Extravascular lung water index, pulmonary vascular permeability index, and global end-diastolic volume index in mechanically ventilated COVID-19 patients requiring prone position ventilation: a preliminary retrospective study.

BACKGROUND: There is a lack of data on extravascular lung water index (EVLWi), pulmonary vascular permeability index (PVPi), and global end-diastolic volume index (GEDVi) during prone position ventilation (PPV) in coronavirus disease 2019 (COVID-19) patients. The objectives of this study were to analyze trends in EVLWi, PVPi, and GEDVi during PPV and the relationships between these parameters and PaO2/FiO2. METHODS: In this preliminary retrospective observational study, we performed transpulmonary thermodilution (TPTD) in seven mechanically ventilated COVID-19 patients without cardiac and pulmonary comorbidities requiring PPV for 18 hours, at specific times (30 minutes pre-PPV, 18 hours after PPV, and 3 hours after supination). EVLWi, PVPi and GEDVi were measured. The relationships between PaO2/FiO2 and EVLWi, and PVPi and GEDVi values, in the supine position were analyzed by linear regression. Correlation and determination coefficients were calculated. RESULTS: EVLWi was significantly different between three time points (analysis of variance, P=0.004). After 18 hours in PPV, EVLWi was lower compared with values before PPV (12.7±0.9 ml/kg vs. 15.3±1.5 ml/kg, P=0.002). Linear regression showed that only EVLWi was correlated with PaO2/FiO2 (ß =-5.757; 95% confidence interval, -10.835 to -0.679; r=-0.58; R2 =0.34; F-test P=0.029). CONCLUSIONS: EVLWi was significantly reduced after 18 hours in PPV and values measured in supine positions were correlated with PaO2/FiO2. This relationship can help clinicians discriminate whether deterioration in gas exchange is related to fluid overload or disease progression. Further clinical research should evaluate the role of TPTD parameters as markers to stratify disease severity and guide clinical management.

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines.

Pancreatic cancer (PC) is related to lifestyle risks, chronic inflammation, and germline mutations in BRCA1/2, ATM, MLH1, TP53, or CDKN2A. Surgical resection and adjuvant chemotherapy are the main therapeutic strategies but are less effective in patients with high-grade tumors. Oxygen-ozone (O2/O3) therapy is an emerging alternative tool for the treatment of several clinical disorders. O2/O3 therapy has been found to ameliorate mechanisms promoting chronic pain and inflammation, including hypoxia, inflammatory mediators, and infection. The advantages of using cannabinoids have been evaluated in vitro and in vivo models of several human cancers. Regarding PDAC, activation of cannabinoid receptors was found to induce pancreatic cancer cell apoptosis without affecting the normal pancreas cells. In a murine model of PDAC, a combination of cannabidiol (CBD) and gemcitabine increased survival length by nearly three times. Herein, we evaluate the anticancer effect of CBD and O2/O3, alone or in combination, on two human PDAC cell lines, PANC-1 and MiaPaCa-2, examining expression profiles of 92 pancreatic adenocarcinoma associated genes, cytotoxicity, migration properties, and cell death. Finally, we assess the combination effects with gemcitabine and paclitaxel. Summarizing, for the first time the antitumoral effect of combined therapy with CBD and oxygen-ozone therapy in PDAC is evidenced.