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PurposeTo evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification.MethodsOur primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24 h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification.ResultsOf 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01–1.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both resolved and confirmed ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal.ConclusionsARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population.Trial RegistrationClinicalTrials.gov NCT02010073.

Abstract Objectives To review the new current diagnostic criteria of transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI) from the literature while highlighting distinguishing features. We provide comprehensive understanding of the importance of hemovigilance and its role in appropriately identifying and reporting these potentially fatal transfusion reactions. Methods A review of the English language literature was performed to analyze TACO and TRALI while providing further understanding of the rationale behind the historical underrecognition and underreporting. Results Our review demonstrates the new 2018 and 2019 case definitions for TACO and TRALI, respectively. With more comprehensive diagnostic strategies, adverse transfusion events can be better recognized from mimicking events and underlying disease. In addition, there are mitigation strategies in place to help prevent complications of blood product transfusion, with emphasis on the prevention of TACO and TRALI. Conclusions TACO and TRALI are potentially fatal adverse complications of blood transfusion. Both have been historically underrecognized and underreported due to poor defining criteria and overlapping symptomatology. Developing a thorough clinical understanding between these two entities can improve hemovigilance reporting and can contribute to risk factor identification and preventative measures.

Background\\nTo better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study.\\nMethods\\nThis is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1–2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort.\\nResults\\nOf the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1–Q3, 7–21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample.\\nConclusions\\nMost patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality.

PurposeAcute respiratory distress syndrome (ARDS) is heterogeneous in etiology, which may affect outcomes. Stratification into biologically-defined subtypes may reduce heterogeneity. However, it is unknown whether pediatric ARDS has clinically relevant subtypes. We aimed to determine whether clinical characteristics and predictors of mortality differed between direct and indirect ARDS, and separately between infectious and non-infectious ARDS.MethodsThis was a single center, prospective cohort study of 544 children with ARDS (Berlin) between July 2011 and June 2017, stratified into direct versus indirect ARDS, and separately into infectious versus non-infectious ARDS. Multiple logistic regression was used to test for predictors of mortality in the entire cohort, and separately within subtypes. Effect modification by subtype was assessed using interaction tests.ResultsDirect ARDS had lower severity of illness (p < 0.001) but worse oxygenation (p < 0.001), relative to indirect. Predictors of mortality were similar for direct and indirect ARDS. When comparing infectious and non-infectious ARDS, infectious ARDS had lower severity of illness (p < 0.001), worse oxygenation (p = 0.014), and lower mortality (p = 0.013). In multivariable analysis, immunocompromised status demonstrated effect modification between infectious and non-infectious ARDS (p = 0.005 for interaction), with no association with mortality in non-infectious ARDS.ConclusionsIn children, direct and indirect ARDS have distinct clinical characteristics, but similar outcomes and similar predictors of mortality. In contrast, infectious and non-infectious ARDS demonstrate heterogeneity of clinical characteristics, mortality, and predictors of mortality, with traditional predictors of ARDS mortality only applicable to infectious ARDS.

The studies done on lung protective strategies in medical ventilators have shown that tidal volume of 6-ml/ kg predicted body weight protects the lungs of a patient during the invasive ventilation for acute respiratory distress syndrome (ARDS) patients in intensive care unit. Corona virus disease 2019 has increased the need for mechanical ventilation, which are operated manually, in changing the settings on the mechanical ventilators. In this study, fuzzy logic method is used to develop a computer-aided decision-making to improve on the accuracy of the reasoning done during the ventilator setting adjustment, by adding the fuzzy reasoning concept into the ARDS Berlin definition. The ARDS positive end-expiratory pressure (PEEP) values were used in building the fuzzy rules of the fuzzy algorithm. From the experimental results, the algorithm mimics the recommended ARDS PEEP values with respect to the values of fraction of inspired oxygen (FiO2); the algorithm as well increases the respiratory rate and tidal volume for potential of Hydrogen (pH) less than 7.2; maintains the respiratory rate and tidal volume for pH between 7.2 and 7.4; decreases the respiratory rate; and maintains the tidal volume for pH greater than 7.4. The developed fuzzy system can therefore be applied as a physician–ventilator interface to guide the clinician/physician during the ventilation, so as, to reduce the human errors and ensure lung protection.

The COVID-19 pandemic has reached direct and indirect medical and social consequences with a subset of patients who rapidly worsen and die from severe-critical manifestations. As a result, there is still an urgent need to identify prognostic biomarkers and effective therapeutic approaches. Severe-critical manifestations of COVID-19 are caused by a dysregulated immune response. Immune checkpoint molecules such as Programmed death-1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1) play an important role in regulating the host immune response and several lines of evidence underly the role of PD-1 modulation in COVID-19. Here, by analyzing blood sample collection from both hospitalized COVID-19 patients and healthy donors, as well as levels of PD-L1 RNA expression in a variety of model systems of SARS-CoV-2, including in vitro tissue cultures, ex-vivo infections of primary epithelial cells and biological samples obtained from tissue biopsies and blood sample collection of COVID-19 and healthy individuals, we demonstrate that serum levels of PD-L1 have a prognostic role in COVID-19 patients and that PD-L1 dysregulation is associated to COVID-19 pathogenesis. Specifically, PD-L1 upregulation is induced by SARS-CoV-2 in infected epithelial cells and is dysregulated in several types of immune cells of COVID-19 patients including monocytes, neutrophils, gamma delta T cells and CD4+ T cells. These results have clinical significance since highlighted the potential role of PD-1/PD-L1 axis in COVID-19, suggest a prognostic role of PD-L1 and provide a further rationale to implement novel clinical studies in COVID-19 patients with PD-1/PD-L1 inhibitors.

COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called “cytokine storm” induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.

BackgroundSurvivors of critical illness often experience poor outcomes after hospitalisation, including delayed return to work, which carries substantial economic consequences.ObjectiveTo conduct a systematic review and meta-analysis of return to work after critical illness.MethodsWe searched PubMed, Embase, PsycINFO, CINAHL and Cochrane Library from 1970 to February 2018. Data were extracted, in duplicate, and random-effects meta-regression used to obtain pooled estimates.ResultsFifty-two studies evaluated return to work in 10 015 previously employed survivors of critical illness, over a median (IQR) follow-up of 12 (6.25–38.5) months. By 1–3, 12 and 42–60 months’ follow-up, pooled return to work prevalence (95% CI) was 36% (23% to 49%), 60% (50% to 69%) and 68% (51% to 85%), respectively (τ 2=0.55, I2=87%, p=0.03). No significant difference was observed based on diagnosis (acute respiratory distress syndrome (ARDS) vs non-ARDS) or region (Europe vs North America vs Australia/New Zealand), but was observed when comparing mode of employment evaluation (in-person vs telephone vs mail). Following return to work, 20%–36% of survivors experienced job loss, 17%–66% occupation change and 5%–84% worsening employment status (eg, fewer work hours). Potential risk factors for delayed return to work include pre-existing comorbidities and post-hospital impairments (eg, mental health).ConclusionApproximately two-thirds, two-fifths and one-third of previously employed intensive care unit survivors are jobless up to 3, 12 and 60 months following hospital discharge. Survivors returning to work often experience job loss, occupation change or worse employment status. Interventions should be designed and evaluated to reduce the burden of this common and important problem for survivors of critical illness.Trial registration numberPROSPERO CRD42018093135.

IntroductionAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of acute respiratory failure arising from the same underlying pathophysiological processes and are associated with substantial morbidity and mortality worldwide. Although corticosteroids such as Dexamethasone are commonly administered to patients with moderate-to-severe ARDS, their clinical benefit remains controversial, and systemic administration is often associated with significant adverse effects.MethodsWe developed a targeting ligand-free, sulfonium lipid nanoparticle (sLNP)-based drug delivery system, Dex/DOSEH, for intravenous lung-targeted delivery of dexamethasone.ResultsIn a lipopolysaccharide (LPS)-induced murine ALI model, treatment with Dex/DOSEH formulation significantly reduced proinflammatory cytokine production, decreased immune cell infiltration, preserved capillary-alveolar barrier integrity, and attenuated histopathological lung injury compared with controls.DiscussionOur findings demonstrate that Dex/DOSEH drug formulation enables effective lung-targeted delivery of dexamethasone and achieves robust anti-inflammatory therapeutic efficacy in ALI. This platform represents a promising therapeutic strategy for the treatment of ALI/ARDS.

Acute respiratory distress syndrome (ARDS) is an overwhelming inflammatory disorder of the lung due to direct and indirect insults to the lungs. ARDS is characterized by increased vascular permeability, protein-rich edema, diffuse alveolar infiltrate, and loss of aerated lung tissue, leading to decreased lung compliance, tachypnea, and severe hypoxemia. COVID-19 is generally associated with ARDS, and it has gained prime importance since it started. The mortality rate is alarmingly high in COVID-19-related ARDS patients regardless of advances in mechanical ventilation. Several pharmacological agents, including corticosteroids, nitric oxide, neuromuscular blocker, anti-TNF, statins, and exogenous surfactant, have been studied and some are under investigation, like ketoconazole, lisofylline, N-acetylcysteine, prostaglandins, prostacyclin, and fish oil. The purpose of this review is to appraise the understanding of the pathophysiology of ARDS, biomarkers, and clinical trials of pharmacological therapies of ARDS and COVID-19-related ARDS.