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A lesão da parede arterial provocada por balão de angioplastia ou implante de próteses endovasculares em modelos experimentais e humanos pode provocar a reestenose do vaso, principalmente por migração e proliferação de células musculares lisas e síntese de matriz extracelular. Vários estudos demonstraram que a braquiterapia intra-arterial atua nestes fatores e, conseqüentemente, no tratamento da reestenose coronariana. Este estudo tem por objetivo avaliar as alterações vasculares morfológicas e morfométricas induzidas pela braquiterapia com samário-153 (153Sm), utilizando uma dose considerada ideal e outra elevada em coelhos hipercolesterolêmicos. Foram analisados 43 coelhos hipercolesterolêmicos e um total de 86 artérias ilíacas submetidas à lesão por balão de angioplastia, divididos em três grupos, sendo irradiados com as doses de 15Gy (n = 14) e 60Gy (n = 36) e controle (n = 36). Foram realizadas análise morfométrica (área neo-intimal, área da camada média, área do vaso) e análise histológica qualitativa para avaliação tecidual. O colesterol médio foi de 1.362 ± 497mg/dl nos três grupos. O achado mais relevante foi uma significativa inibição da hiperplasia neo-intimal no grupo irradiado com a dose de 15Gy, maior do que o controle e com a dose de 60Gy. Na dose de 60 Gy, além de ineficaz para inibir a proliferação neo-intimal, teve características tissulares e estruturais sugestivas de radiolesão, como presença de células xantomatosas, tecidos hialino e amorfo, proliferação vascular. Estas células, bem como o aumento das dimensões morfométricas do vaso, foram proporcionais aos graus de lesão nas lâminas elásticas interna e externa, sendo observados principalmente com a dose de 60Gy. Os segmentos médios das artérias ilíacas, representando o local de maior contato com o balão, tiveram maiores alterações morfométricas e celulares em relação aos segmentos referenciais (proximal e distal) nos três grupos. Em conclusão, o grupo de artérias submetidas à irradiação de 15Gy foi eficaz para a inibição da proliferação neo-intimal. O grupo irradiado com a maior dose de 60Gy foi ineficaz para inibir a hiperplasia neo-intimal e apresentou características morfométricas e teciduais compatíveis com a radiolesão vascular.

Background: Cases of coronavirus disease 2019 (COVID-19) requiring hospitalization continue to appear in vulnerable populations, highlighting the importance of novel treatments. The hyperinflammatory response underlies the severity of the disease, and targeting this pathway may be useful. Herein, we tested whether immunomodulation focusing on interleukin (IL)-6, IL-17, and IL-2, could improve the clinical outcomes of patients admitted with COVID-19., Methods: This multicenter, open-label, prospective, randomized controlled trial was conducted in Brazil. Sixty hospitalized patients with moderate-to-critical COVID-19 received in addition to standard of care (SOC): IL-17 inhibitor (ixekizumab 80 mg SC/week) 1 dose every 4 weeks; low-dose IL-2 (1.5 million IU per day) for 7 days or until discharge; or indirect IL-6 inhibitor (colchicine) orally (0.5 mg) every 8 hours for 3 days, followed by 4 weeks at 0.5 mg 2x/day; or SOC alone. The primary outcome was accessed in the "per protocol" population as the proportion of patients with clinical improvement, defined as a decrease greater or equal to two points on the World Health Organization's (WHO) seven-category ordinal scale by day 28., Results: All treatments were safe, and the efficacy outcomes did not differ significantly from those of SOC. Interestingly, in the colchicine group, all participants had an improvement of greater or equal to two points on the WHO seven-category ordinal scale and no deaths or patient deterioration were observed., Conclusions: Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective for COVID-19 treatment. These results must be interpreted cautiously because of the limited sample size.

Meplazumab, a humanized CD147 antibody, has shown favourable safety and efficacy in our previous clinical studies. In DEFLECT (NCT04586153), 167 patients with severe COVID-19 were enroled and randomized to receive three dosages of meplazumab and a placebo. Meplazumab at 0.12 mg/kg, compared to the placebo group, showed clinical benefits in significantly reducing mortality by 83.6% (2.4% vs. 14.6%, p = 0.0150), increasing the proportion of patients alive and discharged without supplemental oxygen (82.9% vs. 70.7%, p = 0.0337) and increasing the proportion of patients who achieved sustained clinical improvement (41.5% vs. 31.7%). The response rate in the 0.2 mg/kg group was relatively increased by 16.0% compared with the placebo group (53.7% vs. 46.3%). Meplazumab also reduced the viral loads and multiple cytokine levels. Compare with the placebo group, the 0.3 mg/kg significantly increased the virus negative rate by 40.6% (p = 0.0363) and reduced IL-8 level (p = 0.0460); the 0.2 mg/kg increased the negative conversion rate by 36.9%, and reduced IL-4 (p = 0.0365) and IL-8 levels (p = 0.0484). In this study, the adverse events occurred at a comparable rate across the four groups, with no unexpected safety findings observed. In conclusion, meplazumab promoted COVID-19 convalescence and reduced mortality, viral load, and cytokine levels in severe COVID-19 population with good safety profile., (© 2023. The Author(s).)

Background: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown., Methods: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684., Findings: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group., Interpretation: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis., Funding: Bayer., Competing Interests: Declaration of interests ER reports grants and consulting fees from Bayer and Pfizer; grants from the Brazilian Ministry of Science and Technology; and personal fees from Aspen Pharma, Biomm Pharma, and Daiichi Sankyo, outside of the submitted work. LBA reports grants from Bayer, Pfizer, and the Brazilian Ministry of Science and Technology. DC reports personal fees from Bayer, Janssen, Daiichi Sankyo, and Pfizer; and grants from Stago. ACS reports consulting fees from Janssen Research & Development, Bayer, Portola, Boehringer Ingelheim, Bristol Myers Squibb, and ATLAS group; and grants from Janssen and Boehringer Ingelheim. MLS reports personal fees from Bayer, Pfizer, and Sanofi. EEJ reports consulting and personal fees form Bayer. CD reports consulting and personal fees from Bayer, Novartis, and Daiichi Sankyo. SMVS reports personal fees from Bayer. RCC reports personal fees from Boehringer Ingelheim and AstraZeneca. ATaf reports personal fees from Janssen and Recovery Force and grants from Bio Tap, Idorsia, Bristol Myers Squibb, Novo Nordisk, Janssen, and Doasense. RDL reports grants and personal fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and personal fees from Amgen, Bayer, and Boehringer Ingelheim, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis., Design: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria., Summary: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice. 1 ., Competing Interests: Declaration of interest ER: Research support from Bayer, Pfizer, Bristol-Myers Squibb, Brazilian Ministry of Science and Technology. Consulting fees from Bayer, Daiichi-Sankyo, Aspen Pharma, Biomm Pharma, and Pfizer. DC: Research support from Stago. Consulting fees from Bayer and Janssen. AT: Idorsia, Janssen, Bristol-Myers Squibb, Novo Nordisk, research support. Janssen, Recovery force, educational funding. ACS: Janssen, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb, Portola, ATLAS Group: Consultancy; Janssen, Boehringer-Ingelheim: Research Funding. RDL: Research support from Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer; Consulting fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Merck, Pfizer, Portola., (Copyright © 2021. Published by Elsevier Inc.)

Background: Developing countries struggle to diagnose and treat ST-segment elevation myocardial infarction (STEMI) patients in a timely manner, and subsequent outcomes are suboptimal., Methods: The Latin America Telemedicine Network (LATIN) functioned between 2013 to present in four countries-Brazil, Colombia, Mexico, and Argentina. A Hub and Spoke platform was developed to expand access to >100 million population for STEMI care. Patients were triaged at spokes that included small clinics and primary health care centers in remote South American locations. Three telemedicine command sites provided immediate 24/7 electrocardiogram diagnosis and teleconsultation of the STEMI process at 355 centers in four countries., Results: LATIN Spokes (n = 313) screened up to 30,000 patients per month, and a total of 780,234 patients over the study period. Telemedicine experts diagnosed 8395 (1·1%) with STEMI, of which a total of 3872 (46·1%) were urgently treated at 47 Hubs. A total of 3015 patients (78%) were reperfused with percutaneous coronary intervention. Time-to-telemedicine diagnosis averaged 3·5 min. Average door-to-balloon time improved from 120 to 48 min during the study period and overall STEMI mortality was 5·2%., Interpretation: Telemedicine transcends boundaries and enables access to millions of patients for STEMI care. With this initiative, LATIN has created a template for reducing disparities in STEMI management between developed and developing countries., (© 2021 Wiley Periodicals LLC.)