The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Temporal Reduction in COVID-19-Associated Fatality Among Kidney Transplant Recipients: The Brazilian COVID-19 Registry Cohort Study.

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.

Identification and selection of a new Saccharomyces cerevisiae strain isolated from Brazilian ethanol fermentation process for application in beer production.

The fermented beverage industry is always pursuing alternatives to make products that delight consumers with special or unique characteristics. The identification and improvement of new yeast strains emerge as an opportunity; however, wild strains usually have a limitation in maltose fermentation and/or off-flavors production. Here we report the production of a Blond-style ale beer using a bioethanol isolated strain (LBGA-287) with flavor complexity approved in sensorial panels. LBGA-287 also showed an increase in maltose consumption, growth and fermentation rates when compared to the commercial yeast. Using qPCR analysis, genes related to the (i) efficiency of fermentation (ii) production of aromas/off-flavors, and (iii) metabolization of carbohydrates were found as differentially expressed in the isolated strains when compared to industrial yeast. This suggests that LBGA-287 could have an important impact on beer production, improving brewing efficiency, quality and diversity of this beverage, and most importantly satisfying the final consumer.

Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients.

This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698-0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.

High mortality among kidney transplant recipients diagnosed with coronavirus disease 2019: Results from the Brazilian multicenter cohort study.

BACKGROUND: Kidney transplant (KT) recipients are considered a high-risk group for unfavorable outcomes in the course of coronavirus disease 2019 (COVID-19). AIM: To describe the clinical aspects and outcomes of COVID-19 among KT recipients. METHODS: This multicenter cohort study enrolled 1,680 KT recipients diagnosed with COVID-19 between March and November 2020, from 35 Brazilian centers. The main outcome was the 90-day cumulative incidence of death, for the entire cohort and according to acute kidney injury (AKI) and renal replacement therapy (RRT) requirement. Fatality rates were analyzed according to hospitalization, intensive care unit (ICU) admission, and mechanical ventilation (MV) requirement. Multivariable analysis was performed by logistic regression for the probability of hospitalization and death. RESULTS: The median age of the recipients was 51.3 years, 60.4% were men and 11.4% were Afro-Brazilian. Comorbidities were reported in 1,489 (88.6%), and the interval between transplantation and infection was 5.9 years. The most frequent symptoms were cough (54%), myalgia (40%), dyspnea (37%), and diarrhea (31%), whereas the clinical signs were fever (61%) and hypoxemia (13%). Hospitalization was required in 65.1%, and immunosuppressive drugs adjustments were made in 74.4% of in-hospital patients. ICU admission was required in 34.6% and MV in 24.9%. In the multivariable modeling, the variables related with the probability of hospitalization were age, hypertension, previous cardiovascular disease, recent use of high dose of steroid, and fever, dyspnea, diarrhea, and nausea or vomiting as COVID-19 symptoms. On the other hand, the variables that reduced the probability of hospitalization were time of COVID-19 symptoms, and nasal congestion, headache, arthralgia and anosmia as COVID-19 symptoms. The overall 90-day cumulative incidence of death was 21.0%. The fatality rates were 31.6%, 58.2%, and 75.5% in those who were hospitalized, admitted to the ICU, and required MV, respectively. At the time of infection, 23.2% had AKI and 23.4% required RRT in the follow-up. The cumulative incidence of death was significantly higher among recipients with AKI (36.0% vs. 19.1%, P < 0.0001) and in those who required RRT (70.8% vs. 10.1%, P < 0.0001). The variables related with the probability of death within 90 days after COVID-19 were age, time after transplantation, presence of hypertension, previous cardiovascular disease, use of tacrolimus and mycophenolate, recent use of high dose of steroids, and dyspnea as COVID-19 symptom. On the other hand, the variables that reduced the risk of death were time of symptoms, and headache and anosmia as COVID-19 symptoms. CONCLUSION: The patients diagnosed with COVID-19 were long-term KT recipients and most of them had some comorbidities. One in every five patients died, and the rate of death was significantly higher in those with AKI, mainly when RRT was required.

The profiles of angiology and vascular surgery academic leagues and their effectiveness in specialty education.

BACKGROUND: Academic leagues are extracurricular student organizations that are supervised by professors on the faculty of a higher education institution and are dedicated to improving knowledge in certain areas. There has recently been a marked growth in the number of new leagues, giving undergraduate students access to additional information, lectures, internships, and conferences. Angiology and vascular surgery is one of the specialties that have such organizations. OBJECTIVES: To determine the academic profile of the angiology and vascular surgery academic leagues at medical schools in the state of São Paulo, Brazil, and investigate the academic performance of their members. METHODS: This is a cross-sectional, descriptive, and analytical study that recruited undergraduate medical students who had joined angiology and vascular surgery academic leagues in the state of São Paulo. On-line questionnaires were used to collect data on each league and the students took examinations to determine their performance. RESULTS: Most leagues had an entrance exam for enrollment, with an obligatory introductory course. Monthly theoretical lectures were held by 42.9% of the leagues. Practical activities were provided by 85.7% of the leagues. The majority of the leagues (71.4%) were involved in scientific research. Paired-sample comparison of students' performance in the exams revealed a significant increase in mean scores, from 61.1 to 72.6 (p < 0.05). CONCLUSIONS: The angiology and vascular surgery academic leagues in the state of São Paulo all function in a similar manner, but the range of theoretical, practical and scientific activities they offer are not uniform. For the sample investigated, the academic leagues appear to be effective at teaching angiology and vascular surgery during undergraduate courses.

O perfil das ligas acadêmicas de angiologia e cirurgia vascular e sua eficácia no ensino da especialidade / The profiles of angiology and vascular surgery academic leagues and their effectiveness in specialty education

As ligas acadêmicas são organizações estudantis extracurriculares que contam com a supervisão de um docente vinculado à instituição de ensino e visam aprimorar o conhecimento em determinadas áreas. Verificou-se, nos últimos anos, um crescimento do número de novas ligas, nas quais os graduandos têm acesso a informações complementares através de aulas, estágios e congressos. A especialidade de angiologia e cirurgia vascular encontra-se entre aquelas que dispõem dessas organizações. Objetivos Determinar o perfil acadêmico das ligas de angiologia e cirurgia vascular das faculdades de Medicina do estado de São Paulo e verificar o desempenho dos membros dessas ligas no ensino. Métodos Este estudo transversal, descritivo e analítico incluiu graduandos de Medicina membros de ligas acadêmicas de angiologia e cirurgia vascular do estado de São Paulo. Foram utilizados questionários on-line para determinação dos dados de cada liga e foram aplicadas provas para verificação do desempenho. Resultados O ingresso ocorreu prioritariamente por prova, com curso introdutório obrigatório. Realizaram-se aulas teóricas mensalmente em 42,9% das ligas. Quanto a atividades práticas, 85,7% das ligas as realizaram. A maioria das ligas (71,4%) relataram realizar atividades científicas. A comparação pareada do desempenho dos alunos nas provas demonstrou um aumento significativo na média, de 61,1 para 72,6 (p < 0,05). Conclusões As ligas acadêmicas de angiologia e cirurgia vascular do estado de São Paulo apresentam modos de funcionamento semelhantes e um perfil heterogêneo quanto a atividades teóricas, práticas e científicas. A partir da presente amostra, as ligas acadêmicas aparentam ser efetivas no ensino de angiologia e cirurgia vascular durante a graduação

Academic leagues are extracurricular student organizations that are supervised by professors on the faculty of a higher education institution and are dedicated to improving knowledge in certain areas. There has recently been a marked growth in the number of new leagues, giving undergraduate students access to additional information, lectures, internships, and conferences. Angiology and vascular surgery is one of the specialties that have such organizations. Objectives To determine the academic profile of the angiology and vascular surgery academic leagues at medical schools in the state of São Paulo, Brazil, and investigate the academic performance of their members. Methods This is a cross-sectional, descriptive, and analytical study that recruited undergraduate medical students who had joined angiology and vascular surgery academic leagues in the state of São Paulo. On-line questionnaires were used to collect data on each league and the students took examinations to determine their performance. Results Most leagues had an entrance exam for enrollment, with an obligatory introductory course. Monthly theoretical lectures were held by 42.9% of the leagues. Practical activities were provided by 85.7% of the leagues. The majority of the leagues (71.4%) were involved in scientific research. Paired-sample comparison of students' performance in the exams revealed a significant increase in mean scores, from 61.1 to 72.6 (p < 0.05). Conclusions The angiology and vascular surgery academic leagues in the state of São Paulo all function in a similar manner, but the range of theoretical, practical and scientific activities they offer are not uniform. For the sample investigated, the academic leagues appear to be effective at teaching angiology and vascular surgery during undergraduate courses

Optimized culture and growth curves of two ciliated protozoan strains of Paramecium caudatum Ehrenberg, 1833 to use in ecotoxicologycal assays

Protozoans are microbial eukaryotes known to be ideal for aquatic ecotoxicological testing. Therefore, aiming to evaluate their possible use in standardized ecotoxicity assays we determined the best cultivation conditions and growth curves for two strains of the ciliated protozoan Paramecium caudatum Ehenberg 1833. One strain (PC1) was isolated from the Monjolinho reservoir-SP (22° 01’ S and 47° 53’ W) where the mean dissolved O2 is 5.205 mgL-1, pH 6.43 and electrical conductivity 34.75 μS cm-1. The other strain (PC2) from the Óleo lagoon in Jataí Ecological Station- SP (21° 36’ S and 47° 49’ W), with mean dissolved of 4,42 mgL-1, pH 4.90 and electrical conductivity 10.96 μS cm-1. The higher mean cellular biovolume and density obtained were used to evaluate different cultivation parameters such as temperature, pH, light exposition, stirring regimen and cultivation flask size. Considering protozoan densities and cell biovolume, the best culture conditions for PC1 strain was pH 9.0 at 30 °C and for PC2 was pH 7.0 at 27.5 °C. For both strains and evaluated parameters (biovolume and density), the bottle size did not interfered in the results and absence of light resulted in better ones. Concerning agitation, for PC2, there was no significant difference for this parameter and for PC1 in the absence of shaking we obtained better results. Therefore we decided to make the tests in the absence of light and without shaking. Regarding cell biovolume, the best condition was pH 9.0 at 25 ° C for the PC1 strain and pH 8.0 at 20 ° C for PC2 strain. The generation time calculated in a 96 hours growth curve was 8.35 hours for PC1 and 7.6 hours for PC2.

Optimized culture and growth curves of two ciliated protozoan strains of Paramecium caudatum Ehrenberg, 1833 to use in ecotoxicologycal assays

Protozoans are microbial eukaryotes known to be ideal for aquatic ecotoxicological testing. Therefore, aiming to evaluate their possible use in standardized ecotoxicity assays we determined the best cultivation conditions and growth curves for two strains of the ciliated protozoan Paramecium caudatum Ehenberg 1833. One strain (PC1) was isolated from the Monjolinho reservoir-SP (22° 01 S and 47° 53 W) where the mean dissolved O2 is 5.205 mgL-1, pH 6.43 and electrical conductivity 34.75 μS cm-1. The other strain (PC2) from the Óleo lagoon in Jataí Ecological Station- SP (21° 36 S and 47° 49 W), with mean dissolved of 4,42 mgL-1, pH 4.90 and electrical conductivity 10.96 μS cm-1. The higher mean cellular biovolume and density obtained were used to evaluate different cultivation parameters such as temperature, pH, light exposition, stirring regimen and cultivation flask size. Considering protozoan densities and cell biovolume, the best culture conditions for PC1 strain was pH 9.0 at 30 °C and for PC2 was pH 7.0 at 27.5 °C. For both strains and evaluated parameters (biovolume and density), the bottle size did not interfered in the results and absence of light resulted in better ones. Concerning agitation, for PC2, there was no significant difference for this parameter and for PC1 in the absence of shaking we obtained better results. Therefore we decided to make the tests in the absence of light and without shaking. Regarding cell biovolume, the best condition was pH 9.0 at 25 ° C for the PC1 strain and pH 8.0 at 20 ° C for PC2 strain. The generation time calculated in a 96 hours growth curve was 8.35 hours for PC1 and 7.6 hours for PC2. (AU)

Heart rate variability in shift workers: responses to orthostatism and relationships with anthropometry, body composition, and blood pressure.

In order to investigate the response of heart rate variability (HRV) components to postural change and their association with cardiovascular risk factors in shift workers, a cross-sectional study with 438 Brazilian males rotating shift workers was done. Anthropometric, body composition, and clinical measures were collected. Electrocardiogram was recorded for 3 minutes, in the supine and orthostatic position, and HRV components were extracted. Descriptive analyses showed that mean values of body mass index, waist circumference (WC), waist-to-height ratio, visceral fat area (VFA), and blood pressure (BP) were higher than the reference values. In the regression model, age, WC, VFA, and systolic BP showed negative association with HRV components. These findings suggest the need for determining effective strategies for the evaluation and promotion of health among shift workers focused on the altered variables.

Correção cirúrgica de aneurismas saculares de fístula arteriovenosa para hemodiálise utilizando a técnica de aneurismorrafia / Surgical repair of saccular aneurysms of an arteriovenous fistula for hemodialysis using aneurismorraphy technique

Uma das complicações mais frequentes da fístula arteriovenosa (FAV) para hemodiálise é o desenvolvimento de um aneurisma. A formação de aneurismas geralmente decorre de um enfraquecimento da parede venosa devido às repetidas punções, e sua rotura causa hemorragia intensa que pode levar à morte. Descrevemos o caso de uma paciente com dois aneurismas saculares de FAV, tratados através de aneurismorrafia, detalhando a técnica cirúrgica utilizada e a evolução pós-operatória. A técnica de rafia simples da parede constitui uma boa alternativa no reparo da parede da FAV quando o aneurisma é de curta extensão, evitando a colocação de um material protético e a confecção de duas anastomoses.

One of the most common complications of arteriovenous fistulas (AVF) is aneurysm formation due to weakening of the venous wall after repeated punctures. Its rupture causes severe bleeding that can lead to death. We report the case of a patient with two AVF saccular aneurysms treated by aneurysmorrhaphy. The technique and the postoperative follow-up are presented in detail. Aneurysmorrhaphy is a good option to repair the AVF wall when the aneurysmal segment is short, thus avoiding the placement of prosthetic grafts and the performance of two anastomoses.

Biochemical and molecular characterization of Saccharomyces cerevisiae strains obtained from sugar-cane juice fermentations and their impact in cachaça production.

Saccharomyces cerevisiae strains from different regions of Minas Gerais, Brazil, were isolated and characterized aiming at the selection of starter yeasts to be used in the production of cachaça, the Brazilian sugar cane spirit. The methodology established took into account the screening for biochemical traits desirable in a yeast cachaça producer, such as no H2S production, high tolerance to ethanol and high temperatures, high fermentative capacity, and the abilities to flocculate and to produce mycocins. Furthermore, the yeasts were exposed to drugs such as 5,5',5"-trifluor-D,L-leucine and cerulenin to isolate those that potentially overproduce higher alcohols and esters. The utilization of a random amplified polymorphic DNA-PCR method with primers based on intron splicing sites flanking regions of the COX1 gene, as well as microsatellite analysis, was not sufficient to achieve good differentiation among selected strains. In contrast, karyotype analysis allowed a clear distinction among all strains. Two selected strains were experimentally evaluated as cachaça producers. The results suggest that the selection of strains as fermentation starters requires the combined use of biochemical and molecular criteria to ensure the isolation and identification of strains with potential characteristics to produce cachaça with a higher quality standard.