Background COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARS-CoV-2, associated clotting or inflammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efficient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efficacy of three intravenous doses of UC-MSCs (umbilical cord MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is one of the few reports that presents the longest follow-up after MSC treatment in COVID-19 patients. Methods This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation—critically ill patients—were included. The patient infusion was three doses of 5 × 105 cells/kg UC-MSCs, with a dosing interval of 48 h (n = 11) or placebo (n = 6). The evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. Results The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1-CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in extension of lung damage was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up. Conclusions UC-MSCs infusion is safe and can play an important role as an adjunctive therapy, both in the early stages, preventing severe complications and in the chronic phase with postacute sequelae reduction in critically ill COVID-19 patients. Trial registration Brazilian Registry of Clinical Trials (ReBEC), UTN code-U1111-1254-9819. Registered 31 October 2020—Retrospectively registered, https://ensaiosclinicos.gov.br/rg/RBR-3fz9yr
The coronavirus pandemic is one of the most significant public health events in recent history. Currently, no specific treatment is available. Some drugs and cell-based therapy have been tested as alternatives to decrease the disease’s symptoms, length of hospital stay, and mortality. We reported the case of a patient with a severe manifestation of COVID-19 in critical condition who did not respond to the standard procedures used, including six liters of O2 supplementation under a nasal catheter and treatment with dexamethasone and enoxaparin in prophylactic dose. The patient was treated with tocilizumab and an advanced therapy product based on umbilical cord-derived mesenchymal stromal cells (UC-MSC). The combination of tocilizumab and UC-MSC proved to be safe, with no adverse effects, and the results of this case report prove to be a promising alternative in the treatment of patients with severe acute respiratory syndrome due to SARS-CoV-2.
To investigate the association of leprosy with hepatitis B virus (HBV) infection, as yet unknown for South Brazil, we assessed hepatitis B virus coinfection in 199 South Brazilian leprosy patients (119 lepromatous, 15 tuberculoid, 30 borderline, 12 undetermined and 23 unspecified) and in 681 matched blood donors by screening for the hepatitis B virus markers HBSAg and anti-HBc, using ELISA. Positive samples were retested and anti-HBc+ only samples were tested for the hepatitis B surface antibody (anti-HBs). There was a strong association between leprosy and hepatitis B virus infection (OR=9.8, 95% CI=6.4-14.7; p=0.004 · E(-30)), as well as an association between HBV infection and lepromatous leprosy, compared to other forms (OR=2.4, 95% CI=1.2-4.8; p=0.017). We also found that confinement due to leprosy was associated with hepatitis B virus infection (OR=3.9, 95% CI=2.1-7.4; p=0.015 · E(-3)). Leprosy patients are susceptible to develop hepatitis B virus infection, especially lepromatous. Institutionalized patients, who probably present a stronger Th2 response, have higher risk of being exposed to hepatitis B virus. This clearly emphasizes the need for special care to leprosy patients in preventing hepatitis B virus coinfection in South Brazil.
Background: The rapid evaluation of non-contrast-enhanced computed tomography (NCCT) brain scans in patients with anterior stroke symptoms saves time and favors optimal and prompt treatment. e-ASPECTS is a tool that automatically calculates the Alberta Stroke Program Early CT Score (ASPECTS) values, leading to a more accurate and timely image evaluation. Objective: To determine the ability of e-ASPECTS in differentiating images with and without injury. Methods: One-hundred sixteen patients admitted to a stroke unit in a Brazilian tertiary hospital underwent a CT scan at admission and at least one control brain imaging (NCCT or magnetic resonance imaging - MRI) 24 hours after admission. ASPECTS evaluation was performed by three neuroradiologists, three neurologists, and three neurology residents, all blinded to the symptoms and the injury side. The scores were compared to the ground truth, and an ASPECTS score was provided by two independent non blinded evaluators. Sensitivity and specificity were analyzed, and receiver operating characteristic curves, Bland-Altman plots with mean error score, and Matthews correlation coefficients (MCCs) were obtained for ASPECTS scores, assuming values equal to 10 for images without injury and values other than 10 for images with ischemic injury. Results: e-ASPECTS demonstrated similar performance to that of neuroradiologists and neurologists, with an area under the curve of 0.78 and an MCC value of 0.48 in the dichotomous analysis. The sensitivity and specificity of e-ASPECTS were 75% and 73%, respectively. Conclusion: e-ASPECTS is a validated and reliable tool for determining early signs of ischemia in NCCT.
Background and Purpose: Precise evaluation of brain computerized tomography (CT) is a crucial step in acute ischemic stroke evaluation. Electronic Alberta Stroke Program Early CT Score (E-ASPECTS) helps in the selection of patients who may be eligible for thrombolysis. This paper seeks to assess the performance of emergency physicians (EPs) in the evaluation of ASPECTS scores with and without the use of E-ASPECTS and to compare their results with neuroradiologists.Methods: A total of 116 patients were selected. Initially, two EPs and two neuroradiologists evaluated the admission nonenhanced CT without E-ASPECTS. Then, after 30 days, they re-evaluated the images using E-ASPECTS. Sensitivity, specificity, Matthew's correlation coefficients (MCC), and receiver operating characteristic curves were generated for analysis before and after the software use.Results: Eps' performances improved when they used E-ASPECTS, with their results closer to those obtained by neuroradiologists. In the initial evaluation, MCC values for the two EPs were -0.01 and 0.04, respectively. After the software assistance, they obtained 0.38 and 0.43, respectively, which was closer to the scores obtained by the neuroradiologists (0.53 and 0.39, respectively).Discussion: This is the first study that has specifically compared neuroradiologists' and EPs' performances before and after using E-ASPECTS. E-ASPECTS assisted and improved the evaluation of the images of patients with acute ischemic stroke. Conclusion:Artificial intelligence in the emergency room may increase the number of patients treated with tissue-type plasminogen activators.
Background. The effects of dose reduction in lung nodule detection need better understanding. Purpose. To compare the detection rate of simulated lung nodules in a chest phantom using different computed tomography protocols, low dose (LD), ultralow dose (ULD), and conventional (CCT), and to quantify their respective amount of radiation. Materials and Methods. A chest phantom containing 93 simulated lung nodules was scanned using five different protocols: ULD (80 kVp/30 mA), LD A (120 kVp/20 mA), LD B (100 kVp/30 mA), LD C (120 kVp/30 mA), and CCT (120 kVp/automatic mA). Four chest radiologists analyzed a selected image from each protocol and registered in diagrams the nodules they detected. Kruskal–Wallis and McNemar’s tests were performed to determine the difference in nodule detection. Equivalent doses were estimated by placing thermoluminescent dosimeters on the surface and inside the phantom. Results. There was no significant difference in lung nodules’ detection when comparing ULD and LD protocols ( p = 0.208 to p = 1.000 ), but there was a significant difference when comparing each one of those against CCT ( p < 0.001 ). The detection rate of nodules with CT attenuation values lower than −600 HU was also different when comparing all protocols against CCT ( p < 0.001 to p = 0.007 ). There was at least moderate agreement between observers in all protocols (κ-value >0.41). Equivalent dose values ranged from 0.5 to 9 mSv. Conclusion. There is no significant difference in simulated lung nodules’ detection when comparing ULD and LD protocols, but both differ from CCT, especially when considering lower-attenuating nodules.
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