scholarly journals Human endogenous retrovirus K activation in the lower respiratory tract of severe COVID-19 patients associates with early mortality

2021 ◽  
Author(s):  
Thiago Souza ◽  
Jairo Temerozo ◽  
Natalia Fintelman-Rodrigues ◽  
Monique Cristina Santos ◽  
Eugênio Hottz ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Invasive Mechanical Ventilation ◽  
Endogenous Retrovirus ◽  
Early Mortality ◽  
Human Endogenous Retrovirus ◽  
Rt Pcr ◽  
Healthy Donors ◽  
Tracheal Aspirates

Abstract Critically ill 2019 coronavirus disease patients (COVID-19) under invasive mechanical ventilation (IMV) are 10- to 40-times more likely to die than the general population. Although progression from mild to severe COVID-19 has been associated with hypoxia, uncontrolled inflammation and coagulopathy, the mechanisms involved in progression to severity are poorly understood. By analyzing the virome from tracheal aspirates (TA) of 25 COVID-19 patients under IMV, we found higher levels and differential expression of human endogenous retrovirus K (HERV-K) genes compared to nasopharyngeal swabs from mild cases and TA from non-COVID patients. Proteomic analysis and RT-PCR confirmed the presence of HERV-K in these patients. Moreover, increased HERV-K expression was triggered in human primary monocytes from healthy donors after experimental SARS-CoV-2 infection in vitro. In critically ill patients, higher HERV-K levels were associated with early mortality (within 14 days) in the intensive care unit. Increased HERV-K expression in deceased patients associated with IL-17-related inflammation, monocyte activation and higher consumption of clotting/fibrinolysis factors. Our data implicate the levels of HERV-K transcripts in the outcome of critical COVID-19 patients under invasive mechanical ventilation.

scholarly journals Etiology, incidence, and outcomes of patient–ventilator asynchrony in critically-ill patients undergoing invasive mechanical ventilation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yongfang Zhou ◽  
Steven R. Holets ◽  
Man Li ◽  
Gustavo A. Cortes-Puentes ◽  
Todd J. Meyer ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Invasive Mechanical Ventilation ◽  
Surgical Intensive Care ◽  
Mechanically Ventilated ◽  
History Of ◽  
Training Background ◽  
The Relationship

AbstractPatient–ventilator asynchrony (PVA) is commonly encountered during mechanical ventilation of critically ill patients. Estimates of PVA incidence vary widely. Type, risk factors, and consequences of PVA remain unclear. We aimed to measure the incidence and identify types of PVA, characterize risk factors for development, and explore the relationship between PVA and outcome among critically ill, mechanically ventilated adult patients admitted to medical, surgical, and medical-surgical intensive care units in a large academic institution staffed with varying provider training background. A single center, retrospective cohort study of all adult critically ill patients undergoing invasive mechanical ventilation for ≥ 12 h. A total of 676 patients who underwent 696 episodes of mechanical ventilation were included. Overall PVA occurred in 170 (24%) episodes. Double triggering 92(13%) was most common, followed by flow starvation 73(10%). A history of smoking, and pneumonia, sepsis, or ARDS were risk factors for overall PVA and double triggering (all P < 0.05). Compared with volume targeted ventilation, pressure targeted ventilation decreased the occurrence of events (all P < 0.01). During volume controlled synchronized intermittent mandatory ventilation and pressure targeted ventilation, ventilator settings were associated with the incidence of overall PVA. The number of overall PVA, as well as double triggering and flow starvation specifically, were associated with worse outcomes and fewer hospital-free days (all P < 0.01). Double triggering and flow starvation are the most common PVA among critically ill, mechanically ventilated patients. Overall incidence as well as double triggering and flow starvation PVA specifically, portend worse outcome.

scholarly journals Impact of dexamethasone on the incidence of ventilator-associated pneumonia and blood stream infections in COVID-19 patients requiring invasive mechanical ventilation: a multicenter retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ines Gragueb-Chatti ◽  
Alexandre Lopez ◽  
Dany Hamidi ◽  
Christophe Guervilly ◽  
Anderson Loundou ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Retrospective Study ◽  
Length Of Stay ◽  
Critically Ill ◽  
Invasive Mechanical Ventilation ◽  
Blood Stream ◽  
Hospital Length Of Stay ◽  
Ventilator Associated Pneumonia ◽  
Blood Stream Infections ◽  
Second Wave

Abstract Background Dexamethasone decreases mortality in patients with severe coronavirus disease 2019 (COVID-19) and has become the standard of care during the second wave of pandemic. Dexamethasone is an immunosuppressive treatment potentially increasing the risk of secondary hospital acquired infections in critically ill patients. We conducted an observational retrospective study in three French intensive care units (ICUs) comparing the first and second waves of pandemic to investigate the role of dexamethasone in the occurrence of ventilator-associated pneumonia (VAP) and blood stream infections (BSI). Patients admitted from March to November 2020 with a documented COVID-19 and requiring mechanical ventilation (MV) for ≥ 48 h were included. The main study outcomes were the incidence of VAP and BSI according to the use of dexamethasone. Secondary outcomes were the ventilator-free days (VFD) at day-28 and day-60, ICU and hospital length of stay and mortality. Results Among the 151 patients included, 84 received dexamethasone, all but one during the second wave. VAP occurred in 63% of patients treated with dexamethasone (DEXA+) and 57% in those not receiving dexamethasone (DEXA−) (p = 0.43). The cumulative incidence of VAP, considering death, duration of MV and late immunosuppression as competing factors was not different between groups (p = 0.59). A multivariate analysis did not identify dexamethasone as an independent risk factor for VAP occurrence. The occurrence of BSI was not different between groups (29 vs. 30%; p = 0.86). DEXA+ patients had more VFD at day-28 (9 (0–21) vs. 0 (0–11) days; p = 0.009) and a reduced ICU length of stay (20 (11–44) vs. 32 (17–46) days; p = 0.01). Mortality did not differ between groups. Conclusions In this cohort of COVID-19 patients requiring invasive MV, dexamethasone was not associated with an increased incidence of VAP or BSI. Dexamethasone might not explain the high rates of VAP and BSI observed in critically ill COVID-19 patients.

scholarly journals Dynamic Changes of the Neutrophil-to-Lymphocyte Ratio, Systemic Inflammation Index, and Derived Neutrophil-to-Lymphocyte Ratio Independently Predict Invasive Mechanical Ventilation Need and Death in Critically Ill COVID-19 Patients

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1656
Author(s):  
Emanuel Moisa ◽  
Dan Corneci ◽  
Silvius Negoita ◽  
Cristina Raluca Filimon ◽  
Andreea Serbu ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Critically Ill ◽  
Systemic Inflammation ◽  
Predictive Value ◽  
Cox Regression ◽  
Invasive Mechanical Ventilation ◽  
Neutrophil To Lymphocyte Ratio ◽  
Dynamic Changes ◽  
Hematological Indices ◽  
Lymphocyte Ratio

Background: Hematological indices can predict disease severity, progression, and death in patients with coronavirus disease-19 (COVID-19). Objectives: To study the predictive value of the dynamic changes (first 48 h after ICU admission) of the following ratios: neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), systemic inflammation index (SII), and derived neutrophil-to-lymphocyte (dNLR) for invasive mechanical ventilation (IMV) need and death in critically ill COVID-19 patients. Methods: Observational, retrospective, and multicentric analysis on 272 patients with severe or critical COVID-19 from two tertiary centers. Hematological indices were adjusted for confounders through multivariate analysis using Cox regression. Results: Patients comprised 186 males and 86 females with no difference across groups (p > 0.05). ΔNLR > 2 had the best independent predictive value for IMV need (HR = 5.05 (95% CI, 3.06–8.33, p < 0.0001)), followed by ΔSII > 340 (HR = 3.56, 95% CI 2.21–5.74, p < 0.0001) and ΔdNLR > 1 (HR = 2.61, 95% CI 1.7–4.01, p < 0.0001). Death was also best predicted by an NLR > 11 (HR = 2.25, 95% CI: 1.31–3.86, p = 0.003) followed by dNLR > 6.93 (HR = 1.89, 95% CI: 1.2–2.98, p = 0.005) and SII > 3700 (HR = 1.68, 95% CI: 1.13–2.49, p = 0.01). Conclusions: Dynamic changes of NLR, SII, and dNLR independently predict IMV need and death in critically ill COVID-19 patients.

scholarly journals Prediction of prolonged mechanical ventilation for intensive care unit patients: A cohort study

2013 ◽  
pp. 184-188 ◽  
Author(s):  
Alvaro Sanabria ◽  
Ximena Gomez ◽  
Valentin Vega ◽  
Luis Carlos Dominguez ◽  
Camilo Osorio
Keyword(s):  
Intensive Care Unit ◽  
Mechanical Ventilation ◽  
Cohort Study ◽  
Intensive Care ◽  
Critically Ill ◽  
Medical Condition ◽  
Prolonged Mechanical Ventilation ◽  
Invasive Mechanical Ventilation ◽  
Adult Patients ◽  
Saps Ii Score

Introduction: There are no established guidelines for selecting patients for early tracheostomy. The aim was to determine the factors that could predict the possibility of intubation longer than 7 days in critically ill adult patients. Methods: This is cohort study made at a general intensive care unit. Patients who required at least 48 hours of mechanical ventilation were included. Data on the clinical and physiologic features were collected for every intubated patient on the third day. Uni- and multivariate statistical analyses were conducted to determine the variables associated with extubation. Results: 163 (62%) were male, and the median age was 59±17 years. Almost one-third (36%) of patients required mechanical ventilation longer than 7 days. The variables strongly associated with prolonged mechanical ventilation were: age (HR 0.97 (95% CI 0.96-0.99); diagnosis of surgical emergency in a patient with a medical condition (HR 3.68 (95% CI 1.62-8.35), diagnosis of surgical condition-non emergency (HR 8.17 (95% CI 2.12-31.3); diagnosis of non-surgical-medical condition (HR 5.26 (95% CI 1.85-14.9); APACHE II (HR 0.91 (95% CI 0.85-0.97) and SAPS II score (HR 1.04 (95% CI 1.00-1.09) The area under ROC curve used for prediction was 0.52. 16% of patients were extubated after day 8 of intubation. Conclusions: It was not possible to predict early extubation in critically ill adult patients with invasive mechanical ventilation with common clinical scales used at the ICU. However, the probability of successfully weaning patients from mechanical ventilation without a tracheostomy is low after the eighth day of intubation.

scholarly journals Clinical review: Helmet and non-invasive mechanical ventilation in critically ill patients

Critical Care ◽  
2013 ◽  
Vol 17 (2) ◽  
pp. 223 ◽  
Author(s):  
Antonio M Esquinas Rodriguez ◽  
Peter J Papadakos ◽  
Michele Carron ◽  
Roberto Cosentini ◽  
Davide Chiumello
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Review ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Invasive Mechanical Ventilation ◽  
Non Invasive

scholarly journals Membrane Binding and Subcellular Localization of Retroviral Gag Proteins Are Differentially Regulated by MA Interactions with Phosphatidylinositol-(4,5)-Bisphosphate and RNA

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Jingga Inlora ◽  
David R. Collins ◽  
Marc E. Trubin ◽  
Ji Yeon J. Chung ◽  
Akira Ono
Keyword(s):  
Virus Assembly ◽  
Membrane Binding ◽  
Endogenous Retrovirus ◽  
Single Amino Acid ◽  
Human Endogenous Retrovirus ◽  
Structural Protein ◽  
Acidic Phospholipid ◽  
Specific Localization ◽  
Hiv 1

ABSTRACTThe matrix (MA) domain of HIV-1 mediates proper Gag localization and membrane binding via interaction with a plasma-membrane (PM)-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2]. HIV-1 MA also interacts with RNA, which prevents Gag from binding to membranes containing phosphatidylserine, a prevalent cellular acidic phospholipid. These results suggest that the MA-bound RNA promotes PM-specific localization of HIV-1 Gag by blocking nonspecific interactions with cellular membranes that do not contain PI(4,5)P2. To examine whether PI(4,5)P2dependence and RNA-mediated inhibition collectively determine MA phenotypes across a broad range of retroviruses and elucidate the significance of their interrelationships, we compared a panel of Gag-leucine zipper constructs (GagLZ) containing MA of different retroviruses. We found thatin vitromembrane binding of GagLZ via HIV-1 MA and Rous sarcoma virus (RSV) MA is both PI(4,5)P2dependent and susceptible to RNA-mediated inhibition. The PM-specific localization and virus-like particle (VLP) release of these GagLZ proteins are severely impaired by overexpression of a PI(4,5)P2-depleting enzyme, polyphosphoinositide 5-phosphatase IV (5ptaseIV). In contrast, membrane binding of GagLZ constructs that contain human T-lymphotropic virus type 1 (HTLV-1) MA, murine leukemia virus (MLV) MA, and human endogenous retrovirus K (HERV-K) MA is PI(4,5)P2independent and not blocked by RNA. The PM localization and VLP release of these GagLZ chimeras were much less sensitive to 5ptaseIV expression. Notably, single amino acid substitutions that confer a large basic patch rendered HTLV-1 MA susceptible to the RNA-mediated block, suggesting that RNA readily blocks MA containing a large basic patch, such as HIV-1 and RSV MA. Further analyses of these MA mutants suggest a possibility that HIV-1 and RSV MA acquired PI(4,5)P2dependence to alleviate the membrane binding block imposed by RNA.IMPORTANCEMA basic residues in the HIV-1 structural protein Gag interact with phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] and RNA. RNA inhibits HIV-1 MA binding to non-PI(4,5)P2acidic lipids. This inhibition may promote PM specificity of Gag membrane binding, an early essential step in virus assembly. However, whether and how relationships between these interactions have developed among retroviruses are poorly understood. In this study, by comparing diverse retroviral MA domains, we elucidated a strong correlation among PI(4,5)P2dependence, susceptibility to RNA-mediated inhibition, and cellular behaviors of Gag. Mutagenesis analyses suggest that a large basic patch on MA is sufficient to confer susceptibility to RNA-mediated inhibition but not for PI(4,5)P2-dependent membrane binding. Our findings highlight RNA’s role as a general blocker of large basic patches and suggest a possibility that some retroviruses, including HIV-1, have evolved to bind PI(4,5)P2, while others have adopted smaller basic patches on their MA domains, to overcome the RNA-mediated restriction of membrane binding.

Predictors of Mortality of Critically Ill Gynecological Patients

2016 ◽  
Vol 8 (2) ◽  
pp. 96-100
Author(s):  
Rahat Qureshi ◽  
Sheikh Irfan Ahmed ◽  
Amir Raza ◽  
Azra Amerjee
Keyword(s):  
Mechanical Ventilation ◽  
Intensive Care ◽  
Critically Ill ◽  
Gynecological Cancer ◽  
Invasive Mechanical Ventilation ◽  
Central Line ◽  
University Hospital ◽  
Arterial Line ◽  
Predictors Of Mortality ◽  
Line Insertion

ABSTRACT Background Gynecological patients with serious underlying morbidities require admission into intensive care units (ICUs) albeit being few in numbers. Objectives To review gynecological cases with non-pregnancyrelated illness, admitted to ICU with respect to diagnosis, associated risk factors, intervention required, aspects of management, and rate of mortality. Materials and methods Retrospective record view of gynecological patients admitted in the ICU from 2005 to 2014. Setting Aga Khan University Hospital, Karachi. Findings Twenty-six patients were admitted with complications secondary to gynecological indications. The most common reason was pulmonary edema (26.9%); sepsis was documented in 23.1% of all patients. Hemorrhagic shock was found in 11.5% gynecological ICU admissions, cardiogenic shock in 15.4%, and renal failure in 7.7%. Fourteen critically ill women with gynecological cancer were admitted to the ICU (ovarian cancer, n = 8; cervical cancer, n = 1; and endometrial cancer, n = 5). The overall mortality of gynecological patients was 26.92%. The most common interventions were mechanical ventilation (96%) followed by arterial line insertion (88%) and central line insertion (85%). Conclusion Critically ill gynecological patients requiring invasive mechanical ventilation, central hemodynamic monitoring, and invasive arterial pressure monitoring should be admitted to an intensive care unit. How to cite this article Qureshi R, Ahmed SI, Raza A, Amerjee A. Predictors of Mortality of Critically Ill Gynecological Patients. J South Asian Feder Obst Gynae 2016;8(2):96-100.

BCR-ABL-Induced Transcriptional Repression of the Interferon Regulatory Factor 8 (IRF-8/ICSBP) Leads to Depletion of Plasmocytoid Dendritic Cells (PDC), Which May Contribute to Leukemogenesis in a Murine Model of Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 36-36 ◽  
Author(s):  
Sabrina Inselmann ◽  
Simone Liebler ◽  
Cornelia A Brendel ◽  
Steffen Koschmieder ◽  
Andreas Neubauer ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cpg Odn ◽  
Toll Like Receptor ◽  
Rt Pcr ◽  
Healthy Donors ◽  
Functional Relevance

Abstract Abstract 36 Introduction: Chronic myeloid leukemia (CML) is caused by the BCR-ABL oncogene. CML patients lack expression of IRF-8 - an interferon-regulated transcription factor that has been shown to exert tumor suppressor functions. IRF-8 is also critical for the development of a rare dendritic cell population, so called plasmocytoid dendritic cells (PDC). PDC are quantitatively significantly reduced or absent in the peripheral blood of first diagnosis CML patients. PDC are also the major producers of IFN-alpha (IFNa) in man. IFNa is a cytokine that has significant therapeutic efficiency in the treatment of CML patients. We here wished to experimentally test, whether BCR-ABL expression and loss of IRF-8 may be causally linked to a reduction of PDC in murine CML and whether there could be any functional relevance for PDC loss in CML development or treatment. Methods: PDC counts were studied from peripheral blood samples of primary CML patients at diagnosis, at the time of remission or from healthy donors. PDC function was assessed in vitro by treatment of magnetic bead-enriched PDC with Toll-like receptor 9-specific oligos (ODN 2216) and subsequent assessment of the intracellular IFNa expression in stimulated PDC. A supposed link between BCR-ABL expression, IRF-8 repression and loss of PDC counts was studied in vivo using a murine CML transduction-transplantation model (C57/Bl6 mice, 7Gy sub-lethal irradiation for conditioning). Multiparameter flow cytometry and cell sorting were performed to analyze and enrich, BCR-ABL-positive (GFP+) hematopoietic subpopulations and PDC in order to then quantitate their IRF-8 and BCR-ABL transcript level by RT-PCR. In order to also test the functional relevance of PDC during CML leukemogenesis, CML mice were injected intravenously, weekly from day +5 after transplantation with in vitro generated PDC. Mice were simultaneously also s.c.-injected weekly with ODN 2216 to stimulate IFNα secretion in adoptively transferred PDC in vivo. Results: As previously reported, newly diagnosed CML patients displayed a significantly reduced PDC count when compared to healthy donors (p<0.001). Upon remission induction with imatinib, PDC counts restored partially, but to a much lesser extend in patients successfully treated with IFNa therapy. Importantly, albeit significantly reduced in number, BCR-ABL-positive first diagnosis CML PDC seem to be functionally intact: CML and healthy donor PDC produced comparable amounts of IFNa in response to Toll-like receptor 9 -specific CpG ODN 2216 stimulation. This suggested that BCR-ABL may compromise PDC function by quantitative rather than qualitative dysregulation. CML mice developed a fatal, BCR-ABL-positive myeloproliferation within 13 to 29 days with 88% penetrance. Compared to control mice (n=8), CML mice (n=14) showed a 7-fold and 3-fold reduction of the frequency of B220+mPDCA-1+ PDC in bone marrow and spleen, respectively. This was associated with a statistically significant (4-fold) suppression of IRF8 mRNA expression in sorted BCR-ABL(GFP)-positive PDC relative to BCR-ABL-negative PDC from the same mice (n=3) or from control transplantations (n=5). By RT-PCR, there was a trend also for lower IRF8 expression in CML progenitor cells (Lin− c-Kit+ Sca-1- GFP+), but not in the stem cell enriching population (Lin− c-Kit+ Sca-1+ GFP+). This implied that IRF8 expression is lost during BCR-ABL-induced leukemogenesis in more mature compartments, which supposedly include PDC precursors. Intriguingly, a once weekly adoptive transfer of in vitro generated (to > 30% enriched) PDC for three successive weeks combined with a once weekly subcutaneous injection of CpG ODN 2216 for three weeks was sufficient to almost double survival of CML mice. Conclusions: Using a murine model of CML, we provide first experimental evidence that BCR-ABL induced myeloproliferation is causally linked to a quantitative suppression of PDC, and that this is associated with a BCR-ABL-mediated suppression of IRF8 transcription. Since adoptively transferred PDC were capable of counteracting murine CML development, BCR-ABL may facilitate leukemogenesis in part by obstructing PDC maturation. PDC could thus be a novel immunological effector cell population that exerts and/or integrates anti-leukemic immune responses in CML. Disclosures: No relevant conflicts of interest to declare.

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