Current standard treatment of COVID-19 lacks in effective antiviral options. Plitidepsin, a cyclic depsipeptide authorized in Australia for patients with refractory multiple myeloma, has recently emerged as a candidate anti-SARS-CoV-2 agent. The aim of this review was to summarize current knowledge on plitidepsin’s clinical profile, anti-tumour and anti-SARS-CoV-2 mechanisms and correlate this with available or anticipated, preclinical or clinical evidence on the drug’s potential for COVID-19 treatment.PubMed, Scopus, CENTRAL, clinicaltrials.gov, medRxiv and bioRxiv databases were searched.Plitidepsinexerts its anti-tumour and antiviral properties primarily through acting on isoforms of the host cell’s eukaryotic-translation-elongation-factor-1-alpha (eEF1A). Through inhibiting eEF1A and therefore translation of necessary viral proteins, it behaves as a “host-directed” anti-SARS-CoV-2 agent. In respect to its potent anti-SARS-CoV-2 properties, the drug has demonstrated superior ex vivo efficacy compared to other host-directed agents and remdesivir, and it might retain its antiviral effect against the more transmittable B.1.1.7 variant. Its well-studied safety profile, also in combination with dexamethasone, may accelerate its repurposing chances for COVID-19 treatment. Preliminary findings in hospitalized COVID-19 patients, have suggested potential safety and efficacy of plitidepsin, in terms of viral load reduction and clinical resolution. However, the still incomplete understanding of its exact integration into host cell–SARS-CoV-2 interactions, its intravenous administration exclusively purposing it for hospital settings the and precocity of clinical data are currently considered its chief deficits. A phase III trial is being planned to compare the plitidepsin–dexamethasone regimen to the current standard of care only in moderately affected hospitalized patients. Despite plitidepsin’s preclinical efficacy, current clinical evidence is inadequate for its registration in COVID-19 patients.Therefore, multicentre trials on the drug’s efficacy, potentially also studying populations of emerging SARS-CoV-2 lineages, are warranted.

Cell senescence constitutes a physiological process that serves as protection from malignant transformation of cells. However, recent scientific discoveries also identify cell senescence as pivotal in hepatocellular cancer (HCC) biology. The review herein aimed to accumulate evidence on senescence as a mediator of HCC occurrence in hepatitis B (HBV), C (HCV) virus infections, and non-alcoholic fatty liver disease (NAFLD). In HBV infection, the carcinogenic HBV X protein frequently mutates during chronic infection, and subsequently exhibits different effects on senescence. In HCV infection, senescent non-functional T-cells do not effectively clear pre-malignant hepatocytes. Furthermore, the HCV Core protein inhibits the occurrence of normal stress-induced hepatocyte senescence, allowing damaged cells to maintain their proliferative potential. In NAFLD-mediated HCC, current data point towards the gut microbiome and hepatic stellate cell senescence. Additionally, senescence contributes in the development of resistance in targeted therapies, such as sorafenib. Finally, the promising role of senotherapeutics in HCC was also explored. Overall, although we may still be at a primitive stage in fully unraveling the role of senescence in cancer, it seems that understanding and harnessing senescence may have the potential to revolutionize the way we treat hepatocellular cancer.

Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting a connection between dysregulated coagulant and fibrinolytic pathways in ARDS progression, it is plausible that this dysregulation also exists in AHRF. The aim of this study was to explore whether levels of soluble endothelial protein C receptor (sEPCR) and plasminogen differentiate patients admitted to the emergency department (ED) with AHRF. sEPCR and plasminogen levels were measured in 130 AHRF patients upon ED presentation by ELISA. Our results demonstrated that patients presenting to the ED with AHRF had elevated levels of sEPCR and plasminogen. It seems that dysregulation of coagulation and fibrinolysis occur in the early stages of respiratory failure requiring hospitalisation. Further research is needed to fully comprehend the contribution of sEPCR and plasminogen in AHRF.

Intraabdominal adhesions develop spontaneously or after an inflammatory process or surgical procedure in the abdomen. They are the most common cause of small bowel obstruction (SBO). SBO occasionally leads to intestinal ischemia (InIs) which can be a life-threatening condition that requires management as soon as possible. We herein report a case of SBO with InIs presented in our institution and treated without intestinal resection. A 34-year-old man presented at the emergency department after a 12-h-onset diffuse abdominal pain, bloating and nausea. He had a history of traumatic right hepatectomy 11 years ago as well as adhesiolysis and resection of a long part of small bowel 2 years ago. An abdominal computed tomography (CT) showed dilated loops that led to the diagnosis of SBO. Due to deteriorating lactic acidosis, the patient was operated. Torsion of the small bowel around an adhesion led to 2.30 m of ischemic ileum. After the application of N/S 40 °C for 20 min, the intestine showed signs of improvement and it was decided to avoid resection and instead temporary close the abdomen with vacuum-pack technique. At the second-look laparotomy 48 h later, the intestine appeared normal. The patient was discharged on the 8th post-op day in excellent condition. In case of SBO caused by adhesions, extreme caution is needed if InIs is present, as the clinical signs are mild and you should rely for diagnosis in CT findings and lactate levels. Conservative surgical approach could reverse the effects of InIs, if performed quickly, so that intestinal resection is avoided and should be used even when minimum signs of viability are present.

Introduction: A hypoinflammatory and a hyperinflammatory subphenotype of acute respiratory distress syndrome (ARDS) have been previously identified with the latter being less prevalent and associated with higher mortality than the former. Keeping into mind the immunosenescence and inflammaging, we explored whether differences in terms of prevalence and mortality associated with those inflammatory subphenotypes persist among older patients with ARDS. Methods: We performed a secondary analysis of individual patient-level data from seven ARDS Network and PETAL Network randomized controlled trials. Using a recently published open-source AI Clinical Classifier, we categorized patients with ARDS into inflammatory subphenotypes. Results: Of 5363 patients with ARDS, 3713 (69%) were classified as hypoinflammatory and 1650 (30%) as hyperinflammatory. The prevalence of inflammatory subphenotypes did not differ between patients younger than 65 years old compared to those older than 65 years old (p=0.836). Mortality in the hyperinflammatory phenotype was higher compared to the hypoinflammatory phenotype in both age groups (40% vs. 17% for patients younger than 65 years, and 62% vs. 44% for patients older than 65 years old; p<0.001 for both comparisons). Conclusion: The prevalence of hypoinflammatory and hyperinflammatory did not differ by age, and the association between the subphenotypes and mortality was consistent across adult lifespan.