PCSK-9 Inhibitors in a Real-World Setting and a Comparison Between Alirocumab and Evolocumab in Heterozygous FH Patients.

A real-world setting study of familial hypercholesterolemia (FH) patients who received Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in a specialized referral center in Mexico City. Ten patients between the ages of 18 and 70 years, with a diagnosis of FH according to Dutch Lipid Clinic Network (DLCN) criteria, with failure to achieve their Low-density lipoprotein Cholesterol (LDL-C) goals, and with standard therapy between 2016 and 2017 enrolled in a simple randomization in which a group of 5 participants received alirocumab (75 mg every 2 weeks) and the remaining 5 patients received evolocumab (140 mg every 2 weeks). Comparative analysis was made, analyzing the means of LDL at baseline at 4, 6, and 12 weeks. The evolocumab group had an average initial LDL-C of 277 mg/dL, which, after 12 weeks of treatment, was significantly reduced to 116 mg/dL; P = 0.04 (95% confidence interval [CI]: 11.5-310.9). The alirocumab group with a mean initial LDL-C of 229 mg/dL showed a reduction of LDL-C levels at 12 weeks of treatment to 80 mg/dL; P = 0.008 (95% CI: 63.8-233.7). In conclusion, PCSK9 inhibitors are an excellent treatment option in patients with FH who do not reach their LDL-C goals with standard therapy or due to intolerance to the standard therapy. There is no difference in the lipid-lowering effect between both PSCK9 inhibitors.

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.

Successful Multimodal Treatment of an IGF2-Producing Solitary Fibrous Tumor With Acromegaloid Changes and Hypoglycemia.

Doege-Potter syndrome with acromegaloid facial changes is extremely rare. Uncooked cornstarch along with glucocorticoids have been used as supportive care in patients with non-islet cell tumor hypoglycemia (NICTH). Preoperative embolization of hepatic solitary fibrous tumors (SFT) with NICTH has yielded unsatisfactory results. Herein we present the case of a 61-year-old man with a 3-month history of severe frequent hypoglycemic episodes and acromegaloid facial changes. During a spontaneous hypoglycemia (26 mg/dL), laboratory values showed a hypoinsulinemic pattern with low levels of GH, IGFPB3, and an IGF2/IGF1 ratio of 8.5:1. Cross-sectional imaging revealed a large (16 × 13 × 11 cm) hepatic tumor, and cytology was consistent with SFT. A preoperative right portal embolization was performed in an effort to induce normal remnant liver hypertrophy to allow for safe tumor resection. After the procedure, uncooked starch treatment followed by prednisone was started, achieving complete remission of hypoglycemic episodes in the preoperative setting. He subsequently underwent partial hepatectomy. The histologic diagnosis was compatible with a potentially malignant SFT. The patient had an excellent outcome with complete remission of hypoglycemia, improvement of facial acromegaloid changes, and no further evidence of disease. To our knowledge, this is the first case of a patient with Doege-Potter syndrome with acromegaloid facial changes induced by a potentially malignant liver SFT, treated successfully with a multimodal approach consisting of uncooked cornstarch, low-dose prednisone, preoperative embolization, and complete surgical resection. The use of cornstarch and low-dose glucocorticoids may be an adequate treatment in advance of undergoing surgery.

Modelo de atención integral en el segundo nivel: Experiencia de la Unidad de Especialidades Médicas / Care models at the second level: Experience of the Medical Specialties Unit

Resumen Objetivo: Reportar la implementación y los beneficios del Modelo de atención integral en el segundo nivel: Experiencia de la Unidad de Especialidades Médicas, su utilidad en el manejo y seguimiento de los pacientes con enfermedades crónicas. Material y métodos: Se lograron implementar 9 consultorios de atención médica de la siguiente forma, 2 de Endocrinología, 3 consultorios de Clínica de Enfermedades Crónicas, uno de educación en diabetes e hipertensión, así como 3 de apoyo nutricional. Se midió valores absolutos del número de consultas durante los años 2017, 2018, 2019 y parte del 2020. Así mismo se buscó identificar las patologías más prevalentes con la idea en tener un mejor control y seguimiento de los pacientes, con una mejor organización de personal de atención médico y de enfermería. Resultados y discusión: Se lograron incrementar los números de consulta, con un control y seguimiento más estricto de los pacientes, además de los beneficios en cuanto a la formación y capacitación de médicos residentes, generales tanto militares como profesionales de la salud civiles para enfrentar estos padecimientos prevalentes en nuestro país.

Abstract Objective: To report the implementation as well as the benefits of the Comprehensive Care Model at the second level: Experience of the Medical Specialties Unit, and assess its usefulness in the management and monitoring of patients with chronic diseases. Material and methods: 9 medical care clinics were implemented as follows, 2 for Endocrinology, 3 Clinics for Chronic Diseases, one for education in diabetes and hypertension, as well as 3 for nutritional support. Absolute values of the number of consultations were measured during the years 2017, 2018, 2019 and part of 2020. Likewise, it was sought to identify the most prevalent pathologies with the idea of having a better control and monitoring of patients, with a better organization of medical and nursing care personnel. Results and discussion: It was possible to increase the consultation numbers, with a stricter control and monitoring of patients, in addition to the benefits in terms of training and training of resident doctors, both military generals and civilian health professionals to face these prevalent conditions in our country.

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.