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Background The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality. Objective We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19. Methods Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR. Results Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/μL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively). Conclusions Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV.

Cases Septic cardiomyopathy is defined as a reversible left ventricular systolic dysfunction. Patients with severe septic cardiomyopathy have a high mortality rate, even if they receive conventional therapy. For those patients, previous reports showed intra-aortic balloon pump (IABP) efficacy. We report two rare cases with IABP introduction leading them to drastic improvement, and survival from severe septic cardiomyopathy. Case 1 is a 78-year-old woman diagnosed with renal calculus pyelonephritis, septic shock, and septic cardiomyopathy. Case 2 is a 62-year-old man diagnosed with pneumonia, septic shock, and septic cardiomyopathy. Outcome In both cases, despite conventional therapy for cardiomyopathy, including high-dose catecholamine therapy, shock was not reversed, and the IABP was inserted. Circulatory status was improved after the introduction of the IABP. Conclusion Our findings suggest that an IABP can be useful for salvaging patients with septic cardiomyopathy who do not respond to conventional therapy.

Abdominal aortic aneurysm (AAA) is a progressive disease that has an increasing prevalence with aging, but no effective pharmacological therapy to attenuate AAA progression is currently available. We reported that the prostaglandin E receptor EP4 plays roles in AAA progression. Here, we show the effect of CJ-42794, a selective EP4 antagonist, on AAA using two mouse models (angiotensin II- and CaCl2 -induced AAAs) and human aortic smooth muscle cells isolated from AAA tissue. Oral administration of CJ-42794 (0.2 mg/kg per day) for 4 weeks significantly decreased AAA formation in ApoE-/- mice infused with angiotensin II (1 μg/kg per min), in which elastic fiber degradation and activations of matrix metalloproteinase (MMP)-2 and MMP-9 were attenuated. Interleukin-6 (IL-6) proteins were highly expressed in the medial layer of angiotensin II-induced mouse AAA tissues, whereas this expression was significantly decreased in mice treated with CJ-42794. AAA formation induced by periaortic CaCl2 application in wild-type mice was also reduced by oral administration of CJ-42794 for 4 weeks. After oral administration of CJ-42794 beginning 2 weeks after periaortic CaCl2 application and continuing for an additional 4 weeks, the aortic diameter and elastic fiber degradation grade were significantly smaller in CJ-42794-treated mice than in untreated mice. Additionally, in smooth muscle cells isolated from human AAA tissues, stimulation of CJ-42794 inhibited PGE2 -induced IL-6 secretion in a dose-dependent manner and decreased PGE2 -induced MMP-2 activity. These data suggest that inhibition of EP4 has the potential to be a pharmacological strategy for attenuation of AAA progression.