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

Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barré syndrome and systemic lupus arythematosus

Immuneglobulins isotypes (IgG and IgM) for myelin basic protein (MBP), cerebrosides (CER), gangliosides (GANG) and cardiolipin (CARD) were detected in the cerebrospinal fluid (CSF) from 33 patients with multiple sclerosis (MS), 18 with Guillain-Barré syndrome (GBS) and 30 with systemic lupus erythematosus (SLE). In MS patients occurred positive and significant levels of IgG-MBP in 51,5% (p<0.05) and IgM-MBP in only 18.2%, IgG-CARD in 46.2%, as long as CER and GANG were detected in almost 20%. From serum samples of MS patients 20.6% presented IgG-MBP, while 53% showed positive levels foi IgM-MBP. The CSF analysis of patients with GBS showed that 56.3% revealed IgG-MBP (p<0.05), 53% for IgM-MBP. 3&.5% for IgG-CER and 23% for IgM-CER, while 50% of patients had IgG-CARD, as long -as 31% also had IgG-GANG. The serum evaluation from 14 patients showed that 18.8% had positive concentrations of IgG-MBP and 56.3% presented IgM-MBP (p<0.05) Except for 50% of patients with SLE who presented positive CSF levels of IgG-CARD. only 24.1% had positive levels of IgG-MBP. We believe that the presence of antiphosphohoid antibodies in CSF of the above mentioned diseases occurred as immune epiphenomena, but their appearance would permit the maintenance of and perpetuate the immune event

Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production

Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR) that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice.This study was supported by RETICS 06/0016 (VFM, RS) and FIS PI 09/0064 (RS) from the Fondo de Investigaciones Sanitarias (Health Research Fund). MLC was funded by SAF 2013-47611-R, SAF 2010-21249, and SAF 2007-61201 from the Ministerio de Economía y competitividad. MRO was supported by RETICS 12/0021,S2012DMD2321 from the Comunidad Autónoma de Madrid, PI 11/01854 from Fondo Investigaciones Sanitarias. GTGM was supported by Renal Foundation Íñigo Álvarez de Toledo, FIBHULP, and by Severo Ochoa FoundationPeer Reviewe

Dermatopolimiosite: avaliação de 63 pacientes

Sessenta e três pacientes com dermatopolimiosite são avaliados mediante exames clínico, laboratorial, eletroneuromiográfico e anatomopatológico (tecido muscular corado pela hematoxilina-eosina) e pela resposta terapêutica. Trinta e nove são do sexo feminino e 24 do sexo masculino. Média etária de 36,83 ± 15,64 anos. Duração média da doença de 3,74 ± 4,26 anos. São verificadas influências do uso de corticosteróides e ou drogas citolíticas no comportamento enzimático e resposta clínica dos pacientes. Análises são realizadas com intuito de se determinar fatores que pudessem definir os grupos quanto a resposta clínica à terapêutica empregada

Polymorphism +17 C/G in Matrix Metalloprotease MMP8 decreases lung cancer risk

<p>Abstract</p> <p>Background</p> <p>Matrix metalloproteases (MMPs) constitute a family of enzymes capable of degrading different components of the extracellular matrix and are implicated in the invasion of tumor cells through the basement membrane. Polymorphisms in MMP genes may result in changes in the expression of MMPs being associated with the development and progression of cancer. We have investigated the association between three polymorphisms (-1607 1G/2G, +17 C/G and -77 A/G) in the human collagenases MMP1, MMP8 and MMP13 and the risk of development or progression of lung cancer.</p> <p>Methods</p> <p>A hospital-based case-control study was designed including 501 lung cancer patients and 510 controls matched. Genotypes were determined by PCR-RFLP. Results were analyzed using unconditional logistic regression, Cox's proportional hazard regression, and the Kaplan-Meier method.</p> <p>Results</p> <p>The MMP1 and MMP13 promoter polymorphisms were not associated with lung cancer risk, while the C/G polymorphism in MMP8 was associated with a statistically significant decreased risk of developing lung cancer (ORadj = 0.65; 95%CI = 0.45–0.93). The Kaplan-Meier analysis showed that the polymorphisms in MMP1, MMP8 and MMP13 not seem to modify the overall survival. Multivariate analysis revealed that MMP1, MMP8 and MMP13 polymorphisms are not independent prognostic factors for overall survival.</p> <p>Conclusion</p> <p>This study suggests that the polymorphism in MMP8 is associated with a decreased lung cancer risk, which can be used as a prognostic marker in lung cancer.</p

Terapêutica intravenosa com metilprednisolona e ciclofosfamida na vasculite do sistema nervoso periférico: avaliação de oito pacientes Intravenous theraphy with methylprednisolone and cyclophosphamide in vasculitis of peripheral nervous system: evaluation of eight patients

O comprometimento do sistema nervoso periférico é frequente nas vasculites sistêmicas e contribui decisivamente para o diagnóstico. Oito pacientes foram estudados: sete do sexo feminino e um do sexo masculino; cinco brancos, dois negros, um amarelo; média de idade de 55,9 anos; quatro com poliarterite nodosa, um com lúpus eritematoso sistêmico, um com artrite reumatóide, um com vasculite isolada do sistema nervoso periférico e um com vasculite livedóide. Todos foram submetidos a terapêutica intravenosa com pulsos mensais de metilprednisolona (1 g/dia/3dias) e ciclofosfamida (1 g/dia). Cinco pacientes melhoraram, dois permaneceram inalterados e um faleceu. A melhora neurológica objetiva ocorreu após o terceiro ou quarto pulso e nos pacientes com menor duração da doença.<br>The peripheral nervous system is frequently involved in systemic vasculitis and it may be helpful in the disease diagnosis. We report on eight patients: seven women and one man; five white, two black and one yellow; age mean 55.9 years; four had polyarteritis nodosa, one had systemic lupus erythematosus, one had isolated peripheral nerve vasculitis and one had livedoid vasculitis. All of them received endovenous therapy with "pulse" of methylprednisolone (1 g/day/3days) and cyclophosphamide (1 g/1day). Five patients improved, two remained unchanged and one died. The neurological improvement occurred after the third or fourth pulse and in the patients who have had a shorter time of disease

HPLC-PDA-MS and NMR characterization of a hydroalcoholic extract of Citrus aurantium L. var. amara peel with antiedematogenic activity

The phytochemical profile of a hydroalcoholic extract of Citrus aurantium var. amara L. peel, used as herbal medicine, was characterized by HPLC-PDA-MS. Two di-C-glycosyl flavones (vincenin II and diosmetin 6,8-di-C-glucoside), a series of flavones (luteolin 7-O-neohesperidoside, rhoifolin, and neodiosmin), and flavanone (neoeriocitrin, naringin, and neohesperidin) 7-O-neohesperidosides and two methoxyflavones (nobiletin and tangeretin), commonly present in Citrus, were identified. Furthermore, brutieridin and melitidin, two 3-hydroxy-3-methylglutaryl flavanone glycosides, were also characterized along with rhoifolin 4′-glucoside and three coumarins (8,3′-β-d-glucopyranosyloxy-2′-hydroxy-3′-methylbutyl-7-methoxycoumarin, merazin hydrate, and isomerazin). A preparative isolation procedure followed by NMR spectroscopy confirmed the proposed structures of the major flavonoids and identified the coumarins. The phenolic content was found to be 14.8 mg mL–1, and naringin and neohesperidin were the compounds present in the highest concentration (3.6 and 2.6 mg mL–1). The extract of C. aurantium peel inhibited significantly (p < 0.05) both histamine- and dextran-induced edema in rats in a concentration-dependent manner (IC50 = 119.6 and 118.3 mg kg–1, respectively), providing evidence for the therapeutic use of C. aurantium var. amara peel