Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes. This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories. Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar–hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables. Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure. Trial registration: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

Historically, the admission of hematological patients in the ICU shortly after the start of a critical illness is associated with better survival rates. Early intensive interventions administered by MET could play a role in the management of hematological critically ill patients, eventually reducing the ICU admission rate. In this retrospective and monocentric study, we evaluate the safety and effectiveness of intensive treatments administered by the MET in a medical ward frame. The administered interventions were mainly helmet CPAP and pharmacological cardiovascular support. Frequent reassessment by the MET at least every 8 to 12 h was guaranteed. We analyzed data from 133 hematological patients who required MET intervention. In-hospital mortality was 38%; mortality does not increase in patients not immediately transferred to the ICU. Only three patients died without a former admission to the ICU; in these cases, mortality was not related to the acute illness. Moreover, 37% of patients overcame the critical episode in the hematological ward. Higher SOFA and MEWS scores were associated with a worse survival rate, while neutropenia and pharmacological immunosuppression were not. The MET approach seems to be safe and effective. SOFA and MEWS were confirmed to be effective tools for prognostication.

BACKGROUND:CO2 rebreathing is one of the risks associated with noninvasive ventilation (NIV), possibly contributing to failure. In a bench study, we showed that a novel mask design, with separate limbs for inflow and outflow gases, significantly reduced CO2 rebreathing in different ventilation settings.OBJECTIVES:The study aimed to test whether a new mask design could 1) reduce CO2 rebreathing in healthy volunteers during NIV (phase 1) and 2) reduce minute ventilation (phase 2).MATERIALS AND METHODS:Healthy volunteers were randomly assigned to NIV using two masks in a crossover design: a traditional single-limb mask for inflow and outflow gases and a mask with two separated limbs. In phase 1, six ventilation settings were tested for each mask: CPAP (PEEP 5 cmH2O) and pressure support ventilation (PSV, PS Level 5 cmH2O) using a mechanical ventilator with a bias flow of 8 or 20 L/min; free-flow CPAP (PEEP 5 cmH2O) with 60 or 90 L/min of gas flow. A nasal cannula was inserted in one nostril of the volunteers and connected to a CO2 gas analyzer to measure CO2 during the respiratory cycle. In phase 2, volunteers underwent a prolonged time of ventilation in CPAP 90 L/min and PSV with 20 L/min of bias flow. During free-flow CPAP, electrical impedance tomography was used to record the change in impedance during tidal breathing and then estimate tidal volume.RESULTS:Ten healthy adults were enrolled in phase 1, and 8 volunteers in phase 2. CO2 during inspiration was significantly lower in each setting with the two-limb versus the one-limb mask (p < 0.001). The maximum CO2 reduction was observed in the continuous-flow CPAP settings. EtCO2 was lower with the two-limb mask compared to the one-limb mask (p < 0.001). However, no difference in minute ventilation was observed between the two masks.CONCLUSION:The new mask design with two ports for inhaled and exhaled gases reduced the amount of CO2 rebreathing in all tested ventilation settings. The CO2 rebreathing reduction did not decrease minute ventilation in healthy volunteers.

Nitric oxide (NO) is a key molecule in the biology of human life. NO is involved in the physiology of organ viability and in the pathophysiology of organ dysfunction, respectively. In this narrative review, we aimed at elucidating the mechanisms behind the role of NO in the respiratory and cardio-cerebrovascular systems, in the presence of a healthy or dysfunctional endothelium. NO is a key player in maintaining multiorgan viability with adequate organ blood perfusion. We report on its physiological endogenous production and effects in the circulation and within the lungs, as well as the pathophysiological implication of its disturbances related to NO depletion and excess. The review covers from preclinical information about endogenous NO produced by nitric oxide synthase (NOS) to the potential therapeutic role of exogenous NO (inhaled nitric oxide, iNO). Moreover, the importance of NO in several clinical conditions in critically ill patients such as hypoxemia, pulmonary hypertension, hemolysis, cerebrovascular events and ischemia–reperfusion syndrome is evaluated in preclinical and clinical settings. Accordingly, the mechanism behind the beneficial iNO treatment in hypoxemia and pulmonary hypertension is investigated. Furthermore, investigating the pathophysiology of brain injury, cardiopulmonary bypass, and red blood cell and artificial hemoglobin transfusion provides a focus on the potential role of NO as a protective molecule in multiorgan dysfunction. Finally, the preclinical toxicology of iNO and the antimicrobial role of NO—including its recent investigation on its role against the Sars-CoV2 infection during the COVID-19 pandemic—are described.

The pathogenesis of COVID-19 appears to be characterized by a dysregulated immune response. During the first pandemic wave in Lombardy, we started to administer glucocorticoids to some patients with severe respiratory failure requiring support with Continuous Positive Airway Pressure (CPAP) therapy. We retrospectively collected data to identify the effect of glucocorticoids in this COVID-19 particular population. With a multidisciplinary consensus, we administered to selected patients with severe COVID-19 disease (PaO2/FiO2 159±71 mmHg) 0,91 mg/kg/die of methylprednisolone equivalent dose after a median of 8 days of hospitalization. In our study we compared 57 patients from the steroid group with 123 from the control group: the event of invasive mechanical ventilation or death was reduced by 43% between steroid group and control group (19.3 % vs. 34.1 % respectively, p=0.001) and mortality was reduced by about 31% between steroid and usual care alone (15.8 % vs. 22.8 % respectively, p=0.011). Corticosteroids in selected COVID-19 patients may have a relevant impact on outcome, better profiling of the heterogeneity of this disease may be essential to guarantee the best treatment choices.

BACKGROUND: Lung ultrasound can be used to assess lung density and aeration at the bedside. Few authors have investigated scores based on the ultrasonographic interstitial syndrome for this purpose, but none have compared them with the gold standard computed tomography in children.METHODS: Children <10 kilograms undergoing a chest computed tomography for clinical purposes at a tertiary hospital Pediatric Intensive Care Unit were enrolled in the study. An ultrasound scan was performed shortly after computed tomography. Each hemithorax was divided in six zones, and each zone was scored: 1, no B lines; 2, <3 B lines; 3, >3 well separated B lines; 4, crowded, coalescent B lines; 5, white lung; 6, consolidation. The pediatric lung ultrasound score was obtained by adding all zones. Interobserver variation for two separate operators was calculated.RESULTS: Ten children, median age 95 days (range 23-721) were enrolled. Mean pediatric lung ultrasound score had a significant correlation with lung density (r=0.68) and percentage of hypoaerated lung (r=0.51). Median density and percentage of hypoaerated lung increased along the ultrasound patterns values (P<0.05) although not all patterns were significantly different from adjacent ones in the pairwise comparison. Interobserver variability in scoring of ultrasonographic patterns was moderate.CONCLUSIONS: The pediatric lung ultrasound score correlates with lung density and percentage of hypoaerated lung measured with computed tomography.

BACKGROUND:Noninvasive ventilation (NIV) is used to treat respiratory failure because it reduces the risks of endotracheal intubation and postextubation respiratory failure. A wide range of different interfaces is available, but concerns exist about rebreathing. This study evaluated a total face mask with a 2-limb ventilation circuit and separate access for inflow and outflow gas, which was developed to reduce rebreathing.METHODS:In a bench test, a standard total face mask (with a single connector to the ventilation circuit) and the modified total face mask were applied to a mannequin connected to an active breathing simulator. A known CO2 flow (V̇CO2 ) was delivered to the mannequin's trachea. We tested the following settings: CPAP with the mechanical PEEP valve set at 8 cm H2O (with 60 and 90 L/min continuous flow) and pressure support of 6 and 12 cm H2O (with 2 and 15 L/min bias flow). The settings were tested at simulated breathing frequencies of 15 and 30 breaths/min and with V̇CO2 of 200 and 300 mL/min. The active simulator generated a tidal volume of 500 mL. Airway pressure, air flow, CO2 concentration, and CO2 flow as the product of air flow and CO2 were recorded.RESULTS:The mean volume of CO2 rebreathed and the minimum CO2 inspiratory concentration were significantly lower with the modified mask than with the standard mask. The 15 L/min bias flow significantly decreased rebreathing with the DiMax0 mask, whereas it had no effect with the traditional mask.CONCLUSIONS:A face mask with a two-limb ventilation circuit and separate access for inflow and outflow gas reduces rebreathing during NIV. The addition of bias flow enhances this effect. Further studies are required to verify the clinical relevance.