Diagnóstico precoce de acetonemia subclínica em vacas holandesas por mensuração de corpos cetônicos / Early diagnosis of subclinical acetonemia in holstein cows by measuring ketone bodies / Diagnóstico precoz de acetonemia subclínica en vacas holstein mediante la medición de cuerpos cetónicos

O trabalho foi realizado em uma fazenda de exploração leiteira em Castrolanda, no município de Castro ­ PR. O sistema de manejo é free-stall, com 220 vacas da raça Holandesa com RHA305 de 6.740 litros. Foram coletadas amostras de sangue de 18 vacas de pré-parto, 4 dias antes da data prevista para o parto; e nos dias 4, 7 e 12 pós-parto, mediante punção venosa coccígea, utilizando-se SnapTest digital Ketovet®, constituindo 72 amostras, no período de fevereiro a maio de 2020. Em 4 vacas o BHB do sangue total apresentou-se acima do limite para cetose subclínica no quarto dia após o parto e 17 apresentaram-se acima do limite no sétimo dia, declinando em seguida, principalmente devido às intervenções clínicas. As médias e desvios-padrão foram: D - 4: 0,89 ± 0,257061; D 4: 1,05 ± 0,283279; D 7: 1,81 ± 0,456131; e D 12: 1,19 ± 0,437762. O benefício do monitoramento de BHB foi a imediata intervenção clínica, evitando-se a severidade por instalação de quadro clínico e as enfermidades concomitantes.(AU)

The study was carried out on a dairy farm in Castrolanda, in the county of Castro - PR. The management system is free stall, with 220 Holstein cows with RHA305 of 6,740 liters. Blood samples were collected from 18 pre-calving cows, 4 days before the expected date of calving; and on days 4, 7 and 12 postpartum, by means of coccygeal venipuncture, using SnapTest digital Ketovet®, constituting 72 samples, from February to May 2020. In 4 cows the BHB of whole blood was shown above the limit for subclinical ketosis on the fourth day after delivery and 17 presented above the limit on the seventh day, then declining mainly due to clinical interventions. The means and standard deviations were D -4: 0.89 ± 0.257061; D 4: 1.05 ± 0.283279; D 7: 1.81 ± 0.456131; and D 12: 1.19 ± 0.437762. The benefit of monitoring BHB was immediate clinical intervention, avoiding clinical ketosis and concomitant illnesses.(AU)

El estudio se realizó en una explotación lechera de Castrolanda, en la comarca de Castro - PR. El sistema de manejo es estabulación libre, con 220 vacas Holstein con RHA305 de 6.740 litros. Se recogieron muestras de sangre de 18 vacas pre- parto, 4 días antes de la fecha prevista de parto; y en los días 4, 7 y 12 postparto, mediante venopunción coccígea, utilizando SnapTest digital Ketovet®, constituyendo 72 muestras, desde febrero a mayo de 2020. En 4 vacas la BHB de sangre total se mostró por encima del límite para cetosis subclínica en el cuarto día después del parto y 17 presentaron por encima del límite en el séptimo día, disminuyendo después debido principalmente a intervenciones clínicas. Las medias y desviaciones estándar fueron D -4: 0,89 ± 0,257061; D 4: 1,05 ± 0,283279; D 7: 1,81 ± 0,456131; y D 12: 1,19 ± 0,437762. El beneficio de monitorizar la BHB fue la intervención clínica inmediata, evitando la cetosis clínica y las enfermedades concomitantes.(AU)

Clinical and immunological characteristics of PD-1 associated fulminant type 1 diabetes mellitus / 中南大学学报(医学版)

OBJECTIVES@#Programmed death 1 (PD-1) associated fulminant type 1 diabetes (PFD) is a rare acute and critical in internal medicine, and its clinical characteristics are still unclear. This study aims to analyze the clinical characteristics of PFD patients to improve clinical diagnosis and treatment.@*METHODS@#We retrospectively analyzed the clinical data of 10 patients with PFD admitted to the Second Xiangya Hospital of Central South University, combined with the data of 66 patients reported in the relevant literature, analyzed and summarized their clinical and immunological characteristics, and compared the patients with PFD with different islet autoantibody status.@*RESULTS@#Combined with our hospital and literature data, a total of 76 patients with PFD were reported, with the age of (60.9±12.1) years old, 60.0% male and body mass index of (22.1±5.2) kg/m2. In 76 patients, the most common tumors were lung cancer (43.4%) and melanoma (22.4%). Among PD-1 inhibitors, the most common drugs are nivolumab (37.5%) and pembrolizumab (38.9%). 82.2% of PFD patients developed diabetes ketoacidosis. The median onset time from PD-1 related inhibitor treatment to hyperglycemia was 95 (36.0, 164.5) d, and the median treatment cycle before the onset of diabetes was 6 (2.3, 8.0) cycles. 26% (19/73) of PFD patients had positive islet autoantibodies, and the proportion of ketoacidosis in the positive group was significantly higher than that in the negative group (100.0% vs 75.0%, P<0.05). The onset time and infusion times of diabetes after PD-1 inhibitor treatment in the autoantibody positive group were significantly lower than those in the autoantibody negative group (28.5 d vs 120.0 d; 2 cycles vs 7 cycles, both P<0.001).@*CONCLUSIONS@#After initiation of tumor immunotherapy, it is necessary to be alert to the occurrence of adverse reactions of PFD, and the onset of PFD with islet autoantibody positive is faster and more serious than that of patients with autoantibodies negative. Detection of islet autoantibodies and blood glucose before and after treatment with PD-1 inhibitors is of great value for early warning and prediction of PFD.

Hematological Parameters to Predict the Severity of Hyperemesis Gravidarum and Ketonuria / Parâmetros hematológicos para prever a gravidade da hiperêmese gravídica e da cetonúria

Abstract Objective Hyperemesis gravidarum (HG) is a pregnancy complication that can progress with persistent nausea and vomiting. The aim of the present study is to evaluate the relationship between hematological parameters and HG. Method A total of 532 pregnant women with HG who were admitted to the Department of Obstetrics and Gynecology between March 2019 and February 2021, and 534 healthy pregnant women with characteristics similar to those of the case group were included in the study. The hematological parameters of both groups were compared. In addition, the hematological parametersof patients with HG according to the severity of ketonuria were compared. Results Themean age of the HG group (n=532) was 26.3 ± 4.1 years, and that of the control group (n=534) was 25.9 ± 4.8 years. Among patients with HG, 46% (n=249) had ketone(+), 33% (n=174), ketone(++), and 21% (n=109), ketone(+++). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were higher in the HG group than in the control group: 3.8 (2.8-5.8)/3.2 (2.6-4.0); p<0.001; and 135.2 ± 30.4/108.9 ± 62.2; p<0.001 respectively. The neutrophil count, NLR, and PLR were higher in the group with ketone(+++) than in the groups with ketone(+) or ketone(++): 7.6 ± 1.9/5.5 ± 2.4; p<0.001; 3.8(2.8-4.6)/2.9(2.3- 3.6); p<0.001; and 149.9 ± 48.0/135.9 ± 65.7; p<0.001 respectively. The mean corpuscular hemoglobin (MCH) level, the NLR, and the PLR were identified as independent predictors of the presence of HG and the level of ketone positivity in HG patients. Conclusion The NLR and PLR were high in patients with HG, suggesting the its inflammatory activity. They may be important markers associated with the presence and severity of HG.

Resumo Objetivo A hiperêmese gravídica (HG) é uma complicação da gravidez que pode evoluir com náuseas e vômitos persistentes. O objetivo deste estudo é avaliar a relação entre os parâmetros hematológicos e a HG. Método Foram incluídas neste estudo 532 gestantes com HG internadas no Departamento de Obstetrícia e Ginecologia entre março de 2019 e fevereiro de 2021, e 534 gestantes saudáveis com características semelhantes às do grupo de caso. Os parâmetros hematológicos foram comparados entre gestantes com e sem HG. Além disso, os parâmetros hematológicos foram comparados entre as pacientes com HG de acordo com a gravidade da cetonúria. Resultados A média de idade do grupo GH (n=532) foi de 26,3 ± 4,1 anos, e a do grupo de controle (n=534) foi de 25,9 ± 4,8 anos. Entre as pacientes com HG, 46% (n=249) tinham cetona(+), 33% (n=174), cetona(++), e 21% (n=109), cetona (+++). A razão de neutrófilos para linfócitos (RNL) e a razão de plaquetas para linfócitos (RPL) forammaiores no grupo HG do que no grupo de controle: 3,8 (2,8-5,8)/3,2 (2,6-4,0); p<0,001; e 135,2 ± 30,4/108,9 ± 62,2; p<0,001, respectivamente). A contagem de neutrófilos, a RNL e a RPL foram maiores no grupo com cetona(+++) do que nos grupos comcetona(+) e cetona(++): 7,6 ± 1,9/5,5 ± 2,4; p<0,001; 3,8 (2,8- 4,6)/2,9 (2,3-3,6); p<0,001; e 149,9 ± 48,0/135,9 ± 65,7; p<0,001, respectivamente. O nível médio de hemoglobina corpuscular (MHC), a RNL e a RPL foram identificados como preditores independentes da presença de HG e do nível de positividade de cetona em pacientes com HG. Conclusão A RNL e RPL estavam elevadas em pacientes com HG, o que sugere a sua atividade inflamatória. Elas podem ser marcadores importantes associados à presença e à gravidade da HG.

The first series of cases of ketosis-prone type 2 diabetes (flatbush diabetes) in Brazilian adults

SUMMARY Ketosis-prone type 2 diabetes (KPD) is an emerging form of diabetes mellitus characterized by unprovoked ketoacidosis, absence of autoimmunity and beta-cell dysfunction. The KPD may improve after initial glycemic compensation and evolve to exogenous insulin independence, most cases were observed in populations with African or Hispanic backgrounds. We reviewed the literature on KPD and, to date, only one case of KPD has been described in Brazil's multi-ethnic population. A group of adult Brazilian KPD patients without autoimmunity and insulinopenia was identified for this study. We report a retrospective study of four KPD cases (3 males) evaluated in southeast Brazil, the patients were overweight or obese, age between the third and fifth decades of life, had a family history of type 2 diabetes, hyperglycemia (809.5 ± 344.2 mg/dL), acidosis (pH 7.21 ± 0.07; normal range (nr): 7.35-7.45 and bicarbonate 9.1 ± 6.2; nr: 22-26 mEq/mL), ketonuria (142.5 ± 114.4 mg/dL; nr: absence), absence of glutamic acid decarboxylase antibodies (GAD-65), and beta-cell function reserve (C-peptide 1.19 ± 0.53 ng/mL - nr: 1.1-4.4 ng/mL) on diagnosis. After glycemic compensation, there was increase of C-peptide (2.21 ± 0.41) indicating the recovery of beta-cell function and the time to insulin independence was 7.7 ± 3.5 months. They evolved after the period of glucotoxicity with insulin withdrawal and could be treated with oral antidiabetic therapy. This is the first case series of KPD described in Brazil being characterized by ketoacidosis at diagnosis, absence of autoimmunity, recovery of beta-cell function and insulin independence.

Muerte súbita por cetoacidosis alcohólica en etilistas crónicos: reporte de 3 casos / Sudden death by alcoholic ketoacidosis in chronic alcoholics: report of 3 cases

Resumen En Patología Forense es común estudiar cadáveres de individuos con antecedente de alcoholismo crónico, que son encontrados fallecidos y cuyo deceso no fue presenciado; por lo que en gran cantidad de autopsias la determinación de la causa de muerte es compleja. La cetoacidosis alcohólica constituye un síndrome complejo derivado de una alteración del metabolismo en el contexto de un consumo excesivo de alcohol e ingesta calórica insuficiente. Se trata de un diagnóstico diferencial importante como causa de muerte en alcohólicos crónicos que fallecen posterior a un ayuno de algunos días, secundario a molestias abdominales como gastritis inducida por etanol, usualmente asociada a vómitos. Clínicamente estas personas presentan además dolor abdominal, taquicardia y alteraciones respiratorias. El diagnóstico postmortem se confirma mediante la presencia de cuerpos cetónicos, especialmente beta-hidroxibutirato, en sangre, humor vítreo u orina. A continuación se presentan tres casos de muerte súbita por cetoacidosis alcohólica con historia de abuso crónico de bebidas etílicas; se discute su fisiopatología, hallazgos al momento de la autopsia y resultados de exámenes complementarios (análisis toxicológico y estudio histopatológico).

Abstract In the forensic pathology setting, it is frequent to study corpses of individuals that were known to be chronic alcoholics and suffered a sudden death. Therefore, many autopsies are performed, in which determining the cause of death is a complex task. Alcoholic ketoacidosis refers to a complex syndrome derived from a metabolic disarrangement, related to excessive consumption of alcohol and an insufficient caloric intake. It is an important diagnosis that should be considered in sudden deaths of chronic alcoholics with a recent history of fasting, due to abdominal complains such as gastritis induced by alcohol and usually associated with recurrent vomiting. Clinically these patients present with abdominal pain, tachycardia and respiratory anomalies. The diagnosis can be confirmed when elevated ketone bodies, especially beta-hydroxybutyrate, are found in blood, vitreous humour or urine. In this paper we present three cases of sudden death by alcoholic ketoacidosis with a history of chronic abuse of alcohol, discussing it´s pathophysiology, autopsy findings and the results of additional studies (toxicologic screening and histopathology).

Subclinical ketosis risk prediction in dairy cows based on prepartum metabolic indices / [Previsão do risco de cetose subclínica em vacas de leite, baseado nos índices metabólicos pré-parto]

Ketosis can seriously impair cow performance. This study detected changes in prepartum blood metabolic parameters for predicting postpartum ketosis occurrence in dairy cows. Body condition score (BCS) was assessed before and after delivery. Blood samples of 63 cows were collected from 10 days before calving to 10 days after calving to measure metabolic parameters including ß-hydroxybutyric acid (BHBA), non-esterified fatty acid (NEFA), glucose (GLU), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total protein (TP), albumin (ALB), globulin (GLO), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). There was a postpartum subclinical ketosis incidence of 42.25%. Compared with prepartum, plasma, levels of BHBA, AST, and NEFA significantly increased postpartum, and prepartum AST (R=0.57) and NEFA (R=0.45) showed a significant positive correlation with ketosis postpartum. Plasma GLU level significantly decreased postpartum and was significantly negatively correlated with ketosis (R=-0.21). Receiver operating characteristic curve analysis revealed prepartum BSC < 2.88, and prepartum plasma AST > 68.0 U/L, GLU < 3.97mmol/L, NEFA > 0.27mmol/L, and BHBA > 0.43mmol/L, indicating a high risk of subclinical ketosis postpartum. These levels can be used as risk indicators to predict the occurrence of subclinical ketosis in postpartum cows.(AU)

A cetose pode trazer sérios prejuízos ao desempenho da vaca. Este estudo detectou alterações nos parâmetros metabólicos do sangue pré-parto para prever a cetose pós-parto que ocorre em vacas leiteiras. O escore de condição corporal (ECC) foi avaliado antes e após o parto. Foram coletadas amostras de sangue de 63 vacas entre 10 dias antes e 10 dias após o parto para medir os parâmetros metabólicos, incluindo ácido ß-hidroxibutírico (BHBA), ácido graxo não esterificado (NEFA), glicose (GLU), bilirrubina total (TBIL), bilirrubina direta (DBIL), bilirrubina indireta (IBIL), proteína total (TP), albumina (ALB), globulina (GLO), alanina aminotransferase (ALT) e aspartato aminotransferase (AST). Houve uma incidência de cetose subclínica pós-parto de 42,25%. Em comparação com o pré-parto, o plasma, os níveis de BHBA, AST e NEFA aumentaram significativamente no pós-parto, e AST no pré-parto (R = 0,57) e NEFA (R = 0,45) mostraram uma correlação significativa positiva com cetose pós-parto. O nível plasmático de GLU diminuiu significativamente no pós-parto e foi negativamente correlacionado com a cetose de forma significativa (R = -0,21). A análise da curva característica de operação do receptor revelou BSC pré-parto <2,88 e AST plasmático pré-parto> 68,0 U / L, GLU <3,97mmol / L, NEFA> 0,27mmol / L e BHBA> 0,43mmol / L, indicando um alto risco de cetose subclínica pós-parto. Esses níveis podem ser usados ​​como indicadores de risco para prever a ocorrência de cetose subclínica em vacas no pós-parto.(AU)

Concentraciones séricas de Beta-hidroxibutirato y su asociación con enfermedades posparto en bovinos de leche / Serum Beta-hydroxybutyrate concentrations and its association with postpartum diseases in dairy cows

RESUMEN Objetivo. Determinar la prevalencia de cetosis bovina según las concentraciones séricas (mmol/Lt) de beta-hidroxibutirato (βHB) y estimar su asociación con enfermedades del posparto temprano en vacas lecheras. Materiales y métodos. Se llevó a cabo un estudio epidemiológico de corte transversal con información individual de los niveles sanguíneos de βHB y presentación clínica de enfermedades puerperales de n=1149 animales; además se evaluó la eficiencia de la prueba como predictora de enfermedad posparto. Posteriormente, se realizó X 2 y un modelo de regresión logística final para explorar los factores asociados con hipercetonemia. La relación entre βHB sanguíneo, la presentación de cetosis y la ocurrencia de enfermedades puerperales se calculó analizando Característica Operativa del Receptor (Receiver Operating Characteristic -ROC). Resultados. Según los niveles de -3HB, la prevalencia de cetosis fue de 7.9%, cetosis clínica 0.6% y cetosis subclínica 7.3%. La prueba fue predictora de enfermedad puerperal (LR+ del 13.6). La condición corporal ≥3.5, número de partos igual a 2 y ≥3, la presentación de retención de placenta, fiebre de leche y la enfermedad posparto, son factores de riesgo de cetosis. El análisis de la curva ROC mostró que la medición de βHB (≥1.2 mmol/Lt) en sangre sirve para diagnosticar cetosis (p<0.0001). Conclusiones. La medición de niveles sanguíneos de βB permitió determinar que la presentación de cetosis es baja, es una alerta no solamente para esta enfermedad sino para las enfermedades del posparto temprano. Los resultados de este estudio confirman lo reportado en estudios previos sobre los factores de riesgo de cetosis.

ABSTRACT Objective. Determine the prevalence of bovine ketosis based on serum concentrations (mmol/Lt) of beta-hydroxybutyrate (βHB) and estimate its association with early postpartum diseases in dairy cows. Materials and methods. An epidemiological cross-sectional study was carried out with individual information on blood levels of βHB and clinical presentation of puerperal diseases in 1149 animals; In addition, the efficiency of the test was evaluated as a predictor of postpartum disease. Subsequently, univariate analysis and a final logistic regression model were performed to explore the factors associated with hyperketonemia. The association between blood βHB, the presentation of ketosis and the occurrence of puerperal diseases was calculated by analyzing the Receiver Operating Characteristic -ROC. Results. According to βHB levels, the prevalence of ketosis was 7.9%, clinical ketosis 0.6% and subclinical ketosis 7.3%. The test was a predictor of puerperal disease (LR+ of 13.6). Body condition score ≥3.5, number of births 2 and ≥3, presentation of retained fetal membranes, milk fever and postpartum disease, are risk factors for ketosis. The analysis of the ROC curve showed that the measurement of βHB (≥1.2 mmol/Lt) in blood serves to diagnose ketosis (p<0.0001). Conclusions. The measurement of βHB blood levels allowed to determine that ketosis presentation is low, it is an alert not only for this disease but for early postpartum diseases. The results of this study confirm risk factors observed in previous studies.

Cetoacidosis normoglicémica en paciente embarazada con neumonía por COVID-19. Reporte de un caso clínico / Euglycaemic ketoacidosis in a pregnant woman with COVID-19 pneumonia. A case report

RESUMEN Introducción: La cetoacidosis en el embarazo es una emergencia médica que requiere tratamiento en Unidad de Cuidados Intensivos debido a su asociación con morbimortalidad maternofetal. Las gestantes pueden presentar una forma atípica del cuadro llamada cetoacidosis normoglicémica, siendo muy infrecuente en pacientes sin antecedente de diabetes. Caso Clínico: Se presenta una gestante cursando tercer trimestre de embarazo, sin antecedente de diabetes, ingresada en Unidad de Paciente Crítico debido a neumonía por COVID-19 y acidosis metabólica con anión gap aumentado. Se realizó diagnóstico de cetoacidosis normoglicémica posterior al ingreso, iniciándose tratamiento intensivo de trastorno ácido-base con buena evolución. Conclusión: La infección por SARS-CoV-2 puede causar cetoacidosis normoglicémicas en embarazadas no diabéticas; se requiere una alta sospecha clínica para realizar el diagnóstico y tratamiento oportuno.

ABSTRACT Introduction: Ketoacidosis in pregnancy is a medical emergency that requires treatment in an intensive care unit due to its association with maternal-fetal morbimortality. Pregnant women may present an atypical form of the condition called normoglycemic ketoacidosis, being very rare in patients with no history of diabetes. Clinical Case: We present a pregnant woman in the third trimester of pregnancy, without history of diabetes, admitted to a critical patient unit due to COVID-19 pneumonia and metabolic acidosis with an increased anion gap. A diagnosis of normoglycemic ketoacidosis was made after admission, and intensive treatment of acid-base disorder was initiated, with good evolution. Conclusion: SARS-CoV-2 infection can cause normoglycemic ketoacidosis in non-diabetic pregnant women; is required a high clinical suspicion to make the diagnosis and appropriate treatment.

Alterações urinárias em cães com diabetes mellitus / Urinary alterations in dogs with diabetes mellitus / Alteraciones urinarias en perros con diabetes mellitus

A diabetes mellitus (DM) é uma doença comum na rotina veterinária, de caráter multifatorial, gerando graves consequências na saúde dos pacientes acometidos. O diagnóstico é possível por meio de manifestações clínicas apresentadas e da realização de exames laboratoriais complementares. Entre esses exames, estão a dosagem da glicose sérica e a urinálise, as quais trazem ao clínico diversas informações, que podem ser correlacionadas aos demais achados, tornando possível o diagnóstico conclusivo de DM. Dessa forma, o presente trabalho teve como objetivo avaliar as alterações urinárias e de glicemia em cães com DM. Para isto, foram analisados laudos de amostras urinárias e de glicose sérica de 15 animais, onde o diagnóstico foi conclusivo para DM. Verificou-se presença de glicosúria em 100% dos casos, sendo observado em 66,67% das amostras glicosúria maior que 1000 mg/dL e, em 33,33% amostras, de 500 mg/dL; a cetonúria esteve presente em 66,67 %; proteinúria em 66,67% e bacteriúria presente em 73,33 dos dados analisados. Já a hiperglicemia foi constatada em 13 pacientes (86,67%). Assim, conclui-se que a urinálise é um exame de suma importância para o estabelecimento do diagnóstico, da melhor terapêutica para cada caso e do prognóstico dos pacientes.(AU)

Diabetes mellitus (DM) is a common disease on the veterinary routine. It has a multifactorial character generating severe consequences on the health of the patient. It can be diagnosed by clinical manifestations and by making additional laboratory tests. These tests include the measurement of serum glucose and urinalysis, which provides the physician with additional information to be correlated with other findings, in order to reach a conclusive diagnosis of DM. Therefore, this study aimed at evaluating urinary and glycemic alterations in dogs with DM. It analyzed reports of urine and serum glucose samples from 15 animals with a conclusive diagnosis for DM. Glycosuria was present in 100% of the cases. In addition, it was also observed that in 66.67% of the samples, glycosuria was higher than 1000 mg/dL, and in 33.33%, it was 500 mg/dL. Ketonuria was present in 66.67% of the samples, while proteinuria was observed in 66.67%. Bacteriuria was present in 73.33% of the samples on the analyzed data. Hyperglycemia was observed in 13 of these patients (86.67%), and thus, it can be concluded that urinalysis is an extremely important test for diagnosis, to choose the best therapy for each case and prognosis of the patients.(AU)

Diabetes mellitus (DM) es una enfermedad común en la rutina veterinaria, con un carácter multifactorial, que genera graves consecuencias en la salud de los pacientes afectados. El diagnóstico es posible a través de las manifestaciones clínicas presentadas y mediante realización de pruebas de laboratorio complementarias. Entre esas pruebas, están la medición de la glucosa en suero y el análisis de orina, que brindan al médico informaciones diversas que pueden ser correlacionadas a otros hallazgos, lo que permite hacer un diagnóstico concluyente de DM. Por lo tanto, el presente estudio tuvo como objetivo evaluar las alteraciones urinarias y glucémicas en perros con DM. Para esto, se analizaron informes de muestras de glucosa en suero y orina de 15 animales, donde el diagnóstico fue concluyente para DM. La glucosuria estuvo presente en el 100% de los casos, observándose en el 66,67% de las muestras glucosuria mayor de 1000 mg / dL y, en el 33,33% de las muestras, de 500 mg / dL; la cetonuria estuvo presente en 66.67%; proteinuria en 66.67% y bacteriuria presente en 73.33 de los datos analizados. Se observó hiperglucemia en 13 de esos pacientes (86,67%). Por lo tanto, se concluye que el análisis de orina es una prueba extremadamente importante para establecer el diagnóstico, el mejor tratamiento para cada caso y el pronóstico de los pacientes.(AU)

Cetoacidosis por estrés: caso clínico en paciente con atrofia muscular espinal / Stress induced ketoacidosis in spinal muscular atrophy: report of one case

Spinal muscular atrophy is an uncommon cause of ketoacidosis, where there is a decrease in muscle mass, an abnormal metabolism of glucose and fatty acids, and changes in neuroendocrine function. These conditions favor the accumulation of keto acids and the development of metabolic acidosis. We report a 26-year-old female, with a history of spinal muscular atrophy type III, consulting for abdominal pain and vomiting lasting one week. She was admitted to the emergency service somnolent and poorly perfused. She had a pH of 6.98, HCO3- of 3.8 mmol/L, pCO2 of 16.4 mmHg, BE of -26 mmol/L, delta ratio of 1.05, anion gap of 31 mEq/L, creatinine of 0.37 mg/dL, sodium of 147 mEq/L, potassium of 3.7 mEq/L, chloride of 112 mEq/L, lactate of 1.2 mmol/L, glucose of 108 mg/dL, albumin of 4.2 g/dL, ketonemia +++, ketonuria +, measured plasma osmolality of 322 mOsm/kg, estimated osmolality of 314 mOsm/kg, toxilab negative, salicylate levels < 3 µg/mL, acetaminophen levels < 1.2 µg/mL. Intravenous hydration and bicarbonate were started, without satisfactory response. Interpreting the clinical picture as a ketoacidosis induced by stress in a patient with spinal muscular atrophy, it was handled with glucose, amino acids, vitamins and trace elements, with a favorable response.

Clinical Implications of Ketosis in Children with Benign Convulsions with Mild Gastroenteritis

Evaluation of different sites for blood collection for ß-hydroxybutyrate assessment in dairy cows using hand-held meter / Avaliação de diferentes locais de coleta de sangue para avaliação de ß-hidroxibutirato em vacas de leite usando aparelho portátil automático

Cetose subclínica é uma grande preocupação em rebanhos leiteiros, e seu diagnóstico e prevenção podem ter um grande impacto na saúde animal. Este estudo comparou quatro locais diferentes para a coleta de amostras de sangue (jugular, veias mamárias e coccígeas e ponta da cauda) para medição de ß-hidroxibutirato (BHBA), usando-se um medidor portátil automático. Foram utilizadas seis vacas Holandesas, e a coleta de sangue foi feita no segundo, quinto, 10º, 15º e 21º dias pós-parto. Os resultados do medidor portátil foram semelhantes aos resultados do laboratório e apresentaram uma correlação forte de 0,83. As concentrações séricas de BHBA nas amostras de sangue coletadas na ponta da cauda, na jugular e na coccígea foram semelhantes. No entanto, o sangue retirado da veia mamária tinha uma concentração mais baixa. Portanto, as amostras de sangue para aferição de BHBA podem ser recolhidas nas veias jugular e coccígeas e na ponta da cauda, sendo as duas últimas as opções mais fáceis para monitorar o BHBA em rebanho leiteiro.(AU)

Comparação de métodos para avaliação de beta-hidroxibutirato em ovelhas / Comparison of methods for evaluation of beta-hydroxybutyrate in ewes

Atualmente o uso de sensores portáteis para mensuração de corpos cetônicos está padronizado e difundido na rotina clínica, contudo estudos em ovinos são escassos. Assim, a presente pesquisa objetivou avaliar a acurácia dos sensores portáteis de uso humano e de uso veterinário para a determinação de beta-hidroxibutirato (BHB) em ovelhas no final da gestação e no pós-parto recente. Foram utilizadas 37 amostras de sangue provenientes de nove ovelhas mestiças Corriedale. A determinação bioquímica de BHB no soro, considerada como o padrão-ouro, foi realizada utilizando-se metodologia enzimática colorimétrica. A média obtida na bioquímica sérica foi de 0,497mmol/L; no sensor de uso humano, a média foi igual a 0,537mmol/L, enquanto no sensor de uso veterinário foi de 0,751mmol/L. Foi verificada alta correlação entre o dosímetro de uso humano e o padrão-ouro (r=0,93, P<0,001). A média do aparelho de uso veterinário diferiu das demais (51%; P<0,05), superestimando os resultados em ovelhas. As medições obtidas no aparelho veterinário também apresentaram menor precisão e veracidade. Concluiu-se que o sensor portátil de uso humano é mais acurado e mais preciso no diagnóstico precoce de toxemia da gestação em ovelhas.

Currently the use of portable sensors for measuring ketone bodies is standardized and diffused in the clinical routine, however, studies in sheep are scarce. Therefore, the present study aimed to evaluate the accuracy of the human portable sensor and the veterinary portable sensor for the determination of beta-hydroxybutyrate (BHB) in sheep at the end of gestation and postpartum. We used 37 samples of blood from nine crossbred Corriedale sheep. Biochemical determination of serum BHB, considered gold standard, was performed using colorimetric enzymatic methodology. The mean serum biochemistry was 0.497mmol/L, in the human sensor the mean was 0.537mmol/L, while in the veterinary sensor it was 0.751mmol/L. A high correlation was verified between the dosimeter for human use and the gold standard (r= 0.93, P< 0.001). The mean of the veterinary apparatus differed from the others, being 51% (P< 0,05), higher than the standard, that is, it was less accurate and had lower veracity, overestimating the results in sheep. It was concluded that the portable sensor for human use is more accurate and accurate in the early diagnosis of toxemia of pregnancy in sheep.

Experimental protocol for metabolic acidosis induction by intravenous administration of hydrochloric acid in sheep / Protocolo de indução experimental de acidose metabólica por administração intravenosa de ácido clorídrico em ovinos

The aim of this study was to assess the magnitude and duration of blood and urine changes and the side effects of hyperchloremic acidosis induced by the intravenous administration of hydrochloric acid in sheep. Five healthy, crossbred adult ewes, with a mean body weight of 44±2.9kg were used. The hydrochloric acid solution was administered intravenously at a rate of 25mL/kg/h for 4 hours continuously. Venous blood and urine samples were collected and pH values, blood carbon dioxide partial pressure, bicarbonate, base excess, strong ion difference, anion gap, total concentration of nonvolatile buffers, creatinine, plasma L-lactate, plasma and urine sodium, potassium, and chloride were determined. The experimental protocol induced severe hyperchloremic acidosis at the end of the infusion, with a decreased plasma strong ion difference. The fractional excretion of sodium and chloride remained increased during 4 hours after the infusion. Aciduria was observed at approximately 24 hours. Twenty-four hours after the infusion, the animals showed mild and compensated metabolic acidosis. This protocol was effective in inducing severe and long-lasting hyperchloremic acidosis and did not cause serious side effects. Therefore, this protocol can be used safely in adult sheep for studies on the treatment of this condition.(AU)

O objetivo deste estudo foi avaliar a magnitude e a duração das alterações sanguíneas e urinárias, bem como os efeitos colaterais da acidose hiperclorêmica induzida por administração intravenosa de ácido clorídrico, em ovinos. Foram utilizadas cinco ovelhas mestiças, adultas, sadias, com peso médio de 44±2,9kg. A solução de ácido clorídrico foi administrada por via intravenosa, na velocidade de 25mL/kg/h, totalizando quatro horas de administração contínua. Amostras de sangue venoso e de urina foram colhidas, e determinaram-se os valores de pH, pressão parcial de dióxido de carbono, bicarbonato, excesso de bases, diferença dos íons fortes, ânion-gap, creatinina, lactato L, sódio, potássio e cloro. O protocolo de indução experimental foi capaz de induzir acidose hiperclorêmica grave ao término da infusão, com diminuição da diferença dos íons fortes plasmáticos. Houve aumento da excreção fracionada de sódio e cloro por até quatro horas após o término da infusão. A acidúria foi observada por cerca de 24 horas. Após 24 horas do início da infusão, os animais apresentaram acidose metabólica leve e compensada. Esse protocolo foi eficaz na indução da acidose hiperclorêmica grave e duradoura e não causou efeitos colaterais. Conclui-se que o protocolo pode ser usado com segurança em ovelhas adultas, para estudos sobre tratamento dessa condição.(AU)

Characterization of ruminal acidosis and initial phase of laminitis inducted by oligofructose in crossbred calves / Caracterização da acidose ruminal e da fase inicial da laminite induzidas por oligofrutose em bezerros mestiços

One of the ways to study cattle laminitis is its experimental induction by supplying a large amount of high fermentation carbohydrate. The most effective protocol until now has been the use of oligofructose. The objective of this study was to evaluate clinical and histological aspects of the hoof in experimental induction of ruminal acidosis and laminitis in calves using oligofructose. Six crossbred (Bos taurus x Bos indicus) yearling calves divided into Group I (GI) and Group II (GII) were used. Animals in GI and GII received intraruminal oligofructose in doses of 13 and 17g/kg, respectively. During 28 hours the calves were clinically evaluated and 30 hours after induction, samples were taken from coronary and abaxial wall of the hoof for histologic evaluation. Were noticed signs of ruminal and metabolic acidosis like rumen distension with fluid, diarrhea, ruminal pH reduction and, at blood gas analysis, pH and bicarbonate below reference range. Lameness was not observed however, some animals had a slower gait and apathy, possibly due to metabolic acidosis, though. Histologically, typical lesions of laminitis like circulatory changes and inflammatory infiltrate in the dermis, irregularities and areas of detachment at basement membrane and morphologic changes in cells from basal epidermis were found. The protocol induced, in the first 30 hours, clinical signs of ruminal and metabolic acidosis and low grade histologic lesions in the digits. Lameness and digit pain were not observed, characterizing the prodromic phase of the disease.(AU)

Uma das formas de se estudar a laminite bovina é sua indução experimental por meio do fornecimento de grande quantidade de carboidrato de alta fermentação. O protocolo mais eficaz até o momento foi o uso de oligofrutose. Objetivou-se avaliar aspectos clínicos e histológicos dos dígitos de bovinos na indução experimental de acidose ruminal e laminite usando oligofrutose. Utilizaram-se seis bezerros mestiços (Bos taurus x Bos indicus) de um ano, divididos em Grupo I (GI) e Grupo II (GII). Os animais em GI e GII receberam oligofrutose por via intrarruminal nas doses de 13 e 17g/kg respectivamente. Os bovinos foram avaliados clinicamente por 28 horas e fragmentos de coroa e muralha abaxial dos dígitos foram colhidos para histologia 30 horas após a indução. Foram identificados sinais de acidose ruminal e metabólica como distensão ruminal com líquido, diarreia e baixo pH ruminal. Os resultados de hemogasometria indicaram baixos pH e nível plasmático de bicarbonato. Os animais não apresentaram claudicação, entretanto, observaram-se apatia e marcha mais lenta, atribuídas à acidose metabólica. Histologicamente foram observadas lesões indicativas de laminite como alterações circulatórias e infiltrado inflamatório na derme, irregularidades e áreas de destacamento da membrana basal e alterações morfológicas de células da epiderme basal. O protocolo induziu, nas primeiras 30 horas, sinais de acidose ruminal e metabólica e lesões histológicas de baixa intensidade nos dígitos. Não foi observada claudicação ou sensibilidade nos dígitos, caracterizando a fase prodrômica da enfermidade.(AU)

A Rare Cause of Life-Threatening Ketoacidosis: Novel Compound Heterozygous OXCT1 Mutations Causing Succinyl-CoA:3-Ketoacid CoA Transferase Deficiency

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare inborn error of ketone body utilization, characterized by episodic or permanent ketosis. SCOT deficiency is caused by mutations in the OXCT1 gene, which is mapped to 5p13 and consists of 17 exons. A 12-month-old girl presented with severe ketoacidosis and was treated with continuous renal replacement therapy. She had two previously unrecognized mild-form episodes of ketoacidosis followed by febrile illness. While high levels of ketone bodies were found in her blood and urine, other laboratory investigations, including serum glucose, were unremarkable. We identified novel compound heterozygous mutations in OXCT1:c.1118T>G (p.Ile373Ser) and a large deletion ranging from exon 8 to 16 through targeted exome sequencing and microarray analysis. This is the first Korean case of SCOT deficiency caused by novel mutations in OXCT1, resulting in life-threatening ketoacidosis. In patients with unexplained episodic ketosis, or high anion gap metabolic acidosis in infancy, an inherited disorder in ketone body metabolism should be suspected.

Two cases of ketosis-prone diabetes mellitus in Korean adolescents

In recent years, reports of diabetes mellitus (DM) cases that do not fit the traditional classification system have increased in prevalence. While insulin deficiency appears as type 1 DM (T1DM), the new type also has the clinical features of type 2 DM (T2DM); as such, this new type of DM is called ketosis-prone diabetes (KPD) and is correlated with findings of severe hyperglycemia and ketoacidosis. To provide a clear, clinical classification of DM, new classification systems are being studied. Among these, the Aβ system demonstrates the highest sensitivity and specificity in predicting clinical features and prognosis. We report 2 cases of KPD in Korean pediatric patients. The first patient was referred while in a state of diabetic ketoacidosis (DKA) and was considered to have T1DM. However, their blood glucose was well-controlled even with small doses of insulin, and the treatment was able to be changed to metformin therapy. The second patient seemed to be a typical case of T2DM because of his obesity and strong family history. However, blood glucose was not well-controlled with a regular diet, and ketosis occurred. After performing a glucagon stimulation test, both patients showed different clinical features that were finally diagnosed as type A-β+ KPD. The rapid and accurate diagnosis of KPD can reduce the duration of inappropriate insulin use and improve patients' quality of life. Further, the treatment of KPD children should be individualized according to each patient's lifestyle to preventing recurrent DKA.

Cuidados pós-ressuscitação-cardiopulmonar (RCP) / Post-cardiopulmonary resuscitation (CPR) care

Evitar novos episódios de parada cardiorrespiratória (PCR). Identificar e tratar as causas que levaram o paciente à PCR. Oferecer suportes ventilatório, hemodinâmico, neurológico e metabólico. Realizar a modulação terapêutica de temperatura para todos os pacientes que retornaram à circulação espontânea. Indicação de cateterismo cardíaco para pacientes sem causa estabelecida de PCR quando a causa pode ser um evento coronariano

Avoid further episodes of cardiopulmonary arrest (CPA). Identify and treat the causes of the patient's CPA. Provide ventilatory, hemodynamic, neurological and metabolic support. Perform therapeutic temperature modulation for all patients who have resumed spontaneous circulation. Indication of cardiac catheterization for patients with no established cause of CPA when the cause may be a coronary event

Effective Management of Diabetic Ketoacidosis / 임상당뇨병

Diabetic ketoacidosis (DKA) is serious complication of diabetes mellitus that requires prompt recognition, diagnosis and treatment. It is characterized by a triad of uncontrolled hyperglycemia, metabolic acidosis, and increased total body ketone concentration. The overall DKA mortality rate recorded among children and adults is < 1%. For patients with DKA, appropriate administration of intravenous fluids and insulin with attention to associated fluid and electrolyte disorders can effectively and rapidly resolve metabolic dysregulation. Following acute management and restoration of physiological glucose levels, DKA requires identification of the precipitating cause to prevent recurrence of potentially life-threatening diabetic complications.

Diabetic Ketoacidosis Following Colonoscopy in Fulminant Type 1 Diabetes: A Case Report / 대한내과학회지

Fulminant type 1 diabetes is a distinct subtype of type 1 diabetes mellitus that is characterized by sudden, complete destruction of pancreatic beta cells at the disease onset. Since the disease was first described in 2000 in Japan, a number of case reports have also been published in Korea. However, this disease entity is still not well defined. A 48-year old man with no medical history was admitted with diabetic ketoacidosis. Fulminant type 1 diabetes was diagnosed and he was discharged with multiple insulin injections. His serum glucose level was well controlled in the outpatient clinic. A month later, diabetic ketoacidosis occurred again following a diagnostic colonoscopy. This case suggests that fulminant type 1 diabetes is an aggressive disease in which small stimuli can provoke ketoacidosis. Therefore, for tests that require fasting, close observation by medical staff and patient education about the disease is essential.