RESUMO
Mesenchymal stromal cells (MSC) have immunomodulatory and tissue-regenerative properties and have shown promising results in acute respiratory distress syndrome (ARDS) of multiple causes, including COVID-19. We conducted a randomised (1:1), placebo-controlled, double-blind clinical trial to assess the efficacy and safety of one bone marrow-derived MSC infusion in twenty patients with moderate to severe ARDS caused by COVID-19. The primary endpoint (increase in PaO2/FiO2 ratio from baseline to day 7, MSC 83.3 versus placebo 57.6) was not statistically significant, although a clinical improvement at day 7 in the WHO scale was observed in MSC patients (5, 50% vs 0, 0%, p = 0.033). Median time to discontinuation of supplemental oxygen was also shorter in the experimental arm (14 versus 23 days, p = 0.007), resulting in a shorter hospital stay (17.5 versus 28 days, p = 0.042). No significant differences were observed for other efficacy or safety secondary endpoints. No infusion or treatment-related serious adverse events occurred during the one-year follow-up. This study did not meet the primary endpoint of PaO2/FiO2 increase by day 7, although it suggests that MSC are safe in COVID-19 ARDS and may accelerate patients' clinical recovery and hospital discharge. Larger studies are warranted to elucidate their role in ARDS and other inflammatory lung disorders.Trial Registration: EudraCT Number: 2020-002193-27, registered on July 14th, 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002193-27/ES . NCT number: NCT04615429, registered on November 4th, 2020, https://clinicaltrials.gov/ct2/show/NCT04615429 .
Assuntos
COVID-19 , Transplante de Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , Humanos , Método Duplo-Cego , COVID-19/terapia , COVID-19/complicações , Transplante de Células-Tronco Mesenquimais/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/terapia , Idoso , Adulto , SARS-CoV-2 , Resultado do Tratamento , Células-Tronco Mesenquimais/citologiaRESUMO
The observational signatures of black holes in x-ray binary systems depend on their masses, spins, accretion rate, and the misalignment angle between the black hole spin and the orbital angular momentum. We present optical polarimetric observations of the black hole x-ray binary MAXI J1820+070, from which we constrain the position angle of the binary orbital. Combining this with previous determinations of the relativistic jet orientation, which traces the black hole spin, and the inclination of the orbit, we determine a lower limit of 40° on the spin-orbit misalignment angle. The misalignment must originate from either the binary evolution or black hole formation stages. If other x-ray binaries have similarly large misalignments, these would bias measurements of black hole masses and spins from x-ray observations.