ABSTRACT
INTRODUCTION: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. METHODS: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. RESULTS: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. CONCLUSIONS: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.
Subject(s)
COVID-19 , Exosomes , Respiratory Distress Syndrome , Humans , Male , Middle Aged , Female , SARS-CoV-2 , Single-Blind Method , Immunologic Factors , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/genetics , Drug Carriers , Treatment Outcome , CD24 AntigenABSTRACT
In daily clinical practice, radiologists and pulmonologists are faced with incidental radiographic findings of pulmonary nodules. Deciding how to manage these findings is very important as many of them may be benign and require no further action, but others may represent early disease and importantly early-stage lung cancer and require prompt diagnosis and definitive treatment. As the diagnosis of pulmonary nodules includes invasive procedures which can be relatively minimal, such as bronchoscopy or transthoracic aspiration or biopsy, but also more invasive procedures such as thoracic surgical biopsies, and as these procedures are linked to anxiety and to cost, it is important to have clearly defined algorithms for the description, management, and follow-up of these nodules. Clear algorithms for the imaging protocols and the management of positive findings should also exist in lung cancer screening programs, which are already established in the USA and which will hopefully be established worldwide. This article reviews current knowledge on nodule definition, diagnostic evaluation, and management based on literature data and mainly recent guidelines.
