Mesenchymal stem cells (MSC) have received particular attention due to their ability to inhibit inflammation caused by cytokine storm induced by COVID-19. In this way some patients have been treated successfully. The aim of this study was to evaluate the safety and describe the clinical changes after IV administration of allogeneic human umbilical cord MSC (ahUCMSC), in patients with bilateral pneumonia caused by COVID-19, complicated with severe ARDS, as compassionate treatment. This was a pilot, open-label, prospective, longitudinal study. Five patients that did not improve in their clinical conditions after 48 hours of receiving the standard medical management used by the Medical Center and with persistent PaO2/FiO2 less than 100 mmHg were enrolled. ahUCMSC were infused IV, at dose of 1x10 6 per Kg of body weight over 15 minutes. Patients were monitored after the infusion to detect adverse event. Pa02/FiO2, vital signs, D-dimer, C reactive protein and total lymphocytes were monitored for 21 days after the infusion or until the patient was discharged from the hospital. Descriptive statistics were used with means or medians and standard deviation or interquartile range according to the type of variable. The Wilcoxon's rank-sum was used for stationary samples. Adverse events occurred in three patients and were easily and quickly controlled. Immediately after the infusion of ahUCMSC, constant rise of PaO2/FiO2 was observed in all patients during the first 7 days, with statistical significance. Three patients survived and were extubated on the ninth day post-infusion. Two patients died at 13 and 15 days after infusion. The infusion of ahUCMSC in patients with severe ARDS caused by COVID-19, was safe, and demonstrated its anti-inflammatory capacity in the lungs, by improving the respiratory function expressed by PaO2 / FiO2, which allowed the survival of 3 patients, with extubation at 9 days.
In the treatment of venous insufficiency unsuitable for surgical correction in replanted digits, a small ungual window was surgically created to infiltrate subcutaneous heparin in the congested digit. The initial heparin dose was 1000 units. This dose made possible a continuous bleeding during 24 to 48 hours, solely through the ungual window. Further doses were applied based on the degree of congestion of the replanted digit, but usually it was necessary to infiltrate up to 500 units of heparin every 24 to 48 hours until vascular stability was achieved. Three patients were treated with this technique. One opted for quitting the treatment. A replanted thumb suffered venous congestion on the seventh postoperative day and was treated with local subcutaneous heparin for 3 days. A replanted fingertip suffered venous thrombosis 24 hours after surgery and was treated likewise for 18 days. In these two patients, success was attained. Blood transfusions were carried out in the latter two, and none had any systemic changes in partial thromboplastin or thrombin time. This treatment is based on the mechanism of action of heparin at high doses but applied only to the congested segment. Besides their anticoagulant effect through antithrombin, high doses of heparin slow platelet aggregation, may induce angiogenesis, and have a longer-than-normal half-life. With the above technique, heparin has been applied to the congested segment at an approximate dose of 33,000 to 40,000 units/kg, and continuous bleeding solely through the ungual window for 24 to 48 hours has been achieved, which has allowed us to save two replanted segments with no complications at all. This method may offer another alternative for the medical treatment of venous insufficiency in replanted segments.
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