Resumo: Este estudo comparou as definições de doença hepática gordurosa não alcoólica (DHGNA) e doença hepática esteatótica associada à disfunção metabólica (DHEADM) em relação à predição de diabetes em uma grande população adulta de brasileiros. Como objetivo secundário, comparamos as associações entre DHGNA/DHEADM e diabetes em grupos de diferentes etnias/cor da pele autodeclaradas. O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) é um estudo de coorte prospectivo de servidores públicos brasileiros (35-74 anos) recrutados de 2008 a 2010 e acompanhados nos períodos de 2012-2014 e 2017-2019. Determinamos o diabetes mellitus tipo 2 nas visitas iniciais e de acompanhamento com base em diagnóstico autorreferido, uso de medicação e testes glicêmicos (glicemia em jejum e 2 horas após o teste de tolerância à glicose oral e HbA1c). Foram excluídos indivíduos com consumo pesado de álcool ou cirrose/hepatite autorreferida. Foram analisados 7.073 indivíduos. A DHGNA foi definida por esteatose através de ultrassom. Participantes com esteatose e pelo menos um fator cardiometabólico foram considerados como portadores de DHEADM. Modelos de riscos proporcionais de Cox foram aplicados para avaliar a associação entre DHGNA/DHEADM e a incidência de diabetes mellitus tipo 2. No início do estudo, 33,9% apresentavam DHGNA e 32,5% DHEADM. Ao longo de 9,4 anos de acompanhamento, o aumento relativo na incidência de diabetes foi de 78% para indivíduos com DHGNA (HR = 1,78; IC95%: 1,58-2,01) e 88% para indivíduos com DHEADM (HR = 1,88; IC95%: 1,67-2,12). As associações não diferiram significativamente entre os grupos de etnia/cor de pele (p para interação = 0,10 para DHEADM e 0,08 para DHGNA). Nesta grande coorte de brasileiros de meia-idade e idosos, a incidência relativa de diabetes foi semelhante nas definições de DHGNA e DHEADM, com associações semelhantes entre grupos étnicos.

Abstract: We aimed to compare nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) definitions concerning diabetes prediction in a large sample of Brazilian adults. As a secondary objective, we compared associations between NAFLD/MASLD and diabetes across self-declared race/skin color groups. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study of Brazilian civil servants (35-74 years) enrolled from 2008 to 2010 and followed up from 2012-2014 and 2017-2019. We ascertained type 2 diabetes mellitus at baseline as well as follow-up visits based on self-reported diagnosis, medication use, and glycemic tests (fasting and 2h post-OGTT glucose and HbA1c). We excluded individuals with heavy alcohol consumption or self-reported cirrhosis/hepatitis. We analyzed 7,073 subjects. NAFLD was defined by ultrasound-based steatosis. Participants with steatosis and at least one cardiometabolic factor were considered as having MASLD. Cox proportional hazards models were performed to evaluate the association between NAFLD/MASLD and the incidence of type 2 diabetes mellitus. At baseline, 33.9% of individuals presented NAFLD and 32.5% presented MASLD. Over 9.4 years of follow-up, the relative increase in the incidence of diabetes was 78% for NAFLD (HR = 1.78; 95%CI: 1.58-2.01) and 88% for MASLD (HR = 1.88; 95%CI: 1.67-2.12). Associations did not differ significantly among race/skin color groups (p for interaction = 0.10 for MASLD and 0.08 for NAFLD). In this large cohort of middle-aged and older Brazilian adults, the relative incidence of diabetes was similar for NAFLD and MASLD definitions, with similar associations in all ethnic groups.

Resumen: Este estudio comparó las definiciones de enfermedad del hígado graso no alcohólico (EHGNA) y enfermedad hepática esteatótica asociada con disfunción metabólica (EHDM) con relación a la predicción de diabetes en una gran población adulta de brasileños. Como objetivo secundario, comparamos las asociaciones entre EHGNA/MASLD y diabetes en grupos de diferentes etnias/color de piel autodeclarados. El Estudio Longitudinal de Salud del Adulto (ELSA-Brasil) es un estudio de cohorte prospectivo de servidores públicos brasileños (35-74 años) reclutados entre el 2008 y el 2010 y seguidos en los períodos 2012-2014 y 2017-2019. Determinamos la diabetes mellitus tipo 2 en las visitas iniciales y de seguimiento con base en el diagnóstico autoinformado, el uso de medicación y las pruebas de glucemia (glucemia en ayunas y prueba de tolerancia a la glucosa oral 2 horas después y HbA1c). Se excluyeron las personas con consumo excesivo de alcohol o cirrosis/hepatitis autoinformadas. Se analizaron 7.073 individuos. La EHGNA se definió por esteatosis mediante ecografía. Se consideró que los participantes con esteatosis y al menos un factor cardiometabólico tenían EHDM. Se aplicaron modelos de riesgos proporcionales de Cox para evaluar la asociación entre EHGNA/EHDM y la incidencia de diabetes mellitus tipo 2. Al inicio del estudio, el 33,9% tenía EHGNA y el 32,5% EHDM. Durante 9,4 años de seguimiento, el aumento relativo en la incidencia de diabetes fue del 78% para las personas con EHGNA (HR = 1,78; IC95%: 1,58-2,01) y del 88% para las personas con EHDM (HR = 1,88; IC95%: 1,67-2,12). Las asociaciones no difirieron significativamente entre los grupos étnicos/color de piel (p para interacción = 0,10 para EHDM y 0,08 para EHGNA). En esta gran cohorte de brasileños de mediana edad y ancianos, la incidencia relativa de diabetes fue similar en las definiciones de EHGNA y EHDM, con asociaciones similares entre grupos étnicos.

Resumo: Este estudo comparou as definições de doença hepática gordurosa não alcoólica (DHGNA) e doença hepática esteatótica associada à disfunção metabólica (DHEADM) em relação à predição de diabetes em uma grande população adulta de brasileiros. Como objetivo secundário, comparamos as associações entre DHGNA/DHEADM e diabetes em grupos de diferentes etnias/cor da pele autodeclaradas. O Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) é um estudo de coorte prospectivo de servidores públicos brasileiros (35-74 anos) recrutados de 2008 a 2010 e acompanhados nos períodos de 2012-2014 e 2017-2019. Determinamos o diabetes mellitus tipo 2 nas visitas iniciais e de acompanhamento com base em diagnóstico autorreferido, uso de medicação e testes glicêmicos (glicemia em jejum e 2 horas após o teste de tolerância à glicose oral e HbA1c). Foram excluídos indivíduos com consumo pesado de álcool ou cirrose/hepatite autorreferida. Foram analisados 7.073 indivíduos. A DHGNA foi definida por esteatose através de ultrassom. Participantes com esteatose e pelo menos um fator cardiometabólico foram considerados como portadores de DHEADM. Modelos de riscos proporcionais de Cox foram aplicados para avaliar a associação entre DHGNA/DHEADM e a incidência de diabetes mellitus tipo 2. No início do estudo, 33,9% apresentavam DHGNA e 32,5% DHEADM. Ao longo de 9,4 anos de acompanhamento, o aumento relativo na incidência de diabetes foi de 78% para indivíduos com DHGNA (HR = 1,78; IC95%: 1,58-2,01) e 88% para indivíduos com DHEADM (HR = 1,88; IC95%: 1,67-2,12). As associações não diferiram significativamente entre os grupos de etnia/cor de pele (p para interação = 0,10 para DHEADM e 0,08 para DHGNA). Nesta grande coorte de brasileiros de meia-idade e idosos, a incidência relativa de diabetes foi semelhante nas definições de DHGNA e DHEADM, com associações semelhantes entre grupos étnicos. Resumo (DHGNA (DHEADM secundário DHGNADHEADM etniascor etnias cor autodeclaradas ELSABrasil ELSA Brasil (ELSA-Brasil 3574 35 74 (35-7 200 201 20122014 2012 2014 2012-201 20172019. 20172019 2017 2019. 2019 2017-2019 autorreferido glicemia HbA1c. HbA1c HbAc . HbA c HbA1c) cirrosehepatite cirrose hepatite autorreferida 7073 7 073 7.07 ultrassom 339 33 9 33,9 325 32 5 32,5 94 4 9, 78 HR 1,78 178 1 IC95% IC95 IC 1,582,01 158201 1,58 2,01 58 01 1,58-2,01 88 1,88 188 1,672,12. 167212 1,67 2,12 67 12 1,67-2,12) etniacor etnia p 010 0 10 0,1 008 08 0,0 DHGNA. DHGNA) meiaidade meia idade idosos étnicos 357 3 (35- 20 2012201 2012-20 2017201 2017-201 707 07 7.0 33, 32, 1,7 17 IC9 582 1,582,0 15820 158 1,5 2,0 1,58-2,0 8 1,8 18 672 1,672,12 16721 167 1,6 212 2,1 6 1,67-2,12 0, 00 (35 201220 2012-2 201720 2017-20 70 7. 1, 1,582, 1582 15 2, 1,58-2, 1,672,1 1672 16 21 1,67-2,1 (3 20122 2012- 20172 2017-2 1,582 1,58-2 1,672, 1,67-2, ( 2017- 1,58- 1,672 1,67-2 1,67-

Abstract: We aimed to compare nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) definitions concerning diabetes prediction in a large sample of Brazilian adults. As a secondary objective, we compared associations between NAFLD/MASLD and diabetes across self-declared race/skin color groups. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective cohort study of Brazilian civil servants (35-74 years) enrolled from 2008 to 2010 and followed up from 2012-2014 and 2017-2019. We ascertained type 2 diabetes mellitus at baseline as well as follow-up visits based on self-reported diagnosis, medication use, and glycemic tests (fasting and 2h post-OGTT glucose and HbA1c). We excluded individuals with heavy alcohol consumption or self-reported cirrhosis/hepatitis. We analyzed 7,073 subjects. NAFLD was defined by ultrasound-based steatosis. Participants with steatosis and at least one cardiometabolic factor were considered as having MASLD. Cox proportional hazards models were performed to evaluate the association between NAFLD/MASLD and the incidence of type 2 diabetes mellitus. At baseline, 33.9% of individuals presented NAFLD and 32.5% presented MASLD. Over 9.4 years of follow-up, the relative increase in the incidence of diabetes was 78% for NAFLD (HR = 1.78; 95%CI: 1.58-2.01) and 88% for MASLD (HR = 1.88; 95%CI: 1.67-2.12). Associations did not differ significantly among race/skin color groups (p for interaction = 0.10 for MASLD and 0.08 for NAFLD). In this large cohort of middle-aged and older Brazilian adults, the relative incidence of diabetes was similar for NAFLD and MASLD definitions, with similar associations in all ethnic groups. Abstract (NAFLD dysfunctionassociated dysfunction associated (MASLD adults objective NAFLDMASLD selfdeclared self declared raceskin race skin ELSABrasil ELSA Brasil (ELSA-Brasil 3574 35 74 (35-7 200 201 20122014 2012 2014 2012-201 20172019. 20172019 2017 2019. 2019 2017-2019 followup follow selfreported reported diagnosis use fasting h postOGTT post OGTT HbA1c. HbA1c HbAc . HbA c HbA1c) cirrhosishepatitis cirrhosis hepatitis cirrhosis/hepatitis 7073 7 073 7,07 subjects ultrasoundbased ultrasound 339 33 9 33.9 325 32 5 32.5 94 4 9. followup, up, 78 HR 1.78 178 1 95%CI 95CI CI 95 1.582.01 158201 1.58 2.01 58 01 1.58-2.01 88 1.88 188 1.672.12. 167212 1.67 2.12 67 12 1.67-2.12) p 010 0 10 0.1 008 08 0.0 NAFLD. NAFLD) middleaged middle aged 357 3 (35- 20 2012201 2012-20 2017201 2017-201 707 07 7,0 33. 32. 1.7 17 582 1.582.0 15820 158 1.5 2.0 1.58-2.0 8 1.8 18 672 1.672.12 16721 167 1.6 212 2.1 6 1.67-2.12 0. 00 (35 201220 2012-2 201720 2017-20 70 7, 1. 1.582. 1582 15 2. 1.58-2. 1.672.1 1672 16 21 1.67-2.1 (3 20122 2012- 20172 2017-2 1.582 1.58-2 1.672. 1.67-2. ( 2017- 1.58- 1.672 1.67-2 1.67-

Resumen: Este estudio comparó las definiciones de enfermedad del hígado graso no alcohólico (EHGNA) y enfermedad hepática esteatótica asociada con disfunción metabólica (EHDM) con relación a la predicción de diabetes en una gran población adulta de brasileños. Como objetivo secundario, comparamos las asociaciones entre EHGNA/MASLD y diabetes en grupos de diferentes etnias/color de piel autodeclarados. El Estudio Longitudinal de Salud del Adulto (ELSA-Brasil) es un estudio de cohorte prospectivo de servidores públicos brasileños (35-74 años) reclutados entre el 2008 y el 2010 y seguidos en los períodos 2012-2014 y 2017-2019. Determinamos la diabetes mellitus tipo 2 en las visitas iniciales y de seguimiento con base en el diagnóstico autoinformado, el uso de medicación y las pruebas de glucemia (glucemia en ayunas y prueba de tolerancia a la glucosa oral 2 horas después y HbA1c). Se excluyeron las personas con consumo excesivo de alcohol o cirrosis/hepatitis autoinformadas. Se analizaron 7.073 individuos. La EHGNA se definió por esteatosis mediante ecografía. Se consideró que los participantes con esteatosis y al menos un factor cardiometabólico tenían EHDM. Se aplicaron modelos de riesgos proporcionales de Cox para evaluar la asociación entre EHGNA/EHDM y la incidencia de diabetes mellitus tipo 2. Al inicio del estudio, el 33,9% tenía EHGNA y el 32,5% EHDM. Durante 9,4 años de seguimiento, el aumento relativo en la incidencia de diabetes fue del 78% para las personas con EHGNA (HR = 1,78; IC95%: 1,58-2,01) y del 88% para las personas con EHDM (HR = 1,88; IC95%: 1,67-2,12). Las asociaciones no difirieron significativamente entre los grupos étnicos/color de piel (p para interacción = 0,10 para EHDM y 0,08 para EHGNA). En esta gran cohorte de brasileños de mediana edad y ancianos, la incidencia relativa de diabetes fue similar en las definiciones de EHGNA y EHDM, con asociaciones similares entre grupos étnicos. Resumen (EHGNA (EHDM secundario EHGNAMASLD MASLD etniascolor etnias color autodeclarados ELSABrasil ELSA Brasil (ELSA-Brasil 3574 35 74 (35-7 200 201 20122014 2012 2014 2012-201 20172019. 20172019 2017 2019. 2019 2017-2019 autoinformado HbA1c. HbA1c HbAc . HbA c HbA1c) cirrosishepatitis cirrosis hepatitis autoinformadas 7073 7 073 7.07 individuos ecografía EHGNAEHDM 339 33 9 33,9 325 32 5 32,5 94 4 9, 78 HR 1,78 178 1 IC95% IC95 IC 1,582,01 158201 1,58 2,01 58 01 1,58-2,01 88 1,88 188 1,672,12. 167212 1,67 2,12 67 12 1,67-2,12) étnicoscolor étnicos p 010 0 10 0,1 008 08 0,0 EHGNA. EHGNA) ancianos 357 3 (35- 20 2012201 2012-20 2017201 2017-201 707 07 7.0 33, 32, 1,7 17 IC9 582 1,582,0 15820 158 1,5 2,0 1,58-2,0 8 1,8 18 672 1,672,12 16721 167 1,6 212 2,1 6 1,67-2,12 0, 00 (35 201220 2012-2 201720 2017-20 70 7. 1, 1,582, 1582 15 2, 1,58-2, 1,672,1 1672 16 21 1,67-2,1 (3 20122 2012- 20172 2017-2 1,582 1,58-2 1,672, 1,67-2, ( 2017- 1,58- 1,672 1,67-2 1,67-

ABSTRACT Background: An outbreak of acute hepatitis of unknown etiology in children was recently reported worldwide. We aimed to describe the burden of hospitalizations due to hepatitis of unknown etiology in children/adolescents in Brazilian public hospitals. Methods: We retrieved a database of all hospitalizations in the Brazilian Unified Health System (SUS) from January/2019 to February/2022 using the “microdatasus” R package. Hepatitis of unknown etiology was defined by the following International Classification of Diseases [ICD-10] codes: B19, B19.0, B19.9, K72.0, K72.9, K75, K75.9, R94.5, or R93.2. The incidence rates (95% confidence interval, IC) per 1,000 all-cause hospitalizations in different age strata [< 6 years; 6–11 years and 12–17 years] were estimated. Results: A total of 94,198 hospitalizations due to hepatic or infectious diseases with potential liver injury were analyzed. Of them, 1,535 children/adolescents [48.2% male sex, 41.6% aged < 6 years] were hospitalized with hepatitis with unknown etiology. The top ICD-10 codes were B19.9 [unspecified viral hepatitis without hepatic coma; 39.9% (n = 612)], K72.9 [hepatic failure, unspecified; 29.8% (n = 457)], and K72.0 [hepatic failure, not elsewhere classified; 14.5% (n = 223)]. A total of 8.5% (n = 131) of individuals required liver transplantation and 7.0% (n = 107) died during the hospital-stay. In 2021, the incidence rates (95% CI) of hospitalizations for hepatitis with unknown etiology were 7.80 (7.63–7.98), 17.96 (17.46–18.48) and 13.28 (12.95–13.62) per 1,000 all-cause hospitalizations in subjects aged < 6 years, 6–11 years and 12–17 years-old, respectively. Similarly, the incidence rates of hospitalization due to hepatitis with unknown etiology per 1,000 all-cause hospitalizations (CI95%) in January-February/2022 were 7.52 (7.11–7.94), 16.82 (15.68–18.03), and 13.96 (13.10–14.85) for children/adolescents with age < 6 years, 6–11 years, and 12–17 years, respectively. Conclusions: A non-negligible number of hospitalizations due to hepatitis with unknown etiology in children/adolescents was observed in the last years in Brazil. Up to 15% of those cases needed liver transplantation or died. Background worldwide childrenadolescents adolescents hospitals Methods SUS (SUS January2019 January 2019 January/201 February2022 February 2022 February/202 microdatasus “microdatasus package ICD10 ICD 10 [ICD-10 B19 B B190 0 B19.0 B199 9 K720 K K72 K729 K75 K759 K75.9 R945 R94 5 R94.5 R932 R93 2 R93.2 95% 95 (95 interval IC 1000 1 000 1,00 allcause cause [ 611 11 6–1 1217 12 17 12–1 estimated Results 94198 94 198 94,19 analyzed them 1535 535 1,53 48.2% 482 48 [48.2 sex 416 41 41.6 ICD-1 B19. unspecified coma 399 39 39.9 n 612, 612 , 612)] K72. failure 298 29 8 29.8 457, 457 457)] classified 145 14 14.5 223. 223 . 223)] 85 8.5 131 70 7 7.0 107 hospitalstay. hospitalstay hospital stay. stay hospital-stay 2021 CI 780 80 7.8 7.63–7.98, 763798 7.63–7.98 63 98 (7.63–7.98) 1796 96 17.9 17.46–18.48 17461848 46 18 (17.46–18.48 1328 13 28 13.2 12.95–13.62 12951362 62 (12.95–13.62 yearsold, yearsold old, old years-old respectively Similarly CI95% CI95 (CI95% JanuaryFebruary/2022 JanuaryFebruary2022 JanuaryFebruary January-February/202 752 52 7.5 7.11–7.94, 711794 7.11–7.94 (7.11–7.94) 1682 16 82 16.8 15.68–18.03, 15681803 15.68–18.03 15 68 03 (15.68–18.03) 1396 13.9 13.10–14.85 13101485 (13.10–14.85 Conclusions nonnegligible non negligible Brazil January201 201 January/20 February202 202 February/20 ICD1 [ICD-1 B1 K7 K75. R9 R94. R93. (9 100 00 1,0 61 6– 121 12– 9419 19 94,1 153 53 1,5 48.2 4 [48. 41. ICD- 3 39. 612) 29. 45 457) 14. 22 223) 8. 7. 78 76379 7.63–7.9 (7.63–7.98 179 17. 17.46–18.4 1746184 (17.46–18.4 132 13. 12.95–13.6 1295136 (12.95–13.6 CI9 (CI95 JanuaryFebruary/202 JanuaryFebruary202 January-February/20 75 71179 7.11–7.9 (7.11–7.94 168 16. 1568180 15.68–18.0 (15.68–18.03 139 13.10–14.8 1310148 (13.10–14.8 January20 20 January/2 February20 February/2 [ICD- ( 1, 941 94, 48. [48 7637 7.63–7. (7.63–7.9 17.46–18. 174618 (17.46–18. 12.95–13. 129513 (12.95–13. (CI9 JanuaryFebruary/20 JanuaryFebruary20 January-February/2 7117 7.11–7. (7.11–7.9 156818 15.68–18. (15.68–18.0 13.10–14. 131014 (13.10–14. January2 January/ February2 February/ [ICD [4 763 7.63–7 (7.63–7. 17.46–18 17461 (17.46–18 12.95–13 12951 (12.95–13 (CI JanuaryFebruary/2 JanuaryFebruary2 January-February/ 711 7.11–7 (7.11–7. 15681 15.68–18 (15.68–18. 13.10–14 13101 (13.10–14 76 7.63– (7.63–7 17.46–1 1746 (17.46–1 12.95–1 1295 (12.95–1 JanuaryFebruary/ January-February 71 7.11– (7.11–7 1568 15.68–1 (15.68–18 13.10–1 1310 (13.10–1 7.63 (7.63– 17.46– 174 (17.46– 12.95– 129 (12.95– 7.11 (7.11– 156 15.68– (15.68–1 13.10– (13.10– 7.6 (7.63 17.46 (17.46 12.95 (12.95 7.1 (7.11 15.68 (15.68– 13.10 (13.10 (7.6 17.4 (17.4 12.9 (12.9 (7.1 15.6 (15.68 13.1 (13.1 (7. (17. 12. (12. 15. (15.6 (13. (7 (17 (12 (15. (13 (1 (15

ABSTRACT The accuracy of commercially available tests for COVID-19 in Brazil remains unclear. We aimed to perform a meta-analysis to describe the accuracy of available tests to detect COVID-19 in Brazil. We searched at the Brazilian Health Regulatory Agency (ANVISA) online platform to describe the pooled sensitivity (Se), specificity (Sp), diagnostic odds ratio (DOR) and summary receiver operating characteristic curves (SROC) for detection of IgM/IgG antibodies and for tests using naso/oropharyngeal swabs in the random-effects models. We identified 16 tests registered, mostly rapid-tests. Pooled diagnostic accuracy measures [95%CI] were: (i) for IgM antibodies Se = 82% [76-87]; Sp = 97% [96-98]; DOR = 168 [92-305] and SROC = 0.98 [0.96-0.99]; (ii) for IgG antibodies Se = 97% [90-99]; Sp = 98% [97-99]; DOR = 1994 [385-10334] and SROC = 0.99 [0.98-1.00]; and (iii) for detection of SARS-CoV-2 by antigen or molecular assays in naso/oropharyngeal swabs Se = 97% [85-99]; Sp = 99% [77-100]; DOR = 2649 [30-233056] and SROC = 0.99 [0.98-1.00]. These tests can be helpful for emergency testing during the COVID-19 pandemic in Brazil. However, it is important to highlight the high rate of false negative results from tests which detect SARS-CoV-2 IgM antibodies in the initial course of the disease and the scarce evidence-based validation results published in Brazil. Future studies addressing the diagnostic performance of tests for COVID-19 in the Brazilian population are urgently needed.

ABSTRACT Background. Cirrhosis remains the most frequent liver-related cause of death worldwide and we aimed to evaluate its burden in Brazil from 2000 to 2012. Material and methods. The Brazilian National Death Registry was analyzed from 2000 to 2012. Death by cirrhosis was defined by the presence of I85, K73 and/or K74 ICD 10 codes in contributing or underlying causes of death on the death certificate (DC). Crude mortality rates were calculated as the ratio of the absolute number of deaths and the estimated population. Mortality rates were age-adjusted by the direct standardization method using the WHO standard population. Results. A total of 265,180 deaths where cirrhosis was mentioned on the DC [77% male, aged 56 years] occurred from 2000 to 2012. Cirrhosis codes were present in 46% of liver-related deaths and 2% of all deaths in this period. Despite an increase in the absolute number of deaths (n = 18,245 to 22,340), the age-standardized mortality rates (95%CI) decreased from 13.32 (13.16-13.48) to 11.71 (11.59-11.83) per 100,000 inhabitants from 2000 to 2012 (p < 0.001). This trend was not uniform across the country, with decreases in death rates in the South [14.46 (14.07-14.87) to 10.89 (10.59-11.19)] and Southeast [15.85 (15.6-16.09) to 12.52 (12.34-12.70)] and increases in the North [8.84 (8.24-9.43) to 11.53 (11.08-11.99)] and Northeast [9.41 (9.13-9.69) to 10.93 (10.68-11.17)] (p < 0.001 for all). Conclusion. Cirrhosis remains a major public health issue, despite the reduction in mortality rates in the last decade.

Colorectal cancer is the third most frequent cancer in men and the second most frequent in women, with a worldwide incidence of approximately 1.2 million new cases per year. Our primary objective was to study the relationship between clinical and histological features of individuals with colorectal cancer and the mutational status of codons 12 and 13 of the KRAS gene (7 validated mutations), in order to find a histopathological marker to mutated tumors. The secondary objective was to determine how many patients had additional mutations in codons 15 and 61 of the KRAS gene, and codon 600 of the BRAF gene, which could modify the tumor phenotype. Sixty individuals with colorectal cancer (30 wild-type subjects and 30 with validated mutations in codons 12 and 13 of the KRAS gene) were selected. Exons 2 and 3 of the KRAS gene, and exon 15 of the BRAF gene were amplified and sequenced. The data collected were reviewed by a descriptive, univariate and/or multivariate analysis, as appropriate. In conclusion, no relation was found between clinical and histological features of individuals with colorectal cancer and their mutational status for codons 12 and 13 of the KRAS gene. This suggests that those easily available data do not allow predicting the response to anti-EGFR therapy. In patients with advanced colorectal adenocarcinomas and KRAS wild-type status, further study of codon 600 of the BRAF gene could be required.

El cáncer colorrectal es el tercer cáncer más frecuente en hombres y el segundo más frecuente en mujeres, con una incidencia mundial aproximada de 1.2 millones de casos nuevos por año. Nuestro objetivo primario fue estudiar la relación existente entre las características clínico-histológicas en individuos con cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS (7 mutaciones validadas), con el fin de hallar un marcador histopatológico para los tumores mutados. El objetivo secundario fue determinar cuántos pacientes tenían mutaciones adicionales en los codones 15 y 61 del gen KRAS y 600 del gen BRAF que podrían modificar el fenotipo tumoral. Fueron seleccionados 60 individuos con cáncer colorrectal (30 wild-type y 30 con mutaciones validadas en los codones 12 y 13 del gen KRAS). Se amplificaron y secuenciaron del gen KRAS los exones 2 y 3, y del gen BRAF el exón 15. La información recolectada se examinó mediante un análisis descriptivo, análisis univariado y/o análisis multivariado, según correspondiese. En conclusión, no se encontró relación entre las características clínico-histológicas de los tumores de individuos con diagnóstico de cáncer colorrectal y el estado mutacional de los codones 12 y 13 del gen KRAS. No hallamos un marcador histopatológico para los tumores mutados. En pacientes con adenocarcinomas colorrectales avanzados y KRAS wild-type resulta de interés considerar el estudio del codón 600 del gen BRAF.

La adherencia o cumplimiento terapéutico es la realización del tratamiento de la hepatitis C con dosis suficientes de Interferon pegilado y Ribavirina durante el tiempo previsto, es decir 80% de las dosis inicialmente indicada, en el 80% del tiempo establecido. El objetivo de esta investigación fue determinar la adherencia al tratamiento en el grupo seleccionado, el cumplimiento de la terapia depende de varios factores que incluyen: paciente, efectos colaterales, personal médico y paramédico y todo aquello que impida reducir dosis o interrumpir la terapia. En este trabajo se revisaron 41 historias del archivo interno de la consulta de hígado del Hospital Miguel Pérez Carreño a quien se le indico tratamiento con Peg-Interferon y RBV por diagnostico de Hepatitis C, independientemente del genotipo. Se tomaron en cuenta los siguientes parámetros: sexo, edad, morbilidad asociada, efectos colaterales, motivo para suspender terapia, % de pacientes que culminaron tratamiento, etc. Se utilizo procesador Word y Excel, y análisis estadístico simple. El hallazgo primordial fue que aproximadamente solo el 29% culmino la terapia. La conclusión de esta revisión es entender la importancia de profundizar la relación médico-paciente y la conformación del equipo multidisciplinario como punto indispensable para lograr la adherencia al tratamiento y por ende una respuesta viral sostenida, objetivo primordial de la terapia.

Adherence or compliance to therapy is to apply the treatment for Hepatitis C, with the maximum dosage of Pegylated Interferon and Ribavirin along the foreseen period, i.e. 80% of the dosage initially prescribed during 80% of the established time. The completion of this objective depends on numerous factors: 1. Relating to Patients: a) patient’s education and understanding to realize the consequences of the disease and b) encouraging the patient to comply with the therapy. 2. Inherent to the treatment itself: a) appropriate management of adverse effects and b) drug tolerance of the patient. 3. Setting up a multidisciplinary team: medical doctor, nurse, psychologist, hematologist, etc. which positively influence the attitude of patient preventing dose reduction and drop-out of therapy. In this paper we reviewed 41 patient’s medical records from the internal archive of the Hepatic Department, Miguel Pérez Carreño Hospital. Those patients were treated with Peg-Interferon and RBV (Ribavirin) due to Hepatitis C diagnosis, independently on the genotype. The following parameters were taken into account: gender, age, associate morbidity, side effects, reasons for suspending therapy, % of patients who completed therapy, etc. Word processor and Excel were used and the simple statistical analysis. With the fundamental finding that, approximately, only the 29% of patients culminated the therapy. Reviewing this series allowed us to assess the importance of deepen the doctor-patient relationship, as well as setting up a multidisciplinary team, as an essential point in order to achieve the adherence to treatment and, therefore, a sustained viral response: the paramount objective of the therapy.

The oil of the fruits of Euterpe oleracea Mart., Arecaceae (OEO), was evaluated in models of inflammation and hyperalgesia in vivo to study its effects on these conditions. The experimental models contained the writhing test in mice, rat paw edema, granuloma test in rats, vascular permeability in rats, cell migration to the peritoneal cavity in rats and ear erythema induced by croton oil in mice. Doses of 500, 1000 and 1500 mg/kg of OEO were administered orally. The observed number of writhes was inhibited by 33.67, 45.88 and 55.58%, respectively. OEO produced a dose-dependent effect, with linear correlation coefficient R=0.99 (y=0.0219x+23.133), and the median effective dose found was 1226.8 mg/kg. The oral administration of 1226.8 mg/kg of OEO inhibited carrageenan-induced edema by 29.18% (p<0.05) when compared to the control group. The daily administration of OEO for six days inhibited the formation of granulomatous tissue by 36.66% (p<0.01). In ear erythema induced by croton oil, OEO presented a significant inhibition (37.9%). In the vascular permeability test, treatment with OEO decreased the response to histamine, inhibiting vascular permeability by 54.16%. In carrageenan-induced peritonitis, OEO reduced the number of neutrophils migrating compared to the control group by 80.14%. These results suggested that OEO has anti-inflammatory and antinociceptive activities, probably of peripheral origin and linked to prostaglandin biosynthesis inhibition.