ABSTRACT 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.

ABSTRACT The study aimed to assess the effect of progressive neutralization on the antimicrobial properties against bacteria and yeasts of wood vinegar obtained from the pyrolysis of Eucalyptus urograndis (clone I144) wood. Wood samples were carbonized at a heating rate of 0.9 °C min-1 until a final temperature of 450 °C, totalizing 8 hours of carbonization. The raw pyrolysis liquids were left to settle, and the aqueous fraction was separated. Then, the aqueous fraction (raw wood vinegar - WV) was purified to yield the WV. WV samples were collected and neutralized from pH 2.5 until 7.5 (2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, and 7.5, by adding NaOH solution. Through the broth microdilution method, the antimicrobial effect of the neutralized samples at each pH was assessed on Pseudomonas aeruginosa (ATCC 27853), Salmonella enteritidis (ATCC 13076), Staphylococcus aureus (ATCC 25923), Streptococcus agalactiae (CEPA CLINICA), and Candida albicans (ATCC 10231). The minimum inhibitory concentration (MIC) and minimum bactericidal (and fungicidal) concentrations were determined through in vitro technics. Results were subjected to logarithmic regression analysis, and statistical models were fitted for each microorganism in the assessed pH range; as pH increased, a progressive decrease in the CIM increased, demanding higher concentrations of WV to inhibit microbial growth. The more resistant strains were S. aureus and S. agalactiae, which required an increase in WV concentration from a minimum of 6.25% at pH 2.5 to reaching 50% at pH 6.0. When at pH 7.0, both strains were not inhibited even at 50% (the highest concentration evaluated in the study). In contrast, C. albicans proved to be the most sensitive strain, starting from 3.12% EP at pH 2.5 and requiring only 25% for inhibition at pH 7.0. The behavior of P. aeruginosa and S. enteritidis followed the pattern of C. albicans, differing only at pH 7.0, where they required 50% of EP. As observed, even at neutral and slightly alkaline pH, the inhibitory activity of EP on microbial growth was maintained to some extent. Nevertheless, even when neutral and slightly alkaline pH values are reached, the inhibitory activity remains at a certain level. Higher pH values of the WV were associated with lower antimicrobial activity. However, its activity remained even at neutral and slightly alkaline pH values.

RESUMO O presente trabalho teve como objetivo avaliar o efeito da neutralização progressiva na atividade antimicrobiana do extrato pirolenhoso (EP) da madeira do híbrido Eucalyptus urophylla x Eucalyptus grandis (clone I144). Amostras de madeira foram carbonizadas a uma taxa de aquecimento de 0.9 °C min-1 até a temperatura final de 450 °C, perfazendo 8 horas de carbonização. Os líquidos brutos da carbonização foram deixados em repouso e a fração aquosa foi separada. A fração aquosa correspondente ao EP bruto foi destilada obtendo o EP purificado. Alíquotas de EP purificado foram progressivamente neutralizadas do pH 2.5 até 7.5, respectivamente, 2,5, 3,0, 3,5, 4,0, 4,5, 5,0, 5,5, 6,0, 6,5, 7,0, e 7,5, por meio da adição de NaOH. Com o método da micro-diluição em caldo, o efeito antimicrobiano das amostras neutralizadas em cada pH foi avaliado contra Pseudomonas aeruginosa (ATCC 27853), Salmonella enteritidis (ATCC 13076), Staphylococcus aureus (ATCC 25923), Streptococcus agalactiae (CEPA CLINICA) e Candida albicans (ATCC 10231). As concentrações inibitórias mínimas e as concentrações bactericida e fungicida mínimas foram determinadas por técnicas in vitro. Os resultados foram analisados por regressão logarítmica e modelos estatísticos foram ajustados para cada microrganismo em cada pH. Na determinação da CIM, foi detectada uma perda progressiva da atividade antimicrobiana do EP com a neutralização, exigindo, conforme o pH caminhava para 7.0, concentrações mais elevadas de EP para resultar em inibição. As cepas que demonstraram maior resistência foram S. aureus e S. agalactiae. Esses microrganismos partiram da exigência de concentrações de 6.25% de EP, em pH inicial (2.5), e chegaram a requerer 50% em pH 6.0. Quando em pH 7.0, ambas as cepas não foram inibidas nem a 50% (maior concentração avaliada no estudo). Em contrapartida, C. albicans se mostrou a cepa mais sensível, partindo de 3.12% de EP, em pH de 2.5, e exigindo apenas 25% para inibição em pH 7.0. O comportamento de P. aeruginosa e S. enteritidis acompanhou o padrão da C. albicans, diferenciando-se apenas em pH 7.0, onde exigiram 50% de EP. Como observado, mesmo em pH neutro e ligeiramente alcalino, a atividade inibitória do EP ao crescimento microbiano se manteve em certa extensão.

Objetivo:Com o aumento da expectativa de vida no mundo, as fraturas por osteoporose se tornaram mais frequentes e aumentaram também os gastos no tratamento. Avaliar a melhora da dor e da qualidade de vida de pacientes com fraturas vertebrais osteoporóticas compressivas submetidos a vertebroplastia.Métodos:Foram submetidos à vertebroplastia 18 pacientes com 27 vértebras fraturadas e avaliados pelo questionário de limitações de Oswestry 2.0 de forma pré-operatória, 24 horas e seis meses no pós-operatório.Resultados:Melhora de 75% da dor e da qualidade de vida, com Oswestry médio pré-operatório de 40%, em 24 horas de 10% e após seis meses da cirurgia, de 9%. (p ≤ 0,05).Conclusão:A vertebroplastia é efetiva no manejo das fraturas vertebrais osteoporóticas por compressão e melhora da dor e da qualidade de vida dos pacientes no pós-operatório imediato e médio prazo.

Objective:with increasing life expectancy around the world, fractures due to osteoporosis have become more common and the expenditure for treating them has also increased. The aim here was to evaluate the improvement in pain and quality of life among patients with compressive osteoporotic vertebral fractures undergoing vertebroplasty.Methods:eighteen patients with 27 fractured vertebrae underwent vertebroplasty and were evaluated using the Oswestry 2.0 limitations questionnaire before the operation and 24 h and six months after the operation.Results:there was a 75% improvement in pain and quality of life, going from a mean preoperative Oswestry of 40% to 10% 24 h after the operation and 9% six months after the operation (p ≤ 0.05).Conclusion:vertebroplasty is effective in managing compressive osteoporotic vertebral fractures, with improvement in pain and quality of life in the immediate postoperative period and over the medium term.

Relatamos o caso de uma paciente, de 36 anos de idade, que desenvolveu quadro de coréia após dois meses do início do uso de anticoncepcional oral, acompanhando-se, posteriormente, de trombocitopenia, úlcera mucosa em cavidade oral, artrite, positividade para os anticorpos antinuclear (FAN), anti-DNA e anti-Sm, preenchendo critérios para lúpus eritematoso sistêmico, segundo o Colégio Americano de Reumatologia. A pesquisa para os anticorpos anticoagulante lúpico e anticardiolipina (IgG e IgM) foi negativa. A paciente foi tratada com prednisona, fenitoína, fenobarbital e clonazepam, obtendo melhora clínica e laboratorial. Discutimos a ocorrência da coréia e outros movimentos anormais como primeira manifestação do lúpus eritematoso sistêmico, sua relação com os anticoncepcionais orais e os anticorpos antifosfolípides.

We describe a 36 year-old woman who developed chorea two months after starting the use of oral contraceptives. She also developed thrombocitopenia, oral ulcers, arthritis, positive antinuclear antibodies (ANA), anti-Sm and anti-DNA, filling criteria for sistemic lupus erythematosus, as defined by the American College of Rheumatology. The tests for lupus anticoagulant and anticardiolipin (IgG and IgM) were negative. The patient was treated with prednisone, phenitoin, phenobarbital and clonazepam, obtaining clinical and laboratorial improvement. We discuss the ocurrence of chorea and other movement disorders as first manifestation of systemic lupus erythematosus, its relationship with oral contraceptives and antiphospholipid antibodies.