Endothelium-related biomarkers enhanced prediction of kidney support therapy in critically ill patients with non-oliguric acute kidney injury.

Acute kidney injury (AKI) is a common condition in hospitalized patients who often requires kidney support therapy (KST). However, predicting the need for KST in critically ill patients remains challenging. This study aimed to analyze endothelium-related biomarkers as predictors of KST need in critically ill patients with stage 2 AKI. A prospective observational study was conducted on 127 adult ICU patients with stage 2 AKI by serum creatinine only. Endothelium-related biomarkers, including vascular cell adhesion protein-1 (VCAM-1), angiopoietin (AGPT) 1 and 2, and syndecan-1, were measured. Clinical parameters and outcomes were recorded. Logistic regression models, receiver operating characteristic (ROC) curves, continuous net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used for analysis. Among the patients, 22 (17.2%) required KST within 72 h. AGPT2 and syndecan-1 levels were significantly greater in patients who progressed to the KST. Multivariate analysis revealed that AGPT2 and syndecan-1 were independently associated with the need for KST. The area under the ROC curve (AUC-ROC) for AGPT2 and syndecan-1 performed better than did the constructed clinical model in predicting KST. The combination of AGPT2 and syndecan-1 improved the discrimination capacity of predicting KST beyond that of the clinical model alone. Additionally, this combination improved the classification accuracy of the NRI and IDI. AGPT2 and syndecan-1 demonstrated predictive value for the need for KST in critically ill patients with stage 2 AKI. The combination of AGPT2 and syndecan-1 alone enhanced the predictive capacity of predicting KST beyond clinical variables alone. These findings may contribute to the early identification of patients who will benefit from KST and aid in the management of AKI in critically ill patients.

ELMO CPAP: an innovative type of ventilatory support for COVID-19-related acute respiratory distress syndrome.

OBJECTIVE: To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. METHODS: This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. RESULTS: ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. CONCLUSIONS: The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

BACKGROUND: The clinical picture of coronavirus disease 2019 (COVID-19)-associated sepsis is similar to that of sepsis of other aetiologies. The present study aims to analyse the role of syndecan-1 (SDC-1) as a potential predictor of septic shock in critically ill patients with COVID-19. METHODS: This is a prospective study of 86 critically ill patients due to COVID-19 infection. Patients were followed until day 28 of hospitalization. Vascular biomarkers, such as vascular cell adhesion protein-1, SDC-1, angiopoietin-1 and angiopoietin-2, were quantified upon admission and associated with the need for vasopressors in the first 7 d of hospitalization. RESULTS: A total of 86 patients with COVID-19 (mean age 60±16 y; 51 men [59%]) were evaluated. Thirty-six (42%) patients died during hospitalization and 50 (58%) survived. The group receiving vasopressors had higher levels of D-dimer (2.46 ng/ml [interquartile range {IQR} 0.6-6.1] vs 1.01 ng/ml [IQR 0.62-2.6], p=0.019) and lactate dehydrogenase (929±382 U/l vs 766±312 U/l, p=0.048). The frequency of deaths during hospitalization was higher in the group that received vasoactive amines in the first 24 h in the intensive care unit (70% vs 30%, p=0.002). SDC-1 levels were independently associated with the need for vasoactive amines, and admission values >269 ng/ml (95% CI 0.524 to 0.758, p=0.024) were able to predict the need for vasopressors during the 7 d following admission. CONCLUSIONS: Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

Endothelial Biomarkers in Critically Ill COVID-19 Patients: Potential Predictors of the Need for Dialysis.

INTRODUCTION: The aim of this was to evaluate the function of vascular biomarkers to predict the need for hemodialysis in critically ill patients with COVID-19. METHODS: This is a prospective study with 58 critically ill patients due to COVID-19 infection. Laboratory tests in general and vascular biomarkers, such as VCAM-1, syndecan-1, angiopoietin-1, and angiopoietin-2, were quantified on intensive care unit (ICU) admission. RESULTS: There was a 40% death rate. VCAM and Ang-2/Ang-1 ratio on ICU admission were associated with the need for hemodialysis. Vascular biomarkers (VCAM-1, syndecan-1, angiopoietin-2/angiopoietin-1 ratio) were predictors of death and their cutoff values were useful to stratify patients with a worse prognosis. In the multivariate cox regression analysis with adjusted models, VCAM-1 (OR 1.13 [CI 95%: 1.01-1.27]; p = 0.034) and Ang-2/Ang-1 ratio (OR 4.87 [CI 95%: 1.732-13.719]; p = 0.003) were associated with the need for dialysis. CONCLUSION: Vascular biomarkers, mostly VCAM-1 and Ang-2/Ang-1 ratio, showed better efficiency to predict the need for hemodialysis in critically ill COVID-19 patients.

Syndecan-1 predicts hemodynamic instability in critically ill patients under intermittent hemodialysis.

Introduction: Up to 70% of intermittent hemodialysis (IHD) sessions in critically ill patients are complicated by hemodynamic instability. Although several clinical characteristics have been associated with hemodynamic instability during IHD, the discriminatory capacity of predicting such events during IHD sessions is less defined. In the present study, we aimed to analyse endothelium-related biomarkers collected before IHD sessions and their capacity to predict hemodynamic instability related to IHD in critically ill patients. Methods: In this prospective observational study, we enrolled adult critically ill patients with acute kidney injury who required fluid removal with IHD. We screened each included patient daily for IHD sessions. Thirty minutes before each IHD session, each patient had a 5-mL blood collection for measurement of endothelial biomarkers-vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-1 and -2 (AGPT1 and AGPT2) and syndecan-1. Hemodynamic instability during IHD was the main outcome. Analyses were adjusted for variables already known to be associated with hemodynamic instability during IHD. Results: Plasma syndecan-1 was the only endothelium-related biomarker independently associated with hemodynamic instability. The accuracy of syndecan-1 for predicting hemodynamic instability during IHD was moderate [area under the receiver operating characteristic curve 0.78 (95% confidence interval 0.68-0.89)]. The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.67 to 0.82 (P < .001) and improved risk prediction, as measured by net reclassification improvement. Conclusion: Syndecan-1 is associated with hemodynamic instability during IHD in critically ill patients. It may be useful to identify patients who are at increased risk for such events and suggests that endothelial glycocalyx derangement is involved in the pathophysiology of IHD-related hemodynamic instability.

Chronic kidney disease prevention campaign: relationship between proteinuria and elderly people / Campanha de prevenção de doença renal crônica: relação entre proteinúria e idosos

ABSTRACT Objective: To verify the relationship between the presence of proteinuria as a renal injury marker in elderly without history of systemic arterial hypertension and cardiovascular diseases. A cross-sectional study was developed from January 2014 to December 2019, through kidney disease prevention campaigns promoted by the Federal University of Ceará in the city of Fortaleza. Methods: The sample consisted of 417 elderlies. A questionnaire was used to characterize individuals and assess previous diseases, and urinalysis reagent strips were used to assess proteinuria. Results: Statistically significant differences (p < 0.05) and moderate effect sizes were found for blood pressure levels (CI 0.53-0.93), systolic blood pressure, and diastolic blood pressure (CI 0.21-0.61). Significant differences in capillary glycemia were also found between groups (p = 0.033), but with a low effect size (0.02-0.42). The group with comorbidities was 2.94 times more likely to have proteinuria than those without comorbidities (OR 2.94, CI 1.55-4.01; p < 0.05). In the group without cardiovascular disease/high blood pressure, a statistically significant association was found for previous diabetes and proteinuria (p = 0.037), presenting 2.68 times higher risk of proteinuria in those with diabetes mellitus (OR 2.68, CI 1.05-6.85). Significant association was also found between age groups, with the older group having 2.69 times higher risk of developing proteinuria (75 to 90 compared to 60 to 74 years) (CI 1.01-7.16; p = 0.045). Conclusion: Even without systemic arterial hypertension or cardiovascular disease, diabetes and older age can be considered high risk factors for proteinuria.

Resumo Objetivo: Verificar a relação entre a presença de proteinúria como marcador de lesão renal em idosos sem histórico de hipertensão arterial sistêmica e doenças cardiovasculares. Um estudo transversal foi desenvolvido de Janeiro de 2014 a Dezembro de 2019, por meio de campanhas de prevenção a doenças renais promovidas pela Universidade Federal do Ceará, na cidade de Fortaleza. Métodos: A amostra foi composta por 417 idosos. Um questionário foi usado para caracterizar indivíduos e avaliar doenças prévias, e foram utilizadas tiras reagentes de urinálise para avaliar proteinúria. Resultados: Diferenças estatisticamente significativas (p < 0,05) e tamanhos de efeito moderados foram encontrados para níveis de pressão arterial (IC 0,53-0,93), pressão arterial sistólica e pressão arterial diastólica (IC 0,21-0,61). Também foram encontradas diferenças significativas na glicemia capilar entre grupos (p = 0,033), mas com um tamanho de efeito baixo (0,02-0,42). O grupo com comorbidades apresentou 2,94 vezes mais probabilidade de ter proteinúria do que aqueles sem comorbidades (OR 2,94; IC 1,55-4,01; p < 0,05). No grupo sem doença cardiovascular/hipertensão, foi encontrada uma associação estatisticamente significativa para diabetes anterior e proteinúria (p = 0,037), apresentando risco 2,68 vezes maior de proteinúria naqueles com diabetes mellitus (OR 2,68; IC 1,05-6,85). Também foi encontrada uma associação significativa entre faixas etárias, com o grupo mais velho apresentando risco 2,69 vezes maior de desenvolver proteinúria (75 a 90 em comparação com 60 a 74 anos) (IC 1,01-7,16; p = 0,045). Conclusão: Mesmo sem hipertensão arterial sistêmica ou doença cardiovascular, o diabetes e a idade avançada podem ser considerados fatores de alto risco para proteinúria.

Use of probiotics in patients with chronic kidney disease on hemodialysis: a randomized clinical trial / Uso de probióticos em pacientes com doença renal crônica em hemodiálise: um ensaio clínico randomizado

ABSTRACT Introduction: Supplementation with probiotics for patients with chronic kidney disease (CKD) may be associated with decreased systemic inflammation. Objective: To assess the impact of oral supplementation with probiotics for patients with CKD on hemodialysis. Method: This double-blind randomized clinical trial included 70 patients on hemodialysis; 32 were given oral supplementation with probiotics and 38 were in the placebo group. Blood samples were collected at the start of the study and patients were given oral supplementation with probiotics or placebo for three months. The probiotic supplement comprised four strains of encapsulated Gram-positive bacteria: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 and Bifidobacterium longum A101. Patients were given one capsule per day for 3 months. Blood samples were taken throughout the study to check for inflammatory biomarkers. Non-traditional biomarkers Syndecan-1, IFN-y, NGAL, and cystatin C were measured using an ELISA kit, along with biochemical parameters CRP, calcium, phosphorus, potassium, PTH, GPT, hematocrit, hemoglobin, glucose, and urea. Results: Patients given supplementation with probiotics had significant decreases in serum levels of syndecan-1 (239 ± 113 to 184 ± 106 ng/mL, p = 0.005); blood glucose levels also decreased significantly (162 ± 112 to 146 ± 74 mg/dL, p = 0.02). Conclusion: Administration of probiotics to patients with advanced CKD was associated with decreases in syndecan-1 and blood glucose levels, indicating potential improvements in metabolism and decreased systemic inflammation.

Resumo Introdução: A suplementação com probióticos na doença renal crônica (DRC) pode estar associada à redução do processo inflamatório sistêmico. Objetivo: Avaliar a suplementação oral com probióticos em pacientes com DRC em hemodiálise. Método: Ensaio clínico, duplo cego, randomizado com 70 pacientes em hemodiálise, sendo 32 do grupo que recebeu o suplemento de probióticos e 38 do grupo placebo. Inicialmente ocorreu a coleta de sangue e suplementação oral com probióticos ou placebo durante três meses. O suplemento probiótico foi composto pela combinação de 4 cepas de bactérias Gram-positivas encapsuladas: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 e Bifidobacterium longum A101, sendo 1 cápsula do suplemento ao dia, durante 3 meses. Após esse período foram feitas novas coletas de sangue para dosagem dos biomarcadores inflamatórios. Foram analisados os biomarcadores não tradicionais: Syndecan-1, IFN-y, NGAL e cistatina C pelo método ELISA, e os seguintes parâmetros bioquímicos: PCR, cálcio, fósforo, potássio, PTH, TGP, hematócrito, hemoglobina, glicose e ureia. Resultados: Os pacientes que receberam suplemento tiveram diminuição significativa dos níveis séricos de syndecan-1 (de 239 ± 113 para 184 ± 106 ng/mL, p = 0,005). Outro parâmetro que diminuiu significativamente nos pacientes que receberam suplemento foi a glicemia (de 162 ± 112 para 146 ± 74 mg/dL, p = 0,02). Conclusão: O uso de probióticos na DRC avançada esteve associado à redução dos níveis de syndecan-1 e glicemia, sinalizando possível melhora no metabolismo e redução do processo inflamatório sistêmico.

Monitoring Renal Function in HIV Patients Without Kidney Disease Using Endothelial Biomarkers: A Prospective Pilot Study.

This study aimed to investigate the association between novel biomarkers and renal injury in people with HIV (PWH). A cohort study was carried out with PWH under chronic use of antiretroviral therapy (ART), followed at a public outpatient service. Clinical and laboratory parameters of the patients were evaluated year by year, from 2015 [at baseline (year 1, Y1)] to 2019 [year 5 (Y5)]. At baseline, biomarkers of renal damage (e.g., neutrophil gelatinase-associated lipocalin-NGAL, monocyte chemoattractant protein-1-MCP-1, and kidney injury molecule-1-KIM-1) and endothelial activation or glycocalyx damage [e.g., intercellular adhesion molecule 1 (ICAM-1), E-selectin, and syndecan-1] were quantified using enzyme-linked immunosorbent assays and their levels were used to classify patients into different groups. However, only syndecan-1 showed a significant correlation with serum creatinine (p < .001) and glomerular filtration rate (GFR) (p = .003) over the years. Moreover, both serum creatinine and GFR in almost 5 years were significantly associated with serum levels of syndecan-1 at baseline. The multivariate linear regression with confounders showed a significant and independent association between GFR and levels of syndecan-1 and CD4 cell count in the beginning of the study, as well as age in Y5. The data reinforce the screening for kidney diseases with novel biomarkers, especially syndecan-1, as an important strategy for a timely diagnostic and therapeutic approach.

Development and validation of a simple machine learning tool to predict mortality in leptospirosis.

Predicting risk factors for death in leptospirosis is challenging, and identifying high-risk patients is crucial as it might expedite the start of life-saving supportive care. Admission data of 295 leptospirosis patients were enrolled, and a machine-learning approach was used to fit models in a derivation cohort. The comparison of accuracy metrics was performed with two previous models-SPIRO score and quick SOFA score. A Lasso regression analysis was the selected model, demonstrating the best accuracy to predict mortality in leptospirosis [area under the curve (AUC-ROC) = 0.776]. A score-based prediction was carried out with the coefficients of this model and named LeptoScore. Then, to simplify the predictive tool, a new score was built by attributing points to the predictors with importance values higher than 1. The simplified score, named QuickLepto, has five variables (age > 40 years; lethargy; pulmonary symptom; mean arterial pressure < 80 mmHg and hematocrit < 30%) and good predictive accuracy (AUC-ROC = 0.788). LeptoScore and QuickLepto had better accuracy to predict mortality in patients with leptospirosis when compared to SPIRO score (AUC-ROC = 0.500) and quick SOFA score (AUC-ROC = 0.782). The main result is a new scoring system, the QuickLepto, that is a simple and useful tool to predict death in leptospirosis patients at hospital admission.

Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil.

BACKGROUND: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. METHODS: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. RESULTS: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. CONCLUSIONS: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Chronic kidney disease prevention campaign: relationship between proteinuria and elderly people.

OBJECTIVE: To verify the relationship between the presence of proteinuria as a renal injury marker in elderly without history of systemic arterial hypertension and cardiovascular diseases. A cross-sectional study was developed from January 2014 to December 2019, through kidney disease prevention campaigns promoted by the Federal University of Ceará in the city of Fortaleza. METHODS: The sample consisted of 417 elderlies. A questionnaire was used to characterize individuals and assess previous diseases, and urinalysis reagent strips were used to assess proteinuria. RESULTS: Statistically significant differences (p < 0.05) and moderate effect sizes were found for blood pressure levels (CI 0.53-0.93), systolic blood pressure, and diastolic blood pressure (CI 0.21-0.61). Significant differences in capillary glycemia were also found between groups (p = 0.033), but with a low effect size (0.02-0.42). The group with comorbidities was 2.94 times more likely to have proteinuria than those without comorbidities (OR 2.94, CI 1.55-4.01; p < 0.05). In the group without cardiovascular disease/high blood pressure, a statistically significant association was found for previous diabetes and proteinuria (p = 0.037), presenting 2.68 times higher risk of proteinuria in those with diabetes mellitus (OR 2.68, CI 1.05-6.85). Significant association was also found between age groups, with the older group having 2.69 times higher risk of developing proteinuria (75 to 90 compared to 60 to 74 years) (CI 1.01-7.16; p = 0.045). CONCLUSION: Even without systemic arterial hypertension or cardiovascular disease, diabetes and older age can be considered high risk factors for proteinuria.

Use of probiotics in patients with chronic kidney disease on hemodialysis: a randomized clinical trial.

INTRODUCTION: Supplementation with probiotics for patients with chronic kidney disease (CKD) may be associated with decreased systemic inflammation. OBJECTIVE: To assess the impact of oral supplementation with probiotics for patients with CKD on hemodialysis. METHOD: This double-blind randomized clinical trial included 70 patients on hemodialysis; 32 were given oral supplementation with probiotics and 38 were in the placebo group. Blood samples were collected at the start of the study and patients were given oral supplementation with probiotics or placebo for three months. The probiotic supplement comprised four strains of encapsulated Gram-positive bacteria: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 and Bifidobacterium longum A101. Patients were given one capsule per day for 3 months. Blood samples were taken throughout the study to check for inflammatory biomarkers. Non-traditional biomarkers Syndecan-1, IFN-y, NGAL, and cystatin C were measured using an ELISA kit, along with biochemical parameters CRP, calcium, phosphorus, potassium, PTH, GPT, hematocrit, hemoglobin, glucose, and urea. RESULTS: Patients given supplementation with probiotics had significant decreases in serum levels of syndecan-1 (239 ± 113 to 184 ± 106 ng/mL, p = 0.005); blood glucose levels also decreased significantly (162 ± 112 to 146 ± 74 mg/dL, p = 0.02). CONCLUSION: Administration of probiotics to patients with advanced CKD was associated with decreases in syndecan-1 and blood glucose levels, indicating potential improvements in metabolism and decreased systemic inflammation.

Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil

ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

Association between endothelial biomarkers and lipid and glycemic levels: a cross-sectional study with diabetic patients.

Background: Biomarkers can help understand the impact of achieving therapeutic goals in developing vascular diseases in diabetics. Aim: To assess the association between lipid and glycemic profiles and endothelial biomarkers in diabetics. Methods: Cross-sectional study that evaluated lipid and glycemic levels and biomarkers (VCAM-1, Sdc-1, FGF-23 and KIM-1 in diabetics. Results: Higher VCAM-1 levels were associated with higher low-density lipoprotein cholesterol and non-high-density lipoprotein (HDL) cholesterol levels (in the group with inadequate glycohemoglobin A1c [HbA1c] levels), with higher glycemic levels (in the group with inadequate HDL cholesterol levels) and with lower HDL cholesterol levels (both groups). VCAM-1 was independently associated with not achieving adequate HbA1c levels. Conclusion: In uncontrolled diabetics, VCAM-1 was independently associated with having inadequate HbA1c levels, suggesting they may already have endothelial damage.

ELMO CPAP: an innovative type of ventilatory support for COVID-19-related acute respiratory distress syndrome / ELMO-CPAP: um suporte ventilatório inovador para síndrome do desconforto respiratório agudo por COVID-19

ABSTRACT Objective: To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. Methods: This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. Results: ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. Conclusions: The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

RESUMO Objetivo: Avaliar se o uso do ELMO, um capacete para ventilação não invasiva criado no Brasil, teve impacto positivo no prognóstico de pacientes com insuficiência respiratória hipoxêmica por COVID-19 grave. Métodos: Estudo retrospectivo com 50 pacientes críticos com COVID-19. Dados epidemiológicos, clínicos e laboratoriais foram coletados na admissão na UTI e antes, durante e após o uso do ELMO. Os pacientes foram divididos em dois grupos (sucesso e falha) de acordo com o desfecho. Resultados: O uso do ELMO melhorou parâmetros de oxigenação como Pao2, Fio2 e relação Pao2/Fio2, e isso contribuiu para uma redução gradual da Fio2, sem aumento do CO2, conforme determinado pela gasometria arterial. Os pacientes do grupo sucesso apresentaram sobrevida significativamente maior (p < 0,001), conforme determinado pela análise de Kaplan-Meier, menor necessidade de intubação (p < 0,001), menos dias de hospitalização e menor incidência de lesão renal aguda em comparação com os do grupo falha. Conclusões: A significativa melhora nos parâmetros de oxigenação, a maior sobrevida, refletida pela menor necessidade de intubação e pela taxa de mortalidade, e a ausência de lesão renal aguda sugerem que o sistema ELMO CPAP é uma ferramenta promissora para o tratamento da SDRA e de condições clínicas semelhantes.

Topiramate in an Experimental Model of Epilepsy - Similarity between Generic, Similar and Reference Drugs.

Background and Purpose: The literature is still controversial in relation to therapeutic differences between innovative, generic, and similar anti-seizures medications (ASM). Topiramate (TPM) is an ASM used in the treatment of various seizure types and in different epileptic syndromes, as well as in other groups of morbidities, and it is available in many generic and similar forms, besides the innovator. The aim of this translational work was to compare different brands of TPM by using animal models of seizures induced by pentylenetetrazole (PTZ). Methods: Five brands of TPM (one reference, two similar and two generics) were tested in mice. Animals were previously treated with TPM (n=6/brand) and latencies from PTZ injection to onset of manifestations, first seizure and death were measured and compared between groups. Experiment was conducted in two settings: acute seizure model (PTZ 80 mg/kg) and kindling model (PTZ 20, 30, and 40 mg/kg in 8 alternate days). Results: The experiment did not demonstrate significant differences between the TPM brands regarding the protective effect in the acute seizure and kindling models. Conclusions: In conclusion, results can be explained by true therapeutic equivalence or insufficiency of the PTZ model to reveal differences among brands.

Endothelial biomarkers as predictors for haemodialysis need in severe leptospirosis patients (Weil's disease).

OBJECTIVE: To investigate the prediction ability of vascular injury biomarkers for haemodialysis requirement in patients with severe leptospirosis. METHODS: Prospective study with severe leptospirosis patients hospitalised in Fortaleza, Brazil. Blood samples were collected hospital admission to quantify vascular injury biomarkers: syndecan-1, ICAM-1, VCAM-1, angiopoietin-2 and FGF-23. Two groups were evaluated according to haemodialysis requirement during hospital stay. RESULTS: Twenty-seven patients were included, with a mean age of 39 ± 18 years. 88.9% were males. 53.8% needed haemodialysis and presented higher levels on hospital admission of syndecan-1 (572 [300-811] vs. 263 [106-421] ng/ml; p = 0.03), angiopoietin-2 (1.52 [0.72-2.72] vs. 0.63 [0.4-1.38] ng/ml; p = 0.01), and FGF-23 (291 [56-2031] vs. 10 [10-806] pg/ml; p = 0.021). Syndecan-1 showed significant correlation with creatinine (r = 0.546; p = 0.05) and total bilirubin levels (r = 0.534; p = 0.013) on hospital admission. Angiopoietin-2 showed significant correlation with creatinine levels (r = 0.513; p = 0.009) on hospital admission and with number of haemodialysis sessions (r = 0.406; p = 0.049). No significant correlation was found with FGF-23. Regarding prognostic performance, combined syndecan-1 and angiopoietin-2 levels had a better ability to predict haemodialysis need in patients with severe leptospirosis (AUC-ROC = 0.744 [95% CI: 0.545-0.943] p = 0.035). CONCLUSION: Syndecan-1 and angiopoietin-2 were associated with haemodialysis need in patients with severe leptospirosis and may be useful to improve therapeutic approach and reduce mortality.

Risk factors for mortality in patients with dengue: A systematic review and meta-analysis.

OBJECTIVE: To investigate risk factors for mortality in dengue. METHODS: We performed a systematic review and meta-analysis searching MEDLINE, Embase, SciELO, LILACS Bireme, and OpenGrey databases to identify eligible observational studies of patients with dengue, of both genders, aged 14 years or older, that analysed risk factors associated with mortality and reported adjusted risk measures with their respective confidence intervals (CIs). We estimated the pooled weighted mean difference and 95% CIs with a DerSimonian and Laird random-effects model. We assessed the methodological quality using the Newcastle-Ottawa Scale. RESULTS: Of 1,170 citations reviewed, 18 papers, with a total of 25,851 patients, were included in the systematic review and 12 in the meta-analysis. Severe hepatitis (OR 29.222, 95% CI 3.876-220.314), dengue shock syndrome (OR 23.575, 95% CI 3.664-151.702), altered mental status (OR 3.76, 95% CI 1.67-8.42), diabetes mellitus (OR 3.698, 95% CI 1.196-11.433), and higher pulse rate (OR 1.039, 95% CI 1.011-1.067) are associated with mortality in patients with dengue. All studies included were classified as having a high quality. CONCLUSIONS: Proper identification and management of these risk factors should be considered to improve patient outcomes and reduce the hidden burden of this neglected tropical disease. Future well-designed studies are needed to investigate the association of other clinical, radiological, and laboratorial findings with mortality in dengue, as well as to develop prognostic models based on the risk factors found in our study.

Critically ill COVID-19 patients in northeast Brazil: mortality predictors during the first and second waves including SAPS 3.

BACKGROUND: The Simplified Acute Physiology Score (SAPS) 3 is a reliable score to predict mortality. This study aims to investigate the predictive values of SAPS 3 and other clinical parameters for death in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This is a prospective study in a tertiary hospital for patients who required intensive care due to COVID-19 infection in northeast Brazil. Two distinct groups were constructed according to the epidemiological data: first wave and second wave. The severity of patients admitted was estimated using the SAPS 3 score. RESULTS: A total of 767 patients were included: 290 were enrolled in the first wave and 477 in the second wave. Patients in the first wave had more comorbidities, were put on mechanical ventilation and required dialysis and vasopressors more frequently (p<0.05). During the second wave, non-invasive ventilation was more often required (p<0.05). In both periods, older patients and higher SAPS 3 scores on admission were associated with death (p<0.05). Non-invasive ventilation use showed a negative association with death only in the second wave period. In the first wave, the SAPS 3 score was more useful (area under the curve [AUC] 0.897) in predicting death in critically ill COVID-19 patients than in the second wave (AUC 0.810). CONCLUSION: The SAPS 3 showed very reliable predictive values for death during the waves of the COVID-19 pandemic, mostly together with kidney and pulmonary dysfunction.