The aim of the study was to explore the involvement of interleukin 6 in SARS-CoV-2 infection, and to position the drug siltuximab in the management of severe forms of COVID-19. A bibliographic search was performed in Pubmed on the immune response to the disease, and in ClinicalTrials.gov on clinical trials with interleukin 6 blockers. Interleukin 6 is involved in the cytokine cascade, which originates as a consequence of an excessive immune response secondary to viral infection, aggravating lung affectation. Blockers of this cytokine (tocilizumab, sarilumab and siltuximab) are being studied as a strategy for treating the disease. Siltuximab is a monoclonal antibody indicated in Castleman's disease that could be administered in a single dose of 11 mg/kg in severe forms of COVID-19 that have increased interleukin 6.
Objectives
To analyse the effectiveness and safety of baricitinib for severe COVID-19 in cytokine storm syndrome based on its potential role as an anti-inflammatory immunomodulator and inhibitor of viral endocytosis.
Methods
This was an observational retrospective study of hospitalised patients treated with baricitinib for severe COVID-19. Outcomes were clinical improvement on an ordinal scale of 1–8 on day 1 of baricitinib compared with day 14 (where 8=death and 1=not hospitalised with no limitations of activities), overall survival, time to recovery since baricitinib treatment started (days until hospital discharge) and laboratory parameters related to COVID-19 poor prognosis. Adverse events related to baricitinib during the admission period were also reported.
Results
Forty-three patients (70% men, mean age 70 years (IQR 54–79)) treated with baricitinib daily for 6 days (IQR 5–7) were included. Thirty-six patients were treated with corticosteroids (84%). Clinical improvement was 3 points (IQR 1–4) in patients on an ordinal scale of 4–6, overall survival was 100% at day 30 and day 60 with a mean time to recovery of 12 days (IQR 9–25) from start of baricitinib treatment. No adverse events of interest were found and all poor prognosis risk factors improved at day 14: interleukin-6, C-reactive protein, ferritin, lymphocytes, platelets and D-dimers.
Conclusions
Patients treated with baricitinib for severe COVID-19 showed improvements in clinical and analytical values without relevant adverse events and 100% overall survival. Clinical randomised trials are needed to confirm the clinical benefit of baricitinib.
ObjectivesTo present a case report of succesfully metyrapone treatment of a neonatal patient with McCune–Albrigth syndrome (MAS), a rare disease caused by a genetically mosaic disorder and is characterized by variable hyperfunctional endocrinopathies, bone dysplasia, and café-au-lait spots.Case presentationA preterm newborn was admitted to hospital and she presented difficulty controlling hypertension, café-au-lait spots, and failure to thrive. An abdominal ultrasound and a magnetic resonance showed a high volume of both suprarenal glands. Therefore, MAS was suspected. Laboratory data confirmed adrenocorticotropic hormone-independent Cushing’s syndrome with hepatic dysfunction and metyrapone treatment was initiated. A progressive normalization of cortisol levels was achieved despite poor oral tolerance.ConclusionOur case shows that metyrapone is useful in the management of neonatal Cushing’s syndrome due to McCune–Albright syndrome.
Acquired thrombocytopenic thrombotic purpura (aTTP) is an autoantibody-mediated disease against the enzyme A Disintegrin and Metalloprotease domain with ThromboSpondin-1 type motif 13, which until now has been treated with plasma exchange (PEX) and corticosteroids. A 29-year-old female patient, who presented with aTTP in the context of pregnancy, has developed multiple relapses after treatment with PEX, corticosteroids, and rituximab. Recently, caplacizumab, a nanobody against von Willebrand factor, has been approved for the treatment of aTTP. In our patient, caplacizumab achieved better disease control, with a lower platelet count restoration time, days of PEX and hospitalization duration, as compared to standard therapy, reproducing the results of clinical trials. Caplacizumab represents a significant advance in the treatment of aTTP, especially in cases of recurrent relapses.
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