Phlegmasia cerulea dolens superimposed on disseminated intravascular coagulation in covid-19

COVID-19 infection has several cardiovascular implications, and coagulopathy is a common abnormality in these patients, often coupled with elevated plasma fibrinogen and D-dimer levels, contributing to adverse outcomes. Phlegmasia cerulea dolens (PCD) is a rare manifestation of deep vein thrombosis. It is life-threatening and can rapidly lead to venous gangrene of the extremity. Only a few cases of COVID-19 associated with PCD are reported in the literature, despite thromboembolism being the common paradigm between the two diseases. We present the case of a 64-year-old adult with acute severe COVID-19 pneumonia who developed PCD despite constantly elevated activated partial thromboplastin time and international normalized ratio. (www.actabiomedica.it)

Antigenic characterization of recombinant, lymphoblastoid, and leukocyte IFN-alpha by monoclonal antibodies

To gain more insight into similarities of different interferon-alpha (IFN-alpha) species, we evaluated neutralization and immunoactivity of a variety of IFN preparations with various monoclonal antibodies (IFN-alpha mAb), Nine IFN-alpha mAb obtained through immunization with recombinant IFN-alpha (rmAb), lymphoblastoid IFN-alpha (LY mAb), and leukocyte IFN-alpha (LE mAb) were tested. The IFN-alpha mAb were evaluated for their ability to neutralize the antiviral activity of 11 recombinant IFN-alpha subtypes, two recombinant IFN-alpha hybrids, and lymphoblastoid and leukocyte IFN-alpha preparations. The same IFN-alpha mAb were also used in immunoblotting, and some of them were used in immunoaffinity chromatography. The results of the neutralization assay reveal that the IFN-alpha mAb significantly differ in their ability to neutralize the individual IFN-alpha species. Interestingly, none of the IFN-alpha mAb was able to neutralize all the IFN-cu species, In particular, rmAb were unable to neutralize LE-IFN-alpha or LY-IFN-alpha, whereas LE mAb and LY mAb efficiently neutralized rIFN-alpha 2. In some cases, the epitopes to which IFN-alpha mAb are directed were identified through the use of synthetic fragments of IFN-alpha 2 or by evaluating the selectivity in binding to IFN-alpha subtypes

High dose esomeprazole as an anti-inflammatory agent in sepsis: Protocol for a randomized controlled trial

Background: Sepsis is caused by dysregulated immune responses due to infection and still presents high mortality rate and limited efficacious therapies, apart from antibiotics. Recent evidence suggests that very high dose proton pump inhibitors might regulate major sepsis mediators' secretion by monocytes, which might attenuate excessive host reactions and improve clinical outcomes. This effect is obtained with doses which are approximately 50 times higher than prophylactic esomeprazole single daily administration and 17 times higher than the cumulative dose of a three day prophylaxis. We aim to perform a randomized trial to investigate if high dose esomeprazole reduces organ dysfunction in patients with sepsis or septic shock. Methods: This study, called PPI-SEPSIS, is a multicenter, randomized, double blind, placebo-controlled clinical trial on critically ill septic patients admitted to the emergency department or intensive care unit. A total of 300 patients will be randomized to receive high dose esomeprazole (80 mg bolus followed by 12 mg/h for 72 h and a second 80 mg bolus 12 h after the first one) or equivolume placebo (sodium chloride 0.9%), with 1:1 allocation. The primary endpoint of the study will be mean daily Sequential Organ Failure Assessment (SOFA) score over 10 days. Secondary outcomes will include antibiotic-free days, single organ failure severity, intensive care unit-free days at day 28, and mortality. Discussion: This trial aims to test the efficacy of high dose esomeprazole to reduce acute organ dysfunction in patients with septic shock. Trial registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03452865 in March 2018