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The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.

In patients with the novel coronavirus (COVID-19) infection, the echocardiographic assessment of the right ventricle (RV) represents a pivotal element in the understanding of current disease status and in monitoring disease progression. The present manuscript is aimed at specifically describing the echocardiographic assessment of the right ventricle, mainly focusing on the most useful parameters and the time of examination. The RV direct involvement happens quite often due to preferential lung tropism of COVID-19 infection, which is responsible for an interstitial pneumonia characterized also by pulmonary hypoxic vasoconstriction (and thus an RV afterload increase), often evolving in acute respiratory distress syndrome (ARDS). The indirect RV involvement may be due to the systemic inflammatory activation, caused by COVID-19, which may affect the overall cardiovascular system mainly by inducing an increase in troponin values and in the sympathetic tone and altering the volemic status (mainly by affecting renal function). Echocardiographic parameters, specifically focused on RV (dimensions and function) and pulmonary circulation (systolic pulmonary arterial pressures, RV wall thickness), are to be measured in a COVID-19 patient with respiratory failure and ARDS. They have been selected on the basis of their feasibility (that is easy to be measured, even in short time) and usefulness for clinical monitoring. It is advisable to measure the same parameters in the single patient (based also on the availability of valid acoustic windows) which are identified in the first examination and repeated in the following ones, to guarantee a reliable monitoring. Information gained from a clinically-guided echocardiographic assessment holds a clinical utility in the single patients when integrated with biohumoral data (indicating systemic activation), blood gas analysis (reflecting COVID-19-induced lung damage) and data on ongoing therapies (in primis ventilatory settings).

Purpose In view of the expected 2009 influenza A(H1N1) pandemic, the Italian Health Authorities set up a national referral network of selected intensive care units (ICU) able to provide advanced respiratory care up to extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS). We describe the organization and results of the network, known as ECMOnet. Methods The network consisted of 14 ICUs with ECMO capability and a national call center. The network was set up to centralize all severe patients to the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria for both patient transfer and ECMO institutions. Results Between August 2009 and March 2010, 153 critically ill patients (53% referred from other hospitals) were admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to ECMOnet criteria. All referred patients were successfully transferred to the ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO within 7 days from the onset of mechanical ventilation was 77%. The length of mechanical ventilation prior to ECMO was an independent predictor of mortality. Conclusions A network organization based on preemptive patient centralization allowed a high survival rate and provided effective and safe referral of patients with severe H1N1-suspected ARDS.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71–93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

ObjectivesSeveral physiological abnormalities that develop during COVID-19 are associated with increased mortality. In the present study, we aimed to develop a clinical risk score to predict the in-hospital mortality in COVID-19 patients, based on a set of variables available soon after the hospitalisation triage.SettingRetrospective cohort study of 516 patients consecutively admitted for COVID-19 to two Italian tertiary hospitals located in Northern and Central Italy were collected from 22 February 2020 (date of first admission) to 10 April 2020.ParticipantsConsecutive patients≥18 years admitted for COVID-19.Main outcome measuresSimple clinical and laboratory findings readily available after triage were compared by patients’ survival status (‘dead’ vs ‘alive’), with the objective of identifying baseline variables associated with mortality. These were used to build a COVID-19 in-hospital mortality risk score (COVID-19MRS).ResultsMean age was 67±13 years (mean±SD), and 66.9% were male. Using Cox regression analysis, tertiles of increasing age (≥75, upper vs <62 years, lower: HR 7.92; p<0.001) and number of chronic diseases (≥4 vs 0–1: HR 2.09; p=0.007), respiratory rate (HR 1.04 per unit increase; p=0.001), PaO2/FiO2 (HR 0.995 per unit increase; p<0.001), serum creatinine (HR 1.34 per unit increase; p<0.001) and platelet count (HR 0.995 per unit increase; p=0.001) were predictors of mortality. All six predictors were used to build the COVID-19MRS (Area Under the Curve 0.90, 95% CI 0.87 to 0.93), which proved to be highly accurate in stratifying patients at low, intermediate and high risk of in-hospital death (p<0.001).ConclusionsThe COVID-19MRS is a rapid, operator-independent and inexpensive clinical tool that objectively predicts mortality in patients with COVID-19. The score could be helpful from triage to guide earlier assignment of COVID-19 patients to the most appropriate level of care.

Aim of the present study was to investigate the effects of ongoing treatment with DOACs on time from trauma to surgery and on in-hospital clinical outcomes (blood losses, need for transfusion, mortality) in patients with hip fracture. Moreover we evaluated the adherence to current guidelines regarding the time from last drug intake and surgery. In this observational retrospective study clinical records of patients admitted for hip fracture from January 2016 to January 2019 were reviewed. 74 patients were in treatment with DOACs at hospital admission. Demographic data, comorbidities and functional status before trauma were retrieved. As control group we evaluated 206 patients not on anticoagulants matched for age, gender, type of fracture and ASA score. Time to surgery was significantly longer in patients treated with DOACs (3.6 + 2.7 vs. 2.15 ± 1.07 days, p < 0.0001) and treatment within 48 h was 47% vs. 80% in control group (p < 0.0001). The adherence to guidelines’ suggested time from last drug intake to surgery was 46%. Neither anticipation nor delay in surgery did result in increased mortality, length of stay or complication rates with the exception of larger perioperative blood loss (Hb levels < 8 g/dl) in DOACs patients (34% vs 9% p < 0.0001). Present results suggest that time to surgery is significantly longer in DOAC patients in comparison to controls and adherence to guidelines still limited.

The clinical pathway of a patient who experiences cardiac arrest and subsequently dies (with or without organ donation) is complex. It involves uncontrolled (u-) donation after circulatory death (DCD), controlled (c-) DCD, and donor after brain death (DBD). The present paper aims to summarize existing evidence on organ donation rates among out-of-hospital cardiac arrest (OHCA) patients, with a focus on these three donor categories (uDCD, DBD, and cDCD). Furthermore, the potential to expand each donor pathway in OHCA patients will be highlighted, based on available evidence. Among non-survivor OHCA patients, the prevalence of brain death (BD) is estimated to be low, though reported data are not uniform. The diagnosis of BD is made 3 to 6 days after return of spontaneous circulation. The implementation of uDCD is known to be quite challenging due to logistical, ethical, and resource issues. Its rationale is still well grounded, mainly considering two factors: (a) the high incidence of OHCA, such that uDCD donors can be considered an existing pool of potential donors; (b) the uDCD pathway shows feasibility both under organizational (i.e., only lung uDCD program) and clinical views (normothermic regional perfusion, ex vivo machine perfusion, and an appropriate donor–recipient match). Controlled DCDs are donors who died after a planned withdrawal of life-sustaining therapy (WLST). Data on the percentage of cDCD among OHCA patients is not uniform since the percentage of utilized cDCD has been estimated at around 10%. According to available evidence, each donor pathway in OHCA has the potential to be expanded, mainly by the identification of potential donors and the implementation of DCD programs.

BackgroundLung ultrasound (LU) is a useful tool for monitoring lung involvement in novel coronavirus (COVID) disease, while information on echocardiographic findings in COVID disease is to date scarce and heterogeneous. We hypothesized that lung and cardiac ultrasound examinations, serially and simultaneously performed, could monitor disease severity in COVID-related ARDS.MethodsWe enrolled 47 consecutive patients with COVID-related ARDS (1st March–31st May 2020). Lung and cardiac ultrasounds were performed on admission, at discharged and when clinically needed.ResultsMost patients were mechanically ventilated (75%) and veno-venous extracorporeal membrane oxygenation was needed in ten patients (21.2%). The in-ICU mortality rate was 27%%. On admission, not survivors showed a higher LUS score (p = 0.006) and a higher incidence of consolidations (p = 0.003), lower values of LVEF (p = 0.027) and a higher RV/LV ratio (0.008). At discharge, a significant reduction in the incidence of subpleural consolidations (p < 0.001) and, thus, in LUS score (p < 0.001) and an increase in patter A findings (p < 0.001) together with reduced systolic pulmonary arterial pressures were detectable. In not survivors at final examination, an increased in LUS score (p < 0.001), and in RV/LV ratio (p < 0.001) associated with a reduction in TAPSE (p = 0.013) were observed. A significant correlation was observed between LUS and systolic pulmonary arterial pressure (p = 0.04). LUS and RV/LV resulted independent predictors of in-ICU death.ConclusionsIn COVID-related ARDS, the combined lung and cardiac ultrasound proved to be an useful clinical tool in monitoring disease progression and in identifying parameters (LU score and RV/LV ratio) able to risk stratifying these patients.

Background: The Macklin effect recently demonstrated a high positive predictive value for barotrauma in the COVID-19 ARDS population. However, there was less evidence available regarding the ARDS population without SARS-CoV-2 infection. We aim to analyze COVID-19 and non-COVID-19 ARDS subjects to assess the sensitivity and specificity of the Macklin effect in predicting the development of barotrauma in both groups. Methods: We retrospectively analyzed subjects with ARDS admitted to our center from January 2018 to November 2022. Experienced radiologists examined the presence of the Macklin effect on chest computed tomography scans. Subjects were then divided into two groups based on the presence or absence of the Macklin effect to assess its predictive power regarding barotrauma. Finally, we analyzed the impact of the Macklin effect and barotrauma on Intensive Care Unit and in-hospital mortality. Results: We analyzed 225 patients; the Macklin effect was observed in 44 subjects. In our cohort, the Macklin effect exhibited a sensitivity of 44.6% and a specificity of 90.6% in predicting barotrauma. After excluding the COVID-19 ARDS cases, the Macklin effect showed a sensitivity of 34.7% and a specificity of 93.6%. Nonetheless, in our population, the presence of the Macklin effect or the occurrence of barotrauma did not lead to increased ICU or in-hospital mortality. Conclusions: Our analysis highlighted that the Macklin effect demonstrates high specificity in predicting barotrauma but a low sensitivity; moreover, the development of barotrauma did not impact mortality, possibly due to the exclusion of mild to moderate ARDS and the inclusion of a significant number of ECMO recipients. Finally, the Macklin effect appears early during ARDS and may serve as an early indicator of lung frailty, potentially becoming an additional criterion for referral to centers for advanced ARDS treatment.

PurposePregnant women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have a higher risk of hospitalization, admission to intensive care unit (ICU) and invasive ventilation, and of acute respiratory distress syndrome (ARDS). In case of ARDS and critical severe coronavirus disease 2019 (COVID-19), the use of extracorporeal membrane oxygenation (ECMO) is recommended when other respiratory support strategies (oxygen insufflation, non-invasive ventilation [NIV], invasive ventilation through an endotracheal tube) are insufficient. However, available data on ECMO in pregnant and postpartum women with critical COVID-19 are very limited.MethodsA case series of three critically ill pregnant women who required ECMO support for COVID-19 in pregnancy and/or in the postpartum period.ResultsThe first patient tested positive for COVID-19 during the second trimester, she developed ARDS and required ECMO for 38 days. She was discharged in good general conditions and a cesarean-section [CS] at term was performed for obstetric indication. The second patient developed COVID-19-related ARDS at 28 weeks of gestation. During ECMO, she experienced a precipitous vaginal delivery at 31 weeks and 6 days of gestation. She was discharged 1 month later in good general conditions. The third patient, an obese 43-year-old woman, tested positive at 38 weeks and 2 days of gestation. Because of the worsening of clinical condition, a CS was performed, and she underwent ECMO. 143 days after the CS, she died because of sepsis and multiple organ failure (MOF). Thrombosis, hemorrhage and infections were the main complications among our patients. Neonatal outcomes have been positive.ConclusionECMO should be considered a life-saving therapy for pregnant women with severe COVID-19.