Tocilizumab in glucocorticoid-resistant graves orbitopathy. A case series report of a mexican population.

PURPOSE: To describe pre- to post-treatment changes in clinical activity score (CAS) and exophthalmometry in patients with Graves orbitopathy treated with tocilizumab (TCZ). MATERIAL AND METHODS: Eight Mexican patients presenting with active Graves orbitopathy (CAS>3/7) previously treated with glucocorticoids received 1 monthly dose of TCZ for 6 months. CAS, EUGOGO severity assessment and exophthalmometry were used to evaluate clinical status, with serum measurement of thyroid-stimulating hormone receptor antibodies (TR-Ab) for biochemical evaluation before and after application of TCZ. RESULTS: Eight patients were analyzed: 6 male (75%), 2 female (25%): mean age, 45.9±11.2 years; mean weight, 85±18.3 kg. Mean TR-Ab level at treatment outset was 291.9±96.4%, mean CAS 4.1±0.3 and mean exophthalmometry 21.2±3.2 mm. After TCZ treatment, mean TR-Ab level fell to 172.7±54% (P=0.001), mean CAS to 1.1±0.6 (P=0.001) and mean exophthalmometry to 19.3±2 mm (P=0.02). CONCLUSIONS: TCZ is a therapeutic option for glucocorticoid-resistant orbitopathy, and should be considered in second line due to the cost of treatment or in first line in patients with contraindications to intravenous GC pulse therapy.

Use of PCSK9 Inhibitor in a Mexican Boy with Compound Heterozygous Familial Hypercholesterolemia: A Case Report.

We report on the case of an 8-year-old Mexican male, with a 3-year-old clinical diagnosis of familial hypercholesterolemia, and the difficulties encountered in his treatment while in our care. His treatment started with a regimen consisting of ezetimibe/simvastatin, cholestyramine, and a dietary plan of 1600 calories, with a limited intake of 200 mg of cholesterol per day. Problems arose when the patient's low-density lipoprotein cholesterol (LDL) levels did not meet ideal targets, which prompted the use of LDL cholesterol apheresis (not available in Mexico) for 6 months. As a last resort, PCSK9 inhibitors were administered but the LDL levels remained in the 600 mg/dL range. AmbryGenetics conducted a genetic test employing the Sanger method. The results suggested that there were 2 different mutations for each allele of the same LDL receptor gene (c.249delTinsGG and p.(Cys109Arg)), located in exons 3 and 4, respectively. We identified compound heterozygous mutations in our index case, with him having both the p.C109R mutation (from the maternal lineage), as well as a c.249delTinsGG mutation (from the paternal lineage). The p.C109R mutation has been previously reported, not only in Mexico, but in European regions (Germany, Czech Republic, Ireland, Italy) as well. Functional studies indicated a residual enzymatic activity of 15% to 30% for heterozygotes. To date, the variant c.249delTinsGG has not been reported. This case study illustrates the fact that in Mexico there are limited options available for treatment in such a scenario. As medical professionals, we are limited by the tools at our disposal.

Obesidad. Pandemia del siglo XXI / Obesity. Pandemia of the century XXI

Resumen La obesidad representa uno de los problemas más importantes de salud de nuestros tiempos; hoy en día se considera un desafío sanitario en los países desarrollados, así como en los que se encuentran en vías de desarrollo, ya que han adoptado los hábitos alimenticios típicos del mundo desarrollado pero, además, por todas las comorbilidades asociadas. La obesidad se asocia con un espectro muy amplio de alteraciones fisiopatológicas como: sobrecarga de volumen, hipertensión, desregulación metabólica, activación neurohumoral e inflamación sistémica. Los genes involucrados en la obesidad son varios y se relacionan con diferentes procesos: en la regulación del apetito, los comportamientos de búsqueda de alimentos y la eficiencia metabólica. La pérdida de peso con cambios de estilo de vida (alimentación y ejercicio) es un camino adecuado para mejorar la salud en pacientes con factores de riesgo asociados a la obesidad. Aunque existen tratamientos medicamentosos y quirúrgicos para lograr la pérdida de peso, éstos no son elegidos de primera intención y sólo son usados cuando el tratamiento primario ha fallado.

Abstract Obesity represents one of the most important health problems of our times, nowadays it is considered a health challenge in developed countries, as well as in those that are developing, as they have adopted the typical eating habits of the developed world, but also because of all the associated comorbidities. Obesity is associated with a very broad spectrum of pathophysiological changes such as: volume overload, hypertension, metabolic dysregulation, neurohumoral activation and systemic inflammation. The genes involved in obesity are several and are related to different processes: in the regulation of appetite, the behaviors of food search and metabolic efficiency. Weight loss with changes in lifestyle (diet and exercise) is an adequate way to improve health in patients with risk factors associated with obesity. Although there are medical and surgical treatments to achieve weight loss, these are not chosen as first intention and are only used when the primary treatment has failed.

Serie de casos: síndrome de Prader-Willi con diagnóstico molecular y citogenético en la Unidad de Especialidades Médicas / Case series: Prader-Willi syndrome with molecular and cytogenetic diagnosis in the Medical Specialities Unit

Resumen El síndrome de Prader-Willi en un trastorno multisistémico; se caracteriza en la infancia por hipotonía, dificultades para la alimentación, retraso en el desarrollo e hipoplasia genital. En la adolescencia y edad adulta, la problemática se centra en las alteraciones del comportamiento, la ausencia de saciedad y el retraso mental leve o moderado. Su diagnóstico temprano requiere una alta sospecha clínica y estudios especiales (estudios de metilación e hibridación fluorescente in situ). La detección temprana se realiza con el fin de disminuir la morbilidad y mortalidad de los pacientes. Existe una clara necesidad de un enfoque multidisciplinario para facilitar el diagnóstico temprano y optimizar el manejo y tratamiento para mejorar la calidad de vida. Se presentan seis casos de SPW que tienen seguimiento en la Unidad de Especialidades Médicas a fin de conocer la prevalencia del SPW, ya que en la actualidad no se cuenta con ningún registro que la documente.

Abstract Prader-Willi syndrome in a multisystem disorder; it is characterized in childhood by hypotonia, feeding difficulties, developmental delay and genital hypoplasia. In adolescence and adulthood, the problem focuses on behavioral changes, the absence of satiety and mild or moderate mental retardation. Its early diagnosis requires a high clinical suspicion and special studies (methylation studies and fluorescent in situ hybridization). An early detection reduces the morbidity and mortality of patients. There is a clear need for a multidisciplinary approach to facilitate early diagnosis and optimize management and treatment to improve quality of life. There are six cases of SPW that are followed in the Medical Specialties Unit; we report them in order to know the prevalence of PWS, since at present there is no record documenting it.