Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Ischemic gastropathy after distal pancreatectomy with celiac axis resection.

Purpose: Stomach-preserving distal pancreatectomy with en bloc resection of the celiac, common hepatic, and left gastric arteries is a radical operation performed for locally advanced cancer of the pancreatic body. However, it is not known whether the collateral pathways that develop immediately from the superior mesenteric artery to the gastroduodenal and hepatic arteries provide sufficient blood flow to support the hepatobiliary system and the stomach. This article examines the ischemic gastropathy that can occur after this procedure and identifies the predisposing conditions. Methods: Between 1997 and 2001, nine patients underwent stomach-preserving distal pancreatectomy with en bloc resection of the celiac, common hepatic, and left gastric arteries. Concomitant resection of the right gastric artery or gastroduodenal artery was performed due to cancer infiltration in three patients. Results: Irregular, shallow, and wide ulcerations thought to be ischemic in origin developed in these three patients, but all the ulcerations healed in 1–2 weeks with antiulcer medication. None of the other six patients had evidence of gastric ischemia. Conclusions Ischemic gastropathy is rare after distal pancreatectomy with celiac axis resection alone; however, division of additional arteries supplying the stomach may predispose to ischemic gastropathy.Figure 1-4 are missed

Replication-competent retrovirus vector-mediated prodrug activator gene therapy in experimental models of human malignant mesothelioma

Replication-competent retrovirus (RCR) vectors have been shown to achieve significantly enhanced tumor transduction efficiency and therapeutic efficacy in various cancer models. In the present study, we investigated RCR vector-mediated prodrug activator gene therapy for the treatment of malignant mesothelioma, a highly aggressive tumor with poor prognosis. RCR vector expressing the green fluorescent protein marker gene (RCR-GFP) successfully infected and efficiently replicated in human malignant mesothelioma cell lines, as compared to non-malignant mesothelial cells in vitro . In mice with pre-established subcutaneous tumor xenografts, RCR-GFP vector showed robust spread throughout entire tumor masses after intratumoral administration. Next, RCR-CD, expressing the yeast cytosine deaminase (CD) prodrug activator gene, showed efficient transmission of the prodrug activator gene associated with replicative spread of the virus, resulting in efficient killing of malignant mesothelioma cells in a prodrug 5-fluorocytosine (5FC)-dose dependent manner in vitro . After a single intratumoral injection of RCR-CD followed by intraperitoneal administration of 5FC, RCR vector-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous tumor growth, and significantly prolonged survival in the disseminated peritoneal model of malignant mesothelioma. These data indicate the potential utility of RCR vector-mediated prodrug activator gene therapy in the treatment of malignant mesothelioma

Outcomes in Two Japanese Adenosine Deaminase-Deficiency Patients Treated by Stem Cell Gene Therapy with No Cytoreductive Conditioning

Objective We here describe treatment outcomes in two adenosine deaminase (ADA)-deficiency patients (pt) who received stem cell gene therapy (SCGT) with no cytoreductive conditioning. As this protocol has features distinct from those of other clinical trials, its results provide insights into SCGT for ADA deficiency. Patients and Methods Pt 1 was treated at age 4.7 years, whereas pt 2, who had previously received T-cell gene therapy, was treated at age 13 years. Bone marrow CD34(+) cells were harvested after enzyme replacement therapy (ERT) was withdrawn; following transduction of ADA cDNA by the gamma-retroviral vector GCsapM-ADA, they were administered intravenously. No cytoreductive conditioning, at present considered critical for therapeutic benefit, was given before cell infusion. Hematological/immunological reconstitution kinetics, levels of systemic detoxification, gene-marking levels, and proviral insertion sites in hematopoietic cells were assessed. Results Treatment was well tolerated, and no serious adverse events were observed. Engraftment of gene-modified repopulating cells was evidenced by the appearance and maintenance of peripheral lymphocytes expressing functional ADA. Systemic detoxification was moderately achieved, allowing temporary discontinuation of ERT for 6 and 10 years in pt 1 and pt 2, respectively. Recovery of immunity remained partial, with lymphocyte counts in pts 1 and 2, peaked at 408/mm(3) and 1248/mm(3), approximately 2 and 5 years after SCGT. Vector integration site analyses confirmed that hematopoiesis was reconstituted with a limited number of clones, some of which were shown to have myelo-lymphoid potential. Conclusions Outcomes in SCGT for ADA-SCID are described in the context of a unique protocol, which used neither ERT nor cytoreductive conditioning. Although proven safe, immune reconstitution was partial and temporary. Our results reiterate the importance of cytoreductive conditioning to ensure greater benefits from SCGT