Lung (extracorporeal CO2 removal) and renal (continuous renal replacement therapy) support: the role of ultraprotective strategy in Covid 19 and non-Covid 19 ARDS. A case-control study.

BACKGROUND: Preliminary studies suggest that moderate ARDS and acute renal failure might benefit from extracorporeal CO2 removal (ECCO2R) coupled with CRRT. However, evidence is limited and potential for this coupled treatment may need to be explored. The aim of the present study was to evaluate whether a protective driving pressure was obtained applying low-flow ECCO2-R plus CRRT in patients affected by moderate ARDS with COVID-19 compared to an historical group without COVID-19. METHODS: A case-control study has been conducted comparing a group of consecutive moderate ARDS patients presenting AKI and affected by COVID-19, who needed low-flow ECCO2-R plus CRRT to achieve an ultra-protective ventilatory strategy, with historical group without COVID-19 that matched for clinical presentation and underwent the same ultra-protective treatment. VT was set at 6 mL/kg predicted body weight then ECCO2R was assessed to facilitate ultra-protective low VT ventilation to preserve safe Pplat and low driving pressure. RESULTS: ECCO2R+CRRT reduced the driving pressure from 17 (14-18) to 11.5 (10-15) cmH2O (p<0.0004) in the fourteen ARDS patients by decreasing VT from 6.7 ml/kg PBW (6.1-6.9) to 5.1 (4.2-5.6) after 1 hour (p <0.0001). In the ARDS patients with COVID-19, the driving pressure reduction was more effective from baseline 18 (14-24) cmH2O to 11 (10-15) cmH2O (p<0.004), compared to the control group from 15 (13-17) to 12(10-16) cmH2O (p< 0.03), after one hour. ECCO2R+CRRT did not affected 28 days mortality in the two groups, while we observed a shorter duration of mechanical ventilation (19 {7-29} vs 24 {22-38} days; p=0.24) and ICU length of stay (19 {7-29} vs 24 {22-78} days; p=0.25) in moderate ARDS patients with COVID-19 compared to control group. CONCLUSIONS: In moderate ARDS patients with or without COVID-19 disease, ECCO2R+CRRT may be and effective supportive treatment to reach protective values of driving pressure unless severe oxygenation defects arise requiring ECMO therapy initiation.

Systematic identification of NF90 target RNAs by iCLIP analysis.

RNA-binding proteins (RBPs) interact with and determine the fate of many cellular RNAs directing numerous essential roles in cellular physiology. Nuclear Factor 90 (NF90) is an RBP encoded by the interleukin enhancer-binding factor 3 (ILF3) gene that has been found to influence RNA metabolism at several levels, including pre-RNA splicing, mRNA turnover, and translation. To systematically identify the RNAs that interact with NF90, we carried out iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation) analysis in the human embryonic fibroblast cell line HEK-293. Interestingly, many of the identified RNAs encoded proteins involved in the response to viral infection and RNA metabolism. We validated a subset of targets and investigated the impact of NF90 on their expression levels. Two of the top targets, IRF3 and IRF9 mRNAs, encode the proteins IRF3 and IRF9, crucial regulators of the interferon pathway involved in the SARS-CoV-2 immune response. Our results support a role for NF90 in modulating key genes implicated in the immune response and offer insight into the immunological response to the SARS-CoV-2 infection.

A challenging complication following SARS-CoV-2 infection: a case of pulmonary mucormycosis.

Severe acute respiratory syndrome coronavirus 2 infection might induce a significant and sustained lymphopenia, increasing the risk of developing opportunistic infections. Mucormycosis is a rare but severe invasive fungal infection, mainly described in immunocompromised patients. The first case of a patient diagnosed with coronavirus disease (COVID-19) who developed a pulmonary mucormycosis with extensive cavitary lesions is here reported. This case highlights how this new coronavirus might impair the immune response, exposing patients to higher risk of developing opportunistic infections and leading to worse outcomes.

Occurrence of ventilator associated pneumonia using a tracheostomy tube with subglottic secretion drainage.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality in critically ill patients who require mechanical ventilation (MV). Subglottic secretions above the endotracheal cuff are associated with bacteria colonization of lower respiratory tract, causing VAP. A preventive strategy to avoid subglottic secretion progression is the drainage with special tracheal tubes effective in preventing both early onset and late onset VAP. The purpose of this study was to measure VAP incidence in tracheostomized patients with suction above the cuff. METHODS: The authors performed a matched cohort study with historical control in three academic Intensive Care Units (ICUs): upon ICU admission, patients requiring MV were submitted to tracheostomy with a tracheal tube allowing drainage of subglottic secretions (treatment group). A control group without suctioning above the cuff was selected applying the propensity score matching on dataset of previous ELT Study. VAP occurrence at 28-days from intubation was the primary endpoint; hospital mortality and ICU-free days at 28-days were the secondary endpoints. RESULTS: Between July 2014 and April 2016, 125 tracheostomized patients were included in the analysis. 232 tracheostomized patients without suctioning were selected as a control group for the matched cohort study. The application of propensity score matching selected 60 patients to compare the two groups. Incidence of VAP was 8% in treatment group and 19.4% in the control group (P value =0.004). After balance with propensity score matching VAP was 8.3% and 21.7% (P value =0.0408), respectively. CONCLUSIONS: Subglottic secretion drainage reduces incidence of VAP in critically ill patients requiring ongoing MV via tracheostomy.