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Objectives The aim of this study was to investigate the effect of daptomycin against methicillin-resistant staphylococci (MRSA and MRSE) bacteremia using computer modeling. Methods A pharmacokinetic/pharmacodynamic (PK/PD) modeling strategy to explain the data from an in vitro dynamic model employing time-kill curves for MRSA and MRSE was proposed. Bacterial killing was followed over time by determining viable counts and the resulting time-kill data was analyzed. Monte Carlo simulations were performed using pharmacokinetic parameters and pharmacodynamic data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration (MIC) targets of daptomycin. Simulations were conducted to assess the reduction in the number of colony-forming units (CFU)/mL for 18 days of treatment with daptomycin at doses of 6, 8, and 10 mg/kg/24 h or 48 h with variations in creatinine clearance (CL CR ): 15–29 mL/min/1.73 m 2 , 30–49 mL/min/1.73 m 2 , 50–100 mL/min/1.73 m 2 , as well as for defining the probability of reaching the target f AUC/MIC = 80 in the same dose and clearance range. A PK/PD model with saturation in the number of bacteria in vitro, growth delay, and bacterial death, as well as Hill’s factor, was used to describe the data for both MRSA and MRSE. Results Monte Carlo simulations showed that for MRSA there was a reduction > 2 log CFU/mL with doses ≥ 6 mg/kg/day in 75th percentile of the simulated population after 18 days of treatment with daptomycin, whereas for MRSE this reduction was observed in 95th percentile of the population. Conclusions The presented in vitro PK/PD model and associated modeling approach were able to characterize the time-kill kinetics of MRSA and MRSE. Our study based on PTAs suggests that doses ≥ 6 mg/kg/day of daptomycin should be used to treat bacteremia caused by MRSA and MRSE in patients with CL CR of 15–29 mL/min/1.73 m 2 . For patients with CL CR  ≥ 50 mL/min/1.73 m 2 , it would be necessary to employ a dose of 10 mg/kg/day to treat complicated bacteremias.

Objectives The aim of this study was to investigate the effect of daptomycin against vancomycin-resistant Enterococcus faecium bacteraemia using computer modelling. Methods Data obtained in vitro from time-kill curves were evaluated by PK/PD modelling and Monte Carlo simulations to determine the logarithmic reduction in the number of colony-forming units (CFU)/mL over 18 days of daptomycin treatment at 6, 8, and 10 mg/kg doses every 24 or 48 h and with variations in creatinine clearance (CL CR ) of 15–29, 30–49, and 50–100 mL/min/1.73 m 2 . Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) for an area under the unbound drug concentration-time curve/minimum inhibitory concentration ( f AUC/MIC) > 36 at the same doses and CL CR . Results Static time-kill model was employed to investigate the antibacterial efficacy of constant daptomycin concentrations. The time-kill curve analysis was performed using mathematical modelling based on a Hill coefficient factor. There was an expressive reduction (> 2 Log CFU/mL) over 18 days of daptomycin treatment in 75th percentile of individuals with CL CR of 15–100 mL/min/1.73 m 2 ) with daptomycin 6–10 mg/kg/day, except for daptomycin every 48 h. Using f AUC/MIC > 36, PTA was > 90% at MICs ≤ 2 μg/mL. Conclusions Higher daptomycin doses were associated with higher mortality in time-kill curves. The simulations indicated that independent of the CL CR the therapeutic responses of VRE occur with doses of daptomycin ≥ 6 mg/kg/day and daptomycin every 48 h is insufficient to treat enterococcal bacteraemia.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.

In this study, we analyzed associations between vaccination knowledge, vaccination intention, political ideology, and belief in conspiracy theories before and during the 2020 Sars-Cov-2 pandemic in the Brazilian population. It was conducted a longitudinal study into three data collections. Participants responded to the Flexible Inventory of Conspiracy Suspicions (FICS), questionnaires measuring their knowledge, and opinion about vaccines, and sociodemographic data. The results were: the greater the belief in conspiracy theories about vaccines, the lesser the intention to get vaccinated, the vaccine knowledge, and the attitudes towards vaccine investment. Religious, prone to right-wing politics, parents, and older people scored more for FICS than atheists/agnostics, and younger people. From 2019 to 2020 the vaccination intention and vaccination investment did not differ, showing that people did not change their opinion about vaccines regardless of personal experience or the pandemic scenario. The research strengthened the relevance of health education as a milestone for public health and protection from dangerous conspiracy theories.

The PD-1/PD-L1 signaling axis is currently the most elucidated mechanism for tumor evasion of T-cell-mediated immunity. Nevertheless, few data are available regarding its impact on cervical cancer and the relationship with lymphocytic infiltrates. A retrospective assessment of all cases of cervical neoplasia treated in Caxias do Sul General Hospital, Brazil, between 2012 and 2016 was performed. Clinical and pathological data were collected from electronic records and analyzed. Original slides were independently reviewed by three pathologists to confirm diagnoses and to assess the immunohistochemical expression of PD-L1 and FoxP3 in tumor cells and lymphocytic infiltrates. PD-L1 staining was present in 32.2% of the 59 cervical samples. Median overall survival time of the PD-L1-negative group was 47.8 months, a time point not yet reached by the PD-L1-positive group ( =0.968). Median progression-free survival was 24.3 months for PD-L1-negative and 11.5 months for PD-L1-positive patients ( =0.263). PD-L1 staining was found in 27.1% of the lymphocytic infiltrates, and survival analysis revealed no difference between PD-L1-positive and PD-L1-negative samples. There was no impact on survival related to FoxP3 staining in neither tumor samples nor lymphocytic infiltrates. Although the median progression-free survival times differed, the difference was not statistically significant. Our study corroborates the rationale that PD-L1 expression in cervical neoplasms has no impact on survival. PD-L1 expression in peritumoral lymphocytes revealed no impact on infiltration volume nor survival. uterine cervical neoplasms, tumor-infiltrating lymphocytes, cancer, tumor microenvironment, survival.

Objective There is a lack of research tools in Portuguese to evaluate racial discrimination. The purpose of this study was to psychometrically assess the Portuguese version of the Schedule of Racist Events (SRE) in a sample of individuals enrolled in a research trial with antiretroviral medications in southern Brazil. Methods Sample of 147 individuals living with HIV and/or AIDS. Research participants completed the Schedule of Racist Events and the WHOQOL-HIV BREF questionnaires. Results The SRE scores of non-white participants were significantly higher than the scores of white-participants. The Crombach’s alpha coefficients, for the three subscales of the Portuguese version of the SRE, were high and significant. There were significant correlations between all subscales of the SRE and relevant domains of the WHOQOL-HIV BREF. Conclusion The original English version of the SRE was successfully adapted to Portuguese. The Portuguese version of SRE constitutes a valid research instrument for evaluating racial discrimination.

Background: The PD-1/PD-L1 signaling axis is currently the most elucidated mechanism for tumor evasion of T-cell-mediated immunity. Nevertheless, few data are available regarding its impact on cervical cancer and the relationship with lymphocytic infiltrates. Methods: A retrospective assessment of all cases of cervical neoplasia treated in Caxias do Sul General Hospital, Brazil, between 2012 and 2016 was performed. Clinical and pathological data were collected from electronic records and analyzed. Original slides were independently reviewed by three pathologists to confirm diagnoses and to assess the immunohistochemical expression of PD-L1 and FoxP3 in tumor cells and lymphocytic infiltrates. Results: PD-L1 staining was present in 32.2% of the 59 cervical samples. Median overall survival time of the PD-L1-negative group was 47.8 months, a time point not yet reached by the PD-L1-positive group (p=0.968). Median progression-free survival was 24.3 months for PD-L1-negative and 11.5 months for PD-L1-positive patients (p=0.263). PD-L1 staining was found in 27.1% of the lymphocytic infiltrates, and survival analysis revealed no difference between PD-L1-positive and PD-L1-negative samples. There was no impact on survival related to FoxP3 staining in neither tumor samples nor lymphocytic infiltrates. Conclusion: Although the median progression-free survival times differed, the difference was not statistically significant. Our study corroborates the rationale that PD-L1 expression in cervical neoplasms has no impact on survival. PD-L1 expression in peritumoral lymphocytes revealed no impact on infiltration volume nor survival. Keywords: uterine cervical neoplasms, tumor-infiltrating lymphocytes, cancer, tumor microenvironment, survival

Background In Brazil, we are facing an alarming epidemic scenario of Yellow fever (YF), which is reaching the most populous areas of the country in unvaccinated people. Vaccination is the only effective tool to prevent YF. In special situations, such as patients with chronic immune-mediated inflammatory diseases (CIMID), undergoing immunosuppressive therapy, as a higher risk of severe adverse events may occur, assessment of the risk-benefit ratio of the yellow fever vaccine (YFV) should be performed on an individual level. Main body of the abstract Faced with the scarcity of specific orientation on YFV for this special group of patients, the Brazilian Rheumatology Society (BRS) endorsed a project aiming the development of individualized YFV recommendations for patients with CIMID, guided by questions addressed by both medical professionals and patients, followed an internationally validated methodology (GIN-McMaster Guideline Development). Firstly, a systematic review was carried out and an expert panel formed to take part of the decision process, comprising BRS clinical practitioners, as well as individuals from the Brazilian Dermatology Society (BDS), Brazilian Inflammatory Bowel Diseases Study Group (GEDIIB), and specialists on infectious diseases and vaccination (from Tropical Medicine, Infectious Diseases and Immunizations National Societies); in addition, two representatives of patient groups were included as members of the panel. When the quality of the evidence was low or there was a lack of evidence to determine the recommendations, the decisions were based on the expert opinion panel and a Delphi approach was performed. A recommendation was accepted upon achieving ≥80% agreement among the panel, including the patient representatives. As a result, eight recommendations were developed regarding the safety of YFV in patients with CIMID, considering the immunosuppression degree conferred by the treatment used. It was not possible to establish recommendations on the effectiveness of YFV in these patients as there is no consistent evidence to support these recommendations. Conclusion This paper approaches a real need, assessed by clinicians and patient care groups, to address specific questions on the management of YFV in patients with CIMID living or traveling to YF endemic areas, involving specialists from many areas together with patients, and might have global applicability, contributing to and supporting vaccination practices. We recommended a shared decision-making approach on taking or not the YFV.