Preliminary report of in vitro and in vivo effectiveness of dornase alfa on SARS-CoV-2 infection.

Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). It is well known that novel coronavirus disease 2019 (COVID-19) pneumonia progresses to ARDS and even multiple organ failure. High blood neutrophil levels are an early indicator of COVID-19 and predict severe respiratory diseases. Also it is reported that mucus structure in COVID-19 is very similar to that in cystic fibrosis due to the accumulation of excessive NET in the lungs. In this study, we showed the recovery of three individuals with COVID-19 after including dornase alfa in their treatment. We followed clinical improvement in the radiological analysis (two of three cases), oxygen saturation (Spo2), respiratory rate, disappearance of dyspnoea, coughing and a decrease in NET formation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load after the treatment. Also here, we share our preliminary results suggesting that dornase alfa has an anti-viral effect against SARS-CoV-2 infection in a green monkey kidney cell line, Vero, and a bovine kidney cell line, MDBK, without determined cytotoxicity on healthy peripheral blood mononuclear cells.

Diffusion-Weighted MR Imaging Findings of Cortical Vein Thrombosis at 3 T.

PURPOSE: Diagnosis of cortical vein thrombosis (CVT) on the basis of clot hyperintensity on diffusion-weighted imaging (DWI) has been reported as limited. Our aim was to evaluate different DWI findings of CVT either in isolated form or in combination with sinus thrombosis. METHODS: In this review-board-approved study, patients with the diagnosis of CVT on magnetic resonance venography (MRV) between 2004 and 2011 were evaluated, and 13 patients with 26 CVT (3 isolated and 23 combined CVT) sites were recruited. The evaluated DWI findings were as follows: (1) the hyperintense clot signal (CS) itself, and (2) clot susceptibility signal (CSS) that appears next to the CVT. Two blinded radiologists evaluated the data. Kappa (κ) statistics was applied for interobserver agreement. RESULTS: Both readers reported CS within the vascular clot itself in 6 of 26 (23%) CVT sites on DWI. CSS was reported in 16 of 26 (61.5%) CVT sites by reader 1, and in 14 of 26 (54%) of the CVT sites by reader 2. At four CVT sites with thrombosed veins on MRV, both readers reported no DWI findings. When both CS and CSS were evaluated together, reader 1 reported a positive DWI finding in 22 of 26 (84%) of the CVT sites, and reader 2 reported in 20 of 26 (79%) of the sites. κ Statistics showed a very good agreement (κ: 0.87). CONCLUSIONS: Besides the hyperintense CS, with additional evaluation of the presence of CSS, DWI can provide an additional clue in CVT patients and may suggest its diagnosis, which is important in clinically unsuspected patients.

Acute ischemic infarction defined by a region of multiple hypointense vessels on gradient-echo T2* MR imaging at 3T.

BACKGROUND AND PURPOSE: During the hyperacute phase of stroke, multiple hypointense vessels were identified specifically in the ischemic territory on gradient-echo T2*-weighted MR images (GRE-T2* WI) at 3T. The area was named a "region of multiple hypointense vessels (RMHV)." The aim of this study was to assess the usefulness of RMHV for the diagnosis of acute ischemic stroke (AIS) and to establish the relationship of this finding to other MR imaging studies. MATERIALS AND METHODS: Twenty patients with AIS underwent MR imaging at 3T consisting of GRE-T2*, diffusion-weighted images (DWI), and perfusion-weighted images (PWI) within 6 hours of symptom onset and follow-up images at 72 hours. RMHV was defined as an area containing multiple hypointense vessels strictly in the region of the ischemic territory on GRE-T2*. The RMHV volume on GRE-T2*, initial ischemic lesion volumes on DWI, PWI maps, and on follow-up images were measured and compared with the RMHV volume. RESULTS: RMHV on GRE-T2* was identified in 20 patients. There was no significant difference between the ischemic lesion volumes on mean transit time (247.3 +/- 88.1 mL), time-to-peak (228.6 +/- 88.8 mL), cerebral blood flow (200.6 +/- 89.7 mL), RMHV on GRE-T2* (214.4 +/- 86 mL), and the infarct volume at 72 hours (210.3 +/- 90.4 mL) (P = .975). CONCLUSIONS: RMHV on GRE-T2* can be used as a supportive imaging finding for the diagnosis of hyperacute ischemic stroke. RMHV volume provides information that is in accordance with the infarct volume at 72 hours and the data supplied by PWI.