Editorial

Universidade Federal de São Paulo (UNIFESP) Departamento de MedicinaUNIFESP, Depto. de MedicinaSciEL

Cancer and virus

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Medical DepartmentUNIFESP, EPM, Medical DepartmentSciEL

O laboratório clínico e os intervalos de referência

Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Importância da determinação da hemoglobina glicada no monitoramento do paciente portador de diabetes mellitus

Universidade de São Paulo Faculdade de MedicinaFMUSP Hospital das Clínicas Laboratório CentralHospital Israelita Albert Einstein Departamento de Patologia ClínicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaFleury - Centro de Medicina DiagnósticaUNIFESP, EPMSciEL

Glycohemoglobin importance in the diabetes mellitus control and in the risk evaluation of chronic complications

Diabetes mellitus remains a subject of study due to the fact that clinical trials and new laboratory resources have increasingly added updated information to medical practice. High glycemic levels are harmful and their persistence results in complications such as tissue damage, loss of normal function and failure of several organs. Glycated hemoglobin control has been a useful tool to monitor diabetic patients, and this analyte was validated by two major clinical studies about the impact assessment of rigid glycemic control on the incidence and progression of diabetes complications: Diabetes Control and Complications Trial (DCCT, 1993) and United Kingdom Prospective Diabetes Study (UKPDS, 1998). These studies showed that glycated hemoglobin level below 7% reduces the risk of complications in diabetes. In 2004, the Interdisciplinary Group of Standardization of Glycated Haemoglobin-A1C, a group of specialists from scientific societies and pharmaceutical companies in Brazil, published an official statement about the importance of glycated hemoglobin for the assessment of glycemic control. It discusses the clinical and laboratory aspects, which includes pre-analytical and analytical variations. The recommendations for the use of the test and the ideal control levels for adults, children and elderly people were established. According to this document, A1C tests should be performed at least twice a year by all patients with diabetes mellitus. However, when the results are not appropriate and/or changes are made in the therapeutic scheme, the test should be performed after three months. It is recommended for individuals with diabetes types 1 and 2 and the goal to be achieved is below 7% for effective control in both adults and youngsters. For children during the prepubertal stage the acceptable level of A1C is up to 8% and in pubertal stage, up to 8.5%. In elderly patients, A1C up to 8% is considered appropriate insofar as the attempt to a rigid glycemic level in this age group as well as in prepubertal and pubertal stages may cause side effects such as hypoglycemia. Glycated hemoglobin control is not recommended for pregnant women. The fasting blood glucose test, the glucose level after meals and the fructosamine determination, which corresponds to the group of glycated serum proteins, are more efficient in this case. The main difference between A1C and fasting blood glucose is that the levels of A1C vary more slowly, depending on the half-life of red blood cells. Therefore, they do not return to normality immediately after the normalization of glucose in the blood. The time to reach appropriate levels of A1C after a period of hyperglycemia is approximately 10 weeks. Consequently, A1C exams should be repeated only two to three months after the beginning or the modification of the therapeutic scheme in order to assess its effectiveness. Diseases that affect the survival of red blood cells, such as hemolytic anemia and hemorrhage, may result in false low A1C values due to the reductions of their half-life. On the other hand, anemia caused by iron, vitamin B12 or folate deficiencies, which increase the half-life of red blood cells, may result in false elevated A1C values. Depending on the methodology applied, other medical conditions, such as hypertriglyceridemia, hyperbilirubinemia, uremia, chronic alcoholism and chronic use of opiates or salicylates, may interfere in the results of A1C. Not only is the Brazilian official recommendation the use of DCCT traceable methods, certified by the National Glycohemoglobin Standardization Program (NGSP), but it also encourages participation in specific proficiency testing programs of glycated hemoglobin.O diabetes mellitus (DM) continua sendo objeto de pesquisa, dadas as constantes informações que os estudos clínicos e os novos recursos laboratoriais incorporam à prática médica a cada dia e com maiores rapidez e eficiência. Níveis glicêmicos persistentemente elevados são danosos ao organismo e o descontrole prolongado resulta em complicações, incluindo danos em diversos tecidos, perda da função normal e falência de vários órgãos. Para o acompanhamento do portador de DM, a hemoglobina glicada (A1C) tem se firmado como ferramenta útil depois de ter sido validada pelos dois estudos clínicos mais importantes sobre a avaliação do impacto do rígido controle glicêmico sobre a incidência e a progressão das complicações do diabetes: o Diabetes Control and Complications Trial (DCCT, 1993) e o United Kingdom Prospective Diabetes Study (UKPDS, 1998). Essas pesquisas demonstraram que manter o nível de A1C abaixo de 7% reduz o risco de desenvolvimento das complicações dessa doença. O Grupo Interdisciplinar de Padronização da Hemoglobina Glicada - A1C, criado pela associação de diversas sociedades científicas e farmacêuticas do Brasil, publicou, em 2004, um documento de posicionamento oficial acerca da importância da A1C para a avaliação do controle glicêmico, abordando os principais aspectos clínicos e laboratoriais, incluindo as condições de variação pré-analítica e analítica. Foram estabelecidas as recomendações a respeito das indicações do teste e dos valores ideais de controle para adultos, crianças e idosos. Segundo este posicionamento, os testes de A1C devem ser realizados pelo menos duas vezes ao ano por todos os portadores de DM. Quando os resultados não forem adequados e/ou forem realizadas alterações no esquema terapêutico, a dosagem deve ser feita depois de três meses. A dosagem está indicada tanto para os portadores de diabetes mellitus tipo 1 (DM1) quanto tipo 2 (DM2), sendo que a meta a ser atingida, representando efetivo controle, em ambas as condições é abaixo de 7%, tanto no adulto como no adulto jovem. Para as crianças durante a fase pré-puberal, o nível aceitável de A1C é de até 8% e, na fase puberal, até 8,5%. Nos pacientes idosos, a A1C de até 8% é considerada apropriada, uma vez que a tentativa de um controle muito rígido da glicemia nesta faixa etária, assim como nas fases pré-puberal e puberal, pode induzir a efeitos colaterais indesejados, como, por exemplo, hipoglicemia. Para a paciente gestante não está indicado o acompanhamento do controle glicêmico pela dosagem de A1C, sendo mais eficiente o controle dos níveis das glicemias de jejum e duas horas após as refeições e a dosagem de frutosamina, que corresponde ao conjunto das proteínas plasmáticas glicosadas. O grande diferencial da A1C em relação à glicemia de jejum é que os níveis daquela variam mais lentamente, dependendo da meia-vida das hemácias, portanto não retornam ao normal imediatamente depois da normalização da glicose no sangue. O tempo para que a A1C atinja os níveis adequados após um período de hiperglicemia é de aproximadamente dez semanas. Assim, a repetição do exame de A1C para avaliar a eficácia de um tratamento deve ser realizada somente dois a três meses depois do início ou da modificação do esquema terapêutico. Doenças que alteram a sobrevida das hemácias, como anemia hemolítica e hemorragia, por reduzirem sua vida média, podem resultar em valores falsamente baixos de Hb A1C, enquanto as anemias por carência de ferro, de vitamina B12 ou de folato, que aumentam a vida média das hemácias, resultam em valores falsamente elevados. Na dependência da metodologia utilizada, outras condições clínicas podem interferir no resultado de A1C, como hipertrigliceridemia, hiperbilirrubinemia, uremia, alcoolismo crônico, uso prolongado de opiáceos ou de salicilatos. O posicionamento oficial brasileiro recomenda a utilização de métodos rastreáveis do Diabetes Control and Complications Trial (DCCT), conforme certificado pelo National Glycohemoglobin Standardization Program (NGSP), e estimula a participação em programas de ensaios de proficiência específicos para A1C.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de MedicinaSciEL

Benefits of physical activity on the lipid profile of type 1 diabetic subjects

We assessed the response of lipid profile to short-term non-pharmacological intervention and investigated if lipoprotein abnormalities were present before overt diabetic nephropathy (DN) in 46 type 1 diabetic (DM1) youngsters aged 15.5±1.5 yrs. They were submitted to a 8-day program of adequate diet and exercise, during stable glycemic control (mean glycemia 110.3±27.1mg/dl and HbA1c 6.9±1.3%) to minimize the influence of disturbed glucose homeostasis on urinary albumin excretion and lipid profile. Mean albumin-to-creatinine ratio was 9.0±8.0mg/g creatinine. At the beginning of the program, 65% of the subjects had total cholesterol > 160mg/dl (95% CI 0.51-0.78), whereas only 38% (95% CI 0.51-0.24) maintained such levels at the end. The improvement in lipid profile was even better concerning LDL fraction, considering that initially 67% of the subjects showed values > 100mg/dl (95% CI 0.55-0.78) and 24% (95% CI 0.12-0.36) at the end. Initial HDL-cholesterol was 160mg/dl (IC 95% 0,51-0,78), enquanto que ao final somente 38% (IC 95% 0,24-0,51) tinham tais níveis. A melhora no perfil lipídico foi ainda melhor para a fração LDL, considerando que inicialmente 67% mostravam valores acima de 100mg/dl (IC 95% 0,55-0,78) e 24% (IC 95% 0,12-0,36) ao final. Valores de HDL-colesterol subnormais (< 40mg/dl) ocorreram em 38% (95% IC 0,24-0,51) e 11% (IC 95% 0,02-0,20) deles, no início e final do período. A razão albumina/creatinina média foi 9,0±8,0mg/g de creatinina. Encontramos fracas correlações entre a razão albumina/creatinina e os níveis de colesterol total (r= 0,21), LDL (r= 0,24), VLDL (r= 0,30), HDL (r= -0,17) e de triglicérides (r= 0,31). Dentro da faixa de referência de albuminúria, não foi encontrada nenhuma associação entre a excreção urinária de albumina e os níveis de lípides nos pacientes com DM1 estável. Um programa de exercícios regulares é eficaz em otimizar o perfil lipídico nestes pacientes, independentemente do controle glicêmico. Nossos dados não apoiam a hipótese de que mudanças no metabolismo lipídico precederiam a microalbuminúria no curso da ND.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de EndocrinologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Clínica MédicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina PreventivaUNIFESP, EPM, Disciplina de EndocrinologiaUNIFESP, EPM, Depto. de Clínica MédicaUNIFESP, EPM, Depto. de Medicina PreventivaSciEL

COVID-19 - Diagnóstico Laboratorial para Clínicos

COVID-19 (coronavirus disease 2019) is an infectious disease caused by the new coronavirus associated with severe acute respiratory syndrome 2 (SARS-CoV-2). Coronaviridae comprises a large family and at least seven members are known to cause respiratory diseases in humans. Coronaviruses have the ability to infect virtually all major groups of animals and, eventually, can infect humans. SARS-CoV-2 is the third coronavirus to cross the species barrier and infect humans. This virus was identified in an outbreak of pneumonia in the city of Wuhan, Hubei province, China, in December 2019. Its entire genome is inscribed on a single ribbon of ribonucleic acid. Some proteins present on the surface of the virus act as facilitators of its entry into host cells, others, apparently, are related to its pathogenesis. Coronaviruses are responsible for respiratory infections in humans and some animals. The infection is often mild to moderate in intensity, but some coronaviruses can cause serious illnesses, such as Severe Acute Respiratory Syndrome (SARS) (SARS), which occurred in 2002 and the Middle East respiratory syndrome. (MERS, from Middle East respiratory syndrome). Coronaviruses can activate an excessive and unregulated immune response, which can promote SRAG development. Although the lung is one of the target organs, the hypoxia mechanism is systemic and other organs suffer both the lack of oxygen and the disruption of inflammation control mechanisms.COVID-19 (do inglês coronavirus disease 2019) é uma doença infecciosa causada pelo novo coronavírus associado à síndrome respiratória aguda grave 2 (SARS-CoV-2). Coronaviridae compreende uma grande família e, pelo menos, sete membros são conhecidos por causarem doenças respiratórias em humanos. Os coronavírus têm a capacidade de infectar praticamente todos os principais grupos de animais e, eventualmente, podem passar a contaminar humanos. O SARS-CoV-2 é o terceiro coronavírus a transpor a barreira entre espécies e infectar humanos. Esse vírus foi identificado em um surto de casos de pneumonia na cidade de Wuhan, província de Hubei, China, em dezembro de 2019. Todo o seu genoma está inscrito em uma fita única de ácido ribonucleico. Algumas proteínas presentes na superfície do vírus atuam como facilitadores do seu ingresso nas células hospedeiras, outras, aparentemente, estão relacionadas com a sua patogenia. Os coronavírus são responsáveis por infecções respiratórias em seres humanos e em alguns animais. Frequentemente, a infecção é de intensidade leve a moderada, mas alguns coronavírus podem causar doenças graves, como a Síndrome Respiratória Aguda Grave (SRAG) (SARS, do inglês Severe Acute Respiratory Syndrome), que ocorreu em 2002 e a síndrome respiratória do Oriente Médio (MERS, do inglês Middle East respiratory syndrome). Os coronavírus podem ativar uma resposta imune excessiva e desregulada, a qual pode propiciar o desenvolvimento SRAG. Ainda que o pulmão seja um dos órgãos alvo, o mecanismo de hipóxia é sistêmico e outros órgão passam a sofrer tanto a falta de oxigênio quando a desregulação dos mecanismos de controle da inflamação

The combination of atorvastatin and ethanol is not more hepatotoxic to rats than the administration of each drug alone

Animal studies and premarketing clinical trials have revealed hepatotoxicity of statins, primarily minor elevations in serum alanine aminotransferase levels. The combined chronic use of medicines and eventual ethanol abuse are common and may present a synergistic action regarding liver injury. Our objective was to study the effect of the chronic use of atorvastatin associated with acute ethanol administration on the liver in a rat model. One group of rats was treated daily for 5 days a week for 2 months with 0.8 mg/kg atorvastatin by gavage. At the end of the treatment the livers were perfused with 72 mM ethanol for 60 min. Control groups (at least 4 animals in each group) consisted of a group of 2-month-old male Wistar EPM-1 rats exposed to 10% ethanol (v/v) ad libitum replacing water for 2 months, followed by perfusion of the liver with 61 nM atorvastatin for 60 min, and a group of animals without chronic ethanol treatment whose livers were perfused with atorvastatin and/or ethanol. The combination of atorvastatin with ethanol did not increase the release of injury marker enzymes (alanine aminotransferase, aspartate aminotransferase, and lactic dehydrogenase) from the liver and no change in liver function markers (bromosulfophthalein clearance, and oxygen consumption) was observed. Our results suggest that the combination of atorvastatin with ethanol is not more hepatotoxic than the separate use of each substance.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de BioquímicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUNIFESP, EPM, Depto. de BioquímicaUNIFESP, EPM, Depto. de MedicinaSciEL

Salivary gland ultrasonography as a predictor of clinical activity in Sjogren's syndrome

Purpose Primary Sjogren's syndrome is a multisystem autoimmune disease characterized by hypofunction of salivary and lacrimal glands and possible multi-organ system manifestations. Over the past 15 years, three sets of diagnostic criteria have been proposed, but none has included salivary gland ultrasonography. However, recent studies support its role in the diagnosis and prognostic evaluation of patients with Sjogren's syndrome. This study aimed to determine the value of salivary gland ultrasonography in the diagnosis and prognosis of Sjogren's syndrome by relating ultrasonography severity scores to clinical and laboratory data. Methods Seventy patients who fulfilled the 2002 American-European Consensus Group diagnostic criteria for primary Sjogren's syndrome were selected from 84 patients receiving care in specialized outpatient clinics at our institution from November 2013 to May 2016. Their serology, European League Against Rheumatism Sjogren's syndrome disease activity index (ESSDAI), salivary flow rate, immunoglobulin G, and salivary and serum beta-2 microglobulin levels were measured. Salivary gland ultrasonography was performed by an experienced radiologist, using scores of 1-4 to classify salivary gland impairment. Results Salivary gland ultrasonography scores of 1 or 2 were associated with an ESSDAI = 5 (p = 0.064), a positive antinuclear antibody test (p = 0.006), positive anti-Ro/SSA antibodies (p = 0.003), positive anti-La/SSB antibodies (p = 0.077), positive rheumatoid factor (p = 0.034), and immunoglobulin G levels >1600 mg/dL (p = 0.077). Salivary flow rate was lower in patients with scores 3 or 4 (p = 0.001). Conclusion This study provides further evidence that salivary gland ultrasonography can be used not only for diagnosis but also for prognostic evaluation of primary Sjogren's syndrome. These findings confirm what has been reported in the literature. However, further analyses involving larger matched samples are required to support this finding and include salivary gland ultrasonography as part of the diagnostic criteria for Sjogren's syndrome.Univ Fed São Paulo UNIFESP, Dept Evidence Based Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Radiol, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Lab Med, São Paulo, SP, BrazilUniv Fed São Paulo UNIFESP, Dept Evidence Based Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Radiol, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Lab Med, São Paulo, SP, BrazilWeb of Scienc

Salivary gland ultrasonography as a predictor of clinical activity in Sjogren's syndrome

Purpose Primary Sjogren's syndrome is a multisystem autoimmune disease characterized by hypofunction of salivary and lacrimal glands and possible multi-organ system manifestations. Over the past 15 years, three sets of diagnostic criteria have been proposed, but none has included salivary gland ultrasonography. However, recent studies support its role in the diagnosis and prognostic evaluation of patients with Sjogren's syndrome. This study aimed to determine the value of salivary gland ultrasonography in the diagnosis and prognosis of Sjogren's syndrome by relating ultrasonography severity scores to clinical and laboratory data. Methods Seventy patients who fulfilled the 2002 American-European Consensus Group diagnostic criteria for primary Sjogren's syndrome were selected from 84 patients receiving care in specialized outpatient clinics at our institution from November 2013 to May 2016. Their serology, European League Against Rheumatism Sjogren's syndrome disease activity index (ESSDAI), salivary flow rate, immunoglobulin G, and salivary and serum beta-2 microglobulin levels were measured. Salivary gland ultrasonography was performed by an experienced radiologist, using scores of 1-4 to classify salivary gland impairment. Results Salivary gland ultrasonography scores of 1 or 2 were associated with an ESSDAI = 5 (p = 0.064), a positive antinuclear antibody test (p = 0.006), positive anti-Ro/SSA antibodies (p = 0.003), positive anti-La/SSB antibodies (p = 0.077), positive rheumatoid factor (p = 0.034), and immunoglobulin G levels >1600 mg/dL (p = 0.077). Salivary flow rate was lower in patients with scores 3 or 4 (p = 0.001). Conclusion This study provides further evidence that salivary gland ultrasonography can be used not only for diagnosis but also for prognostic evaluation of primary Sjogren's syndrome. These findings confirm what has been reported in the literature. However, further analyses involving larger matched samples are required to support this finding and include salivary gland ultrasonography as part of the diagnostic criteria for Sjogren's syndrome.Univ Fed São Paulo UNIFESP, Dept Evidence Based Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Radiol, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Lab Med, São Paulo, SP, BrazilUniv Fed São Paulo UNIFESP, Dept Evidence Based Med, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Radiol, São Paulo, SP, BrazilUniv Fed São Paulo, Dept Lab Med, São Paulo, SP, BrazilWeb of Scienc