cord-000072-2ygb80sc	2009	All three functions are involved in MODS, in which ECs are shed, blood flow regulation is hampered, vessels become leaky, cells migrate out of the vessel and into the surrounding tissue, and coagulation and inflammation pathways are activated [16] . The Ang/Tie system, which was discovered after vascular endothelial growth factor (VEGF) and its receptors, is mainly restricted to EC regulation and is the focus of this review. In sepsis, VEGF and its soluble receptor sFLT-1 (soluble VEGFR-1) are also increased in a disease severity-dependent manner [40] [41] [42] .The picture that emerges from these studies is that the Ang/Tie signalling system appears to play a crucial role in the symptoms of MODS. Ang-2 acts as an antagonist of Ang-1, stops Tie2 signalling, and sensitizes endothelium to inflammatory mediators (for example, tumour necrosis factor-α) or facilitates vascular endothelial growth factor-induced angiogenesis. Hypoxia and vascular endothelial growth factor acutely up-regulate angiopoietin-1 and Tie2 mRNA in bovine retinal pericytes
cord-000086-bnkbwh3w	2009	RSV LRTD is pathophysiologically characterized by sloughed necrotic epithelium, excessive mucus secretion, bronchial mucosal oedema and peribronchial inflammation that contributes to airway obstruction resulting in increased airway resistance with subsequent air-ANOVA: analysis of variance; ARDS: acute respiratory distress syndrome; CO 2 : carbon dioxide; Cstat: static compliance; EELV: end-expiratory lung volume; EIT: electrical impedance tomography; ELISA: enzyme-linked immunosorbent assay; ET-CO 2 : end-tidal carbon dioxide; FiO 2 : fraction of inspired oxygen; LRTD: lower respiratory tract disease; MAP: mean airway pressure; MV: mechanical ventilation; OI: oxygenation index; PaCO 2 : partial pressure of arterial carbon dioxide; PaO 2 : partial pressure of arterial oxygen; PEEP: positive end-expiratory pressure; PEFR: peak expiratory flow rate; PICU: paediatric intensive care unit; PIP: positive inspiratory pressure; Ptrach: intratracheal pressure; relative Δ EELV : relative change in end-expiratory lung volume; Rlung: lung resistance; Rrs: respiratory system resistance; RSV: respiratory syncytial virus; SPO 2 : oxygen saturation; V D : dead space; VI: ventilation index; Vte: expiratory tidal volume.
cord-000161-hxjxczyr	2009	Primary influenza pneumonia has a high mortality rate during pandemics, not only in immunocompromised individuals and patients with underlying comorbid conditions, but also in young healthy adults. Pneumonia and the acute respiratory distress syndrome (ARDS) account for the majority of severe morbidity and mortality that accompany pandemic influenza infection [14] . A recent analysis of lung specimens from 77 fatal cases of pandemic H1N1v 2009 infection found a prevalence of concurrent bacterial pneumonia in 29% of these patients [31] . A recent World Health Organization treatment guideline for pharmacological management of 2009 pandemic H1N1v influenza A recommends the consideration of higher doses of oseltamivir (150 mg twice a day) and longer duration of treatment for patients with severe influenza pneumonia or clinical deterioration [44] . The rapid progression from initial typical influenza symptoms to extensive pulmonary involvement, with acute lung injury, can occur both in patients with underlying respiratory or cardiac morbidities and in young healthy adults, especially if obese or pregnant.
cord-000217-chd9ezba	2010	Furthermore, intratracheal treatment of CD14-defi cient mice with sCD14 restored the infl ammatory response to the level present in wildtype mice, whereas treatment with wild-type alveolar macrophages restored the neutrophil infi ltration of the lung but not pulmonary TNF release [26] . Th ese fi ndings indicate that sCD14, and CD14 and TLR4 on the surface of alveolar macrophages contribute to the development of LPS-induced lung infl ammation. In line with the fi ndings that CD14 contributes to LPSinduced lung infl ammation in mice, a number of studies have shown that CD14 is essential for the host defense response in the lung against Gram-negative bacteria, such as nontypeable Haemophilus infl uenzae, a possible cause of community acquired pneumonia, and A. coli-induced pneumonia has not been investigated in mice, whereas the role of the other components of the LPS receptor complex (TLR4, MD-2, MyD88, TRIF) has been determined using gene-defi cient or mutant mice.
cord-000492-ec5qzurk	2011	Plasmid transfer (closed Easily produced at low cost No specifi c cell targeting Electroporation-mediated gene transfer of the dsDNA circles) Very ineffi cient Na + ,K + -ATPase rescues endotoxin-induced lung injury [60] Nonviral DNA complexes Complexes protect DNA Less effi cient than viral vectors Cationic lipid-mediated transfer of the Na + ,K + -(lipoplexes or polyplexes) Modifying transgene DNA to eliminate bacterial motifs [75, 76] Development of high-effi ciency tissue-specifi c promoters [77] [78] [79] [80] Development of promoters that regulate gene expression [83] Enhanced therapeutic targeting Nebulization technologies [9] Strategies to target the pulmonary endothelium [10] Improved cellular uptake of vector Surface active agents to enhance vector spread [84] Reduce ubiquitination of viral capsid proteins [85] Better therapeutic targets Enhancement or restoration of lung epithelial and/or endothelial cell function [86] Strengthening lung defense mechanisms against injury [87] Speeding clearance of infl ammation and infection Enhancement of the repair process following ALI/ARDS [88] .
cord-000498-absjerdt	2010	To and colleagues found higher plasma levels of proinflammatory cytokines and chemokine in the group of patients with acute respiratory distress syndrome (ARDS) caused by viral A(H1N1) influenza, throughout the initial 10 days after symptom onset [8] . The aim of our study was to further investigate the profile of Th1 and Th17 mediators and interferoninductible protein-10 (IP-10), an innate-immunity mediator, as early host response in a group of critical and noncritical hospitalized patients with nvA(H1N1) from Cluj-Napoca, Romania, and to correlate them with the clinical aspects. IL-15 is significantly higher at admission (P1) and 3 days later (P2) in the nvA(H1N1)-ARDS group for nonsurvivors versus survivors, so it might be pathogenic in lung injury influenza A virus infection. An increased level of IP-10 was found in the Spanish group as early response to nvA(H1N1) infection in both hospitalized and mild patient disease, as in the present study, while in the Hong Kong group IP-10 was significantly higher in critical patients only.
cord-000522-d498qj2b	2002	Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced. The interventions discussed encompassed low tidal volume in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) (Edward Abraham), early goal-directed therapy (EGDT) (Emanuel Rivers), drotrecogin alfa (activated) (Gordon Bernard), moderate-dose corticosteroids (Djillali Annane), and tight control of blood sugar (Greet Van den Berghe).
cord-000705-w52dc97h	2011	METHOD: This was a multicenter, prospective inception cohort study including adult patients with acute respiratory failure requiring mechanical ventilation (MV) admitted to 20 ICUs in Argentina between June and September of 2009 during the influenza A (H1N1) pandemic. Although a mild form of the disease was prevalent, it soon became evident that the 2009 influenza A (H1N1) virus could also provoke severe, acute respiratory failure requiring admission to the intensive care unit (ICU) for mechanical ventilation [16] , which was reflected in the severe pathological injury found at autopsy [17] . This was a multicenter, inception cohort study that included patients aged > 15 years admitted to the ICU with a previous history of influenza-like illness, evolving to acute respiratory failure that required mechanical ventilation during the 2009 winter in the Southern Hemisphere. We report on a large, prospective cohort of 2009 influenza A (H1N1) patients that were mechanically ventilated for acute respiratory failure due to diffuse pneumonitis during the pandemic in Argentina.
cord-000891-5r2in1gw	2012	Suspected and unsuspected cases were compared, and significant differences were found for age (53 versus 69 median years), severe respiratory failure (68.8% versus 20%), surgery (6.3% versus 60%), median days of ICU stay before diagnosis (1 versus 4), nosocomial infection (18.8% versus 66.7%), cough (93.8% versus 53.3%), localized infiltrate on chest radiograph (6.3% versus 40%), median days to antiviral treatment (2 versus 9), pneumonia (93.8% versus 53.3%), and acute respiratory distress syndrome (75% versus 26.7%). The variables recorded were age, sex, classification of the severity of underlying conditions according to the Charlson comorbidity index [6] , type of ICU, date and cause of ICU admission, APACHE II score [7] on admission to the ICU, date of onset of influenza symptoms, clinical manifestations and radiologic findings at diagnosis, date of TA sample collection, other samples tested for influenza and result, date of initiation of antiviral treatment, complications (septic shock, acute respiratory distress syndrome (ARDS)), outcome including mortality within 30 days after influenza diagnosis, and length of ICU and hospital stay.
cord-000892-l9862er0	2012	An on-line screening registry allowed a daily report of ICU beds occupancy rate by flu infected patients (Flu-OR) admitted in French ICUs. METHODS: We conducted a prospective inception cohort study with results of an on-line screening registry designed for daily assessment of ICU burden. Here, we report the exact rate of ICU bed occupancy by flu-infected patients (Flu-OR) during the pandemic in a representative subset of French ICUs. The French REVA-SRLF registry was a multi-center prospective observational survey based on a website registry, and several results of this registry have been published elsewhere [13] [14] [15] . Even if ICUs were encouraged to do a daily assessment of the presence of patients with A (H1N1), we chose to report the calculation per week first to be consistent with the French organization and the National Institute for Public Health Surveillance (NIPHS), which displayed the time course of the pandemic weekly, and also to simplify data notification for participating centers.
cord-001293-dfaxj3bv	2014	In response to the failure of therapies aiming to target either the up-stream microbial activators or the effector molecules of the inflammatory cascade, a new concept has emerged of boosting the immune system to counter immunosuppression that develops in patients who survive the initial, hyperinflammatory period of sepsis [1] . One can conjecture that systemic treatment with IL-7 may act in undesired places, as illustrated by the following: IL-7 worsens graft-versus-host-induced tissue inflammation [81] ; favors inflammation in colitis [82] , contributes to arthritis severity [83] ; upregulates chemokines, IFNγ, macrophage recruitment, and lung inflammation [84] ; and, finally, increases production of inflammatory cytokines by monocytes and T cells [85] . Not only are PD-1-deficient mice markedly protected from the lethality of sepsis, accompanied by a decreased bacterial burden and suppressed inflammatory cytokine response [98] , but also blockade of PD-1 or PD-L1 improves survival in a murine model of sepsis, reverses immune dysfunction, inhibits lymphocyte apoptosis, and attenuates organ dysfunction [99] [100] [101] .
cord-001319-mlkaowqr	2013	RESULTS: Serum IgM was decreased in septic shock compared to patients with systemic inflammatory response syndrome (SIRS) and patients with severe sepsis. The current study was designed in order to embed into the changes of circulating IgM levels of patients upon progression to the more severe stages of sepsis in relation with the production of IgM from circulating lymphocytes and with the final outcome. The primary endpoint was the over-time changes of IgM serum levels of patients upon progression to septic shock in relation with the final outcome that is survival or 28-day mortality. The study end point was the kinetics of serum IgM upon progression from severe sepsis to septic shock in relation with final outcome. The time curves of IgM were designed for 30 patients with severe sepsis who progressed into septic shock.
cord-001322-7xmxcm35	2014	Phenotypic data was recorded using a robust clinical database allowing a contemporary analysis of the clinical characteristics, microbiology, outcomes and independent risk factors in patients with severe CAP admitted to ICUs across Europe. A number of more recent, larger studies have focussed on identifying patients with CAP at increased risk of severe sepsis and death, as well as those who may require ventilator or vasopressor support [3, [24] [25] [26] . The aim of the study reported here was to define the clinical characteristics, microbiological aetiology, outcomes and independent risk factors for mortality in a large, contemporary cohort of patients with severe CAP admitted to ICUs across Europe. The British Thoracic Society Research Committee and The Public HealthLaboratory Service: The aetiology, management and outcome of severe community-acquired pneumonia on the intensive care unit A five-year study of severe community-acquired pneumonia with emphasis on prognosis in patients admitted to an intensive care unit
cord-001473-aki28lhp	2014	The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased mortality (53.33% in Ad-shHepc1-treated mice versus 12.5% in Ad-shNeg-treated mice, P <0.05). The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages. These results demonstrated that in the current study the intratracheal administration of Ad-shHepc1 only silenced the hepcidin gene transcription in AECs, which was in accordance with previous studies that adenovirus-mediated intratracheal gene delivery specifically inhibited targeted gene expression in lung epithelial cells but not in alveolar macrophages and other organs [29, 30] . The current study explored the role of AEC-derived hepcidin in polymicrobial sepsis-induced ALI, which is at least partially related to the altered intracellular iron level and function of alveolar macrophages.
cord-001536-ta1i0ata	2014	
cord-001661-dj9bxhwb	2015	title: Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy INTRODUCTION: Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known. A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy. The following data were collected from the hospital chart of each patient and analyzed: age, sex, underlying diseases, acute physiology and chronic health evaluation (APACHE) II score on the day of ICU admission [28] , sequential organ failure assessment (SOFA) score on the day of ICU admission and the day of open lung biopsy [29] , lung injury score (LIS) [30] , PaO 2 /FiO 2 ratio, PEEP, tidal volume, diagnostic procedures before open lung biopsy (HRCT or BAL), complications related to surgery (i.e., postoperative air leak, pneumothorax, subcutaneous emphysema, bleeding, and wound infection), pathological diagnosis, hospital mortality, and therapeutic alterations.
cord-001894-ptuelrqj	2015	Intensive care unit (ICU)-acquired pneumonia (ICUAP) is the leading infection in critically-ill patients, accounting for prolonged mechanical ventilation and length of stay, and poor outcome [1] [2] [3] [4] . Recent investigations have shown that multi-drug-resistant (MDR) or high-risk pathogens have been isolated in around half of patients with an episode of ventilator-associated pneumonia (VAP) or ICUAP confirmed microbiologically [9, 10] . The association between polymicrobial or monomicrobial etiology and patients'' outcomes was adjusted for variables potentially related to mortality, such as age, APACHE-II and SAPS scores at ICU admission, SOFA score, CPIS and arterial partial pressure of oxygen/inspired oxygen fraction (PaO 2 /FiO 2 ) ratio at onset of pneumonia, VAP or NV-ICUAP, and unilateral or bilateral chest x-ray infiltrates.
cord-002240-38aabxh1	2016	The administration of intravenous immunoglobulins seems to reinforce the immune response to the infection in particular in patients with inadequate levels of antibodies and when an enriched IgM preparation has been used; however, more studies are needed to determinate their impact on outcome and to define the population that will receive more benefit. Despite the use of early and appropriate antibiotic treatment, mortality related to community-acquired pneumonia (CAP) is still high [1] , especially in patients with severe disease. In contrast, another meta-analysis [25] demonstrated a reduction in all causes of mortality in patients receiving corticosteroids (12 trials, 1974 In conclusion, all these studies confirm that the use of corticosteroids in CAP is associated with the following benefits: reduced length of hospital stay, reduced time to clinical stability, and prevention of ARDS. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial
cord-003307-snruk3j2	2018	BACKGROUND: Despite modern intensive care with standardized strategies against acute respiratory distress syndrome (ARDS), Pneumocystis pneumonia (PcP) remains a life-threatening disease with a high mortality rate. Based on the high burden of PcP and the likelihood of unfavorable outcome particularly in non-HIV-positive patients, chemoprophylaxis with trimethoprim-sulfame thoxazole (TMP-SMX) is recommended in high-risk populations [13] . We here report comprehensive epidemiological, clinical, laboratory, therapeutic and outcome data on 240 cases of PcP, including a high percentage of non-HIV-positive patients, in a tertiary care center over the last 17 years. For every patient, clinical data on demographic characteristics, underlying disease, status of immune competence, treatment regimens of immunosuppression, PcP therapy regimen and mortality, were gathered in the study database. Outcomes and prognostic factors of non-HIV patients with pneumocystis jirovecii pneumonia and pulmonary CMV co-infection: a retrospective cohort study
cord-003376-2qi4aibx	2018	title: Effect of cytomegalovirus reactivation on the time course of systemic host response biomarkers in previously immunocompetent critically ill patients with sepsis: a matched cohort study Cytomegalovirus (CMV) reactivation is observed in 14-41% of intensive care unit (ICU) patients without known prior immune deficiency [1] [2] [3] and is associated with increased morbidity and mortality [4] [5] [6] . Therefore, this longitudinal study aimed to investigate whether the temporal course of seven host response biomarkers, including both pro-and anti-inflammatory cytokines, in previously immunocompetent ICU patients with sepsis differs between patients with and without CMV reactivation. Time trends of various markers within patients were described by symmetric percentage differences relative to their levels 2 days prior to CMV viremia onset (Fig. 2 for primary comparison, Additional file 1: Figure S1 for secondary comparison). We performed an explorative study to compare time trends of host response biomarkers in patients with reactivation that were matched to non-reactivating control patients who were either seropositive or seronegative for CMV.
cord-003416-c22kw6f4	2019	title: Improvement in the survival rates of extracorporeal membrane oxygenation-supported respiratory failure patients: a multicenter retrospective study in Korean patients Recently, the EOLIA trial reported that in patients with severe acute respiratory distress syndrome (ARDS) there was no significant difference in 60-day mortality between patients who received early ECMO and those who received conventional mechanical ventilation that included ECMO as rescue therapy [6] . Factors associated with mortality in patients supported with ECMO Multiple regression analysis was performed using age, sex, year, APACHE II score, SOFA score, immunocompromised status, CNS dysfunction, corticosteroid, CRRT, prone positioning, nitric oxide, neuromuscular blocker, 1.031, 1.114) ), and prolonged ECMO duration (OR 1.020 (95% CI 1.003, 1.038)) were associated with increased odds of mortality ( Table 4 ). This multicenter study was conducted to evaluate the change in survival rates of patients who received ECMO support for acute respiratory failure in Korea.
cord-003513-hmdikgf5	2019	Risk stratification should take into account the local ecology (prevalence of the pathogen in a specific area) and the patient''s risk factors, especially in cases of severe CAP that are associated with higher mortality rates (20-50%) [1] . baumannii causing CAP, the authors reported that 30% of the isolates were resistant to the majority of the antibiotics; the resistant rates to imipenem and meropenem were 19 and 9%, respectively. baumannii is not a frequent cause of CAP, the capacity to rapidly develop resistance mechanisms to antibiotics and the fulminant clinical presentation (with a mortality rate around 50%) make this pathogen an important health problem, especially in tropical and subtropical areas. Burden and risk factors for pseudomonas aeruginosa community-acquired pneumonia: a multinational point prevalence study of hospitalised patients Risk factors associated with potentially antibiotic-resistant pathogens in community-acquired pneumonia Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia
cord-003532-lcgeingz	2019	It''s proposed to evaluate the association between myocardial injury biomarkers, high-sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-ProBNP), with inflammatory mediators (IL-6, IL-1Β , IL-8, IL-10, IL-12 / IL-23p40, IL17A, IL-21 and TNF-α ) and biomarkers, C protein reactive (CPR) and procalcitonin (PCT), in septic patients Methods: This was a prospective cohort study performed in three intensive care units, from September 2007 to September 2010 enrolling patients with sepsis (infection associated with organ dysfunction), and septic shock (hypotension refractory by fluids infusion requiring vasopressor). Blood samples were collected up to 48h after the development of first organ dysfunction (D0) and on the 7th day after inclusion in the study (D7) Results: Ninety-five patients were enrolled, with median age 64 years (interquatile?48-78), APACHE II: median 19 (14-22), SOFA: median 8 (5-10); 24.2% were admitted in ICU with sepsis and 75.8% with septic shock.
cord-003701-i70ztypg	2019	
cord-003832-q1422ydi	2019	title: Biomarker profiles of coagulopathy and alveolar epithelial injury in acute respiratory distress syndrome with idiopathic/immune-related disease or common direct risk factors This study aimed to investigate the biomarker profiles of coagulopathy and alveolar epithelial injury in two subtypes of ARDS: patients with direct common risk factors (dARDS) and those with idiopathic or immune-related diseases (iARDS), which are classified as "ARDS without common risk factors" based on the Berlin definition. Although no risk factors or causes are identified in this subgroup of ARDS, recent studies have shown that many patients with idiopathic interstitial pneumonia have clinical features that suggest an underlying immune process, indicating that the pathobiology of idiopathic and immunerelated diseases may partially overlap [9, 10] . The aim of this study was to examine the profiles of the plasma biomarkers that reflect coagulopathy and alveolar epithelial injury in patients with idiopathic/immune-related ARDS (iARDS) and in those with common direct risk factors (dARDS).
cord-003870-hr99dwi7	2019	Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. Factors predicted to confer more specific susceptibility to influenza are placed higher in the diagram independently associated with severe disease from either seasonal or pandemic IAV [24] . Susceptibility to severe H1N1 infection was analysed in a recent genome-wide study (integrated with data on genetic variants associated with altered gene expression) which implicated an intronic SNP of GLDC, rs1755609-G [80] . Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age).
cord-003995-53115c1c	2019	
cord-004096-obrq7q57	2020	
cord-004147-9bcq3jnm	2020	title: New-onset atrial fibrillation and associated outcomes and resource use among critically ill adults—a multicenter retrospective cohort study CONCLUSIONS: While NOAF was not associated with death or requiring discharge to long-term care among critically ill patients, it was associated with increased length of stay in ICU and increased total costs. We primarily sought to evaluate the association between NOAF and outcomes, resource utilization, and costs among critically ill adult patients. However, NOAF was associated with higher hospital mortality among ICU patients with suspected infection (aOR 1.21 [95% CI 1.08-1.37]), sepsis (aOR 1.24 [95% CI 1.10-1.39]), and septic shock (aOR 1.28 [95% CI 1.14-1.44]). Among patients with NOAF, factors associated with increased risk of hospital mortality included increasing age, increased MODS score, history of CHF (as identified in the Data Warehouse), and sustained AF (Additional file 5: Table S5 ).
cord-004263-m1ujhhsc	2020	title: The effect of cisatracurium infusion on the energy expenditure of critically ill patients: an observational cohort study METHODS: We studied a cohort of adult critically ill patients requiring invasive mechanical ventilation and treatment with continuous infusion of cisatracurium for at least 12 h. CONCLUSIONS: Our data suggest that continuous infusion of cisatracurium in mechanically ventilated ICU patients is associated with a significant reduction in EE, although the magnitude of the effect is small. Our data suggest that continuous infusion of cisatracurium in mechanically ventilated ICU patients is associated with a significant reduction in EE as estimated by the VCO 2 method, although the magnitude of the effect is small. Validation of carbon dioxide production (VCO2) as a tool to calculate resting energy expenditure (REE) in mechanically ventilated critically ill patients: a retrospective observational study
cord-004268-raayrjmd	2020	title: Real-time shear wave ultrasound elastography: a new tool for the evaluation of diaphragm and limb muscle stiffness in critically ill patients METHODS: Two operators tested in healthy controls and in critically ill patients the intraand inter-operator reliability of the SWE using transversal and longitudinal views of the diaphragm and limb muscles. We therefore designed the present study with the aim of determining the reliability and reproducibility of SWE measurements for limb muscles and the diaphragm in both healthy subjects and in critically ill patients. This study shows that intra-and inter-operator reliability of shear modulus evaluation, a parameter of muscle quality in limb muscles and the diaphragm in both healthy controls and in critically ill patients, is excellent. No study has ever been performed to evaluate shear modulus measurement feasibility and reliability in the critically ill population at high risk of muscle edema.
cord-004299-ydm6j046	2020	title: New-onset atrial fibrillation can be falsely associated with increased length of stay in ICU due to immortal time bias New-onset atrial fibrillation can be falsely associated with increased length of stay in ICU due to immortal time bias Yifang Lu 1 and Tenggao Chen 2* Dear editor, In a recent study published in Critical Care, Fernando SM and colleagues investigated the impact of new-onset atrial fibrillation (NOAF) on clinical outcomes in critically ill patients [1] . The authors would like to thank Drs. Lu and Chen for their comments on our recent article related to outcomes and costs associated with new-onset atrial fibrillation (NOAF) in critically ill adults [1] . Drs. Lu and Chen suggest caution in the interpretation of our study results, particularly as they relate to the length of stay and costs, due to the possibility of immortal time bias.
cord-004327-ofqay81v	2020	We aimed to evaluate the effect of performing rib fixation with the addition of video-assisted thoracoscopic surgery (VATS) on patients with ARF caused by blunt thoracic injury with ventilator dependence. METHODS: This observational study prospectively enrolled patients with multiple bicortical rib fractures with hemothorax caused by severe blunt chest trauma. CONCLUSION: Rib fixation combined with VATS could shorten the length of ventilator use and reduce the pneumonia rate in patients with severe chest blunt injury with ARF. Factors that could affect the ventilator dependence-including consciousness levels, number of fractured ribs, percentage of flail chest, lung contusion scores, AISs, and ISSs-all exhibited no statistically significant differences. In this study, rib fixation with VATS in patients with such severe blunt chest trauma and ARF could greatly decrease the length of ventilator dependence. In contrast with other studies, we performed rib fixation combined with VATS to completely manage chest wall injury, lung laceration, and pleural collections.
cord-004422-oep1grwq	2020	title: Comparison of T-piece and pressure support ventilation as spontaneous breathing trials in critically ill patients: a systematic review and meta-analysis Thus, further research is needed to determine the best approach for SBTs. In this study, we conducted a meta-analysis, which extracted results from published randomized controlled trials (RCTs) to evaluate the effectiveness and safety of two strategies, a T-piece and PSV, for weaning adult patients with respiratory failure that required mechanical ventilation, measuring extubation success and other clinically important outcomes. The inclusion criteria were as follows: (1) randomized controlled trials; (2) adult patients (> 18 years) who underwent at least two different SBT methods; (3) all authors reported our primary outcome of successful extubation rate; (4) clearly comparing PS versus T-piece with clinically relevant secondary outcomes. The major finding of our study suggests that both spontaneous breathing using T-piece and PSV are suitable methods for successful extubation of patients with critical illness from mechanical ventilation.
cord-004427-dy9v9asg	2020	
cord-005495-0mi0n2zn	2020	Depending on the course of disease and concomitant organ dysfunction, some cases of ACS can be managed conservatively whereas some cases of IAH may require immediate aggressive treatment including fast decision to proceed to decompressive laparotomy before reaching the value of 20 mmHg of IAP. Despite this, the optimal treatment choice for a specific patient with IAH/ ACS should take into account three critical elements: (1) the measured IAP value (or the degree/magnitude of IAP increase); (2) organ dysfunction characteristics (or the impact of increased IAP); and (3) nature and course of the underlying disease (Fig. 2 ). Large-volume fluid resuscitation, usually related to systemic inflammatory syndrome and biomediator activation, is one of the most important risk factors for the development of IAH/ ACS, due to its combined effects of increased intra-abdominal volume (both intraand extraluminal due to ascites formation, gut edema, and ileus) and decreased abdominal wall compliance due to tissue edema of the abdominal wall.
cord-005496-cnwg4dnn	2020	
cord-005497-w81ysjf9	2020	The positive NC group had more plasma transfusion (p-value 0.03) and a lower median hematocrit at 24 hrs (p-value 0.013), but similar hospital length of stay (p=0.17) and mortality rate (p=0.80) Conclusions: NC at ICU admission identifies subclinical AKI in TBI patients and it maight be used to predictclinical AKI. In patients with pneumonia requiring intensive care (ICU) admission, we hypothesise that abnormal right ventricular (RV) function is associated with an increased 90-day mortality. The objective of this study was to describe the incidence of each AKI stages as defined by KDIGO definition (with evaluation of urine output, serum creatinine and initiation of renal replacement therapy (RRT)), in a mixed medical and surgical population of patients hospitalized in ICU and PCU over a 10-year period (2008-2018). This study aimed at investigating the relationship of goal-directed energy and protein adequacy on clinical outcomes which includes mortality, intensive care unit(ICU) and hospital length of stay (LOS), and length of mechanical ventilation (LOMV).
cord-005503-hm8tvkt3	2020	Recently, automated infrared pupillometry has been introduced into clinical practice, quickly gaining popularity due to its quantitative precision, low cost, noninvasiveness, bedside applicability, and easy-to-use technology, contributing to a modern precision-oriented approach to medicine. reported that power mode transcranial Doppler had high sensitivity and specificity for diagnosis of brain death, respectively 100% and 98% (flow velocity was assessed in the middle cerebral artery using a transtemporal approach) [32] (Fig. 9 ). Processed EEG was originally intended for the management of the anesthetic state during surgery to avoid accidental awareness and to titrate sedation in critically ill patients where clinical scales represent the gold standard. In addition, clinical scale assessment is performed by disturbing sedated or sleeping patients (processed EEG does not require modification of the sedation state) and can never identify phases of burst suppression or isoelectric traces (total suppression) [39] , which are associated with negative outcomes (e.g., delirium occurrence, prolonged mechanical ventilation, mortality).
cord-007550-2b62zaur	2020	title: Feasibility and safety of watershed detection by contrast-enhanced ultrasound in patients receiving peripheral venoarterial extracorporeal membrane oxygenation: a prospective observational study We assessed the feasibility and safety of contrast-enhanced ultrasound (CEUS) to detect the watershed at the bedside in patients on bifemoral VA ECMO at three ICUs of a European tertiary care facility. The feasibility of CEUS was assessed based on qualitative image evaluation, the amount of contrast media administered, and the rate of bubble detection. In the remaining five patients, contrast-enhanced continuous blood flow was visible throughout the abdominal and thoracic aorta indicating watershed location close to the aortic root. This study assessed the feasibility of CEUS for watershed detection at the bedside in patients on bifemoral VA ECMO. In bifemoral VA ECMO, CEUS may help to identify patients at risk for differential hypoxia, given that left radial arterial pulsatility was present in all study patients, including those in whom the watershed was located near the aortic root.
cord-009274-32adi3hb	2020	
cord-010055-exi8t6jt	2020	title: Whether the GFR measured by renal scintigraphy under non-steady state conditions for critically ill patients with AKI can be used as a predictive parameter for clinical events Whether the GFR measured by renal scintigraphy under non-steady state conditions for critically ill patients with AKI can be used as a predictive parameter for clinical events Guang-wen Zhu 1* , Zhou Gao 2 , Abdoul Rachid 3 Whether the GFR measured by renal scintigraphy under non-steady state conditions for critically ill patients with AKI can be used as a predictive parameter for clinical events Dear Editor: To analyze kidney function in the acute setting, recently, our team completed a special renal scintigraphy for a critically ill patient with the only venous access site-PICC. A dynamic renal scintigraphy of 99mTc-DTPA was performed by PICC in this critical patient with AKI and artificially assisted ventilation.
cord-010697-0eutz8xy	2020	Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. The interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology providing respiratory and circulatory support in patients with refractory cardiogenic shock or cardiac arrest [1] and which may give time to plan future therapeutic decisions such as the insertion of long-term cardiac assist devices or heart transplantation (HTX) [2] . Alveolar edema and decreased pulmonary artery perfusion lead to lung parenchymal ischemia which in turn maintains chronic inflammation and promotes neoangiogenesis and fibrosis generation and polymorphonuclear cells (PMNs), and triggers the intrinsic coagulation cascade, resulting in the rapid generation of thrombin and fibrin within the systemic circulation [13] .
cord-014464-m5n250r2	2013	Results In preliminary analysis of categorical data, a signifi cantly (Fisher exact test) greater proportion of patients with compared with without the following fi ndings did not survive; history of alcohol use (P = 0.05); the presence of lethargy (P = 0.01), confusion (P = 0.03), nausea (P = 0.04), abdominal pain (P = 0.02), or the need for vasopressors (P = 0.002), oxygen, mechanical ventilation, or steroids (all P = 0.004) at presentation; and excessive bleeding at surgery (P = 0.01). Methods To prospectively re-evaluate the normal range and to analyze the potential impact of biometric data on ICG-PDR, we measured ICG-PDR (i.v. injection of 0.25 mg/kg ICG; LiMON, Pulsion, Munich, Introduction Mixed venous oxygen saturation (SVO 2 ) represents a well-recognized parameter of oxygen delivery (DO 2 )-consumption (VO 2 ) mismatch and its use has been advocated in critically ill patients in order to guide hemodynamic resuscitation [1] and oxygen delivery optimization.
cord-027526-ohcu28rk	2020	
cord-028337-md9om47x	2020	Patients with ARDS more often had pulmonary dysfunction as the primary cause of death (28% vs 19%; p = 0.04) and were also more likely to die while requiring significant respiratory support (82% vs 64%; p < 0.01). Specifically, two critical-care trained physicians reviewed each AHRF hospitalization to determine whether patients met Berlin Criteria [15, 16] for ARDS: (1) new or worsening respiratory symptoms began within 1 week of a known clinical insult, (2) PaO 2 /FIO 2 ≤ 300 while receiving a positive end-expiratory pressure ≥ 5 cm H 2 O, (3) bilateral opacities on chest x-ray, (4) unlikely to be cardiogenic pulmonary edema, and (5) no other explanation for these findings. In this contemporary cohort study of 385 patients who died after AHRF, the most common primary causes of death were sepsis and pulmonary dysfunction.
cord-028835-jby1btv7	2020	BACKGROUND: Prone positioning (PP) has shown to improve survival in patients with severe acute respiratory distress syndrome (ARDS). To this point, it is unclear if PP is also beneficial for ARDS patients treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) support. METHODS: We report retrospective data of a single-centre registry of patients with severe ARDS requiring VV ECMO support between October 2010 and May 2018. CONCLUSION: In this propensity score matched cohort of severe ARDS patients requiring VV ECMO support, prone positioning at any time was not associated with improved weaning or survival. In case of severe acute respiratory distress syndrome (ARDS), veno-venous extracorporeal membrane oxygenation (VV ECMO) support may be considered when lung-protective mechanical ventilation is not able to prevent hypoxia or hypercapnia [1] [2] [3] . We performed a retrospective analysis of ARDS patients treated with PP during ECMO support at our centre.
cord-029183-3aotgq6m	2020	We evaluated the relevance of a new syndromic rapid multiplex PCR test (rm-PCR) on respiratory samples to guide empirical antimicrobial therapy in adult patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-acquired pneumonia (VAP). CONCLUSIONS: Use of a syndromic rm-PCR test has the potential to reduce unnecessary antimicrobial exposure and increase the appropriateness of empirical antibiotic therapy in adult patients with pneumonia. Therefore, in pneumonia patients, international guidelines state that an attempt should be made to obtain respiratory samples and recommend to start early empirical treatment while awaiting for the results of culture and antimicrobial susceptibility testing (AST) [3] . The BioFire® FilmArray® Pneumonia Panel (bioMerieux S.A., Marcy-l''Etoile, France) is a novel assay able to simultaneously identify 27 of the most common pathogens involved in lower respiratory tract infections (semi-quantitative results for 11 Gram-negative and 4 Gram-positive bacteria, qualitative results for 3 atypical bacteria and 9 viruses) as well as 7 antibiotic resistance genes (Fig. 1) .
cord-029516-tj93wo1s	2020	METHODS: A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO(2)) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). In a prospective study on 16 ICU patients undergoing MV, 668 nursing procedures were observed and blood oxygen desaturation ≤ 90% was the most frequent adverse event described, representing 29% of the overall major physiological changes reported by the authors [10] . Our study suggests AV may have a protective effect when compared to CV in terms of SpO 2 values and the incidence and severity of blood oxygen desaturation during DNPs. A prospective randomized controlled study of 60 post-cardiac surgery patients showed that in comparison to CV, INTELLiVENT-ASV® significantly reduces MV duration before inclusion-days 4 ± 4 (4-5)
cord-029991-0sy417j0	2020	BACKGROUND: Besides airway suctioning, patients undergoing invasive mechanical ventilation (iMV) benefit of different combinations of chest physiotherapy techniques, to improve mucus removal. The presence of an endotracheal tube impairs the bronchial mucus velocity transport in anaesthetized dogs [2] ; in critically ill patients undergoing invasive mechanical ventilation (iMV), it seriously impairs cough reflex and mucociliary escalator function [3, 4] , promoting the accumulation of tracheobronchial secretions, leading to sequestration and densification of secretions in the lower airways and increasing the risk of pneumonia [5] and lung atelectasis [6] . The aim of this pilot randomized physiological study is assessing the effects of HFCWO on lung aeration and ventilation distribution, as assessed by EIT, in normosecretive and hypersecretive mechanically ventilated patients. Our study shows that chest physiotherapy by HFCWO may improve lung aeration of hypersecretive mechanically ventilated patients, without affecting gas exchange.
cord-030131-klhg7x8z	2020	
cord-030277-x9zvx3fp	2020	title: Effect of dexmedetomidine on inflammation in patients with sepsis requiring mechanical ventilation: a sub-analysis of a multicenter randomized clinical trial We explored the effects of administering dexmedetomidine on the levels of C-reactive protein (CRP) and procalcitonin, and thus on inflammation, in patients with sepsis enrolled in a randomized clinical trial. METHODS: The DESIRE trial was a multicenter randomized clinical trial in which adult patients with sepsis were sedated with (DEX group) or without (non-DEX group) dexmedetomidine while on mechanical ventilators. We analyzed data derived from a randomized clinical trial and found that the administration of dexmedetomidine to patients with sepsis on ventilators improved CRP and PCT levels during the first 14 days in the ICU. In the present study, the use of dexmedetomidine for sedation reduced both CRP and PCT levels in patients with sepsis. Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis: a randomized clinical trial
cord-030677-t94cu81n	2020	We sought to determine the relationship between mean arterial pressure (MAP) and mortality in the cardiac intensive care unit (CICU) patients with CS. By contrast, a recent multicenter randomized controlled trial of patients 65 years and older who were admitted to the ICU with septic shock demonstrated that permissive hypotension (MAP 60-65 mmHg) reduced vasopressor exposure without increasing the risk of mortality or AKI (including patients with and without hypertension) [9] . Hospital mortality and incidence of severe acute kidney injury (AKI) as a function of the 24-hour average mean arterial pressure (mMAP 24 ), among patients with (A) and without (B) cardiac arrest. Hospital mortality and incidence of severe acute kidney injury (AKI) as a function of the 24-hour average mean arterial pressure (mMAP 24 ), among patients with (A) and without (B) a pre-admission diagnosis of hypertension.
cord-031033-v4yetn4f	2020	
cord-034948-w59wxu8i	2020	We conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the cuff leak test for predicting post-extubation airway complications in intubated adult patients in critical care settings. We included studies that examined the diagnostic accuracy of cuff leak test if post-extubation airway obstruction after extubation or reintubation was explicitly reported as the reference standard. Subgroup analyses suggested that the type of cuff leak test and length of intubation might be the cause of statistical heterogeneity of sensitivity and specificity, respectively, for post-extubation airway obstruction. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of the cuff leak test for predicting post-extubation airway obstruction and subsequent reintubation. We included observational studies (cross-sectional and cohort studies) that examined the diagnostic accuracy of cuff leak test in critical care settings if: (1) the data were extractable into a 2 × 2 table from the reported data, (2) post-extubation airway obstruction after extubation or reintubation was explicitly reported as the reference standard.
cord-048199-5yhe786e	2001	Although many questions remain, many laboratory and clinical studies, including a recent randomized controlled trial (RCT), have established that transfusing to normal haemoglobin concentrations does not improve organ failure and mortality in the critically ill patient. Clinical evidence is also insufficient to definitively establish a correlation between the age of RBCs being transfused and patient mortality; however, laboratory evidence has shown many storage-related changes that may result in impairment of blood flow and oxygen delivery at the microcirculatory level. RBC transfusions in particular improved outcome in critically ill patients with cardiovascular disease, but increased the risk of myocardial infarction in coronary artery bypass surgery patients. However, two recent cohort studies suggested that anaemia may increase the risk of mortality in critical illness [73] and following surgery in patients with cardiovascular disease [74] . Although many questions remain, the TRICC trial and many laboratory and clinical studies have established that transfusing to normal haemoglobin concentrations does not improve organ failure and mortality in the critically ill patient.
cord-048343-nzk8m912	2006	
cord-048447-chz8luni	2007	
cord-048448-kfwbqp4p	2007	
cord-048449-mzn448zk	2007	Contingency planning should, therefore, be multi-faceted, involving a robust health command structure, the facility to expand critical care provision in terms of space, equipment and staff and cohorting of affected patients in the early stages. Properly constructed plans for the delivery of critical care during an influenza pandemic must include the ability to deal with excessive demand, high and possibly extreme mortality, and the risk to the health of critical care staff. A number of intensive care scoring systems have demonstrated their power in using physiological derangement to predict mortality or higher resource requirements, whatever the presenting diagnosis [45] [46] [47] [48] [49] . Physiological scores have also been demonstrated to be good predictors of requirement for higher level care on hospital wards [50] , in medical assessment units [51, 52] and in the Emergency Department [53] .
cord-104180-f3hoz9bu	2003	They looked at end-organ epithelial cell apoptosis in a rabbit model of ARDS and at the effects of plasma on epithelial cells from recipients of the injurious ventilatory strategy, and analyzed samples from a previous trial into lung protective ventilation [8] . Choosing the right ventilation strategy for ARDS patients has more benefits than just lung protection, and therapeutic targeting of these factors that induce end organ apoptosis may be the next step. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study
cord-252473-i4pmux28	2004	It could be argued that visitation restrictions, in light of a potential outbreak of a contagious disease, are ethically sound because of the compelling need to protect public health. In a health care institution, visitation restrictions not only affect inpatients but also have an impact on ambulatory patients who must come for diagnostic tests or interventions and who, if deprived access, might develop urgent or emergent conditions. Furthermore, to be consistent with expectations of transparency, the criteria by which exceptionality to the rules of visitation restriction exists should also be published openly throughout the organization for staff, patients and visitors. For example, although current policy allows for specific times of visitation and numbers of visitors per day, a sudden outbreak might dictate a quick lockdown of the facility without patients or family members receiving prior notice. It is ethical to accept that public health protection trumps individual rights to liberal visitation.
cord-252890-of29g89s	2020	A plea for avoiding systematic intubation in severely hypoxemic patients with COVID-19-associated respiratory failure Eduardo Villarreal-Fernandez 1 , Ravi Patel 1 , Reshma Golamari 2 , Muhammad Khalid 2 , Ami DeWaters 2 and Philippe Haouzi 1* Indeed, since a profound hypoxemia appears to be the hallmark of COVID-19-associated pneumonia, the initial consensus [2] was to start invasive mechanical ventilation as soon as possible due to the overwhelming number of patients in respiratory failure presenting at the same time in a hospital and to prevent the risk of hypoxic cardiac arrest; (2) avoidance of high-flow nasal cannula (HFNC) to reduce respiratory droplet aerosolization for healthcare workers [3] in what was seen as "inevitable" intubations. After an initial increase in oxygen requirement through day 6, patients in this group were all able to be discharged at a time when most of the early-intubated patients were still mechanically ventilated (Fig. 1) .
cord-253006-r2a2ozrc	2020	title: Duration of SARS-CoV-2 viral RNA in asymptomatic carriers Notably, patient 2 carried SARS-CoV-2 viral for 32 days continuously after exposure to COVID-19 and tested positive for viral RNA in the respiratory sample for 13 days after first positive test onset. The results indicate that asymptomatic human can carry SARS-CoV-2 viral RNA after exposure to COVID-19, and the carriage seems long-lived. Further study is needed to determine the potential for and mode of contagion of asymptomatic carriers to develop more scientific control strategies. The long duration of asymptomatic infection with SARS-CoV-2 may warrant a reassessment of quarantine as the current outbreak. The US Centers for Disease Control and Prevention recommends that contacts of asymptomatic carriers self-isolate for 14 days [4] . Quarantine of asymptomatic carriers and identification of contacts are a crucial part of these control efforts. There is a great need for further studies on the mechanism by which asymptomatic carriers could acquire and carry SARS-CoV-2 that causes COVID-19.
cord-254287-8q2gdy5n	2020	Respondents (median 45 years [IQR, 39-53], 34% women) were from Middle Europe (25%), South Europe (23%), the United Kingdom (UK) (12%), South America (9%), North Europe (8.1%), Eastern Europe (5.3%), Middle-East (5%), North America (4.7%), Asia (3.3%), India (2.7%), Australia-New Zealand (1.3%), or Africa (0.6%); 54% were living in a large city (> 1 million inhabitants), and 55% were working in university-affiliated hospitals. For instance, prone positioning was performed in 70-85% of the cases in Asia, India, Eastern Europe, Middle Europe, South America, South Europe, and the UK, whereas Africa, Australia-New Zealand, Middle East, North America, and Scandinavia were in the 50-70% range (Fig. 3, P < 0 Antibiotic prescribing was routine for all patients in 44.2% of the respondents and biomarker-guided in 36.5%, without significant variation across regions. This survey highlights important practice variations in the management of severe COVID-19 patients, including differences at regional and individual levels.
cord-255216-87ursh0s	2010	This is the first work reporting the association of a pro-inflamatory immune response with a severe pandemic infection, although it is likely that more studies are needed to understand the detrimental or beneficial roles these cytokines play in the evolution of mild and severe nvH1N1 infection. By analyzing 29 cytokines and chemokines and the hemagglutination inhibition activity, Bermejo-Martin and colleagues [1] assessed the early host innate and adaptive immune responses in patients both mildly and severely infected with nvH1N1. The great majority of infections caused by the pandemic variant of the infl uenza virus (nvH1N1) are self-limited, but a small percentage of patients develop severe symptoms requiring hospitalization. This is the fi rst work reporting the association of a pro-infl amatory immune response with a severe pandemic infection, although it is likely that more studies are needed to understand the detrimental or benefi cial roles these cytokines play in the evolution of mild and severe nvH1N1 infection.
cord-256237-xiv9vxdp	2005	
cord-257361-7q0vbvvd	2020	In May 2020, Médecins Sans Frontières/Doctors Without Borders (MSF) opened three COVID-19 treatment centres (CTC) in Sanaa and Aden, Yemen [1] . MSF''s three CTCs included wards and ICUs. Invasive mechanical ventilation (IMV) received global attention but is only the visible "tip of the iceberg" for COVID-19 care. Each ICU had contextspecific resource constraints resulting in differences in the package of care related to equipment (ultrasound), investigations (laboratory, x-ray), oxygen supply, nutrition, medications, and staff (specialist doctors, nurses, physiotherapists, social workers, pharmacists, logisticians). Prone positioning had never been performed locally, but successfully taught in all 3 ICUs. Teaching critical care concepts within a few days (which typically take years of training) was challenging enough, but further complexity was added by simultaneously managing patients with a new disease, where medical knowledge of COVID-19 was evolving daily.
cord-258087-93yfs7ve	2008	CONCLUSIONS: Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI. This quality assessment of genetic association studies with positive findings in susceptibility or outcome of ALI and ARDS identified a total of 29 articles and 16 genes. ACE, angiotensin-converting enzyme; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; CAP, community-acquired pneumonia; CXCL2, chemokine CXC motif ligand 2; F5, coagulation factor V; IL-6, interleukin-6; IL-10, interleukin-10; MBL2, mannose-binding lectin-2; MIF, macrophage migration inhibitory factor; MV, mechanical ventilation; MYLK, myosin light-chain kinase; NFKB1, nuclear factor kappa light polypeptide gene enhancer in B cells; NFKBIA, nuclear factor kappa light polypeptide gene enhancer in B cells inhibitor alpha; NRF2, nuclear factor erythroid-derived 2 factor; PBEF, pre-B cell-enhancing factor; PLAU, plasminogen activator urokinase; SARS, severe acute respiratory syndrome; SFTPB, surfactant pulmonaryassociated protein B; SIRS, systemic inflammatory response syndrome; SNP, single-nucleotide polymorphism; TNF, tumor necrosis factor; TR, tandem repeat (polymorphism); VEGF, vascular endothelial growth factor. Positive genetic association studies with acute lung injury/acute respiratory distress syndrome susceptibility and/or outcome (by year of publication)
cord-259747-sl9q63oc	2020	
cord-260069-v5qvqxgy	2020	title: Practice of novel method of bedside postpyloric tube placement in patients with coronavirus disease 2019 Practice of novel method of bedside postpyloric tube placement in patients with coronavirus disease 2019 Shou-Tao Yuan 1,2 , Wen-Hao Zhang 1,2 , Lei Zou 1,2 , Jia-Kui Sun 1,2* , Ying Liu 1,2 and Qian-Kun Shi 1, 2 During our clinical work against the epidemic of coronavirus disease 2019 (COVID-19) in Wuhan [1] , we observed a high incidence of malnutrition in critically ill patients (data unpublished). Third, the guide wire is shorter in length compared with the tube; therefore, the rigid tip could not damage the digestive tract during our placing procedure There have been three patients who received our novel method of postpyloric tube placement. Considering the less expensive tube and high success rate, our novel blind bedside postpyloric placement may be easier to perform in patients with COVID-19 worldwide. A novel method of blind bedside placement of postpyloric tubes
cord-260215-gsnjlhjd	2016	
cord-260822-4bselbkq	2020	Unconventional approaches to mechanical ventilation-step-by-step through the COVID-19 crisis Christopher Lotz , Quirin Notz, Peter Kranke, Markus Kredel and Patrick Meybohm * Health care systems around the world face extreme challenges during the pandemic of SARS-CoV-2. ICU ventilators provide the highest performance, fast responding efficient triggering mechanisms, and often a plethora of different ventilation modes to best suit the individual patient. There is also a case study reporting a oneventilator technique during air medical transport of twin newborns [5] and an article that pressure controlled ventilation was simultaneously achieved in two healthy volunteers via mask ventilation [6] . It is of further importance to emphasize that in case of ICU ventilator shortage, the allocation of the ventilators to each patient requires triage. In case of ICU ventilator shortage, this resource can and should be primarily used with a clear conscience in ARDS patients (Fig. 1) . Use of a single ventilator to support 4 patients: laboratory evaluation of a limited concept
cord-262489-cecg3geg	2020	We would like to point out that another phenotype is often presented in COVID-19-associated moderate to severe ARDS, based on our observation and discussions with colleagues treating these patients. Different from the phenotypes described in [1] , the COVID-19 patients we encountered had rather low compliance and their lungs were non-recruitable, despite of large amount of non-aerated tissue. When assessing the lung recruitability with either the bedside estimates suggested in [2] , or with electrical impedance tomography (EIT) [3, 4] , we found that instead of recruiting non-aerated lung tissue, increasing PEEP to around 15 cmH 2 O rather induced overdistension in previously ventilated regions. Lung recruitment in patients with the acute respiratory distress syndrome Lung recruitability in SARS-CoV-2 associated acute respiratory distress syndrome: a single-center, observational study The authors equally contributed to the idea presented in the manuscript, which is derived from the observation of numerous COVID-19 patients treated in the intensive care.
cord-263346-pu1jci26	2020	Abnormal findings include (1) hyperdynamic cardiac function, presented as the increase of cardiac output (CO) and ejection faction (EF) of the left ventricular (LV), with/without the decrease of peripheral vascular resistance, which is often seen in the early stage following the systemic inflammatory response; (2) acute stress-induced (takotsubo) cardiomyopathy, characterized as LV segmental contraction abnormalities and apical ballooning [1] ; (3) right ventricular (RV) enlargement and acute pulmonary hypertension, which are mainly caused by "internal factors" (including alveolar and pulmonary capillary damage caused by inflammation, hypoxia, and hypercapnia, leading to the increase of RV afterload) and "external factors" (including fluid overload, which causes the increase of RV preload, and unsuitable mechanical ventilation parameter setting, which affects the cardiac function by cardiopulmonary interaction); further, LV function will be affected because the right and left hearts are in the same pericardium; and (4) diffuse myocardial inhibition in the late stage, which is often caused by severe hypoxia, and long term of anoxia and inflammation.
cord-263568-ea3k2i69	2020	title: Could the severity of COVID-19 be increased by low gastric acidity? Could the severity of COVID-19 be increased by low gastric acidity? Could low gastric acidity increase the risk of a severe COVID-19 illness? Although it is primarily a respiratory infection, gastrointestinal involvement from swallowed coronaviruses is reported for SARS-CoV-2 (the virus of COVID-19 [1, 2] ), as well as SARS-CoV-1 [3] and MERS-CoV viruses [4] . As well as protection related to immunological factors and possible differences in the ACE2 receptor concentrations in their lungs, children (other than infants) generally have good levels of gastric acid. To determine whether gastric acid gives some protection from COVID-19, the amount of antacids and acid-reducing drugs used by patients with severe infections could be compared with the amount used by patients with mild or no disease. If there is evidence for some protection by gastric acidity, stopping antacids and acid-reducing medications could be considered, particularly at times when patients are at increased risk.
cord-265022-p5cab562	2020	
cord-267348-bkirv9pt	2020	title: Above and beyond: biofilm and the ongoing search for strategies to reduce ventilator-associated pneumonia (VAP) [1] that compared biofilm formation on three endotracheal tube (ETT) types with the finding that biofilm formation was reduced in silicone and noble-metal coated ETTs compared to uncoated ETTs. Their findings have significant implications during the current pandemic given the prolonged intubation times of COVID-19 patients and many develop superimposed pneumonias during their hospital course. It is intriguing that simply changing the ETT''s coating may have significant implications in this patient population with already limited pulmonary reserve that is unable to tolerate additional insults to their lung from a ventilator-associated pneumonia (VAP). However, given the prolonged intubation times of COVID-19 patients, it is likely that the ETT biofilm burden will be substantial no matter which surface coating is utilized. It is widely accepted that two mechanisms lead to VAP: aspiration of oral-gastric contents and microbial biofilm development on the ETT.
cord-267942-ykl2xy7y	2020	We have developed a modified shared ventilator design that allows for individualization of tidal volumes and driving pressures, positive end-expiratory pressure (PEEP), and inspired oxygen fraction (FiO 2 ) [6] , which can thus substantially individualize the delivered breaths, removing the need of pairing (see Fig. 1 ). We have now successfully used this ventilator setup in an in vivo model in a pair of ventilated sheep with different lung compliance, further supporting the potential of this shared ventilator setup as a lifesaving intervention in a crisis setting. We demonstrated the potential to modulate delivered tidal volumes and pressures, PEEP and FiO 2 in a shared ventilator setup in this in vivo model. This setup has allowed to safely ventilate a pair of animals with different lung compliance with a single ventilator, while monitoring and adjusting individual airway pressures and tidal volumes.
cord-270298-zv0t3d0m	2006	Health-care-associated pneumonia (HCAP) refers to a pulmonary infection that develops in individuals recently hospitalised, or undergoing renal replacement therapy or other long-term out-patient care. However, no study had looked at the pathogens of both HCAP and community-acquired pneumonia (CAP) and compared them with those of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The study defined 4,543 positive pneumonias, of which 2,221 were CAP, 988 HCAP, 853 HAP and 499 VAP. The authors suggest that HCAP is a distinct entity from CAP and should be treated as a hospital-acquired type of infection from first presentation; the paper certainly supports the recently published guidelines from the American Thoracic Society [2] . The authors suggest that mitochondrial DNA haplotyping offers a new means of risk stratification in severe sepsis, although further work is clearly needed to identify possible therapeutic avenues.
cord-271751-46oo9xv5	2020	Chloroquine and hydroxychloroquine seem effective in killing SARS-CoV in vitro [1, 3] . Recent reports show it also may be effective at killing SARS-CoV-2-infected cells in vitro [4] . To date, no pre-clinical studies have evaluated the efficacy of hydroxychloroquine in the current SARS-CoV-2 pandemic. A recent article published in Chinese found no benefit with chloroquine in a 1:1 randomized trial with 30 patients [6] . Until data from randomized controlled trials are available, we suggest caution utilizing hydroxychloroquine off label for patients with COVID-19. There are currently no evidence supporting hydroxychloroquine as prophylaxis, but unfortunately these data are being extrapolated to the indication potentially resulting in drug shortages for patients with rheumatic diseases who require this medication. Preliminary study of hydroxychloroquine sulfate in treating common coronavirus disease (COVID-19) patients in 2019 Hydroxychloroquine and azithromycin as a treatment of COVID-19: preliminary results of an open-label nonrandomized clinical trial
cord-275012-fkawgh0e	2020	title: Inhaled nitric oxide in patients admitted to intensive care unit with COVID-19 pneumonia Only 4 (25%) patients were responders, of whom 3 iNO is a free radical gas that diffuses across the alveolar-capillary membrane into the subjacent smooth muscle of pulmonary vessels enhancing endotheliumdependent vasorelaxation and improving oxygenation by increasing blood flow to ventilated lung units [3] . Overall, iNO did not improve oxygenation in COVID-19 patients with refractory hypoxaemia, when administered as a rescue treatment after prone position. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.Ethics approval and consent to participate Informed consent was collected following the ad hoc procedures defined by the local Ethics Committee of Fondazione Policlinico San Matteo IRCCS for the COVID-19 pandemic.Competing interests FM received fees for lectures from GE Healthcare, Hamilton Medical, SEDA SpA, outside the present work.
cord-275154-vwnpred5	2009	
cord-276561-b4cspbuf	2020	
cord-276856-88d3vzbs	2020	title: Single ventilator for multiple patients during COVID19 surge: matching and balancing patients With a potential COVID19-induced ventilator shortage, supporting multiple patients on a single ventilator seems a simple solution to maximize resources. Beyond cross-contamination and increased dead space, matching patients to ensure appropriate individual ventilation peak pressures (P peak ), tidal volumes (V tidal ), and positive endexpiratory pressures (PEEP) is a concern, especially given the dynamic clinical presentation of the COVID19 patients with complicated acute respiratory distress syndrome (ARDS). One-way valves on both inspiratory and expiratory limbs ensured unidirectional flow, which both reduces functional dead space and the risk of crosscontamination between patient A and B, and seemingly also facilitated stable ventilation of B as A deteriorated. Finally, each class of ventilators requires a specific set up; if the method is considered, use the calm before the patient surge to familiarize, and ameliorate the many risks associated with sharing a ventilator. A single ventilator for multiple simulated patients to meet disaster surge
cord-276904-lmqschxy	2020	title: Neuromuscular blocking agents (NMBA) for COVID-19 acute respiratory distress syndrome: a multicenter observational study The benefit of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS) is debated [1] [2] [3] . COVID-19 ARDS appears different from classical ARDS [4] , and we aimed to describe the use of NMBA and analyze their association with day 28 outcome, in a multicentric observational prospective study (21 ICUs from Belgium and France). These latter had higher plateau pressure and rate of prone position and were more frequently in French ICUs. After propensity score matching of 206 patients, the rate and time to breathing without assistance at day 28 did not significantly differ between groups (Table 1 and Fig. 1 ). One can be surprised to observe that matched on severity, time to extubation at day 28 was similar between patients with short or long course of NMBA.
cord-278249-vvhq9vgp	2020	In addition, since most patients need to undergo mechanical ventilation in this context, ventilator-induced lung injury (VILI) could exacerbate tissue damage as well as local and systemic inflammation, thus acting as a "second hit." Our team has previously shown that mitochondrial alarmins (i.e., mitochondrial DNA) are released by human epithelial cells submitted to cyclic stretch, and these alarmins are also recovered from bronchoalveolar lavage (BAL) fluid obtained from either ventilated rabbits or ARDS patients. This comprehensive evaluation of systemic and pulmonary immune response showed that the higher CXCL10 concentrations in both the systemic and alveolar compartments of patients with COVID-19 ARDS were associated with a longer duration of mechanical ventilation. Finally, in both COVID-19 and non-COVID-19 patients, higher mitochondrial DNA concentrations in the plasma and ELF compartment were highly correlated with alveolar inflammation, as assessed by BALF cell count and ELF IL-8 and IL-1β concentrations.
cord-278838-qraq5aho	2017	
cord-280129-a97rvtzl	2020	authors: Honore, Patrick M.; Barreto Gutierrez, Leonel; Kugener, Luc; Redant, Sebastien; Attou, Rachid; Gallerani, Andrea; De Bels, David title: Liver injury without liver failure in COVID-19 patients: how to explain, in some cases, elevated ammonia without hepatic decompensation Liver injury without liver failure in COVID-19 patients: how to explain, in some cases, elevated ammonia without hepatic decompensation Patrick M. Both patients were treated with classical medical therapy including lactulose, but, despite increasing doses of lactulose for 3 days, ammonia levels remained unchanged. Retrospectively, we hypothesize that the pre-admission diarrhea may have resulted in secondary carnitine deficiency, as described in the literature [3] , leading to hyperammonemia unresponsive to medical therapy [4] . As we did not measure serum carnitine levels and we did not supply the patients with carnitine supplementation, the diagnosis of carnitine deficiency in these cases remains only a hypothesis. Liver injury in critically ill patients with COVID-19: a case series
cord-280233-avmisu31	2020	In light of the COVID-19 pandemic, this commonsense approach was recently clarified in a SCCM-ASA-AARC-AACN-ASPF-CHEST consensus statement on the Society of Critical Care Medicine (SCCM) website [1] : ''We recommend that clinicians do not attempt to ventilate more than one patient with a single ventilator while any clinically proven, safe, and reliable therapy remains available (ie, in a dire, temporary emergency)'' [1] . In-parallel is a critical point, as inspiration and expiration all take place at the same time, so there is thus no change to respiratory rate (RR) and tidal volume or driving pressure are adjusted for the number of patients. Instead of the same RR and higher tidal volume or driving pressure, in-series breathing doubles the RR and keeps the other ventilator settings the same. PC driving pressure and VC tidal volume would have to be the same as ventilators currently do not have the capability to enable alternating breath settings.
cord-280278-gq1hnnwh	2020	
cord-281191-n9gerpwy	2003	It will include a brief discussion of selection bias in autopsy studies, the important role autopsy plays in tracking disease prevalence over time, its characterization of newly emerging diseases, its contribution to education and quality control programs, and its role in clinical decision-making. Fernandez-Segoviano and colleagues [4] evaluated 100 consecutive autopsies from patients in a multidisciplinary intensive care unit and noted a discrepancy rate of 22% between premortem and postmortem diagnosis. Blosser and colleagues reported a discrepancy rate of 27% on 41 autopsies from medical intensive care unit patients [5] . Autopsy findings may have important implications for quality control programs in the intensive care unit. Withdrawal of life-sustaining treatment is a frequent mode of death in critically ill bone marrow transplant patients, and end-of-life decision-making is based on clinical data. Discrepancies between clinical and post mortem diagnoses in critically ill patients: an observational study
cord-281663-c2okrt2b	2020	title: Positive end-expiratory pressure titration in COVID-19 acute respiratory failure: electrical impedance tomography vs. Electrical impedance tomography (EIT) offers this opportunity by bedside estimating both alveolar collapse and lung overdistension throughout a decremental PEEP trial [5] . This investigation (Ethics Committee approval: Ref: 4853/AO/20-AOP2012) aims to assess the agreement between EIT-based PEEP values and those recommended by the higher and lower PEEP/FiO 2 tables [6] in a series of consecutive intubated COVID-19 hARF patients, admitted to intensive care unit at our institution. In conclusion, we confirm the rationale for individualized PEEP setting in COVID-19 patients intubated for Fig. 1 Bland-Altman plot, evaluating the agreement between PEEP EIT and the PEEP values proposed by the higher (a) and lower (b) PEEP/FiO 2 tables from the ALVEOLI trial [6] . Electrical impedance tomography for positive end-expiratory pressure titration in COVID-19-related acute respiratory distress syndrome Higher versus lower positive endexpiratory pressures in patients with the acute respiratory distress syndrome
cord-281711-whr4pfx9	2020	Whereas some countries have been exposed very early [3] , others had the opportunity to prepare for the ethical challenges that emerge when intensive care resources become scarce. Whereas some guidelines (CH, A) refer to shortterm survival only as a key triaging criterion, others either do not specify survival (UK, BE) or explicitly allow for the possibility that long-term prognosis (G) or a reduced lifespan, due to old age or to comorbidities, could affect a patient''s access to a ventilator (I). Respect for the patient''s will, fair distribution, and maximization of benefits based on chance of survival are at the heart of the recently issued triaging guidelines. The allocation of scarce resources has been debated within medical ethics for a long time, and procedural criteria have been defined. Fair allocation of scarce medical resources in the time of Covid-19 Clinical ethics recommendation for the allocation of intensive care treatments, in exceptional COVID-19 pandemic: triage for intensive-care treatment under resource scarcity
cord-282571-ilf73g71	2020	Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. Autopsies of SARS patients showed that SARS-CoV infection can cause injury to multiple organs, such as the heart, kidney, liver, skeletal muscle, central nervous system, and adrenal and thyroid glands, besides the lungs [30, 31] . Several studies have shown that SARS-CoV infection can downregulate ACE2 expression on cells, thereby disrupting the physiological balance between ACE/ACE2 and Ang-II/angiotensin-(1-7) and subsequently causing severe organ injury [44] [45] [46] [47] . Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS
cord-284355-yb2t5ypa	2020	
cord-286771-77hs34jm	2020	Protective lowtidal volume (Vt) mechanical ventilation (MV), including delivering a physiologic low Vt adjusted by ideal body weight, is currently the standard of care for patients requiring invasive respiratory support, like moderate and severe ARDS. Additionally, we found a significant progression of regional Fig. 2 Regional volumetric strain maps in a 3-h murine model of patient self-inflicted lung injury randomized to two groups: Group I: subjects with induced lung injury on low tidal volume mechanical ventilation at the beginning of the experiment (T1) and at the end of the experiment (T3) (upper left and right panels). Ventilation-induced lung injury exists in spontaneously breathing patients with acute respiratory failure: yes Can high-flow nasal cannula reduce the rate of endotracheal intubation in adult patients with acute respiratory failure compared with conventional oxygen therapy and noninvasive positive pressure ventilation?: a systematic review and meta-analysis
cord-286963-rsmgx2xr	2020	title: Renal replacement therapy is independently associated with a lower risk of death in patients with severe acute kidney injury treated with targeted temperature management after out-of-hospital cardiac arrest BACKGROUND: The effect of renal replacement therapy (RRT) on the outcomes of severe acute kidney injury (AKI) after out-of-hospital cardiac arrest (OHCA) is uncertain. This study aimed to evaluate the association of RRT with 6-month mortality in patients with severe AKI treated with targeted temperature management (TTM) after OHCA. Acute kidney injury (AKI) develops frequently after out-of-hospital cardiac arrest (OHCA) and is associated with long-term mortality and poor neurological outcomes [1] [2] [3] [4] [5] [6] [7] [8] . Additional data from well-designed Table 3 Factors associated with 6-month mortality in patients who developed stage 3 acute kidney injury after an out-of-hospital cardiac arrest observational studies will be needed to clarify the longterm mortality of RRT group after OHCA.
cord-287333-h89tmi0w	2020	title: The importance of a "socially responsible" approach during COVID-19: the invisible heroes of science in Italy The importance of a "socially responsible" approach during COVID-19: the invisible heroes of science in Italy Filippo Sanfilippo 1* , Elena Bignami 2 , Ferdinando Luca Lorini 3 and Marinella Astuto 1 We summarize the "socially responsible" approach of our ICU community in three key points. In summary, Italian ICU physicians avoided "compulsory public notoriety," behaving as "invisible heroes of science." Unfortunately, the same has not happened in other disciplines with compulsory appearance on TV, social media, and newspapers by physicians with low h-index, predatory publication attitude, and no experience in coronavirus delivering highly misleading and scientifically unsupported information. A "socially responsible" approach to public information should be implemented to all fields involved in COVID-19, and the one delivered by the Italian ICU "invisible heroes" should be a leading worldwide example for other disciplines and countries.
cord-287490-g1r9zew2	2020	title: Prone positioning combined with high-flow nasal or conventional oxygen therapy in severe Covid-19 patients Prone positioning combined with high-flow nasal or conventional oxygen therapy in severe Covid-19 patients Cyrielle Despres 1 , Yannick Brunin 1 , Francis Berthier 1 , Sebastien Pili-Floury 1,2 and Guillaume Besch 1,2* Dear Editor, A massive outbreak of coronavirus disease 2019 (Covid-19) occurred in France in March and April 2020. We report the case of 6 severe Covid-19 patients admitted to our critical care unit between March and April 2020, who had PP combined with either highflow nasal oxygen (HFNO) or conventional oxygen therapy (COT). The efficacy of PP combined with HFNO therapy or non-invasive ventilation was recently reported in small cohorts of non-infectious and infectious non-Covid-19 ARDS patients [2, 3] . Considering these observations, PP combined with either HFNO or COT could be proposed in spontaneously breathing, severe Covid-19 patients to avoid intubation. Prone positioning combined with high-flow nasal cannula in severe noninfectious ARDS
cord-288284-fghu8ouc	2005	Infectious diseases, whether they be natural (e.g. SARS [severe acute respiratory syndrome] and influenza) or the result of bioterrorism, have the potential to create a large influx of critically ill into our already strained hospital systems. Core to any disaster management plan are leaders with clear responsibilities to coordinate efforts and develop policies to contain the disease; to coordinate resource allocation and manpower; to advise and share information regarding infection control and treatment; to share data and research endeavours; to maintain staff morale; and to provide information to various levels of government, health care institutions, front-line workers and the public [1, 13] . The model we propose (Fig. 1 ) is one of a Central Critical Care Crisis Team, composed of leaders of different subteams of multidisciplinary professionals responsible for domains of crucial importance: clinical management, infection control, education, communication, team morale, manpower and system thinking, data collection, research and, finally, lobbying to ensure resources are available to meet critical care needs.
cord-290392-kpjp0sx4	2020	In December 2019, an outbreak of coronavirus disease 2019 (COVID19) , which was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), broke out in Wuhan, China [1] [2] [3] . COVID-19 was of clustering onset and mainly affected the respiratory system with some patients rapidly progressing to acute respiratory distress syndrome (ARDS); other organ functions were less involved [5, 6] . In addition, the lung compliance was relatively high in some COVID-19-related ARDS patients, which was inconsistent with the severity of hypoxemia. A previous study reported that more than 50% of patients with moderate and severe ARDS according to the Berlin definition did not show diffuse alveolar damage [17] . Currently published studies did not report the proportion of different respiratory support according to COVID-19-related ARDS classification. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China
cord-290741-y3lvewlz	2020	title: Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series Yingchun Zeng 1 † , Zhongxiang Cai 2 † , Yunyan Xianyu 2 † , Bing Xiang Yang 3* , Ting Song 1* and Qiaoyuan Yan 4* The World Health Organization (WHO) has characterized the disease, coronavirus disease 2019 (COVID-19), as a pandemic on March 11, 2020 (www.who.int). If severe respiratory failure persisted, then ECMO should be started as soon as possible." [6] Worldwide data on prognosis when using ECMO to treat critically ill patients with COVID-19 infection are not available, and whether ECMO plays a role in reducing patient mortality rates is currently unknown. Based on the two cohort case series in this study, nearly half of the critically ill COVID-19 patients with ECMO were dying from septic shock and multiple organ failure.
cord-290776-l6ajq6vp	2020	title: Presence of SARS-CoV-2 in urine is rare and not associated with acute kidney injury in critically ill COVID-19 patients Patients infected with SARS-CoV-2 requiring intensive care due to coronavirus disease 2019 (COVID-19) frequently develop acute kidney injury (AKI) [1] , but the underlying mechanisms are poorly explored. In this report, SARS-CoV-2 RNA levels were prospectively investigated in urine of patients with upper or lower airway swab test PCR-verified COVID-19, admitted to a Swedish intensive care unit (ICU, n = 81). Nucleic acid was extracted from urine samples using NucliSENS® eMAG® (bioMerieux), and the amount of viral RNA was quantitated by detection of SARS-CoV-2 E and N-genes using real-time RT-PCR according to previously described protocols [5, 6] . In this cohort, SARS-CoV-2 RNA was not more frequently detected in urine of patients that died or developed acute kidney injury.
cord-291934-pm3ns6ge	2020	According to a large survey, more than 14% patients were transferred to the intensive care unit care (ICU), and among those who received invasive mechanical ventilation, the mortality was as high as 88.1% [2] . Here we presented the data from a single ICU of Tianyou hospital in Wuhan, and according our experience, the overall mortality decreased in patients receiving Chinese herb therapy. Despite with limited sample size, the mortality rate decreased significantly after applying Chinese herbal to these patients (4/9 vs. 14/16, p = 0.033), especially in patients who received Chinese herbal therapy during the whole disease course. Further, these patients were also divided into two groups according to whether they had used Chinese herbal; a decreased trend of mortality was also observed (9/14 vs. However, in China, Chinese herbal therapy has been fully applied to patients with COVID-19 infection in the middle stage of this epidemic and the effect is positive.
cord-291955-mlju5f9u	2020	The SARS-CoV-2 (COVID-19) pandemic leads to severe shortages of intensive care unit (ICU) facilities in many countries. In this article, we discuss the use of age as a criterion for ICU treatment in times of scarce ICU capacity by contrasting it with deciding under normal conditions. It is proxy for the medical condition of the patient, and advanced age is clearly a factor that should be weighed together with other risk factors for a poor outcome of ICU treatment. Elderly patients admitted to the ICU with COVID-19 are at increased risk of death [7, 8] . Although we need more robust data about short-and long-term outcomes of elderly patients admitted to the ICU because of COVID-19, the mortality rates reported up to now are 40 to 80% [7, 9] . It cannot be justified to withhold ICU admission for all patients above a certain age.
cord-292335-al6v3b9x	2015	METHOD: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. CONCLUSION: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization. The relationship between viral and bacterial respiratory infections creates a difficult situation for clinicians determining the appropriate use of antimicrobials as they treat hospitalized patients with pneumonia while also trying to minimize the development and selection of resistant organisms. This study aimed to describe the use of continued empiric antibacterials in patients with known viral pneumonia and to determine the impact of such therapies on subsequent bacterial infections/colonization and clinical outcomes. This study compared a cohort of 174 patients with viral pneumonia and mixed viral-bacterial infection based on exposure to continued empiric antibacterials after respiratory virus identification.
cord-293167-3bd3adip	2020	Most patients infected by SARS-CoV-2 have presented with a mild clinical course: beginning with fever and dry cough, progressing to a form of mild or moderate respiratory disease, and resolving without specific treatment [2] . A retrospective observational study from Wuhan, China, reported that six (2.8%) patients, out of the 214 reviewed COVID-19 cases, developed ischemic stroke. A retrospective observational study from a different center in Wuhan, China, found eleven (5.0%) patients, out of 221 reviewed COVID-19 cases, developed acute ischemic stroke. Those who had COVID-19 infection with new onset of ischemic stroke were more likely to have a severe SARS-CoV-2 presentation, an advanced age (71.6 ± 15.7 years versus 52.1 ± 15.3 years), and preexisting cardiovascular risk factors including hypertension, diabetes, and previous cerebrovascular disease. A retrospective observational study from Wuhan, China, reported one (0.45%) patient, out of 221 reviewed COVID-19 cases, who developed intracerebral hemorrhage.
cord-293690-pxiv0m7n	2020	authors: Scala, Raffaele; Renda, Teresa; Corrado, Antonio; Vaghi, Adriano One fourth of > 1500 COVID-19 patients died after the admission in Lombardia ICUs; in only 11% of them, noninvasive ventilation (NIV) and/ or high flow nasal cannula (HFNC) was attempted early to prevent respiratory deterioration and invasive mechanical ventilation (IMV). The delayed admission in Lombardia overcrowded ICU of severely hypoxemic COVID-19 patients meeting the criteria for IMV without being offered a HFNC/NIV trial must have played a crucial role. Respiratory high-dependency care units (RHDCUs) are specialised cost-effective environments offering an "intermediate" level of care between ICU and ward, where NIV/HFNC, weaning from IMV and discharge of ventilator-dependent patients are provided [4] . The "gap" between the Italian RHDCU network and pre-COVID-19 respiratory needs might largely explain ICU network failure in Lombardia [4] . The expanded IPU network together with national more restrictive measures against virus dissemination after the Lombardia outbreak has contributed to the mitigation of COVID-19 impact on mortality in other regions.
cord-293766-vpfda3pd	2020	authors: Ji, Jingjing; Zhang, Jinxia; Shao, Ziyun; Xie, Qifeng; Zhong, Li; Liu, Zhifeng Patients were diagnosed as mild type, general type, severe type, and critical type according to the Chinese Recommendations for Diagnosis and Treatment of Novel Coronavirus (SARS-CoV-2) Infection (Trial 7th version) [4] . The current multicenter cohort study demonstrates that GC therapy does not change viral clearance and peripheral lymphocyte counts in COVID-19 patients. Low-dose corticosteroid therapy does not delay viral clearance in patients with COVID-19 Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients Jinxia Zhang, Ziyun Shao, Qifeng Xie, and Li Zhong were responsible for collecting the data. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.Ethics approval and consent to participate
cord-295585-dl29curs	2020	Coronavirus disease 2019 (COVID-19) is associated with severe systemic inflammation and important elevation of fibrinogen and D-dimers that has been associated with a poor prognosis [1, 2] . We retrospectively reviewed characteristics of patients with confirmed SARS-CoV-2 infection and acute PE who were admitted to our tertiary ICU, which serves as an ECMO referral center for the Greater Paris. The ICU database was registered with the national data protection authority (CNIL 1950673) . PE was suspected in 6 patients because of acute cor pulmonale at echocardiographic evaluation (online supplementary data). We describe a series of 8 critically ill patients with massive PE following COVID-19 infection. Four of these patients developed PE while on VV-ECMO for severe ARDS, a condition that was not reported in the 156 patients included in the EOLIA trial [3] who received ECMO and in the 350 VV-ECMO patients of the LIFE-GARDS international multicenter prospective cohort [4] . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan
cord-297062-dmiplvt2	2016	authors: Almekhlafi, Ghaleb A.; Albarrak, Mohammed M.; Mandourah, Yasser; Hassan, Sahar; Alwan, Abid; Abudayah, Abdullah; Altayyar, Sultan; Mustafa, Mohamed; Aldaghestani, Tareef; Alghamedi, Adnan; Talag, Ali; Malik, Muhammad K.; Omrani, Ali S.; Sakr, Yasser BACKGROUND: Middle East respiratory syndrome coronavirus infection is associated with high mortality rates but limited clinical data have been reported. We describe the clinical features and outcomes of patients admitted to an intensive care unit (ICU) with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. METHODS: Retrospective analysis of data from all adult (>18 years old) patients admitted to our 20-bed mixed ICU with Middle East respiratory syndrome coronavirus infection between October 1, 2012 and May 31, 2014. We performed a retrospective study to describe the clinical features and outcomes of patients admitted to our ICU with laboratory-confirmed MERS-CoV infection. This report describes the clinical features and outcomes of 31critically ill patients with confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) infection.
cord-297863-ou432md0	2020	Based on Wuhan''s experience, it is critical to develop tailored infection prevention and control (IPC) protocols for both workplace and non-occupational settings and to conduct effective IPC training. Thus, the following suggestions were summarized based on the first-hand experience of a national medical team from Zhejiang, to facilitate the development of IPC protocols in critical care settings. Generally, all health workers should implement appropriate personal protective equipment (PPE) regarding contact and droplet precautions based on recommendations by WHO [8] . For health workers in ICU, advanced protections are required during routine intensive care and airborne precautions are considered as airborne transmission may happen during aerosol-generating procedures. All information provided in this paper is to strengthen the clinical practice in critical care settings and to better protect front-line health workers in nursing severe COVID-19 patients. Infection prevention and control during health care when COVID-19 is suspected: interim guidance
cord-299650-lhphdjeu	2020	Longitudinal IC data presented here demonstrate a progressive hypermetabolic phenotype beginning 1 week post-intubation in COVID-19 ICU patients, with significantly greater mREE versus predictive equations or ASPEN-recommended 11-14 kcal/kg ABW for obese subjects used currently to determine energy requirements. Our data support use of standard predictive equations or~20 kcal/kg as a reasonable approximation of mREE in 1st ICU week in COVID-19 patients. These data suggest personalization of nutrition delivery, including IC use [3, 5] , should be considered to provide more accurate assessments of energy expenditure and help guide nutrition delivery in COVID-19 ICU patients. Only the authors and investigators at Duke University participated in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
cord-300135-iwvkvs3k	2020	title: Description of an alternative method for optimal and comfortable two-handed face mask ventilation: the transverse mandibular technique Description of an alternative method for optimal and comfortable two-handed face mask ventilation: the transverse mandibular technique Francois Lemay 1,2* and Jeremy Cooper 3 In addition, major difficult airway algorithms already highlight the importance of oxygenation rather than intubation, and many include best attempts at facemask ventilation (FMV) while progressing in cannot intubate cannot oxygenate situations [2, 3] . We would like to share an alternative technique that provides good FMV conditions through improved jaw thrust, mask seal and ergonomic comfort. 5. It can be performed standing in front of the patient, which can be useful in critical situations when many practitioners are managing the airway. Comparison of effectiveness of two commonly used two-handed mask ventilation techniques on unconscious apnoeic obese adults
cord-300510-fhpkdqr0	2020	7. Perform early intubation if poor response to continuous positive airway pressure in terms of oxygenation: do not trust patients'' relatively good respiratory mechanics and feeling of improved dyspnoea, since these patients may have relatively normal lung compliance and the only clinical sign of fatigue may be high respiratory rate. As soon as possible according to gas exchanges (PaO 2 /FiO 2 > 150 with FiO2 < 50%) and lung ultrasound score (≤ 12), start assisted ventilation with a sigh while maintaining moderate to high positive end-expiratory pressure to prevent derecruitment. Abbreviations SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; ICU: Intensive care unit Assessment of lung aeration and recruitment by CT scan and ultrasound in acute respiratory distress syndrome patients Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China The authors read and approved the final manuscript.
cord-300897-lih5f6cj	2010	Two years later, it became the fi rst Department of Critical Care Medicine in mainland China, with a seven-bed general ICU in the Peking Union Medical College Hospital, chaired by Dr Dechang Chen, the well-recognized founding father of critical care medicine in mainland China. Th ere is no census on critical care resources in China, including the number of ICUs, intensivists, ICU nurses, and relevant facilities (for example, bedside monitors, artifi cial ventilators), because no national survey has ever been performed. Considering the above limitations and potential improve ment, we do believe that Chinese intensivists may benefi t from academic exchange with the international medical community with regard to the following: development of a series of training programs fulfi lling international standards; development of a national board exam for critical care medicine; and conduction of multicenter trials compatible with good clinical practice.
cord-303577-2gxo5mft	2020	We review seven major societal recommendations and guidelines addressing the management of coagulopathy in COVID-19 patients: the Centers for Disease Control and Prevention (CDC) [6] , International Society on Thrombosis and Haemostasis interim guidance (ISTH-IG) [7] , American Society of Hematology (ASH) [8, 9] , American College of Chest Physicians (ACCP) [10] , Scientific and Standardization Committee of ISTH (SCC-ISTH) [11] , Anticoagulation Forum (ACF) [12] , and American College of Cardiology (ACC) [13] . Tables 1, 2, 3, 4, 5, 6, and 7 highlights six major societal recommendations and guidelines on the management of CAC focusing on several critical care issues: (1) laboratory testing for risk stratification and triage, (2) use of biomarkers to guide anticoagulation, (3) proposals for alterations of standard prophylactic VTE anticoagulation regimens for the prevention of thrombotic complications, (4) examination of available medications preferred for anticoagulation, (5) considerations for initiation of therapeutic anticoagulation, (6) indications for thrombolytic therapy, (7) decision-making regarding withholding anticoagulation treatment, (8) use of mechanical thromboprophylaxis, (9) monitoring of anticoagulation, (10) duration of therapeutic anticoagulation, (11) necessity of anticoagulation at discharge, and (12) treatment of active bleeding.
cord-303893-47lxq8pi	2020	Interferon beta-1a for COVID-19: critical importance of the administration route Juho Jalkanen 1 , Maija Hollmén 2 and Sirpa Jalkanen 2* Type I interferons, especially IFN-beta, have been appointed as potential leading therapeutics to tackle severe COVID-19 and are currently being evaluated in REMAP-CAP and the WHO''s Solidarity Trial. We wish to highlight the differences of these two treatment methods and also other crucial aspects of IFN-beta treatment for COVID-19 and acute respiratory distress syndrome (ARDS). Nonetheless, the purpose of i.v. administered IFN-beta for the treatment of COVID-19 and ARDS is to maximise bioavailability of the drug at the lung vasculature, as well as other vascular beds. There are a limited number of direct studies on the timing of immunomodulatory treatments such as IFN-beta, but given our basic understanding of human biology and viral defence, we suggest that IFN-beta should be given early to COVID-19 patients.
cord-304070-jw1lxwyd	2004	We evaluated the feasibility and potential benefits of a handheld computer based knowledge access system linking a central academic intensive care unit (ICU) to multiple community-based ICUs. METHODS: Four community hospital ICUs with 17 physicians participated in this prospective interventional study. Before and after the intervention period, participants underwent simulated patient care scenarios designed to evaluate the information sources they accessed, as well as the speed and quality of their decision making. CONCLUSION: An updateable handheld computer system is feasible as a means of point-of-care access to medical reference material and may improve clinical decision making. In the present study we evaluated whether it would be feasible and effective to provide updateable reference information from a central academic centre to handheld computers used by critical care specialists in community hospitals. Information sources that physicians accessed to make clinical decisions were evaluated during simulated patient care scenarios, completed in the physicians'' own ICU utilizing a computerized patient simulator (SimMan; Laerdal Medical Corporation, Wappingers Falls, NY, USA).
cord-304327-mtkgr542	2020	Based on retrospective data, we aimed to describe the discrepancy between prehospital initial RR (RRi) and initial SpO2 (Spo2i; i.e., before oxygen supplementation, FiO2 = 21%) in COVID-19 patients suffering from ARF. After having measured the SpO2i/RRi values in COVID-19 patients, we compared them to those of non-COVID-19 patients (i.e., patients with other causes of ARF treated by the BLS teams over the previous 3 years in the same period). In summary, this retrospective study based on prehospital first responder data highlighted a relatively higher discrepancy between SpO2i and RRi in COVID-19 ARF patients, in comparison with previous non-COVID-19 ARF patients. Fig. 1 Scatter plot representing the initial SPO2 (SPO2i) and initial respiration rate (RRi) values for each patient, for COVID-19 (March 2020) and non-COVID-19 patients from the previous 3 years. RRi, initial respiratory rate; SpO2i, initial pulse oximetry value; N, number of patients included
cord-304746-7yzybukk	2020	title: Cardiac injury associated with severe disease or ICU admission and death in hospitalized patients with COVID-19: a meta-analysis and systematic review BACKGROUND: Cardiac injury is now a common complication of coronavirus disease (COVID-19), but it remains unclear whether cardiac injury-related biomarkers can be independent predictors of mortality and severe disease development or intensive care unit (ICU) admission. Retrospective studies assessing the relationship between the prognosis of COVID-19 patients and levels of troponin I (TnI) and other cardiac injury biomarkers (creatine kinase [CK], CK myocardial band [CK-MB], lactate dehydrogenase [LDH], and interleukin-6 [IL-6]) were included. This systematic review and meta-analysis of 23 highquality retrospective studies systematically evaluated the risk of severe disease, ICU admission, or death associated with COVID-19-related cardiac injury performance. Our analysis suggests that COVID-19 patients with elevated TnI levels are at higher risk of developing severe disease, requiring ICU admission, and death.
cord-305946-ytabywxd	2020	title: Predictive value of neutrophil to lymphocyte and platelet to lymphocyte ratio in COVID-19 Predictive value of neutrophil to lymphocyte and platelet to lymphocyte ratio in COVID-19 Shiping Zhu 1 , Lei Dong 2 and Wanru Cai 2* Keywords: Neutrophil to leucocyte ratio, Platelet to lymphocyte ratio, To the Editor, In a recent study, Dr. Ma [1] investigated the neutrophil to lymphocyte ratio (NLR) in predicting moderate-severe acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection. First, uncontrolled inflammatory response plays a vital role in COVID-19 disease, and both NLR and platelet to lymphocyte ratio (PLR) have been recognized as inflammatory factors in various lung diseases [2, 3] , such as lung cancer and obstructive lung disease. However, one common limitation is that in most previous studies, NLR or PLR was included in the generalized linear models as a continuous variable, with the assumption that there was a linear association between NLR/PLR and the dependent outcomes. Neutrophil-to-lymphocyte ratio as a predictive biomarker for moderate-severe ARDS in severe COVID-19 patients
cord-307512-70j4vn78	2020	The logistics of patient selection, expedient cannulation, healthcare worker safety, and post-resuscitation care must be weighed against the ethical considerations of providing an intervention of contentious benefit at a time when critical care resources are being overwhelmed by pandemic demand. The first is in-hospital cannulation, whereby patients suffering an IHCA or OHCA who fail to achieve ROSC with standard CCPR and advanced cardiac life support (ACLS) may be cannulated for ECPR. b Expedient cannulation and establishment of extracorporeal perfusion is a requisite of an effective ECPR; for OHCA, this may occur: (i) on-scene cannulation by mobile ECMO practitioners and (ii) rapid retrieval to ECPR hospital recognising those patients who might benefit from ECPR, requirements for donning personal protective equipment (PPE), impaired ambulance response times, and lack of critical care resources, may preclude the use of ECPR even in those who would otherwise be eligible.
cord-307592-hyeshh63	2020	A total of 24 COVID-19 patients were enrolled in this study, including 14 (58.3%) severe patients and 10 (41.7%) critical patients (Table 1 ). Levels of VEGF-D, TNF-α, SCF, LIF, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17A, IL-18, IL-1β, and IFN-γ were significantly higher in the critical group than in the severe group (Table 1) . Strikingly, VEGF-D was identified as the most important indicator related to the severity of COVID-19 (ranked as 1, Fig. 1a ). As shown in Fig. 1e , critical patients had higher levels of VEGF-D than the severe cases during the whole course of hospitalization. We hypothesized that elevated VEGF-D level might potentially relate to the storm of blood clots occurring in COVID-19 patients. D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19 All data generated or analyzed during this study are included in this published article.
cord-310561-67kp743f	2020	Therefore, we sought to characterise iron parameters, including serum iron, in COVID-19 intensive care unit (ICU) patients and relate these to disease severity. We retrospectively evaluated any serum iron profiles that were measured in critically ill patients with COVID-19 within 24 h of admission to the ICU, John Radcliffe Hospital, Oxford, UK, between March 31, 2020, and April 25, 2020. Our data suggest that serum iron may be a useful biomarker for identifying disease severity in COVID-19, whilst also being a potential therapeutic target. Serum iron was lower when compared with other cohorts of non-COVID-19 ICU patients reported previously, including those with sepsis [4] . Abbreviations: APACHEII Acute Physiology and Chronic Health Evaluation II, CRP C-reactive protein, ICU intensive care unit, IQR interquartile range, SD standard deviation Fig. 1 Associations between markers of iron status, lymphocyte count and severity of hypoxemia.
cord-310776-4iqu18gi	2020	Following initial reports describing Interleukin-6 (IL-6) as a predictive factor for a negative outcome, extracorporeal cytokine adsorption was discussed as a possible treatment option for severe COVID-19 cases. A major advantage of extracorporeal cytokine adsorption over the other therapeutic approaches discussed in this debate is that it does not selectively block a specific receptor or signal transduction cascade, but it rather reduces particularly elevated concentrations of various inflammatory mediators such as interleukins, TNF-α, and also interferons; these factors have both pro-and anti-inflammatory functions. These two aspects may be particularly relevant, e.g., in the case of bacterial superinfection in severe COVID-19 when an adequate immune response is required. Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
cord-310997-ulgemn42	2020	title: Letter to the editor—Mortality rate of acute kidney injury in SARS, MERS, and COVID-19 infection: a systematic review and meta-analysis Firstly, the mortality rate for COVID-19 patients with AKI is different in the text (i.e., 76.5%; 95% CI 61.0-89.0) from one reported in the authors'' Figure 1 (i.e., 78.0%; 95% CI 63.0-90.0). Letter to the editor-Mortality rate of acute kidney injury in SARS, MERS, and COVID-19 infection: a systematic review and meta-analysis" As the author pointed out, the reported results of mortality rate for coronavirus disease 2019 (COVID-19) patients with acute kidney injury (AKI) is different from the text and Figure 1c in the original publication of our article [1] . In addition, our research letter aimed to overview the AKI mortality in patients with different coronaviruses, but the clinical heterogeneity between studies should be also noted. Mortality rate of acute kidney injury in SARS, MERS, and COVID-19 infection: a systematic review and meta-analysis
cord-312484-epbhdx55	2020	title: COVID-19 infection epidemic: the medical management strategies in Heilongjiang Province, China Education and training of staffs As soon as the outbreak of COVID-19 began in Wuhan, the Heilongjiang provincial health administration department started to launch training protocols for all the medical staffs. Heilongjiang province set up a multidisciplinary team (MDT) soon after the outbreak of COVID-19, including intensive care unit (ICU), emergency department, infectious disease department, respiratory department, psychological department, infection control department, administrative department, and nursing department. Medical staffs of the whole province, especially intensivist, respiratory physician, emergency physician, and infectious disease physician, were assigned to work in the designated hospitals. The group members included provincial health authorities, medical experts, and infection control experts. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China We would like to thank all the medical staffs and local authorities of Heilongjiang province for their efforts in combating the outbreak of COVID-19.
cord-313914-m09lw0i4	2020	Extracorporeal membrane oxygenation (ECMO), as a temporary life support technique for refractory respiratory or cardiac failure, has been applied in COVID-19 patients [1] . Referring to the present case series and the COVID-19 cohort in China, the mortality of patients undergoing ECMO ranged from 42 to 83% [2, 3] . The Chinese Society of Extracorporeal Life Support (CSECLS) performed a survey of ECMO programs for COVID-19 in China, aimed at investigating the program organization and the potential factors associated with outcomes during the pandemic. One hundred eleven individual responses from 79 ECMO programs (30 in Hubei and 49 outside Hubei) applied ECMO in patients with COVID-19 pneumonia and ARDS were analyzed. That might be the main reason for more ECMO programs outside Hubei applied ECMO in older patients (age > 65), aiming at minimizing the local mortality of COVID-19. Prognosis when using extracorporeal membrane oxygenation (ECMO) for critically ill COVID-19 patients in China: a retrospective case series
cord-314310-g1zmggf4	2020	Honore * , Leonel Barreto Gutierrez, Luc Kugener, Sebastien Redant, Rachid Attou, Andrea Gallerani and David De Bels Gucyetmez et al., noting that elevated D-dimer levels have been found as a predictor for mortality in patients with COVID-19 pneumonia, concluded that therapeutic plasma exchange (TPE) seems to be a treatment that may improve outcomes by effectively removing fibrin degradation products (FDPs) and restoring coagulation status [1] . Firstly, we should emphasize three important points about our study: (1) we investigated the effect of therapeutic plasma exchange (TPE) on overall mortality, not mortality predictors, (2) we emphasized that "major thromboembolic events" were not detected, not only thromboembolic events, and (3) we did not mention the cause of deaths because all of them were multi-organ failure (MOF) caused by COVID-19 [1] . Therapeutic plasma exchange in patients with COVID-19 pneumonia in intensive care unit: a retrospective study
cord-314737-2fun90ze	2020	title: Age, sex, and comorbidities predict ICU admission or mortality in cases with SARS-CoV2 infection: a population-based cohort study This was a retrospective analysis from a nationwide prospective registry, including confirmed (nasal/pharynx swab real-time polymerase chain reaction) cases of SARS-CoV2 infection notified to the Directorate-General of Health from March 02 until April 21, 2020, in Portugal. The model''s calibration plot showed a very good predictive performance up to estimated probabilities of Among cases with SARS-CoV2 infection at an early phase of the epidemic in Portugal, pre-hospital characteristics like age, sex, and the number of comorbidities were useful to predict ICU admission or all-cause mortality [5] . Dr. Cardoso conceived and designed the study, performed statistical and data analyses, drafted the manuscript, revised the manuscript, and provided final approval. Dr. Fidalgo contributed to the conception and design of the study and data analysis and interpretation, contributed to drafting and revision of the manuscript, and provided final approval.
cord-314872-njlgggzq	2020	We interrogated the associations between plasma concentrations of sACE2 and biomarkers of metabolic syndrome (body mass index, BMI; blood pressure; glycemic markers; and lipid levels), adiposity (plasma leptin and serum adiponectin), inflammation (high-sensitivity Creactive protein, hsCRP, white blood cell count, and interleukin-8), and liver damage (alanine aminotransferase, aspartate transaminase, and gamma-glutamyltransferase, GGT) in a large cohort of participants in a commercial wellness program who had undergone comprehensive multi-omic profiling (N = 2051; 1238 women and 813 men, aged 22 to 87 years, M = 47.3, SD = 11.71) (see [5] for details). BMI, body mass index; MAP, mean arterial blood pressure; HbA1c, glycohemoglobin A1c; HOMA-IR, homeostatic model assessment of insulin resistance; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; IL-8, interleukin 8; hsCRP, high-sensitivity C-reactive protein; ALAT, alanine aminotransferase; ASAT, aspartate transaminase; GGT, gamma-glutamyl-transferase Individuals who met World Health Organization''s diagnostic criteria for metabolic syndrome (MetS) (N = 171) displayed elevated plasma sACE2 levels compared to controls (N = 1880; P = 4.7 × 10 − 5 ); the effect was stronger in men (P int = 8.9 × 10 − 5 ).
cord-315685-ute3dxwu	2020	The systematic search identified 101 studies and 326 preprints, of which 400 articles were excluded because they were reviews, non-original articles, unrelated to the COVID-19 infection, or experimental animals that do not support SARS-CoV-2 replication such as pigs, ducks, and chickens ( Fig. 1 and Additional file 2). The aims were to investigate the pathogenesis of COVID-19 (n = 15), testing drugs and vaccines (n = 14), the host Table 1 Search strategy and selection criteria We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research describing or using an animal model of SARS-CoV-2 induced COVID published in English from January 1, 2020, to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). We used the search terms (COVID-19) OR (SARS-CoV-2) AND, (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs).
cord-316829-wm6y6uwm	2020	Logistic and organizational aspects of a dedicated intensive care unit for COVID-19 patients Maria Vargas 1* , Giuseppe De Marco 1 , Stefania De Simone 2 and Giuseppe Servillo 1 Dear Editor, On 31 March, the World Health Organization (WHO) reported 750,890 confirmed globally confirmed cases of COVID-19 [1] . 1. The most experienced ICU physician is the work shift coordinator and stays in the green area to control the compliance of the staff with the procedures and to check the patients from the centralized monitoring area. 4. The nursing and medical staff performed the first entry in the ICU boxes and stay inside for 4 h. According to our experience, a simple logistic project and clear organizational plan may be the keys to the success of surging the ICU capacity with dedicated facilities during the COVID-19 outbreak. Lower box-organization of ICU dedicated to COVID-19 patients. The green area inside the ICU is a clean zone where the medical and nursing staff may stay during the 12-h shift.
cord-317729-ruvx9zwd	2020	Indeed, a recent study investigating gene upregulation in patients with systemic capillary leak syndrome (SCLS), characterised by plasma leakage into peripheral tissue and transient episodes of hypotensive shock and oedema, found that ADM was not only one of the most upregulated genes, but that subsequent application to endothelial cells resulted in a protective effect on vascular barrier function [3] . Furthermore, recent clinical studies on sepsis patients upon emergency department (ED) presentation and during intensive care (ICU) treatment using the stable protein surrogate, mid-regional proadrenomedullin (MR-proADM), found that its assessment could accurately identify disease progression in patients with nonsevere clinical signs and symptoms, safely increase outpatient treatment with decreased readmission rates and no subsequent mortalities [4] , and identify patients requiring a rapid administration of antibiotics or triage to the ICU [5] . Abbreviations ADM: Adrenomedullin; ED: Emergency department; ICU: Intensive care unit; MR-proADM: Mid-regional proadrenomedullin; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; SCLS: Systemic capillary leak syndrome
cord-319101-2vdd10mu	2020	Intensive care units (ICUs) overwhelmed by critically ill patients may create non-conventional ICU spaces and even consider triaging invasive mechanical ventilation to those most likely to benefit [2] . The use of ECMO taxes many resources, but none more so than staffing-increased nursing ratios, need for ECMO specialists, disproportionate medical provider time, not to mention other staff, such as respiratory or physical therapists, who would be needed elsewhere for the care of other patients [9] . During non-pandemic times, in hospitals or regions with sufficient staffing reserves and provider availability, it may be understandable why clinicians might attempt ECMO in a candidate with a low, but acceptable, probability of benefit (e.g., a post-partum patient with refractory shock in multisystem organ failure). Position paper for the organization of extracorporeal membrane oxygenation programs for acute respiratory failure in adult patients
cord-319936-5uze06rp	2008	INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. Studies in animal models of ALI have demonstrated that nebulised heparin improved the PaO 2 /FiO 2 ratio and reduced histological ALI = acute lung injury; APTT = activated partial thromboplastin time; BAL = bronchoalveolar lavage; ELISA = enzyme-linked immunosorbent assay; PaO 2 /FiO 2 = arterial oxygen partial pressure to inspired oxygen fraction ratio; PTF = prothrombin fragments; TCT = thrombin clotting time; t-PA = tissue plasminogen activator. Analysis of variance was used to compare the effect of heparin dose on the P a O 2 /F i O 2 ratio, lung compliance, the alveolar dead space fraction, the APTT, the TCT and intrapulmonary PTF and t-PA levels. We found administration of nebulised heparin to mechanically ventilated patients with ALI was feasible, was not associated with serious adverse events, and increased APTT levels at higher doses.
cord-320637-jn8dh4vk	2015	title: Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1. Here we provide compelling data demonstrating that anti-HMGB1 mAb may provide a novel and effective pharmacological therapeutic strategy for severe influenza virus infection by reducing the inflammatory responses induced by HMGB1. Histologically, influenza virus inoculation increased neutrophil infiltration in the lung, although anti-HMGB1 mAb treatment attenuated this effect (Fig. 2c) . Reverse-transcription PCR in the lung homogenates showed that anti-HMGB1 mAb-treated mice had significantly attenuated RAGE and NF-κB (p65) expression on day 3 after virus inoculation compared with control mice (Fig. 3b) .
cord-321440-sts3re6p	2020	We retrospectively analyzed the incidence of diabetes in all critically ill patients admitted to the four dedicated COVID-19 intensive care units (ICU) at the University Hospital in Innsbruck, Tyrol, Austria, which covers 180,000 inhabitants as primary hospital and also functions as a tertiary referral center for the whole region of Tyrol. Of 47 COVID-19 patients admitted to our ICUs, HbA1c was measured in 44, which were included in the analysis ( Table 1 ). Recent data demonstrating viral particles in endothelial cells of several organs suggest "endotheliitis" as a possible mechanism of organ dysfunction leading to critical illness in COVID-19 patients which may be aggravated by endothelial Abbreviations: IQR interquartile range, BMI body mass index, HbA1c glycated hemoglobin, CRP C-reactive protein, IL-6 interleukin-6, COPD chronic obstructive pulmonary disease, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 *If specified in the patients'' health records dysfunction associated with prediabetes and diabetes [6] .
cord-322726-obnil3b7	2020	title: Early rehabilitation with dedicated use of belt-type electrical muscle stimulation for severe COVID-19 patients Automated EMS is expected to be an ideal mobilization for severe COVID-19 patients. Exposure to medical staff can be minimized while realizing frequent actuation with a longer duration for each bout of stimulation by assigning each COVID-19 patient a dedicated belt-type EMS, for which no belt change would be necessary (Fig. 1) . At Hitachi General Hospital, we assigned each ventilated COVID-19 patients a dedicated belt-type EMS: a measure which achieved better outcomes by administration of 50 min bouts, with three bouts per day, requiring only switching on by a nurse. In conclusion, we propose the use of dedicated belttype EMS for early rehabilitation in severe COVID-19. Fig. 1 Belt-type electrical muscle stimulation for severe COVID-19 patients. Belt-type electrical muscle stimulation EMS for intensive care unit patient with extracorporeal membrane oxygenation.
cord-323327-08p122lw	2020	These findings open new avenues for host-directed therapies in patients with symptomatic SARS-CoV-2 infection and might in addition to antiviral treatment be enough to curb the currently unacceptably high morbidity and mortality associated with COVID-19. Although ICU patients have been treated with glucocorticoids, some experts have even argued, based on studies in Middle-Eastern respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome (SARS), influenza, and respiratory syncytial virus (RSV), that they are likely to do more harm than good [1, 2] . The autoinflammatory loop can exacerbate from increase innate immune response into uncontrolled MAS a spectrum that associates with increasing ferritin levels van de Veerdonk and Netea Critical Care (2020) 24:445 patients in the early phase and reports that high dose intravenous anakinra started in patients outside of the ICU was safe and resulted in clinical benefit in 72% of patients [56] .
cord-323601-qzruawe1	2020	Because some patients may develop refractory or relapsing HLH, alternative treatments targeting specific immune pathways or cytokine signaling have been tested [1] . Tocilizumab, a monoclonal antibody targeting the receptor of IL6, fully reverses the multi-organ failure and the cytokine profile of the CAR-T cell-induced cytokinerelease syndrome [3] . In the herein study, we reviewed the outcomes of nine critically ill patients who received tocilizumab to treat HLH ( Table 1 ). In critically ill patients with severe forms of HLH, etoposide rapidly reverses cytokine storm and improves clinical condition [1] . Alternatives should thus be discussed in adult patients with chemotherapy-induced bone marrow failure, underlying autoimmune diseases requiring cytotoxic agents, or with a moderate form of HLH not related to hematological malignancies. In conclusion, IL-6-R blockade with tocilizumab may be an alternative in critically ill patients with moderate forms of HLH.
cord-324598-z65p60z9	2020	title: Influence of overdistension/recruitment induced by high positive end-expiratory pressure on ventilation–perfusion matching assessed by electrical impedance tomography with saline bolus BACKGROUND: High positive end-expiratory pressures (PEEP) may induce overdistension/recruitment and affect ventilation–perfusion matching (VQMatch) in mechanically ventilated patients. Because of the high degree of inhomogeneity in the respiratory system of ARDS patients, an increase of PEEP introduces regional lung overdistension and recruitment at the same time. Little is known on how the regional lung overdistension and recruitment influence regional ventilation-perfusion (V-Q) matching (shunt and dead space) in response to PEEP increase. The aim of the study was to investigate the association between lung overdistension/recruitment induced by PEEP and ventilation-perfusion matching in patients suffering from or being at high risk of developing ARDS. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial
cord-325626-r7k7u7ro	2020	In the study, we retrospectively collected the virological data, as well as demographic, epidemiological clinical information of 92 patients with confirmed COVID-19 in a single hospital in Zhejiang Province, China. We compared the baseline viral loads between severe patients and those mild to moderate at admission and also between those developing severe disease during hospitalization and those not. We studied 92 patients with confirmed COVID-19 who were admitted from January 19, 2020, to March 19, 2020, in the First Affiliated Hospital of Zhejiang University. The sputum specimens were collected from the lower respiratory tract of each patient at admission and the levels of viral nuclei acid were determined by a real-time PCR (RT-PCR) approach and indicated by the cycle threshold (Ct) values of RT-PCR assays [2] . We found that the viral load of the sputum specimen in the lower respiratory tract tested at baseline is closely related to the severity of COVID-19.
cord-325664-9ool5z9s	2020	authors: Immovilli, Paolo; Morelli, Nicola; Antonucci, Elio; Radaelli, Guido; Barbera, Mario; Guidetti, Donata title: COVID-19 mortality and ICU admission: the Italian experience correlation was observed between the CFR and ICU admission rate (Pearson''s r − 0.53, p value 0.014) and R 2 was 0.24, suggesting an association between mortality and the absence of treatment in ICU (Fig. 1) . However, examining the differing outbreak magnitudes in regions with different ICU availability evidenced a discrepancy in the percentage of ICU-admitted patients. Indeed, there was a higher mortality rate in the northern region where fewer patients could be admitted into an ICU. Paolo Immovilli, Nicola Morelli, Elio Antonucci, Guido Radaelli, Mario Barbera, and Donata Guidetti are responsible for study design and all authors wrote and reviewed the manuscript. There was no funding for this article.Availability of data and materials Data published online by Italian Civil Protection Department (http:// opendatadpc.maps.arcgis.com/apps/opsdashboard/index.html#/b0c68bce2 cce478eaac82fe38d4138b1; seen on March 31, 2020).Ethics approval and consent to participate Not applicable.
cord-325694-xx6m60hv	2020	title: Paediatric and adult critical care medicine: joining forces against Covid-19 Paediatric and adult critical care medicine: joining forces against Covid-19 This could be done by redeploying paediatric critical care physicians and nurses to adult ICUs. However, paediatric ICUs (PICU) are exclusively located in university hospitals in the Netherlands, hence redeployment potentially could reduce capacity for critically ill children [1] . PICU physicians and nurses advocated to remain in their environment and use the well-established working relationships within the PICU bedside team when caring for the adult COVID-19 patients because the general principles of intensive care medicine would not be different between children and adults [3] . Our ICUs admitted 98 adult COVID-19 patients, 12 of them were treated in the PICU by paediatric nurses and intensivists. It made PICU practitioners stronger in many ways and sets in motion a stronger relationship between paediatric and adult critical care medicine in our hospital.
cord-326124-jtpsydy5	2020	title: Fibrin-derived peptide Bβ15-42 (FX06) as salvage treatment in critically ill patients with COVID-19-associated acute respiratory distress syndrome Here, we describe the empirical salvage treatment of critically ill COVID-19 patients in two German tertiary care University Hospitals with FX06 (F4 Pharma, Vienna, Austria), a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bβ15-42). This observational case series includes six patients during their treatment in the intensive care unit. Based on our experience, the salvage use of FX06 in severe COVID-19-associated ARDS could be an effective therapy to improve pulmonary function and vascular leakage in the most severely ill patients. FX06 (fibrin-derived peptide Bbeta15-42)-a potential candidate for myocardial reperfusion therapy EA, BS, and PM analyzed and interpreted the patient data and wrote the manuscript. This study was funded by institutional funds of both University hospitals. The study was approved by the local ethics committee (University Hospital Frankfurt, Frankfurt, Germany) (#20-643).
cord-326315-ncfxlnpj	2011	INTRODUCTION: The frequency and clinical significance of polymicrobial aetiology in community-acquired pneumonia (CAP) patients admitted to the ICU have been poorly studied. The aim of the present study was to describe the prevalence, clinical characteristics and outcomes of severe CAP of polymicrobial aetiology in patients admitted to the ICU. Patients with polymicrobial aetiology had previously received antibiotics less frequently, had a higher proportion of chronic respiratory and neurological diseases, less frequently presented fever at admission, had higher rates of PSI risk class V, had severe CAP according to the IDSA/ATS definition, and fulfilled ARDS criteria. Among these variables, chronic respiratory disease and ARDS criteria at hospital admission were independent predictors of polymicrobial aetiology in the multivariate analysis. • Polymicrobial aetiology is frequent among patients with CAP admitted to the ICU and may result in inappropriate empiric antimicrobial treatment.
cord-326874-rdwvsm4s	2020	In Cox regression analysis using corticosteroid treatment as a time-varying variable, corticosteroid treatment was associated with a significant reduction in risk of in-hospital death within 60 days after adjusting for age, sex, SOFA score at hospital admission, propensity score of corticosteroid treatment, comorbidities, antiviral treatment, and respiratory supports (HR 0.42; 95% CI 0.21, 0.85; p = 0.0160). CONCLUSION: In this clinical practice setting, low-dose corticosteroid treatment was associated with reduced risk of in-hospital death within 60 days in COVID-19 patients who developed ARDS. However, there was comprehensive controversy on its efficacy [9, 10] , due to the results of observational studies that showed corticosteroid treatment was associated with increased mortality and nosocomial infections for influenza and delayed virus clearance for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) [11] . In this observational study, prescription of low-to-moderate dose systemic corticosteroids was associated with lower risk of 60-day in-hospital death among COVID-19 patients who developed ARDS.
cord-327622-ezgufe24	2020	• When removing the endotracheal tube, simultaneously turn off the ventilator • Avoid disconnecting ETT from the ventilator circuit before extubation to reduce spray of contaminated aerosols 9 Transport • Place a filter between the artificial airway and the transport ventilator circuit • Use HME that has filter function (HME-F) • Consider clamping the ETT before disconnection from ventilator circuit 10 Bronchoscopy assist* 2 in vivo [44, 45] • For spontaneously breathing patients, place a surgical mask on patient''s face (Fig. 7a, b) • Use NIV mask with examination port for patients on NIV (Fig. 7d) • Use swivel adapter to insert bronchoscope for intubated patient (Fig. 7c) Abbreviations: HFNC high-flow nasal cannula, IPPB intermittent positive pressure breathing, HME heat moisture exchanger, ETT endotracheal tube, NIV non-invasive ventilation *Based on CDC guidelines, these procedures should ideally be performed in airborne infection isolation rooms entrainment or nonrebreather mask [53] .
cord-329381-uwae8738	2020	title: Cardiovascular phenotypes in ventilated patients with COVID-19 acute respiratory distress syndrome COVID-19 patients with ACP tended to have lower respiratory-system compliance than their counterparts, presumably due to distinct ARDS phenotypes [6] . This first study assessing hemodynamically ventilated COVID-19 patients with TEE shows a lower **Calculated as the tidal volume divided by the driving pressure (difference between the inspiratory plateau pressure and positive end-expiratory pressure) ***One patient was diagnosed with a Tako-tsubo syndrome during transesophageal echocardiography examination performed shortly after tracheal intubation, after 6 days of high-flow nasal cannula; full recovery of left ventricular systolic function was documented under mechanical ventilation 10 days later ****Measured using the Doppler method applied at the left ventricular outflow tract *****As per April 24, with still 6 patients hospitalized in the intensive care unit, 5 of them being invasively ventilated prevalence of LV and RV failure than in flu-related ARDS patients.
cord-331395-12bff84n	2020	Jingwen Li 1 † , Xiaxia Yu 2 † , Shaoping Hu 3 , Zhicheng Lin 4 , Nian Xiong 1,5* and Yi Gao 2* Previous imaging studies of COVID-19 suggested that bilateral lungs be affected [1] . Moreover, the level of right-over-left preference of lung injury was significantly correlated with the potential need for intensive care and inpatient mortality. Pulmonary lesions were imaged by a total of 253 high resolution computed tomographic (CT) chest scans of 103 COVID-19 patients at Wuhan Red Cross Hospital. As a result, 70% (31/103) CT scans showed that the lesion volume of the right lung was larger than that of the left lung. The results suggested that patients with large lesions on the right lung be at a high mortality risk during hospitalization (OR = 2.662, P value = 0.0252 (Fig. 2c, d) .
cord-331700-5rfgyiit	2006	Longitudinal epidemiology studies convey an important additional aspect of the healthcare burden from disease, and may additionally serve to compare the effectiveness and efficiency of healthcare systems, to examine specific patient care strategies and to perform quality control analyses. Data of this kind are essential for determining the optimal ICU utilization for a given condition, tracking the effectiveness and efficiency of healthcare systems according to changes in disease incidence or outcome, and for planning research studies according to the characteristics of the disease. In the present issue of Critical Care, investigators from the Intensive Care National Audit and Research Center report the results of a longitudinal study of severe sepsis encompassing England, Wales and Northern Ireland in the past 10 years [1] . EPISEPSIS: a reappraisal of the epidemiology and outcome of severe sepsis in French intensive care units Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care
cord-334117-8gadvw16	2020	The pandemic has been complicated by the co-occurrence of a large methanol outbreak in Iran, seemingly triggered by false claims that consumption of disinfectants and alcohols could prevent and treat COVID-19 infection. In this research letter, we describe the scale of the Iranian methanol outbreak, based on hospitalization and mortality data collated from databases of the Iranian Ministry of Health (MOH) and Legal Medicine Organization (LMO) for the period of February 23 (first documented COVID-19 case in Iran) until May 2, 2020. In terms of mortality, MOH reported that 534 patients with methanol poisoning were confirmed dead in the hospital setting, equivalent to an estimated case fatality rate of approximately 9% (534/5876). Despite these inconsistencies, the number of Iranian poisoning cases (5876 hospitalizations from late February until early May),\ is already five times higher than the second-largest methanol outbreak in history, which was recorded in Libya in March 2013 and affected 1066 patients [2] .
cord-334391-0172afa1	2020	I would like to humbly add some views to it: there has been two varying reported type I interferon responses in COVID-19 pathogenesis [2] : one stating the suppression of host antiviral type I interferons (IFNs) and interferon stimulated genes (ISGs) and other stating increased expression of different ISGs, with further inductions of chemokines and cytokines [2] . The viral Nsps (particularly Nsp1) and the ORFs (particularly ORF 6) are known to antagonise the host antiviral IFNs initially by suppressing/delaying their expressions, leading to viral persistence and propagating inflammations. Hence, neither type I IFN nor type III IFN, which are known hard-wired for providing antiviral immunity, was activated in early stages of COVID-19. Aberrant production of NETs have been known to cause severe COVID-like pathophysiologies-thrombosis, lung damage, ARDS, multiorgan damage, etc. The initial type 1IFN suppression could lead to enhanced infiltration of neutrophils, NET formation and ensuing pathophysiologies.
cord-335033-cwhm7v0s	2020	title: Clinical ethics recommendations for the allocation of intensive care treatments in exceptional, resource-limited circumstances: the Italian perspective during the COVID-19 epidemic As of March 6, 2020, the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI) issued a series of recommendations [5] and relevant ethical considerations to better inform the clinicians involved in the care of critically-ill COVID-19 patients, in a setting where a disproportionate number of patients requiring life-sustaining treatments was rapidly saturating both the existing and the newly set-up ICU beds. The emerging epidemic is leading to a substantial increase in the number of patients requiring prolonged ventilatory support for acute respiratory failure, potentially resulting in severe imbalances between the population clinical needs and the overall availability of ICU resources. SIAARTI Clinical Ethics Recommendations for the Allocation of Intensive Care Treatments in exceptional, resource-limited circumstances
cord-335172-5ig907on	2020	Likewise, patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) could be at a greater risk due to the mechanism by which SARS-CoV-2 enters the cell. First, because it normally binds to ACE2 during its degradation and hydrolysis into angiotensin-(1-7) [11] , it may compete with the SARS-CoV-2 for the ACE2 receptor (Fig. 1) . Second, the binding of AngII to the AT1 receptor has been shown to cause internalization and downregulation of ACE2 through an ERK1/2 and p38 MAP kinase pathway in both in vitro animal and in vivo human models [12, 13] . However, to date, the link between ACE inhibitors and ARBs and severity of illness of SARS-CoV-2 infection is purely speculative. Ang-2, angiotensin II; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; ACE1, angiotensinconverting-enzyme 1; ACE2, angiotensin-converting-enzyme 2; H 2 O, water; Na + , sodium Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
cord-336314-xf6zvvl8	2020	title: Clinical analysis of sinus bradycardia in patients with severe COVID-19 pneumonia The initial manifestation of severe COVID-19 pneumonia patients was hypoxemic respiratory failure, accompanied by rapid increased reactive heart rate and susceptibility to supraventricular arrhythmia [2] . It is noteworthy that about 1/3 of the patients with severe illness in our study developed sinus bradycardia (Fig. 1) . However, there was no severe myocardial damage or cardiac insufficiency in our patients with sinus bradycardia. In light of those evidences, it may be speculated that the toxic role of virus on cardiac conduction system instead of that generated myocardial damage resulted in a sudden death of patients infected with COVID-19. Moreover, a possible inhibitory influence of the virus on activity of cardiac nervous conduction system including sinus node via ACE2 should not be ignored when studying the pathogenic mechanisms among these patients.
cord-337444-pqoq8aew	2020	title: Nafamostat mesylate treatment in combination with favipiravir for patients critically ill with Covid-19: a case series Through high-throughput screening of 1017 existing drugs, a clinically available serine protease inhibitor nafamostat mesylate was identified as a potent inhibitor of Middle East respiratory syndrome coronavirus entry into human epithelial cells [2] . Eleven adults with reverse transcriptase polymerase chain reaction-confirmed SARS-CoV-2 infection were admitted to the intensive care unit (ICU) at The University of Tokyo Hospital between April 6 and April 21, 2020, and treated with nafamostat mesylate in combination with favipiravir. Although the number of patients in this case series was very small, this low mortality rate suggests that combination treatment of favipiravir and nafamostat mesylate may be effective for critically ill Covid-19 patients. A clinical trial for the combination treatment of nafamostat mesylate and favipiravir against Covid-19 will be initiated in Japan (jRCTs031200026). Nafamostat mesylate blocks activation of SARS-CoV-2: new treatment option for COVID-19
cord-337485-nqcnd9py	2020	Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms'' onset and date of sampling. Our objectives were (1) to describe the viral shedding and the viral load in LRT and (2) to determine THE ASSOCIATION BETWEEN VIRAL PRESENCE AND MORTALITY in critically ill COVID-19 patients. The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the SARS-CoV-2 viral presence in the LRT was associated with the 6week mortality. Diabetes mellitus is a risk factor for prolonged SARS-CoV-2 viral shedding in lower respiratory tract samples of critically ill patients
cord-338134-smrokdsq	2020	title: Therapeutic plasma exchange as a routine therapy in septic shock and as an experimental treatment for COVID-19: we are not sure Therapeutic plasma exchange as a routine therapy in septic shock and as an experimental treatment for COVID-19: we are not sure Patrick M. who concluded that their practice has changed based on their experience, and they now often utilize therapeutic plasma exchange (TPE) earlier in the clinical course of septic shock with multiple organ failure (MODS) and acute respiratory distress syndrome (ARDS) rather than using it as a "rescue therapy" [1] . stated that a major difference between TPE and modern extracorporeal adsorption strategies is based on the fact that the exchange of septic shock plasma with fresh frozen plasma may not lead to an unselective depletion of pro-and anti-inflammatory cytokines and will rather replenish protective factors (within FFPs) that have been consumed by the sepsis [2] .
cord-338990-vrtzyo2o	2020	This includes an "obligation to provide urgent medical care during disasters … even in the face of greater than usual risks to physicians'' own safety, health, or life." Given the large scope of the pandemic and the deadliness of SARS-CoV-2, these statements may not adequately address this ethical quandary. Based on these principles, 6 recommendations have been made for the current outbreak: maximizing benefits including using scarce resources responsibly and saving more lives/years of life, prioritizing COVID-19 resources (i.e., PPE, vaccines) to healthcare workers, invoking equality using random allocation or lottery to distribute resources to those with similar prognoses, thoughtful consideration of resource allocation (e.g., prioritizing older patients, among the most affected by SARS-CoV-2, to receive a vaccine), prioritizing those who have participated in COVID-19-related research, and providing equal resources to those with COVID-19 and those with other medical conditions [9] . Several ethical dilemmas associated with the COVID-19 pandemic affect intensive care physicians.
cord-340205-cwn0gx7h	2020	title: Mortality rate of acute kidney injury in SARS, MERS, and COVID-19 infection: a systematic review and meta-analysis There was no evidence of statistical heterogeneity among studies reporting AKI mortality in SARS (I2: 0.0%, p = 0.589) and MERS (I2: 0.0%, p =v0.758), but there was for COVID-19 infection (I2: 97.0%, p < 0.001) (Fig. 1 ). Possible mechanisms of higher AKI mortality following coronavirus infections are multifactorial (e.g., severe sepsis-related multiorgan failure, direct kidney involvement, and acute respiratory distress syndrome) [26] [27] [28] , although comparative pathogenesis of kidney involvement among the three infections remains unclear. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study
cord-341063-3rqnu5bu	2018	Procacitonin (PCT) emerges as a possible predictive tool in cardiothoracic intensive care unit (CTICU).We aim at testing the predictive power of PCT for early morbidity, prolonged ventilation, ICU and hospital stay, in patients developing early fever after cardiac surgery Methods: A retrospective descriptive study done in tertiary cardiac center, enrolling patients who stayed for more than 24 hours post-operatively in the CTICU Risk stratification included additive Euro score and PCT immunoluminometricaly prior to surgery and every 48 hours in response to onset of fever. Prognostic accuracy of quick sequential organ failure assessment (qSOFA) score for mortality: systematic review and meta-analysis Introduction: The purpose of this study was to summarize the evidence assessing the qSOFA [1] , calculated in admission of the patient in emergency department (ED) or intensive care unit (ICU), as a predictor of mortality.
cord-343940-fdnmeuh8	2020	title: Incidence of ARDS and outcomes in hospitalized patients with COVID-19: a global literature survey Seventeen studies reporting results from 2486 hospitalized COVID-19 patients in five countries fitted the inclusion criteria (Tables 1 and 2 ). Calculation of weighted averages for these parameters incorporating data from individual studies for which data is available indicate that among hospitalized COVID-19 patients, approximately 1/3 (33%) develop ARDS, 1/4 (26%) require transfer to Patient numbers for Chen T study not included an ICU, 1/6 (16%) receive IMV, and 1/6 (16%) die (Table 1 ). For COVID-19 patients transferred to an ICU, nearly 2/3 (63%) receive IMV and 3/4 (75%) have ARDS ( Table 2 ). Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China Treatment for severe acute respiratory distress syndrome from COVID-19 Authors'' contributions SJT conducted the literature search and survey. The authors read and approved the final manuscript.
cord-344965-h945xi7y	2020	reported that there was an extremely high incidence (85.4%) of lower extremity deep venous thrombosis (DVT) among 48 patients with severe coronavirus disease 2019 in Wuhan, China [1] . Thus, we performed a meta-analysis to estimate the pooled prevalence of DVT in confirmed COVID-19 patients. Articles reporting the prevalence of DVT in confirmed COVID-19 patients were included. The meta-regression and subgroup analysis were used to investigate the potential heterogeneity sources (such as sample size, prevalence of prophylaxis in COVID-19 patients, location, design of studies, screening methods of DVT, and COVID-19 patients in intensive care unit (ICU)). The pooled prevalence of DVT in Table 1 Characteristics of the included studies COVID-19 patients treated in ICU was 23% (95% CI 11-38%, P < 0.01, I 2 = 96.44%, Q = 421.29, P < 0.01), which was significantly higher than in COVID-19 patients treated in non-ICU (5%, 95% CI 1-11%, P < 0.01, I 2 = 92.17%, Q = 89.42, P < 0.01) (Fig. 1c, d) . Deep vein thrombosis in hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: prevalence, risk factors, and outcome
cord-345973-fb3gkc0f	2020	Five to 10% of the coronavirus SARS-CoV-2-infected patients, i.e., with new coronavirus disease 2019 (COVID-19), are presenting with an acute respiratory distress syndrome (ARDS) requiring urgent respiratory and hemodynamic support in the intensive care unit (ICU). Up to 30% of the coronavirus SARS-CoV-2-infected patients are presenting with an acute respiratory distress syndrome (ARDS) requiring urgent respiratory and hemodynamic support in the intensive care unit (ICU) [2] . This article was written in the emergency of the epidemic by an expert group, based on the international recommendations on nutrition in the ICU on March 29, and will be updated according to new knowledge about the COVID-19. Indirect calorimetry (IC) should be proposed only for patients staying for more than 10 days in the ICU or those on full parenteral nutrition (PN) to avoid overfeeding IC is the reference method to assess the energy requirements in the non-COVID-19 ICU patients [18] .
cord-346307-xejs2va1	2020	The authors refer to the ATHOSIII trial as support for the use of ANGII in catecholamine-resistant vasodilatory shock despite the known concern for thrombotic and infectious complications associated with ANGII [2] . In addition, the authors suggest to use ANGII in COVID-19 patients recently exposed to angiotensin-converting enzyme inhibitors. In a recent COVID-19 case series, ANGII levels were markedly elevated and linearly associated with viral load and lung injury [4] . Moreover, in a prepublished report currently under journal review, infusion of ANGII in a porcine model rapidly (within hours) induced a clinical syndrome closely reflecting the one seen in COVID-19 patients, including histological changes in the lungs with severe thickening of the alveolar walls, possible hyaline membranes, and clotting of vessels, as previously reported in the human COVID-19 phenotype [5] . Angiotensin II infusion in COVID-19-associated vasodilatory shock: a case series Treatment with angiotensin II in COVID-19 patients may not be beneficial.
cord-346394-rk8jkf19	2020	The data show that in order to deliver higher pressure during NHF, then the flow rate and/or cannula size need to be increased. The results are taken from a bench experiment with inelastic orifices, and patients rarely have a closed system; however, the bench data demonstrate that a small reduction of the leak around the cannula, by occluding a larger area of the nare, may lead to a substantial increase of delivered pressure, particularly in the upper range of NHF rates. Fig. 1 The graph shows the positive airway pressure, cmH2O, that is generated by nasal high flow (NHF) using a smaller cannula (O.D. 6.1 mm) and larger cannula (O.D. 7.2 mm) in "nares" with two different diameters: 10 mm (left panel) and 9 mm (right panel) in the bench top model. Pressure generated by NHF can be increased by higher flow and by occluding a larger area of the nare, which can be achieved by increasing the cannula size
cord-347833-b3yrxkt0	2020	We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients. CONCLUSION: Although dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort. The following covariates were chosen from available variables through directed acyclic graph analysis and a literature review: sepsis; age [1] and sex, all of which have been previously described as independent risk factors for dementia [33] ; CCI; SAPS3 box 2+3; hospital length of stay (H-LoS); ICU-LoS; invasive ventilator therapy; and RRT. However, after adjusting for age, sex, CCI score, SAPS3 box 2+3, H-LoS, ICU-LoS, invasive ventilator therapy, and RRT, sepsis was no longer an independent risk factor for dementia (HR 1.01, 95% CI 0.91-1.11) (Fig. 4) 
cord-351264-zp41u14l	2020	title: Mortality rates of patients with COVID-19 in the intensive care unit: a systematic review of the emerging literature Mortality rates of patients with COVID-19 in the intensive care unit: a systematic review of the emerging literature Pipetius Quah 1* , Andrew Li 1 and Jason Phua 1, 2 The understanding of outcomes in the intensive care unit (ICU) for the coronavirus disease 2019 (COVID-19) remains poor. Studies have reported close to 100% mortality amongst patients requiring mechanical ventilation [1] , and this together with the hypothesis that COVID-19 may not cause classic acute respiratory distress syndrome (ARDS) has led to concerns regarding the use of mechanical ventilation [2, 3] . We searched PubMed for studies published between Dec 1, 2019, and May 8, 2020, with at least ten ICU patients with COVID-19 and reported ICU mortality data. We conclude that while there is a need for further studies which capture patients'' final dispositions, the current preliminary data does not suggest unusually high ICU mortality rates for COVID-19.
cord-351600-bqw9ks4a	2020	title: Development and validation of a risk factor-based system to predict short-term survival in adult hospitalized patients with COVID-19: a multicenter, retrospective, cohort study We aimed to explore the risk factors of 14-day and 28-day mortality and develop a model for predicting 14-day and 28-day survival probability among adult hospitalized patients with COVID-19. Nomogram scoring systems for predicting the 14-day and 28-day survival probability of patients with COVID-19 were developed and exhibited strong discrimination and calibration power in the two external validation cohorts (C-index, 0.878 and 0.839). CONCLUSION: Older age, high lactate dehydrogenase level, evaluated neutrophil-to-lymphocyte ratio, and high direct bilirubin level were independent predictors of 28-day mortality in adult hospitalized patients with confirmed COVID-19. We aimed to explore the risk factors of 28-day mortality and develop a nomogram scoring system for predicting 28-day survival probability among patients with COVID-19.
cord-352227-827987jf	2020	METHODS: In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups—acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)—as well as performed comparison with 23 healthy volunteers. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients. The aim of this study was to analyze the association between the serum and fecal levels of AMM and compare them with the composition of the gut microbiota in critically ill patients in the acute and chronic stages. The aim of this study was to analyze the association between the serum and fecal levels of AMM and compare them with the composition of the gut microbiota in critically ill patients in the acute and chronic stages.
cord-353344-tzyu6j6n	2020	PCT appears to increase in COVID patients with severe disease and/or in those presenting with secondary bacterial infections [6] . The use of biomarkers to predict secondary infections in ICU patients warrants reappraisal in times of COVID-19. We demonstrate that COVID-19 patients who do not develop a bacterial infection present with high initial CRP levels and lowmoderate PCT levels that gradually decrease over time. Furthermore, our data show that, during ICU admission, PCT levels of > 1.00 μg/L rule in, whereas concentrations of < 0.25 μg/L rule out secondary bacterial infections with good predictive values. As CRP is consistently elevated, this biomarker does not have predictive value for bacterial infections in the initial phase of COVID-19. b Serial values of PCT (left panel) and CRP (right panel) in patients (n = 33) with COVID-19 who did develop (n = 33) or did not (n = 33) develop a secondary infection.
cord-354355-i6ot4ef8	2020	title: Endobronchial ultrasound is feasible and safe to diagnose pulmonary embolism in non-transportable SARS-CoV-2 ARDS patients requiring extracorporeal lung support The diagnosis of pulmonary embolism (PE) may be challenging in these patients because computed tomography pulmonary angiogram (CTPA) requires an intrahospital transport with potential adverse effects and also may increase the risk of acute kidney failure (contrast-induced nephropathy). This is even more the case in up to 10% of SARS-Cov-2 ARDS patients who require venovenous extracorporeal membrane oxygenation (vv-ECMO) as an extracorporeal lung support [1] . Here, we describe the feasibility, safety, and diagnostic accuracy of endobronchial ultrasound (EBUS) to detect PE in patients with severe SARS-CoV-2 ARDS requiring vv-ECMO. This case series of EBUS to diagnose PE in severe SARS-CoV-2 ARDS patients requiring vv-ECMO suggests that the EBUS procedure is safe and reliable to detect lobar and even segmental PE at bedside. Martin Dres received personal fees and travel expenses from Lungpacer outside the submitted work.
cord-355847-1ru15s5a	2020	Several drugs, endowed with modulating activity on cytokine pathways, including anti-IL-6, anti-TNF, and Janus kinase (JAK) inhibitors, currently approved for the treatment of immune-mediated inflammatory diseases, have been suggested or could be yet taken into account for experimental use in COVID-19 patients with ARDS and/or pneumonia ( Fig. 1 ). In addition, a multicenter open-label randomized clinical trial is studying the benefit risk profile of siltuximab, as a single therapeutic option or in combination with anakinra, at a single dose of 11 mg/kg, in comparison with tocilizumab or anakinra, alone or in combination, in ARDS patients with COVID-19 [20] . Based on the results expected with tocilizumab and siltuximab, other anti-IL-6 drugs, currently approved for rheumatoid arthritis, namely sarilumab and sirukumab, could be studied in ARDS and pneumonia patients with COVID-19. Anti-JAK drugs (such as ruxolitinib, tofacitinib, baricitinib, oclacitinib, fedratinib, upadacitinib, and peficitinib) [39] should be considered also among the options for clinical investigations in COVID-19-related ARDS and pneumonia patients.