as compared with 83 of 267 women who received placebo (24.7 percent vs. 31.1 percent; relative risk, 0.71; 95 percent confidence interval, 0.51 to 0.98; P=0.04). This regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome (0.73; 95 percent confidence interval, 0.51 to 1.04; P=0.09), progression to WHO stage 4 (0.50; 95 percent confidence interval, 0.28 to 0.90; P=0.02), or progression to stage 3 or higher (0.72; 95 percent confidence interval, 0.58 to 0.90; P=0.003). Multivitamins also resulted in significantly higher CD4+ and CD8+ cell counts and significantly lower viral loads. The effects of receiving vitamin A alone were smaller and for the most part not significantly different from those produced by placebo. Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined. CONCLUSIONS: Multivitamin supplements delay the progression of HIV disease and provide an effective, low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women

The microrna 17-92 cluster in neural progenitor cells is required for stroke-induced neurogenesis and gliogenesis

Background: Molecular mechanisms underlying stroke-induced neurogenesis have not been fully investigated. The microRNA 17-92 cluster (miR17-92) regulates proliferation and differentiation of adult neural progenitor cells (NPCs). The present study investigated whether the miR17-92 cluster in NPCs is required for stroke-induced neurogenesis. Methods and Results: Mice with inducible and conditional knockdown of the miR17-92 cluster in nestin lineage NPCs (nestin-CreERT2/miR17-92-/-, 17-92-cKO, n=9) and wild-type litters (WT, n=9) were treated by tamoxifen. Administration of tamoxifen resulted in more than 60% reduction of individual members of the miR-17-92 cluster (miR-17: 1.0 vs 0.4; miR-19a: 1.0 vs 0.3; miR-19b: 1.0 vs 0.2; miR-20a: 1.0 vs 0.4; miR- 92a: 1.0 vs 0.4 fold in WT, p\u3c0.05) in NPCs localized to the subventricular zone (SVZ). Two days after termination of tamoxifen treatment, these mice were subjected to permanent right middle cerebral artery occlusion (MCAO) and sacrificed 28 days post-MCAo. Compared to WT mice, 17-92-cKO mice exhibited significant (p\u3c0.05) reduction of proliferation of NPCs measured by the number of Ki67+ cells (226±43 vs 471±100 cells/mm2) and the number of DCX+ neuroblasts (11±2% vs 24±4% ) in the ischemic SVZ. Cultured NPCs harvested from ischemic cKO mice showed significant (p\u3c0.05) reduction of BrdU+ cells (37±2% vs 61±4% WT , n=3/group), Tuj1+ neuroblasts (5±0.2% vs 9±0.4% ), GFAP+ cells (33±3% vs 53±2%), and NG2+ oligodendrocyte progenitor cells (OPCs, 3±0.1% vs 5±0.5%). These in vivo and in vitro data indicate that reduction of the miR17-92 cluster suppresses stroke-induced neurogenesis and gliogenesis. Western blot analysis showed that miR17-92 cKO significantly (p\u3c0.05) increased and reduced a cytoskeleton-associated protein, Enigma homolog1 (ENH1, 1.6 vs 1.0 fold), and its down-stream transcription factor, inhibitor of differentiation1 (ID1, 1.0 vs 0.6 fold), respectively. ENH1 is a putative target of the miR17-92 cluster.Conclusion: Our data indicate that the miR17-92 cluster in adult nestin lineage NPCs is required for stroke-induced neurongenesis and gliogenesis, and that the miR17-92 cluster possibly targets ENH1/ID1 signaling

Investigate the Glass Transition Temperature of Hyperbranched Copolymers with Segmented Monomer Sequence

Hyperbranched copolymers with segmented structures were synthesized using a chain-growth copper-catalyzed azide–alkyne cycloaddition (CuAAC) polymerization via sequential monomer addition in one pot. Three AB₂-type monomers that contained one alkynyl group (A), two azido groups (B), and one dangling group, either benzyl or oligo­(ethylene oxide) (EO_<i>x</i>, <i>x</i> = 3 and 7.5), were used in these CuAAC reactions. Varying the addition sequences and feed ratios of the monomers produced a variety of hyperbranched copolymers with tunable compositions, molecular weights, segmented structures, and consequently glass transition temperature (<i>T</i>_g). It was found that the <i>T</i>_g of hyperbranched copolymers was little affected by the polymer molecular weights when <i>M</i>_n ≥ 5000. However, the values of <i>T</i>_g were significantly determined by the compositions of the terminal groups and the outermost segment of the hyperbranched copolymers. The last added AB₂ monomer in the polymerization formed an outermost “shell” and shielded the contribution of inner segments to the glass transition of the copolymers, reflecting a chain sequence effect of hyperbranched polymers on the thermal properties

A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit

Purpose: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world. Methods: We performed a secondary analysis of data from the prospective ICON audit, in which all adult ( &gt;16 years ) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - &lt;= 50, 51-60, 61-70, 71-80, &gt;80 years. Sepsis was defined as infection plus at least one organ failure. Results: A total of 2963 patients had sepsis, with similar proportions across the age groups (&lt;= 50 = 25.2%: 51-60 = 30.3%; 61-70 = 32.8%; 71-80 = 30.7%; &gt;80 = 30.9%). Hospital mortality increased with age and in patients &gt;80 years was almost twice that of patients &lt;= 50 years (493% vs 25.2%, p &lt; .05). The maximum rate of increase in mortality was about 0.75% per year, occurring between the ages of 71 and 77 years. In multilevel analysis, age &gt; 70 years was independently associated with increased risk of dying. Conclusions: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years. (C) 2019 Elsevier Inc. All rights reserved

Correction to collaborators in acknowledgments in: Decision-making on withholding or withdrawing life support in the ICU: A worldwide perspective

The authors have reported to CHEST that the collaborators from the ICON Investigators were omitted from the Acknowledgments in “Decision-Making on Withholding or Withdrawing Life Support in the ICU: A Worldwide Perspective” (Chest. 2017;152(2):321-329). https://doi.org/10.1016/j.chest.2017.04.17