Factores de riesgo de fibrosis avanzada en enfermedad hepática esteatósica asociada a disfunción metabólica en pacientes con diabetes mellitus 2

Determinar factores de riesgo sociodemográficos, antropométricos, bioquímico-metabólicos, clínicos y comorbilidades asociadas a fibrosis avanzada por enfermedad hepática esteatósica asociada a disfunción metabólica en pacientes con diabetes mellitus tipo 2. Estudio de casos y controles. Se revisaron 174 historias clínicas de pacientes con enfermedad hepática esteatósica asociada a disfunción metabólica y diabetes mellitus tipo 2 atendidos en el Hospital Nacional Dos de Mayo de 2009 a 2018. Los casos fueron pacientes con fibrosis avanzada y los controles sin fibrosis. La presencia de fibrosis avanzada fue definida por paneles clínicos predictores y/o resultado de biopsia hepática. Para determinar asociación se calculó odds ratio, chi cuadrado de Pearson y análisis de regresión logística. Se encontró asociación con edad > 60 años, un índice de masa corporal ≥ 25 kg/m2 , perímetro abdominal en varones ≥ 94 cm y perímetro abdominal ≥ 88 cm en mujeres, tiempo de enfermedad de diabetes > 10 años; complicaciones crónicas microvasculares; HDL en mujeres 60 años, índice de masa corporal elevado, perímetro abdominal en mujeres, HDL bajo en mujeres, complicaciones crónicas microvasculares e hipertensión. Se encontraron como factores de riesgo de fibrosis avanzada, edad mayor a 60 años, índice de masa corporal elevado, perímetro abdominal ≥ 88 cm en mujeres, complicaciones crónicas microvasculares, nivel bajo de HDL en mujeres e hipertensión arterial como principal comorbilidad.

To determine sociodemographic, anthropometric, biochemical-metabolic, clinical risk factors and comorbidities associated with advanced fibrosis due metabolic dysfunction associated steatotic liver disease in patients with diabetes mellitus type 2. Case-control study. We reviewed 174 medical records of patients with metabolic dysfunction associated steatotic liver disease and type 2 diabetes mellitus treated at the Hospital Nacional Dos de Mayo from 2009 to 2018. The cases were patients with advanced fibrosis and controls without fibrosis. The presence of advanced fibrosis was defined by predictive clinical panels and/or liver biopsy result. To determine association, odds ratio, Pearson's chi-square and logistic regression analysis were calculated. An association was found with age > 60 years, a body mass index ≥ 25 kg/m2 , abdominal circumference in men ≥ 94 cm and abdominal circumference ≥ 88 cm in women, time of diabetes disease >10 years; chronic microvascular complications; HDL in women 60 years, high body mass index, abdominal circumference in women, low HDL in women, chronic microvascular complications and hypertension remained independent risk factors. The risk factors for advanced fibrosis were age over 60 years, high body mass index, abdominal circumference ≥ 88 cm in women, chronic microvascular complications, low HDL level in women and hypertension as the main comorbidity.

Enfermedad por esteatohepatitis no alcohólica en pacientes diabéticos tipo 2: artículo de revisión

La enfermedad por esteatohepatitis no alcohólica (EHGNA) se genera por el depósito de macrovesículas de triglicéridos en el hígado, y se excluye de otras etiologías como alcohólica, medicamentosa o secundaria a trastornos genéticos. El espectro de este trastorno considera la esteatohepatitis no alcohólica y esteatosis hepática simple. En 2020, un panel internacional de expertos propuso una nueva denominación para esta entidad, y se consideró que el término "enfermedad del hígado graso asociado a disfunción metabólica" (MAFLD, por sus siglas en inglés) sería el más apropiado para referirse a un conjunto completo, pero sencillo, de criterios para el diagnóstico de MAFLD, los cuales son independientes de la cantidad de alcohol consumido y pueden aplicarse a los pacientes en cualquier entorno clínico. La EHGNA es una manifestación del síndrome metabólico, y uno de los grupos de riesgo de prevalencia y progresión rápida son los pacientes con diabetes tipo 2 (DM2). El modelo vigente considera que este proceso ocurre como consecuencia de "múltiples hits" que podrían anteceder a la esteatosis hepática como una explicación más apropiada para considerar la evolución de la EHGNA en un contexto de estado de inflamación. La DM2 agudiza el EHGNA, lo que conduce a la hiperglicemia, por ende, a la creación de un círculo vicioso. Es importante valorar, para el caso de los pacientes diabéticos, el riesgo de fibrosis debido a su impacto en un mayor riesgo cardiovascular y progresión de la enfermedad hepática, para lo cual podrían emplearse pruebas no invasivas, tales como los biomarcadores de fibrosis, elastografía o una biopsia hepática. A medida que se disponga de alternativas de tratamiento más efectivas, será aún más relevante determinar el grado de fibrosis. Actualmente, el manejo de esta entidad incluye cambios en el estilo de vida como una de las medidas terapéuticas más efectivas. Dentro del tratamiento farmacológico, se considera que la intervención más eficaz para esta enfermedad en pacientes diabéticos es el uso de tiazolidinedionas. El tratamiento con agonistas de péptido similar al glucagón tipo 1 (GLP-1), como liraglutida, o con inhibidores del cotransportador 2 de sodio-glucosa también han mostrado resultados prometedores en estudios preliminares.

Nonalcoholic fatty liver disease (NAFLD) is caused by a build-up of triglyceride macrovesicles in the liver not related to other etiologies such as alcoholism, medications or genetic disorders. The spectrum of this condition includes nonalcoholic steatohepatitis (NASH) and simple fatty liver. In 2020, an international panel of experts proposed a new name for this entity and considered that the term "metabolic associated fatty liver disease" (MAFLD) would be the most appropriate to refer to a comprehensive but simple set of criteria for the diagnosis of MAFLD, which is not related to the amount of alcohol consumption and can occur in patients in any clinical setting. NAFLD is a manifestation of metabolic syndrome and shows high prevalence and risk of rapid progression in patients with type 2 diabetes (T2DM). The current model considers that this process occurs as a consequence of "multiple hits" that could precede the fatty liver disease, this being the most appropriate explanation for the evolution of NAFLD in an inflammatory state. T2DM worsens NAFLD, leading to hyperglycemia and thus building a vicious circle. As for patients with diabetes, the risk of fibrosis must be assessed due to its impact on increased cardiovascular risk and progression of liver disease. This task may be accomplished through non-invasive tests such as hepatic fibrosis biomarkers, elastography or liver biopsy. As more effective treatment alternatives become available, determining the degree of fibrosis will be even more important. To date, lifestyle changes are one of the most effective treatments for managing NAFLD. Regarding pharmacotherapy, thiazolidinediones are the most effective intervention for this disease in diabetic patients. Treatment with glucagonlike peptide 1 (GLP-1) agonists, such as liraglutide, or with sodium-glucose cotransporter-2 inhibitors have also shown promising results in preliminary studies.

Evaluación de la efectividad de la vitamina E en la esteatosis hepática no alcohólica en pacientes diabéticos tipo 2 sin fibrosis avanzada

Objetivo: Determinar la efectividad de la vitamina E en la esteatosis hepática no alcohólica (EHGNA) en pacientes diabéticos tipo 2 sin fibrosis avanzada. Materiales y métodos: Estudio analítico de tipo cuasi experimental. Se formaron dos grupos, un grupo experimental que recibió vitamina E de 400 UI además del manejo convencional, y otro grupo de control con manejo convencional. El estudio incluyó a 71 pacientes en cada grupo. Ambos grupos fueron sometidos al cálculo de un puntaje de fibrosis hepática, ecografía hepática y a la medición de la transaminasa glutámico-pirúvica al inicio del estudio y tras 6 meses. Asimismo, para comparar concentraciones de los valores de puntaje de fibrosis y de la transaminasa glutámico-pirúvica dentro de un mismo grupo se empleó la prueba Wilcoxon, y para evaluar diferencias entre el grupo experimental y control se realizó la prueba de U de Mann-Whitney. Para comparar la severidad ecográfica se empleó la prueba de Wilcoxon. Luego se realizó la regresión logística. Se procedió a registrar la información en una ficha de recolección de datos haciendo uso del programa Microsoft Excel, posteriormente, se procedió a codificar y generar una base de datos con el paquete estadístico SPSS v. 23. Resultados: Dentro de los resultados se halló que la vitamina E fue efectiva en reducir el puntaje fibrosis hepática, transaminasas y severidad ecográfica en forma significativa (Z = -4,727 y p < 0,05). De acuerdo al análisis de regresión lineal el nivel de TGP y de score de fibrosis no son explicados significativamente por las variables confusoras incluidas en el modelo al 95 % de confianza. Conclusiones: La vitamina E a una dosis de 400 UI vía oral durante 6 meses es una intervención efectiva para controlar la progresión de la hepatopatía que puede cuantificarse mediante puntaje de fibrosis, disminución de transaminasas y valoración ecográfica tras 6 meses de seguimiento.

Objective: To determine the effectiveness of vitamin E in nonalcoholic fatty liver disease (NAFLD) among type 2 diabetes patients without advanced fibrosis. Materials and methods: A quasi-experimental analytical study consisting of two groups: an experimental one, which received vitamin E 400 IU in addition to the standard treatment, and a control group, which received only the standard treatment. The study included 71 patients in each group. Both groups underwent liver fibrosis scoring, liver ultrasound and glutamate pyruvate transaminase measurement at study baseline and after six months. Moreover, the Wilcoxon test was used to compare the concentrations of fibrosis score and glutamate pyruvate transaminase values within the same group, and the Mann-Whitney U test was used to evaluate the differences between the experimental and control groups. The Wilcoxon test was also used to compare ultrasound severity. Then, a logistic regression analysis was performed. The information was entered into a data collection sheet using Microsoft Excel; afterwards, a database was coded and created using IBM SPSS Statistics statistical software 23.0. Results: Among the results, it was found that vitamin E was significantly effective in reducing liver fibrosis, transaminase and ultrasound severity scores (Z = -4.727 and p < 0.05). According to the logistic regression analysis, glutamate pyruvate transaminase levels and fibrosis score are not substantially explained by the confounding variables included in the model at 95 % confidence. Conclusions: Vitamin E at a dose of 400 IU given orally for six months is an effective intervention to control the progression of liver disease, which can be quantified by fibrosis score, transaminase reduction and ultrasound assessment after a 6-month follow-up.

[Risk factors for advanced fibrosis in metabolic dysfunction-associated steatotic liver disease in patients with diabetes mellitus type 2]. / Factores de riesgo de fibrosis avanzada en enfermedad hepática esteatósica asociada a disfunción metabólica en pacientes con diabetes mellitus 2.

OBJECTIVES: To determine sociodemographic, anthropometric, biochemical-metabolic, clinical risk factors and comorbidities associated with advanced fibrosis due metabolic dysfunction associated steatotic liver disease in patients with diabetes mellitus type 2. MATERIAL AND METHODS: Case-control study. We reviewed 174 medical records of patients with metabolic dysfunction associated steatotic liver disease and type 2 diabetes mellitus treated at the Hospital Nacional Dos de Mayo from 2009 to 2018. The cases were patients with advanced fibrosis and controls without fibrosis. The presence of advanced fibrosis was defined by predictive clinical panels and/or liver biopsy result. To determine association, odds ratio, Pearson's chi-square and logistic regression analysis were calculated. RESULTS: An association was found with age > 60 years, a body mass index >= 25 kg/m2, abdominal circumference in men >= 94 cm and abdominal circumference >= 88 cm in women, time of diabetes disease >10 years; chronic microvascular complications; HDL in women < 50 mg/dL, HDL in men < 40 mg/dL and albumin < 3.5 g/dL. About comorbidities were associations with chronic kidney disease and hypertension. After logistic regression analysis, age > 60 years, high body mass index, abdominal circumference in women, low HDL in women, chronic microvascular complications and hypertension remained independent risk factors. CONCLUSIONS: The risk factors for advanced fibrosis were age over 60 years, high body mass index, abdominal circumference ≥ 88 cm in women, chronic microvascular complications, low HDL level in women and hypertension as the main comorbidity.

Caso de hipoglicemia severa posterior a desviación gástrica en una mujer con enfermedad por esteatosis hepática no alcohólica (EHGNA)

La hipoglucemia posterior la desviación gástrica se caracteriza por hipoglucemia posprandial con hipertrofia de las células de los islotes pancreáticos en pacientes tras someterse a una cirugía bariátrica, en quienes la EHGNA, la obesidad y la secreción alterada de la insulina y del glucagón pueden predisponerlos a presentar hipoglucemia. Se presenta el caso de una paciente de 44 años con obesidad y EHGNA sometida a una desviación gástrica en Y de Roux, quien años después presentó hipoglucemia severa. Fue diagnosticada de hipoglicemia por hiperinsulinismo endógeno con histología de hiperplasia de células beta. La hipoglicemia posterior a una desviación gástrica es un escenario que se afrontará más a menudo, por tal razón, es importante tenerla en cuenta para un tratamiento oportuno.

Post-gastric bypass hypoglycemia is characterized by postprandial hypoglycemia with pancreatic islet-cell hypertrophy in patients who have undergone a bariatric surgery and may be prone to hypoglycemia due to NAFLD, obesity, and impaired insulin and glucagon secretion. We present the case of a 44-year-old obese woman with NAFLD who underwent a Roux-en-Y gastric bypass and years later presented with severe hypoglycemia. She was diagnosed with endogenous hyperinsulinemic hypoglycemia and beta-cell hyperplasia. Post-gastric bypass hypoglycemia is a scenario that will be faced more often; therefore, it is important to take it into account for a timely treatment.

SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay.

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay.

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations.

Objectives The quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed. Methods The laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories. Results Our field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA. Conclusions In conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.

Amygdala Abnormalities in Adults With ADHD.

OBJECTIVE: The suggested neurobiological bases of ADHD focus on the amygdala as a center of emotions processing. Therefore, we hypothesize that patients with ADHD will show an irregular pattern of emotional-related activity of the amygdala region as well as some structural abnormalities. METHOD: Nine adult patients with ADHD and nine group-matched healthy volunteers were studied using a 1.5-T magnetic resonance imaging (MRI) scanner. Morphometric measurements were obtained manually, and they were later processed and compared. Absolute volumes of several structures and nuclei were calculated with FSL-FIRST. For the functional magnetic resonance examination, a set of two paradigms was prepared, using a block design, incorporating images of the International Affective Picture System (IAPS). The patients were unmedicated at the time of the MRI scan. RESULTS: Negative correlation was found between the right amygdala volume and Barrat's impulsivity scores ( r = -.756, p = .018). The age of patients did not turn out to be a significant factor. No significantly higher activation areas were found in patients with unpleasant content images. For the left amygdala, an Region Of Interest (ROI)-based analysis showed moderately higher level of activation in the patients than in the controls with pleasant content images. CONCLUSION: Patients with ADHD tend to have smaller amygdala volumes. ADHD patients presented less activation in the area of the left frontal pole than the controls. There was no amygdala activation stated when presenting the pleasant images. Whereas bigger activation of the left amygdala was found in patients while presenting them unpleasant images. These results might suggest that lower emotional processing and less control of impulsivity is associated with dysfunctional amygdala in ADHD patients.

[Scales for internet addiction in spanish population: A proposal]. / Propuesta de escalas en población española para adicción a internet.

New technologies and internet use have generated such an intimated bound between users and their devices that an increasing preoccupation about problematic use and addiction has raised. Prevalence studies warn about values higher than 5% in the most restrictive studies. There are many differences in the study of this phenomenon attending to the methodology, conceptualization, object of study, device, or even on-line or off-line use. This lack of consensus has generated a number of scales. An article as the present one proposing a minimum set of scales seems necessary. This article refers to some scales which seem adequate for Spanish population due to their easy application, their validity and their extension of use. We present the validated translations for the YIAT20 and the MPPUSA. We have also done a translation where it was not available a Spanish version for the CIAS and Ko's criteria.

Parámetros metabólicos en pacientes con esteatosis hepática no alcohólica y diabetes tipo 2 controlados versus no controlados / Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2

La esteatosis hepática no alcohólica (EHNA) está ampliamente distribuida a nivel mundial y es más frecuente en sujetos con dislipidemia, síndrome metabólico, obesos y con DM2 (34-74%). Sin embargo, la prevalencia de cirrosis por EHNA en la población general no se conoce, lo que es aún materia de investigación en nuestro medio. Objetivo: Determinar si existe diferencia significativa entre los parámetros metábólicos de esteatosis hepática no alcohólica en pacientes con diabetes tipo 2 de reciente diagnóstico controlados y no controlados. Material y métodos: Estudio retrospectivo de tipo caso control, realizado en el Hospital Guillermo Almenara Irigoyen, Lima - Perú, durante los meses de noviembre de 2014 a febrero de 2015. Constó de231 pacientes: 147 pacientes con DM2 de diagnóstico reciente con mal control glicémico y EHNA y 84 pacientes con DM2 de diagnóstico reciente con adecuado control y EHNA. Para el análisis estadístico se utilizó las pruebas de Levene para evaluar homogenidad de varianzas intragrupos y prueba paramétrica de t de student para muestras independientes. Resultados: Luego de aplicar la prueba de homogeneidad de Levene y el t de student para igualdad de medias los parámetros metabólicos significativos fueron el nivel de triglicéridos, el nivel de HbA1C, la dosis de metformina y el género. Conclusiones: Es importante en pacientes diabéticos diagnosticar EHGNA en forma temprana para un control más estricto, no sólo de la glucosa sérica sino de otros parámetros metabólicos, principalmente, los triglicéridos lo cual apoya fuertemente el concepto existente de "múltiples hits " que considera que la EHGNA afecta la homeostasis de la glucosa, y podría ser el punto de partida de nuevas investigaciones que permitan mejorar las intervenciones para reducir la progresión de la cirrosis en pacientes diabéticos y también retrasar la progresión de la diabetes mellitus en pacientes con esteatohepatitis no alcohólica.

Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. Objective: To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. Material and methods: retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). Statistical analysis: Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. Results: After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. Conclusions: It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

[Metabolic parameters in patients with steatosis non alcoholic liver and controlled diabetes type 2 versus uncontrolled diabetes type 2]. / Parámetros metabólicos en pacientes con esteatosis hepática no alcohólica y diabetes tipo 2 controlados versus no controlados.

Non-alcoholic fatty liver (NASH) is widely distributed around the world and is more common in subjects with dyslipidemia, metabolic syndrome obese and DM2 (34-74%). However, the prevalence of cirrhosis by NASH in general population is unknown which is still subject of research. OBJECTIVE: To determine if there are significant differences between metabolic parameters of non-alcoholic fatty liver in controlled versus uncontrolled diabetes type 2 of recent diagnosis. MATERIAL AND METHODS: retrospective case-control study, performed in the Hospital Guillermo Almenara Irigoyen, Lima, Peru from November 2014 to February 2015.This study included 231 patients: 147 patients (NASH with DM2 of recent diagnosis and poor control) and 84 patients (NASH with DM2 ofrecent diagnosis and adequate control). STATISTICAL ANALYSIS: Levene test for evaluating homogeneity of variances intra groups and parametric test for independent samples. RESULTS: After applying Levene test of homogeneity and student test, significant metabolic parameters were the triglycerides, HbA1C level, metformin dose and gender. CONCLUSIONS: It is important in diabetic patients to diagnose NASH early for a tighter control, not only of glucose but other metabolic parameters mainly triglycerides which strongly supports existing concept of "multiple hits" which considers NASH affects glucose homeostasis, and it could be the starting point of new research to improve interventions for decreasing progression from to cirrhosis in diabetic patients and also to delay progression of diabetes mellitus in patients with non alcoholic steatohepatitis.

Correlation between amygdala volume and impulsivity in adults with attention-deficit hyperactivity disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a chronic neurobiological disorder with childhood onset and persistence through adolescence and adulthood. ADHD patients frequently show exaggerated emotional responses. The amygdala plays an important role in emotion processing and in the activation of the frontal lobe. We hypothesised that smaller amygdala volumes in ADHD patients would be associated with less control of impulsivity and emotional instability. METHODS: We studied nine adult patients with ADHD and nine group-matched healthy volunteers using a 1.5 T magnetic resonance imaging scanner. We manually obtained morphometric measurements, which were later processed and compared. RESULTS: Significant negative correlation between the right amygdala volume and Barratt's impulsivity scores was observed (r=-0.756, p=0.018). No correlation was found between impulsivity scores and the volume of the left amygdala. Age was not found to be a contributor of the results. CONCLUSIONS: Smaller amygdala volumes have been observed in patients with ADHD. Our results suggest that greater emotional processing and less control of impulsivity are associated with smaller amygdala volumes in ADHD patients. Furthermore, the right amygdala would play a bigger role in impulsivity and behaviour control than the left amygdala. Further studies involving larger samples of adult patients with ADHD and using multimodal designs are needed.

Treating enuresis in a patient with ADHD: application of a novel behavioural modification therapy.

We report the case of a 6-year-old patient diagnosed with attention-deficit hyperactivity disorder (ADHD) and comorbid enuresis disorder, who was treated with methylphenidate for the past 3 months and a novel behavioural modification therapy by using an application called 'Enuresis Trainer'. This therapeutic application is basically an interactive 'Bedwetting Calendar', based on traditional cognitive behavioural modification therapies and positive reinforcement systems. Enuresis is defined as the failure of voluntary control of the urethral sphincter. The prevalence of enuresis is 15-20% in the child population; however, children with ADHD had a 2.7 times higher incidence of nocturnal enuresis. Bedwetting is a common cause of isolation in children as well as loss of self-esteem and other psychological distress for the child and the family.

Case Report: "ADHD Trainer": the mobile application that enhances cognitive skills in ADHD patients.

We report the case of a 10 year old patient diagnosed with attention deficit hyperactivity disorder (ADHD) and comorbid video game addiction, who was treated with medication combined to a novel cognitive training method based on video games called TCT method. A great risk of developing video game or internet addiction has been reported in children, especially in children with ADHD. Despite this risk, we hypothesize that the good use of these new technologies might be useful to develop new methods of cognitive training. The cognitive areas in which a greater improvement was observed through the use of video games were the visuospatial working memory and fine motor skills. TCT method is a cognitive training method that enhances cognitive skills such as attention, working memory, processing speed, calculation ability, reasoning, and visuomotor coordination. The purpose of reviewing this case is to highlight that regular cognitive computerized training in ADHD patients can improve some of their cognitive symptoms and can help treating video game addition.

Determinación de la mutación BRAF V600E en melanomas de pacientes uruguayos / Determination of BRAF V600E mutation in uruguayan patientÆs melanomas

Introducción: la identificación de cambios genéticos que están en la base de la génesis del melanoma ha permitido el desarrollo de terapias dirigidas específicamente contra ellos, lo que determinó, por primera vez en la historia del tratamiento sistémico del melanoma, un incremento en la sobrevida de los pacientes con enfermedad avanzada. Los mejores resultados se han obtenido con vemurafenib, terapia dirigida con-tra BRAF y que solo es efectiva cuando existe la mutación V600E, por lo que su frecuencia en una población determina-da mide el impacto que podría tener en términos de salud.Objetivo: evaluar la frecuencia de la mutación V600E en BRAF en melanomas provenientes de pacientes uruguayos.Material y método: se tomaron 28 muestras de melanoma microdisecadas y se les realizó la investigación de la mutación V600E mediante ASO-PCR (allele specific oligonucleotide - polymerase chain reaction).Resultados: se logró amplificar el ácido desoxirribonucleico (ADN) en 27 de las 28 muestras y se detectó la mutación en21 de ellas (FR: 0,78).Discusión: trabajos previos muestran una frecuencia menor de melanomas portadores de la mutación V600E de BRAF (40%-60% en población caucásica y 25% en población asiática) a la observada en nuestro estudio. Nuestros resultados, si bien requieren confirmación mediante la inclusión de unmayor número de pacientes, podrían explicarse, al menos en parte, por diferencias en la técnica utilizada y tal vez por una proporción diferente de pacientes con melanomas asociadoscon exposición solar intermitente.

Introduction: identifying genetic changes that occur in melanoma genesis has enabled the development of therapies that are specifically geared against such changes, what resulted in an increase of patientsÆ survival for thefirst time in the history of systemic treatment of melanoma, in patients with advanced disease. The best resultshave been obtained with vemurafenib, a therapy that targets the BRAF protein and is only effective in the presence of the V600E mutation. Thus, its frequency in a certain population measures its potential impact in health figures.Objective: to evaluate the frequency of the V600E mutation in BRAF in melanomas of Uruguayan patients.Method: 28 samples of microdissected melanoma were studied and V600E mutation was tested through ASO-PCR (allele specific oligonucleotide - polymerase chain reaction).Results: we managed to amplify DNA in 27 out of the 28 samples and the mutation was identified in 21 ofthem (FR: 0.78).Discussion: previous works demonstrated a lower presence of melanomas that are carriers of the V600E mutation of BRAF (40%-60% in the Caucasian population and 25% in the Asian population) than what ourstudy revealed. Our results, in spite of the need to include a larger number of patients, could partially be due todifferences in the technique used and maybe as a consequence of a different proportion of patients with melanomas associated to the intermittent sun exposure.

Introdução: a identificação de alterações genéticas associadas a origem do melanoma permitiram desenvolver terapias orientadas especificamente contra elas, o que possibilitou, pela primeira vez na história do tratamento sistêmico do melanoma, um aumento da sobrevida dos pacientes com doença avançada. Os melhores resultados foram obtidos com vemurafenib, terapia dirigida contra BRAF e que somente é efetiva quando existe a mutação V600E; sua frequência em uma população determinada mede o impacto que poderia ter sobre asaúde dessa população.Objetivo: avaliar a frequência da mutação V600E em BRAF em melanomas provenientes de pacientesuruguaios.Material e método: foram obtidas 28 amostras microdissecadas de melanoma nas quais fez-se uma pesquisa da mutação V600E utilizando ASO-PCR (allele specific oligonucleotide - polymerase chain reaction).Resultados: foi possível amplificar o ácido desoxirribonucleico (ADN) em 27 das 28 amostras; a mutação foi detectada em 21(FR: 0,78).Discussão: trabalhos anteriores mostram uma frequência menor de melanomas portadores da mutaçãoV600E de BRAF (40%-60% na população caucásica e 25% na população asiática) à observada no nosso estudo. Nossos resultados, embora seja necessário realizarum estudo com um maior número de pacientes, poderiam ser explicados, pelo menos parcialmente, pelas diferenças na técnica utilizada e talvez por una proporção diferente de pacientes com melanomas associados com exposição solar intermitente.

Papel del tecnólogo en medicina nuclear en el desarrollo de técnicas centellográficas, de cirugía radioguiada y moleculares / Nuclear medicine technologist role in the development of scintigraphy techniques of radioguided and molecular surgery

En nuestro centro el Tecnólogo en Medicina Nuclear interviene activamente en el desarrollo y evaluación de metodologías de Medicina Nuclear y de Biología Molecular vinculadas con la estrategia del ganglio centinela (GC). El objetivo del presente trabajo fue el de validar las técnicas nucleares y moleculares utilizadas mediante parámetros clínicos y pronósticos conocidos de la enfermedad. Incluimos prospectivamente 40 pacientes con melanoma clínicamente localizado, con un espesor medio de Breslow de 3.6 mm (rango: 0.5-15.0 mm). La edad media de los pacientes fue de 54.2 años (rango: 24-82 años), siendo 25 del sexo femenino. Se utilizó como radiofármaco al 99mTc – nanocoloide de albúmina, realizando el estudio linfocentellográfico 16-18 horas antes de la cirugía, con una dosis total de 111-185 MBq. Se adquirieron imágenes secuenciales de 5 minutos en gama cámara, continuando hasta una hora post inyección de no visualizarse precozmente drenaje. Una vez localizado el(los) GC, realizamos vistas ortogonales a los efectos de localizar dichos ganglios en el espacio tridimensional. Los territorios ganglionares identificados mediante linfocentellografía fueron explorados quirúrgicamente mediante la ayuda de una sonda gama intraoperatoria. La radiactividad ganglionar y de los tejidos adyacentes fue medida in vivo y verificada ex vivo luego de la resección. Una relación de conteo ganglio/fondo mayor a 2 in vivo y mayor a 10 veces ex vivo fue considerada a los efectos de considerar un ganglio como GC. Los mismos fueron analizados mediante histopatología y en 14 pacientes se estudió además la expresión mediante RT-PCR, de los marcadores TIR, MART-1 y MIA, usando un protocolo de una fase con 35 ciclos de amplificación. Los experimentos fueron realizados en duplicado e incluyeron controles positivos y negativos. Los GC fueron identificados en 38/39 pacientes operables (97.4 por ciento), extirpándose una media de 1.3 ganglios. Se diagnosticaron metástasis ganglionares por his.