RESUMEN
RATIONALE: Acute respiratory distress syndrome (ARDS) is a major global health concern with a significant unmet need. EXO-CD24 is delivered via inhalation-reduced cytokines and chemokine secretion and lung injury in ARDS and improved survival in mice models of ARDS, influenza, and sepsis. OBJECTIVES: This clinical paper aims to evaluate the potential of EXO-CD24, a novel immunomodulatory treatment, in the compassionate care of critically ill, intubated patients with post-infection-induced acute respiratory distress syndrome (ARDS). METHODS: Eleven critically ill patients diagnosed with post-infection ARDS (10 with COVID-19 and one with an adenovirus-associated infection) were administered EXO-CD24 in four medical centers across Israel. The patients had multiple co-morbidities, including cancer, hypertension, diabetes, and ischemic heart disease, and met the criteria for severe ARDS according to the Berlin classification. EXO-CD24 was administered via inhalation, and adverse events related to its use were carefully monitored. MEASUREMENTS AND MAIN RESULTS: The administration of EXO-CD24 did not result in any recorded adverse events. The median hospitalization duration was 11.5 days, and the overall mortality rate was 36%. Notably, patients treated at the Tel Aviv Medical Center (TASMC) showed a lower mortality rate of 12.5%. The WBC and CRP levels decreased in comparison to baseline levels at hospitalization, and rapid responses occurred even in patients with kidney transplants who were off the ventilator within a few days and discharged shortly thereafter. The production of cytokines and chemokines was significantly suppressed in all patients, including those who died. Among the patients at TASMC, four had kidney transplants and were on immunosuppressive drugs, and all of them fully recovered and were discharged from the hospital. CONCLUSIONS: EXO-CD24 holds promise as a potential therapeutic agent for all stages of ARDS, even in severe intubated cases. Importantly, EXO-CD24 demonstrated a favorable safety profile without any apparent side effects with promising efficacy. Furthermore, the potential of EXO-CD24 as a platform for addressing hyper-inflammatory states warrants exploration. Further research and larger-scale clinical trials are warranted to validate these preliminary findings.
RESUMEN
OBJECTIVES: To review the clinical aspects of cardiac arrhythmias and conduction disturbances in several common and less encountered adult rheumatic diseases and to underline the importance of prompt diagnosis and management in these patients. METHODS: The PubMed database was searched for articles published between the years 1960 and 2008 for keywords referring to autoimmune diseases. All relevant English-written articles were reviewed. Most were uncontrolled series and case reports, due to the lack of prospective studies and randomized trials. RESULTS: Rheumatologic conditions may affect the cardiovascular system and increase morbidity and mortality. Rhythm and conduction defects are usually mild but may be life-threatening; in certain diseases, such as in systemic lupus erythematosus they may resolve following therapy with corticosteroids. Conduction defects occur frequently in patients with spondyloarthropathies and in those with various forms of vasculitis. Enhanced variation of the QT interval may be a sensitive marker of a higher arrythmogenic tendency in patients with autoimmune conditions. CONCLUSIONS: It is important to identify patients at high risk for cardiac arrhythmias. Treating such patients with arrhythmias should not differ fundamentally from other patients. Nevertheless, appropriate clinical attention and judgment should be applied to exclude the possibility that arrhythmias reflect uncontrolled myocardial inflammation.
