Síntesis y uso de histidinato de cobre en niños con enfermedad de Menkes en México.

Menkes disease is a neurodegenerative and lethal pathology caused by gene mutations of the copper-transporting ATP-7A enzyme; it manifests itself by neurological symptoms and connective tissue changes of varying severity. Timely subcutaneous use of copper histidinate (Cu-His) is determinant for quality of life. We report the first experiences in Mexico on Cu-His synthesis and its safe use in 3 cases where hypocupremia and hypoceruloplasminemia were corroborated. With advice of the Hospital for Sick Children of Toronto Canada, we prepared a 500 µg/mL solution. In all three cases were 250 µg of Cu-His applied without relevant undesirable effects for 30 days. Serum copper (Cu, expressed in µg/L) and ceruloplasmin (Cp, in mg/dL) were determined: case 1, Cu days 0 and 30, 8 and 504 µg/L; Cp days 0 and 30, 4 and 10.75 mg/dL; case 2, Cu days 0 and 30, <50 and 502 µg/L; Cp days 0 and 30, 2 and 15 mg/dL; case 3, Cu days 0 and 30, 3 and 84.2 µg/L; Cp days 0 and 30, 4 and 10.7 mg/dL. In Mexico, it is possible to safely synthesize Cu-His and treat MD, which must be intentionally sought.

La enfermedad de Menkes es una patología neurodegenerativa y letal debida a mutaciones génicas de la enzima ATP-7A trasportadora de cobre; se manifiesta por síntomas neurológicos y alteraciones del tejido conectivo de severidad variable. El uso subcutáneo oportuno de histidinato de cobre (Cu-His) es determinante en la calidad de vida. Se reportan las primeras experiencias en México en la síntesis y uso seguro de Cu-His en tres casos en los que corroboramos hipocupremia e hipoceruloplasminemia. Bajo asesoramiento del Hospital for Sick Children, Toronto, Canadá, elaboramos una solución de 500 µg/mL. En los tres casos aplicamos 250 µg de Cu-His, sin efectos indeseables relevantes durante 30 días y observamos las siguientes determinaciones séricas de cobre (Cu en µg/L) y ceruloplasmina (Cp en mg/dL): caso 1, Cu días 0 y 30, 8 y 504 µg/L; Cp días 0 y 30, 4 y 10.75 mg/dL; caso 2, Cu días 0 y 30, < 50 y 502, µg/L; Cp días 0 y 30, 2 y 15 mg/dL; caso 3, Cu días 0 y 30, 3 y 84.2 µg/L; Cp días 0 y 30, 4 y 10.7 mg/dL. En México es posible la síntesis segura de Cu-His y tratar la enfermedad de Menkes, la cual debe ser intencionalmente buscada.

[ROC curves: general characteristics and their usefulness in clinical practice]. / Curvas ROC: características generales y su uso en la práctica clínica.

The use of diagnostic tests to determine the presence or absence of a disease is essential in clinical practice. The results of a diagnostic test may correspond to numerical estimates that require quantitative reference parameters to be transferred to a dichotomous interpretation as normal or abnormal and thus implement actions for the care of a condition or disease. For example, in the diagnosis of anemia it is necessary to define a cut-off point for the hemoglobin variable and create two categories that distinguish the presence or absence of anemia. The method used for this process is the preparation of diagnostic performance curves, better known by their acronym in English as ROC (Receiver Operating Characteristic). The ROC curve is also useful as a prognostic marker, since it allows defining the cut-off point of a quantitative variable that is associated with greater mortality or risk of complications. They have been used in different prognostic markers in COVID-19, such as the neutrophil/lymphocyte ratio and D-dimer, in which cut-off points associated with mortality and/or risk of mechanical ventilation were identified. The ROC curve is used to evaluate the diagnostic performance of a test in isolation, but it can also be used to compare the performance of two or more diagnostic tests and define which one is more accurate. This article describes the basic concepts for the use and interpretation of the ROC curve, the interpretation of an area under the curve (AUC) and the comparison of two or more diagnostic tests.

El uso de pruebas diagnósticas para determinar la presencia o ausencia de una enfermedad es esencial en la práctica clínica. Los resultados de una prueba diagnóstica pueden corresponder a estimaciones numéricas que requieren parámetros cuantitativos de referencia para trasladarse a una interpretación dicotómica como normal o anormal y así, implementar acciones para la atención de una condición o una enfermedad. Por ejemplo, en el diagnóstico de anemia es necesario definir un punto de corte para la variable hemoglobina y crear dos categorías que distingan la presencia o no de anemia. El método utilizado para este proceso es la elaboración de curvas de rendimiento diagnóstico, mejor conocidas por sus siglas en inglés como ROC (Receiver Operating Characteristic). La curva ROC además es útil como marcador pronóstico, ya que permite definir el punto de corte de una variable cuantitativa que se asocia a mayor mortalidad o riesgo de complicaciones. Se han usado en distintos marcadores pronósticos en COVID-19, como el índice neutrófilos/linfocitos y dímero D, en los que se identificaron puntos de corte asociados a mortalidad y/o riesgo de ventilación mecánica. La curva ROC se utiliza para evaluar el rendimiento diagnóstico de una prueba de forma aislada, pero también se puede usar para comparar el rendimiento de dos o más pruebas diagnósticas y definir aquella que es más precisa. En este artículo se describen los conceptos básicos para el uso e interpretación de la curva ROC, la interpretación de un área bajo la curva (ABC) y la comparación de dos o más pruebas diagnósticas.

[Non-satisfaction medical doctors during pediatric training. Prevalence and associated factors]. / Insatisfacción durante la residencia de pediatría. Prevalencia y factores asociados.

INTRODUCTION: The prevalence of medical discontent is approximately 4%. Factors such as gender, age, type of specialization, disillusion with the profession and economical factors have been identified among graduated medical doctors. Residents mentioned educational strategies as an additional factor of discomfort. OBJECTIVE: To identify the prevalence and factors that influence on resident's discontent during their pediatric training program. MATERIAL AND METHODS: The principal motives of dissatisfaction during the period of training in pediatric residence were identified using the semantic nets technique. RESULTS: Prevalence of dissatisfaction was 3.1%. The principal motives were: educational strategies, duration of medical career, work overload, hierarchical systems and abuse. CONCLUSIONS: Prevalence of dissatisfaction during a medical residence is similar to that reported in graduated pediatricians, and occurs during the first two years of residence. Educational strategies were one of the principal causes of discontent, and other local factors such as work overload, jeriarquical systems and abuse were identified.

Síntesis y uso de histidinato de cobre en niños con enfermedad de Menkes en México / Synthesis and use of copper histidinate in children with Menkes disease in Mexico

Resumen La enfermedad de Menkes es una patología neurodegenerativa y letal debida a mutaciones génicas de la enzima ATP-7A trasportadora de cobre; se manifiesta por síntomas neurológicos y alteraciones del tejido conectivo de severidad variable. El uso subcutáneo oportuno de histidinato de cobre (Cu-His) es determinante en la calidad de vida. Se reportan las primeras experiencias en México en la síntesis y uso seguro de Cu-His en tres casos en los que corroboramos hipocupremia e hipoceruloplasminemia. Bajo asesoramiento del Hospital for Sick Children, Toronto, Canadá, elaboramos una solución de 500 µg/mL. En los tres casos aplicamos 250 µg de Cu-His, sin efectos indeseables relevantes durante 30 días y observamos las siguientes determinaciones séricas de cobre (Cu en µg/L) y ceruloplasmina (Cp en mg/dL): caso 1, Cu días 0 y 30, 8 y 504 µg/L; Cp días 0 y 30, 4 y 10.75 mg/dL; caso 2, Cu días 0 y 30, < 50 y 502, µg/L; Cp días 0 y 30, 2 y 15 mg/dL; caso 3, Cu días 0 y 30, 3 y 84.2 µg/L; Cp días 0 y 30, 4 y 10.7 mg/dL. En México es posible la síntesis segura de Cu-His y tratar la enfermedad de Menkes, la cual debe ser intencionalmente buscada.

Abstract Menkes disease is a neurodegenerative and lethal pathology caused by gene mutations of the copper-transporting ATP-7A enzyme; it manifests itself by neurological symptoms and connective tissue changes of varying severity. Timely subcutaneous use of copper histidinate (Cu-His) is determinant for quality of life. We report the first experiences in Mexico on Cu-His synthesis and its safe use in 3 cases where hypocupremia and hypoceruloplasminemia were corroborated. With advice of the Hospital for Sick Children of Toronto Canada, we prepared a 500 µg/mL solution. In all three cases were 250 µg of Cu-His applied without relevant undesirable effects for 30 days. Serum copper (Cu, expressed in µg/L) and ceruloplasmin (Cp, in mg/dL) were determined: case 1, Cu days 0 and 30, 8 and 504 µg/L; Cp days 0 and 30, 4 and 10.75 mg/dL; case 2, Cu days 0 and 30, <50 and 502 µg/L; Cp days 0 and 30, 2 and 15 mg/dL; case 3, Cu days 0 and 30, 3 and 84.2 µg/L; Cp days 0 and 30, 4 and 10.7 mg/dL. In Mexico, it is possible to safely synthesize Cu-His and treat MD, which must be intentionally sought.