Resumo Fundamento A Doença de Chagas (DC) representa um grave problema de saúde pública na América Latina. O Benznidazol (BNZ) é utilizado para o tratamento DC e, apesar do seu amplo uso, poucas informações estão disponíveis sobre sua toxicidade e mecanismos das Reações Adversas ao Medicamento (RAM). Objetivos Identificar e classificar as reações adversas clínicas e laboratoriais ocasionadas pelo uso do BNZ quanto à sua causalidade e gravidade. Métodos Estudo de coorte prospectivo realizado no período de janeiro de 2018 a dezembro de 2021. O acompanhamento do tratamento incluiu consultas e análises laboratoriais antes, 30 e 60 dias após o início do tratamento. As RAM foram classificadas quanto à causalidade e gravidade. Na análise estatística o nível de significância adotado foi p<0,05. Resultados Participaram do estudo 40 pacientes com DC crônica, observou-se alta prevalência de RAM com um total de 161 em 30 (90%) pacientes. Destas, 104 (64,6%) foram classificadas como possíveis e 57 (35,4%) como prováveis. As reações foram classificadas em moderadas e leves. Dos 40 pacientes, nove (22,5%) suspenderam o tratamento. As RAM associadas à interrupção e intervenções foram as que afetaram o sistema dermatológico, sistema nervoso central e periférico ou que culminaram em ageusia. Após 30 dias de tratamento, alterações hematológicas e bioquímicas leves foram observadas como linfopenia. Conclusão Apesar do elevado percentual de RAM, muitos pacientes foram capazes de completar o tratamento, o que se atribui ao êxito da estratégia de acompanhamento com intervenções de tratamento sintomático juntamente ao aconselhamento, levando à compreensão da sintomatologia e manutenção do tratamento. (DC Latina (BNZ RAM. . (RAM) gravidade 201 2021 antes 3 6 p005 p 0 05 p<0,05 4 crônica observouse observou 16 90% 90 (90% Destas 10 64,6% 646 64 (64,6% 5 35,4% 354 35 (35,4% prováveis 22,5% 225 22 (22,5% dermatológico ageusia linfopenia aconselhamento (RAM 20 202 p00 p<0,0 1 9 (90 64,6 (64,6 35,4 (35,4 22,5 2 (22,5 p0 p<0, (9 64, (64, 35, (35, 22, (22, p<0 ( (64 (35 (22 p< (6 (3 (2

Abstract Background Chagas disease (CD) is a serious public health problem in Latin America. Benznidazole (BNZ) is used for the treatment of CD and, despite its wide use, little information is available about its toxicity and mechanisms of adverse drug reactions (ADR). Objectives To identify and classify clinical and laboratory adverse reactions caused by BNZ in terms of causality and severity. Methods Prospective cohort study from January 2018 to December 2021. Treatment follow-up included visits and biochemical tests (complete blood count, liver and kidney function tests) before, during and after treatment. ADR were classified according to causality and severity. In the statistical analysis, the significance level was set at p<0.05. Results Forty patients with chronic CD were included. A high prevalence of ADR was observed 161 ADR in 30 patients [90%]; of these, 104 (64.6%) were classified as possible and 57 (35.4%) as probable. The ADR were classified as moderate and mild. Of the 40 patients, nine (22.5%) discontinued treatment. ADR associated with treatment discontinuation and interventions were those that affected the dermatological system, central and peripheral nervous system and sense organs such as ageusia. Mild hematological and biochemical changes such as lymphopenia were observed after 30 days of treatment. Conclusion Many patients were able to complete the treatment even with ADR, which can be attributed to the successful follow-up strategy with symptomatic treatment and counseling, leading to patient’s awareness of symptoms and treatment adherence. (CD America (BNZ use ADR. . (ADR) severity 201 2021 followup follow up count before analysis p005 p 0 05 p<0.05 16 3 90% 90 [90%] these 10 64.6% 646 64 6 (64.6% 5 35.4% 354 35 4 (35.4% probable mild 22.5% 225 22 (22.5% ageusia counseling patient s adherence (ADR 20 202 p00 p<0.0 1 9 [90% 64.6 (64.6 35.4 (35.4 22.5 2 (22.5 p0 p<0. [90 64. (64. 35. (35. 22. (22. p<0 [9 (64 (35 (22 p< [ (6 (3 (2 (

Abstract This cross-sectional study investigated the association of SNPs rs670 (C>T) and rs693 (G>A) with parameters of lipid metabolism and endothelial activation in 167 subjects, including 86 COVID-19 outpatients and 81 healthy subjects (control group) matched for sex and age. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), triglycerides (TG), apolipoproteins (Apo A-I and B), and vascular cell adhesion molecule-1 (VCAM-1) were determined. The SNPs were genotyped by quantitative polymerase chain reaction (qPCR). A p -value<0.05 was assumed. COVID-19 outpatients showed increases in TC (187.0±48.3 vs . 160.8±32.0 mg/dL), LDL-c (110.3±41.5 vs . 98.8±28.2 mg/dL), non-HDL-c (138.3±45.8 vs . 115.6±31.6 mg/dL), TG (139.7±80.3 vs . 84.9±35.1 mg/dL), and Apo A-I (149.5±40.0 vs . 133.3±20.9 mg/dL), along with a high frequency of hypercholesterolemia and hypertriglyceridemia. VCAM-1 levels were double those of the control (682.7±231.8 vs. 299.3±102.9 ng/mL) and a strong predictor of COVID-19 (AUC=0.946). Moreover, VCAM-1 correlated with TC (r = -0.223) and HDL-c (r = -0.225). The decrease in TG and VCAM-1 is predicted by the dominance of the T allele (rs670) and its codominance with the A (rs693) allele in COVID-19 outpatients. COVID-19 has been shown to be associated with dyslipidemias and endothelial activation, and apolipoprotein polymorphisms may influence this. crosssectional cross sectional rs rs67 C>T CT C (C>T rs69 G>A GA G (G>A 16 8 COVID19 COVID 19 COVID-1 group age TC, , (TC) highdensity density HDLc, HDLc HDL c (HDL-c) lowdensity low LDLc, LDLc LDL (LDL-c) nonhighdensity non nonHDLc, nonHDLc (non-HDL-c) TG, (TG) AI I B, B B) molecule1 molecule 1 molecule- VCAM1 VCAM (VCAM-1 determined qPCR. qPCR (qPCR) value<0.05 value005 value 0 05 -value<0.0 assumed 187.0±48.3 1870483 187 48 3 (187.0±48. 1608320 160 32 160.8±32. mg/dL, mgdL mg/dL mg dL mg/dL) 110.3±41.5 1103415 110 41 5 (110.3±41. 988282 98 28 2 98.8±28. 138.3±45.8 1383458 138 45 (138.3±45. 1156316 115 6 31 115.6±31. 139.7±80.3 1397803 139 7 80 (139.7±80. 849351 84 9 35 84.9±35. 149.5±40.0 1495400 149 40 (149.5±40. 1333209 133 20 133.3±20. hypertriglyceridemia VCAM- 682.7±231.8 68272318 682 231 (682.7±231. 29931029 299 102 299.3±102. ng/mL ngmL ng mL AUC=0.946. AUC0946 AUC AUC=0.946 946 (AUC=0.946) Moreover r 0.223 0223 223 -0.223 0.225. 0225 0.225 225 -0.225) (rs670 (rs693 this rs6 COVID1 COVID- (TC (HDL-c (LDL-c (non-HDL-c (TG (VCAM- (qPCR value<0.0 value00 -value<0. 187.0±48. 187048 18 4 (187.0±48 160832 160.8±32 110.3±41. 110341 11 (110.3±41 98828 98.8±28 138.3±45. 138345 13 (138.3±45 115631 115.6±31 139.7±80. 139780 (139.7±80 84935 84.9±35 149.5±40. 149540 14 (149.5±40 133320 133.3±20 682.7±231. 6827231 68 23 (682.7±231 2993102 29 10 299.3±102 AUC094 AUC=0.94 94 (AUC=0.946 0.22 022 22 -0.22 -0.225 (rs67 (rs69 (VCAM value<0. value0 -value<0 187.0±48 18704 (187.0±4 16083 160.8±3 110.3±41 11034 (110.3±4 9882 98.8±2 138.3±45 13834 (138.3±4 11563 115.6±3 139.7±80 13978 (139.7±8 8493 84.9±3 149.5±40 14954 (149.5±4 13332 133.3±2 682.7±231 682723 (682.7±23 299310 299.3±10 AUC09 AUC=0.9 (AUC=0.94 0.2 02 -0.2 (rs6 value<0 -value< 187.0±4 1870 (187.0± 1608 160.8± 110.3±4 1103 (110.3± 988 98.8± 138.3±4 1383 (138.3± 1156 115.6± 139.7±8 1397 (139.7± 849 84.9± 149.5±4 1495 (149.5± 1333 133.3± 682.7±23 68272 (682.7±2 29931 299.3±1 AUC0 AUC=0. (AUC=0.9 0. -0. (rs value< -value 187.0± (187.0 160.8 110.3± (110.3 98.8 138.3± (138.3 115.6 139.7± (139.7 84.9 149.5± (149.5 133.3 682.7±2 6827 (682.7± 2993 299.3± AUC=0 (AUC=0. -0 187.0 (187. 160. 110.3 (110. 98. 138.3 (138. 115. 139.7 (139. 84. 149.5 (149. 133. 682.7± (682.7 299.3 AUC= (AUC=0 - 187. (187 110. (110 138. (138 139. (139 149. (149 682.7 (682. 299. (AUC= (18 (11 (13 (14 682. (682 (AUC (1 (68 ( (6

Abstract Diabetes mellitus (DM) is a major cause of chronic kidney disease (CKD) and changes in lipoprotein. Literature data suggest that cholesterol associated with high-density lipoprotein (HDLc) plays a protective role against albuminuria and diabetic nephropathy. These factors are related with changes in serum apolipoproteins such Apo A-I. This work aims to evaluate the correlation of apolipoprotein A-I with renal function in diabetic outpatients. Samples were collected from 281 outpatients for analyses of glycated hemoglobin (HbA1c), serum creatinine (SCr), urea (BUN), cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDLc) and estimation of glomerular filtration rate (eGFR). Urinary samples were obtained to assess urine albumin creatinine ratio (UACR). Triglyceride-glucose index (TyG) was calculated to estimate insulin resistance. The mean age was 61,5 ± 16,4 years. Most patients were female, Afro-Mestizo and over 50 years of age. Pearson's revealed negative correlation of creatinine with HDLc and Apo A-I. There was a correlation of eGFR with HbA1c, TG and HDLc. TyG presented a negative correlation with Apo A-I and HDLc. The highest quartiles of UACR presented the highest TyG and the lowest Apo A-I. In conclusion, Apo A-I indicated an association with insulin resistance and changes in renal function parameters, especially as a factor associated with the onset of albuminuria, with a better predictive potential than the HDLc. DM (DM CKD (CKD highdensity high density (HDLc nephropathy AI. AI A I. I 28 HbA1c HbAc , HbA c (HbA1c) SCr, SCr (SCr) BUN, BUN (BUN) TC, TC (TC) TG, (TG) HDLcholesterol HDL eGFR. . (eGFR) UACR. (UACR) Triglycerideglucose Triglyceride glucose (TyG 615 61 5 61, 164 16 4 16, female AfroMestizo Afro Mestizo Pearsons Pearson s conclusion parameters 2 (HbA1c (SCr (BUN (TC (TG (eGFR (UACR 6 1