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INTRODUCTION: The anti-inflammatory effect of macrolides prompted the study of oral clarithromycin in moderate COVID-19. METHODS: An open-label non-randomized trial in 90 patients with COVID-19 of moderate severity was conducted between May and October 2020. The primary endpoint was defined at the end of treatment (EOT) as no need for hospital re-admission and no progression into lower respiratory tract infection (LRTI) for patients with upper respiratory tract infection and as at least 50% decrease of the respiratory symptoms score without progression into severe respiratory failure (SRF) for patients with LRTI. Viral load, biomarkers, the function of mononuclear cells and safety were assessed. RESULTS: The primary endpoint was attained in 86.7% of patients treated with clarithromycin (95% CIs 78.1-92.2%); this was 91.7% and 81.4% among patients starting clarithromycin the first 5 days from symptoms onset or later (odds ratio after multivariate analysis 6.62; p 0.030). The responses were better for patients infected by non-B1.1 variants. Clarithromycin use was associated with decreases in circulating C-reactive protein, tumour necrosis factor-alpha and interleukin (IL)-6; by increase of production of interferon-gamma and decrease of production of interleukin-6 by mononuclear cells; and by suppression of SARS-CoV-2 viral load. No safety concerns were reported. CONCLUSIONS: Early clarithromycin treatment provides most of the clinical improvement in moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04398004.
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Spontaneous rupture of a liver metastasis is a life-threatening complication of metastatic liver disease. Although metastatic liver lesions are much more common than primary tumours, spontaneous rupture of a liver metastasis is rare. Therapeutic decisions must take into account the extent of metastatic liver disease and the patient's performance status. Transarterial embolization may be considered in cases of ongoing haemorrhage despite initial conservative measures. We describe a case of haemoperitoneum due to spontaneous rupture of a liver metastasis in a 72-year-old patient with carcinoma of unknown origin who responded well to conservative management. LEARNING POINTS: Spontaneous rupture of a liver metastasis is a rare but potentially life-threatening complication of metastatic cancer to the liver; risk factors include subcapsular location, rapid tumour growth and tumour necrosis (spontaneous or due to chemotherapy).Unexplained fever often precedes the spontaneous rupture, probably reflecting tumour necrosis or infiltration of the liver capsule, and may raise clinical suspicion for the diagnosis.Transarterial embolization may be considered in cases of ongoing haemorrhage despite initial conservative measures.