Exploring Urinary Extracellular Vesicles and Immune Mediators as Biomarkers of Kidney Injury in COVID-19 Hospitalized Patients.

Kidney injury is an important outcome associated with COVID-19 severity. In this regard, alterations in urinary extracellular vesicles (uEVs) could be detected in the early phases of renal injury and may be reflective of the inflammatory process. This is an observational study performed with a case series of COVID-19 hospitalized patients presenting mild-to-critical disease. Total and podocyte-derived uEVs were identified by nanoscale flow cytometry, and urinary immune mediators were assessed by a multiplex assay. We studied 36 patients, where 24 (66.7%) were considered as mild/moderate and 12 (33.3%) as severe/critical. Increased levels of total uEVs were observed (p = 0.0001). Importantly, total uEVs were significantly higher in severe/critical patients who underwent hemodialysis (p = 0.03) and were able to predict this clinical outcome (AUC 0.93, p = 0.02). Severe/critical patients also presented elevated urinary levels (p < 0.05) of IL-1ß, IL-4, IL-6, IL-7, IL-16, IL-17A, LIF, CCL-2, CCL-3, CCL-11, CXCL-10, FGFb, M-CSF, and CTAcK. Lastly, we observed that total uEVs were associated with urinary immune mediators. In conclusion, our results show that early alterations in urinary EVs could identify patients at higher risk of developing renal dysfunction in COVID-19. This could also be relevant in different scenarios of systemic and/or infectious disease.

Cathepsin B and Plasma Kallikrein Are Reliable Biomarkers to Discriminate Clinically Significant Hepatic Fibrosis in Patients with Chronic Hepatitis-C Infection.

We aimed to determine the biomarker performance of the proteolytic enzymes cathepsin B (Cat B) and plasma kallikrein (PKa) and transforming growth factor (TGF)-ß to detect hepatic fibrosis (HF) in chronic hepatitis C (CHC) patients. We studied 53 CHC patients and 71 healthy controls (HCs). Hepatic-disease stage was determined by liver biopsies, aminotransferase:platelet ratio index (APRI) and Fibrosis (FIB)4. Hepatic inflammation and HF in CHC patients were stratified using the METAVIR scoring system. Cat-B and PKa activities were monitored fluorometrically. Serum levels of TGF-ß (total and its active form) were determined using ELISA-like fluorometric methods. Increased serum levels of Cat B and PKa were found (p < 0.0001) in CHC patients with clinically significant HF and hepatic inflammation compared with HCs. Levels of total TGF-ß (p < 0.0001) and active TGF-ß (p < 0.001) were increased in CHC patients compared with HCs. Cat-B levels correlated strongly with PKa levels (r = 0.903, p < 0.0001) in CHC patients but did not correlate in HCs. Levels of Cat B, PKa and active TGF-ß increased with the METAVIR stage of HF. Based on analyses of receiver operating characteristic (ROC) curves, Cat B and PKa showed high diagnostic accuracy (area under ROC = 0.99 ± 0.02 and 0.991 ± 0.007, respectively) for distinguishing HF in CHC patients from HCs. Taken together, Cat B and PKa could be used as circulating biomarkers to detect HF in HCV-infected patients.

Worsening Renal Function and Congestion in Patients with Acute Heart Failure: A Study with Bioelectrical Impedance Vector Analysis (BIVA) and Neutrophil Gelatinase-Associated Lipocalin (NGAL). / Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL).

BACKGROUND: Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies. OBJECTIVE: We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization). METHODS: Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05. RESULTS: Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22). CONCLUSION: Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.

FUNDAMENTO: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. OBJETIVO: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). MÉTODOS: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p<0.05. RESULTADOS: A idade média foi 60,6 ± 15,0 anos, e 48 (60%) pacientes eram do sexo masculino. A fração de ejeção média foi 35,3±7,8%. O AFR ocorreu em 37,5% da amostra. A creatinina basal associou-se com AFR (p<0,001), mas nem BNP (p=0,35) nem NGAL (p=0,18) na admissão foram preditores de AFR. Usando modelos de riscos proporcionais de Cox, o índice de hidratação na alta, estimado por BIVA, associou-se significativamente com ocorrência de eventos (HR 1,39; IC95% 1,25-1,54, p<0,0001), mas não com AFR (HR 2,14; IC95% 0,62-7,35, p=0,22). CONCLUSÃO: A congestão persistente na alta associou-se com piores desfechos. O AFR parece estar relacionado com alterações hemodinâmicas durante o processo de descongestionamento, mas não com lesões renais.

Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL) / Worsening Renal Function and Congestion in Patients with Acute Heart Failure: A Study with Bioelectrical Impedance Vector Analysis (BIVA) and Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Resumo Fundamento: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. Objetivo: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). Métodos: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p<0.05. Resultados: A idade média foi 60,6 ± 15,0 anos, e 48 (60%) pacientes eram do sexo masculino. A fração de ejeção média foi 35,3±7,8%. O AFR ocorreu em 37,5% da amostra. A creatinina basal associou-se com AFR (p<0,001), mas nem BNP (p=0,35) nem NGAL (p=0,18) na admissão foram preditores de AFR. Usando modelos de riscos proporcionais de Cox, o índice de hidratação na alta, estimado por BIVA, associou-se significativamente com ocorrência de eventos (HR 1,39; IC95% 1,25-1,54, p<0,0001), mas não com AFR (HR 2,14; IC95% 0,62-7,35, p=0,22). Conclusão: A congestão persistente na alta associou-se com piores desfechos. O AFR parece estar relacionado com alterações hemodinâmicas durante o processo de descongestionamento, mas não com lesões renais.

Abstract Background: Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies. Objective: We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization). Methods: Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05. Results: Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22). Conclusion: Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.

Successful DAA therapy for chronic hepatitis C reduces HLA-DR on monocytes and circulating immune mediators: A long-term follow-up study.

INTRODUCTION: After DAA treatment for chronic hepatitis C infection, peripheral monocyte subsets from patients who achieved sustained virological response (SVR) reduced compared to healthy control. Improvement in inflammatory parameters and liver stiffness has been observed. However, little is known about the long-term impact of DAA treatment on peripheral monocyte subsets and immune mediators levels. OBJECTIVES: We aimed to examine peripheral monocyte subsets and immune mediators levels in Brazilian chronic HCV patients after long-term successful IFN-free SOF-based treatment. MATERIAL AND METHODS: We analyzed CD14++CD16-, CD14++CD16+ and CD14+CD16++ monocytes and 27 immune mediators by flow cytometry and analysis of multiple secreted proteins assay, respectively, in monoinfected chronic HCV patients receiving IFN-free sofosbuvir-based regimens followed before treatment, at SVR and one year after the end of treatment (1y). RESULTS: Twenty-one biomarkers decreased significantly at 1y and 55-80 % of patients this reduction at 1y. Experimented patients presented a greater modulation of immune mediators at 1y. HLA-DR expression significantly decreased on CD14++CD16- and CD14++CD16+ monocytes at 1y when compared to SVR. CONCLUSIONS: Successful DAA therapy did not modify monocyte subsets frequency but reduced monocyte activation at 1y and sustained the downregulation and restoration of circulating immune mediators, indicating that long-term reversal of inflammation status could occur after HCV eradication.

Predictors of adverse drug reactions associated with ribavirin in direct-acting antiviral therapies for chronic hepatitis C.

PURPOSE: To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens. METHODS: A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors. RESULTS: A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%. CONCLUSIONS: Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study.

BACKGROUND: Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS: Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS: The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (V˙O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.

Exploring lipid and apolipoprotein levels in chronic hepatitis C patients according to their response to antiviral treatment.

BACKGROUND: Hepatitis C virus is known to be highly dependent of lipid metabolism to infect new cells and replicate. AIMS: To investigate lipid and apolipoprotein profile in chronic HCV patients according to treatment response. METHODS: Patients recruited from the Hepatitis Treatment Center at Niteroi (Brazil) who received interferon (IFN)-based therapies were separated into two groups, those who achieved sustained virological response (SVR) or not (non-SVR). Another group of patients treated with IFN-free direct-acting antiviral (DAA) therapies was followed from before starting the treatment until one year after therapy. Triglycerides, total cholesterol and fractions were determined by colorimetric and/or electrophoresis techniques. Lecithin cholesterol acyltransferase (LCAT) activity and serum levels of apolipoproteins A1, A2, B, C2, C3 and E were assessed by enzymatic and multiplex assays, respectively. RESULTS: We studied 114 patients, and SVR was reached in 28 (39.4%) patients treated with IFN-therapy and in all (100%) patients who received DAA. Non-SVR patients (n = 43) presented altered liver parameters post-treatment. Levels of total cholesterol, LDL-C, VLDL-C and triglycerides were significant higher in SVR group. In contrast, LCAT activity and HDL-C levels were elevated in non-SVR patients. Only apolipoproteins B, C2 and C3 levels were increased in SVR group. The follow-up of SVR-DAA patients (n = 43) revealed a significant and progressive increase in serum levels of total cholesterol, LDL-C, VLDL-C and triglycerides. CONCLUSIONS: After a successful treatment, chronic hepatitis C patients experienced a reestablishment of lipid metabolism. Our results suggest that the monitoring of serum lipids could be a practical and routine laboratory tool to be applied during the treatment follow-up.

Restoring Inflammatory Mediator Balance after Sofosbuvir-Induced Viral Clearance in Patients with Chronic Hepatitis C.

This study aimed at analyzing circulating levels of inflammatory and profibrogenic cytokines in patients with hepatitis C virus (HCV) chronic infection undergoing therapy with direct-acting antiviral agents (DAA) and correlating these immune biomarkers with liver disease status. We studied 88 Brazilian monoinfected chronic hepatitis C patients receiving interferon- (IFN-) free sofosbuvir-based regimens for 12 or 24 weeks, followed-up before therapy initiation and three months after the end of treatment. Liver disease was determined by transient elastography, in addition to APRI and FIB-4 indexes. Analysis of 30 immune mediators was carried out by multiplex or enzymatic immunoassays. Sustained virological response rate was 98.9%. Serum levels of cytokines were increased in HCV-infected patients when compared to control group. CCL-2, CCL-3, CCL-4, CXCL-8, CXCL-10, IL-1ß, IL-15, IFN-γ, IL-4, IL-10, TGF-ß, FGFb, and PAI-1 decreased significantly after antiviral therapy, reaching values similar to noninfected controls. TGF-ß and suPAR levels were associated with fibrosis/cirrhosis. Also, we observed amelioration in hepatic parameters after DAA treatment. Together, our results suggest that viral control induced by IFN-free DAA therapy restores inflammatory mediators in association with improvement in liver function.

Increased Cytokeratin 19 Fragment Levels Are Positively Correlated with Adenosine Deaminase Activity in Malignant Pleural Effusions from Adenocarcinomas.

Adenosine deaminase (ADA) and cytokeratin 19 (CK19) are known pleural biomarkers. Although ADA in humans functions mainly in the immune system, it also appears to be associated with the differentiation of epithelial cells. Keratin filaments are important structural stabilizers of epithelial cells and potent biomarkers in epithelial differentiation. This study aimed to investigate the simultaneous presence of the ADA enzyme and CK19 fragments to assess epithelial differentiation in malignant and benign pleural fluids. Diagnosis of the cause of pleural effusion syndrome was confirmed by means of standard examinations and appropriate surgical procedures. An ADA assay, in which ADA irreversibly catalyzes the conversion of adenosine into inosine, was performed using a commercial kit. The CK19 assay was performed using a CYFRA 21-1 kit, developed to detect quantitative soluble fragments of CK19 using an electrochemiluminescence immunoassay. One hundred nineteen pleural fluid samples were collected from untreated individuals with pleural effusion syndrome due to several causes. ADA levels only correlated with CK19 fragments in adenocarcinomas, with high significance and good correlation (rho = 0.5145, P = 0.0036). However, further studies are required to understand this strong association on epithelial differentiation in metastatic pleural fluids from adenocarcinomas.

Adverse effects of direct acting antiviral-based regimens in chronic hepatitis C patients: a Brazilian experience.

Background Direct-acting antivirals (DAA) are currently used for the treatment of chronic hepatitis C (HCV). However, few studies describe the adverse effects (AE) associated with DAA therapy in "real-word" cohorts. Aim To evaluate AE in Brazilian chronic HCV patients after DAA-therapy. Setting A reference center for hepatitis treatment in Rio de Janeiro, Brazil. Methods An observational "real-world" study was conducted with 102 chronic HCV patients undergoing DAA therapy for 12 or 24 weeks. The self-reported AE were correlated with cirrhosis status, genotype, age, current therapeutic schemes and comorbidities. Serious AE were also investigated. Main outcome measure Frequency of AE during DAA therapy. Results Overall, mean ± SD age was 60.9 ± 9.4 years, 67% were females, HCV-genotype 1 was the most prevalent (81%) and 74% were cirrhotic. Moreover, all patients reached sustained virological response. About 90% of patients reported at least one AE associated with current treatment, with a mean of 2.7 symptoms per patient. The most frequently reported AE were fatigue (43%), headache (42%), neuropsychiatric symptoms (30%) and nausea (26%). Furthermore, hemoglobin < 12 mg/dL was the most frequent (38%) laboratory abnormality observed. Neuropsychiatric symptoms were the only AE significantly different in treatment-experienced group when compared to naïve patients (41.7 vs. 12.5, P = 0.002). The higher frequency of AE did not correlate with the presence of previous treatment, cirrhosis, genotype, age, current therapeutic schemes with DAA or comorbidities. Conclusion DAA-based therapeutic regimens demonstrated safety in a Brazilian "real-world" cohort of chronic hepatitis C patients.

Diet and liver apoptosis in rats: a particular metabolic pathway.

INTRODUCTION: Various studies have indicated an association between modifi cation in dietary macronutrient composition and liver apoptosis. OBJECTIVE: To explain how changes in metabolic pathways associated with a high-protein, high-fat, and low-carbohydrate diet causes liver apoptosis. METHODS: Two groups of rats were compared. An experimental diet group (n = 8) using a high-protein (59.46%), high-fat (31.77%), and low-carbohydrate (8.77%) diet versus a control one (n = 9) with American Institute of Nutrition (AIN)-93-M diet. Animals were sacrificed after eight weeks, the adipose tissue weighed, the liver removed for flow cytometry analysis, and blood collected to measure glucose, insulin, glucagon, IL-6, TNF, triglycerides, malondialdehyde, and ß-hydroxybutyrate. Statistical analysis was carried out using the unpaired and parametric Student's t-test and Pearson's correlation coeffi ents. Significance was set at p < 0.05. RESULTS: Animals from the experimental group presented less adipose tissue than dose of the control group. Percentage of nonviable hepatocytes in the experimental group was 2.18 times larger than the control group (p = 0.001). No statistically significant differences were found in capillary glucose, insulin, glucagon, IL-6, or TNF-α between two groups. Plasmatic ß-hydroxybutyrate and malondialdehyde of the experimental group expressed higher levels and triglycerides lower levels compared with the control group. The results show a positive and significant correlation between the percentage of nonviable hepatocytes and malondialdehyde levels (p = 0.0217) and a statistically significant negative correlation with triglycerides levels (p = 0.006). CONCLUSION: Results suggest that plasmatic malondialdehyde and triglyceride levels are probably good predictors of liver damage associated with an experimental low-carbohydrate diet in rats.

Prevalence of underweight, overweight, and obesity among 2, 162 Brazilian school adolescents.

INTRODUCTION: The nutritional profile of the Brazilian population has changed in recent years. Therefore, this study aimed to assess the prevalence of nutritional status among Brazilian school adolescents during the period from January 2014 to December 2014. METHODS: This study employed an observational design with a cohort of school adolescents. Anthropometric measurement was assessed by nutritionists in government schools. The cut-off points for body mass index according to Brazilian criteria for adolescents of both sexes between 10 years and 19 years old were underweight (≤17.5 kg/m(2)), overweigh (≥25.0 kg/m(2)), and obesity (≥30.0 kg/m(2)). RESULTS: The number of students included in the analysis was 2162, of which 71.0% were males and 29% were females (P = 0.00001). The mean age (years) was 13.14 ± 2.17 for boys and 12.66 ± 1.85 for girls (P = 0.0001). The prevalence of underweight, overweight, and obesity observed in our population of school adolescents according to the Brazilian criteria was 2.8%, 8.1%, and 2.4% for males, respectively, and 23.0%, 10.7%, and 3.6% for females, respectively. For both sexes, there was no statistically significant difference between overweight (P = 0.5469) and obesity (P = 0.7863), but there was for underweight (P = 0.001). CONCLUSIONS: The occurrence of excess weight among Brazilian school adolescents is similar to the international prevalence, but the prevalence of underweight was very high among girls. The nutritional status of adolescents must be considered a public health problem in Brazil.

Infecção do trato urinário em mulheres com vida sexual ativa / Urinary tract infection in women with active sex life

As infecções do trato urinário (ITUs) estão entre as queixas mais frequentes em consultas de atendimento primário, principalmente entre mulheres. As ITUs ocorrem em 1% a 3% das meninas em idade escolar, com aumento acentuado da incidência com o início da atividade sexual. Calcula-se uma incidência anual de 7% em mulheres de todas as idades, atingindo um pico máximo entre 15 e 24 anos de idade e entre mulheres com mais de 65 anos. Escherichia coli e Staphylococcus saprophyticus estão envolvidos em cerca de 80% das infecções urinárias não complicadas encontradas na população. O aumento da resistência aos antibióticos reforça a necessidade da escolha do medicamento com o auxílio de cultura e sensibilidade bacterianas. A profilaxia da ITU está recomendada em determinados casos, principalmente em mulheres que apresentam recorrência; dentre elas estão as sexualmente ativas.

Urinary tract infections (UTIs) are the most common complaint in primary care appointment, mainly for women. UTI occurs between 1% and 3% of school-age children with increasing incidence due to the beginning of sexual life. It is estimated an incidence of 7% in women of all ages reaching the highest peak between the ages of 15-24 and more than 65 years old. Escherichia coli and Staphylococcus are involved in about 80% of uncomplicated urinary infections in population. The increasing antibiotic resistance supports the necessity of medicament choice with bacterial culture and sensitivity assistance. Prophylaxis for urinary tract infections (UTIs) is recommended in some cases, mainly for women who show recurrence; among those that are sexually active.

Adenosina desaminase: uma enzima extraordinária e onipresente Adenosina desaminase: uma enzima extraordinária e onipresente / Adenosine deaminase: an extraordinary and omnipresent enzyme

Depois de introduzir os conceitos básicos da enzima adenosina desaminase (ADA), uma breve discussão sobre a estrutura, o mecanismo enzimático, terapia genética e potencial utilização terapêutica de inibidores de ADA são apresentados. O estudo da ADA é muito mais complexo do que simplesmente seu papel como biomarcador diagnóstico para tuberculose pleural que veio revolucionar o setor de diagnóstico na medicina clínica nos últimos anos. O aumento de sua atividade no líquido pleural, e em outros líquidos orgânicos, impede que o paciente na maioria dos casos com síndrome do derrame pleural por tuberculose seja submetido a procedimentos cirúrgicos invasivos com possíveis complicações potencialmente fatais AU.

After introducing the basic concepts of ADA, a brief discussion on the structure, enzymatic mechanism, gene therapy and potential therapeutic use of ADA inhibitors are presented. The study of the ADA is much more complex than simply its role as a biomarker for pleural tuberculosis that has revolutionized the diagnostic in clinical medicine in recent years. The increase in its activity in the pleural fluid, and other body fluids, prevents the patient in most cases with pleural effusion tuberculosis is subjected to invasive surgical procedures with possible life-threatening complications. AU

Lead Toxicity Risks in Gunshot Victims.

BACKGROUND: Gunshot wounds require surgeons to decide whether to remove or leave bullet fragments in the body. Surgeons also decide how to follow up with patients who have lead fragments retained in their body. Current literature recommends to remove only intra-articular fragments without the need for a follow-up for patients with the metal retained. Therefore, this study investigates chronic lead toxicity for gunshot wounds. METHODS: The study was performed in the metropolitan area of Rio de Janeiro/Brazil, between 2013 and 2015. It was a case-control study that included 45 victims of gunshot lesions with metallic fragments retained for more than 6 months. The 45 controls were matched for gender, age, and race. We compared the lead blood levels and frequency of symptoms. RESULTS: The control group had average blood lead levels of 2.17 µg/dL (95% Confidence Interval [CI]; 1.71-2.63) and median 2.1 µg/dL. The case group had average values of 9.01 µg/dL (CI; 6.07-11.96) and median values of 6.5 µg/dL with p-values < = 0.001. The case group reported the following more frequently: irritancy, bad mood, headache, memory losses, daylight drowsiness, myalgia, weakness, abdominal pain, joint pain, trembling, tingling limbs. There was statistical significance for the differences of symptoms frequencies and for odds ratio between groups. CONCLUSIONS: Although the mean lead levels found were lower than the current laboratory references, low levels have been associated with both rising morbidity and mortality. The WHO stated: "There is no known level of lead exposure that is considered safe". In conclusion, this work showed that bullets retained in the body are not innocuous. There are impacts in the blood lead levels and symptoms related to it, even with few fragments, extra-articular located or existing with low blood lead levels.

Decreased Circulating Levels of APRIL: Questioning Its Role in Diabetes.

Diabetes mellitus is a chronic disease that affects over 382 million people worldwide. Type-1 Diabetes (T1D) is classified as an autoimmune disease that results from pancreatic ß-cell destruction and insulin deficiency. Type-2 Diabetes (T2D) is characterized principally by insulin resistance in target tissues followed by decreased insulin production due to ß-cell failure. It is challenging to identify immunological markers such as inflammatory molecules that are triggered in response to changes during the pathogenesis of diabetes. APRIL is an important member of the TNF family and has been linked to chronic inflammatory processes of various diseases since its discovery in 1998. Therefore, this study aimed to evaluate APRIL serum levels in T1D and T2D. For this, we used the ELISA assay to measure serum APRIL levels of 33 T1D and 30 T2D patients, and non-diabetic subjects as control group. Our data showed a decrease in serum APRIL levels in T1D patients when compared with healthy individuals. The same pattern was observed in the group of T2D patients when compared with the control. The decrease of serum APRIL levels in diabetic patients suggests that this cytokine has a role in T1D and T2D. Diabetes is already considered as an inflammatory condition with different cytokines being implicated in its physiopathology. Our data suggest that APRIL can be considered as a potential modulating cytokine in the inflammatory process of diabetes.

Prognostic value of plasma neutrophil gelatinase-associated lipocalin in patients with heart failure.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We sought to assess the prognostic value of this biomarker in patients with stable chronic heart failure (HF). METHODS: We studied 61 patients with chronic systolic HF who had been receiving optimal medical treatment for at least six months. Biomarkers were measured at baseline and included plasma NGAL, microalbuminuria, serum creatinine, and B-type natriuretic peptide (BNP). Estimated glomerular filtration rate (eGFR) was also calculated. Mean follow-up was 10.6±6.6 months. The primary endpoint was time to first cardiovascular event, defined as a combination of cardiovascular death, HF hospitalization or emergency department visit due to HF. Variables independently related to events were determined using a Cox proportional hazards model. RESULTS: Fifteen (24.6%) patients reached the primary endpoint. Patients with events were more likely to have worse renal function at baseline and also higher NGAL levels (median 316 [interquartile range 122-705] vs. 107 [78-170]; p=0.006). NGAL correlated significantly with creatinine (r=0.50; p<0.0001), albuminuria (r=0.33; p=0.008), and eGFR (r=-0.47; p=0.0001) but not with BNP (r=0.003; p=0.97). The best NGAL cutoff as determined by ROC curve analysis was 179 ng/ml. Event-free survival was lower in patients with NGAL above this cutoff. Variables independently related to events were NGAL (HR 1.0035, 95% CI 1.0019-1.0052; p<0.0001) and male gender (HR 5.9, 95% CI 1.22-28.6; p=0.028). CONCLUSION: NGAL correlated with other biomarkers of renal function but not with BNP and was independently associated with outcomes.

Estresse oxidativo no lúpus eritematoso sistêmico / Oxidative stress in systemic lupus erythematosus

O lúpus eritematoso sistêmico (LES) é uma doença inflamatória crônica caracterizada pela elevada presença de autoanticorpos e por comprometer diversos órgãos e sistemas. O estresse oxidativo celular está envolvido no desenvolvimento das várias características clínicas observadas nesta doença, além de apresentar importante relação com a sua gênese e patogênese. Neste contexto, esse trabalho tem como objetivo fazer umlevantamento bibliográfico das principais moléculas envolvidas no estresse oxidativo no LES e correlacionar seus efeitos no acompanhamento da evolução e patogênese dessa doença, como ferramentas de diagnóstico e prognóstico. Os marcadores de estresse oxidativo mais comuns encontrados foram o malondialdeído, o 4-hidroxi-nonenal, a 8-hidroxideoxiguanosina, o radical hidroxila, o óxido nítrico, além da substância glutationa e enzimas antioxidantes, glutationa peroxidase, catalase e superóxido dismutase. Sendo assim, embora apareçam algumas divergências entre a correlação de alguns marcadoresde estresse oxidativo com a atividade da doença, a maioria dos estudos mostrou importante relação desses marcadores com o desenvolvimento e agravamento do LES. Apesar danecessidade de estudos longitudinais, podemos sugerir grande potencial das moléculas de estresse oxidativo como ferramenta no diagnóstico e prognóstico no LES.

A importância da farmácia clínica no uso racional de antimicrobianos em unidade de terapia intensiva / The importance of clinical pharmacy in the rational use of antimicrobial agents in intensive care unit

As altas taxas de mortalidade diretamente relacionadas ao desenvolvimento de infecção em unidades de terapia intensiva têm levado à utilização de estratégias específicas para melhorar este desfecho. Para uma maior eficiência do tratamento antimicrobiano, o conhecimento das diversas variáveis que estão envolvidas no uso racional de antibióticos é mandatório. O objetivo desta revisão é apresentar os principais tópicos relacionados ao uso racional de antimicrobianos dentro da terapia intensiva e a importância da farmácia clínica neste contexto. Para isto, realizou-se uma revisão de literatura dos últimos quinze anos, através das bases de dados Medline, Pubmed e Scielo. A presente pesquisa permitiu concluir que os estudos avaliados mostram progressos, com maiores taxas de curas clínicas e microbiológicas, quando os antimicrobianos são usados de forma adequada e dentro de parâmetros de racionalidade. Esses novos conhecimentos estão contribuindo para a melhor tomada de decisão em relação aos regimes terapêuticos.

High mortality rates in intensive care unit have a stronger relation with uncontrolled infection emphasizing the need of development of specific strategies to improve this outcome. For greater efficiency of antimicrobial treatment, the knowledge of the different variables involved in the rational use of antibiotics is mandatory. The objective of this review is to present the main topics related to the rational use of antimicrobial agents in intensive therapy and the importance of clinical pharmacy in this context. For this objective a literature review of the last 15 years has been through the data bases Medline, Pubmed and Scielo. This research concluded that the evaluate studies show high rates of clinical and microbiological cure when antimicrobials are used appropriately and within rationality parameters. These newfindings may contribute to better decision-making in relation to therapeutic treatment.