A prospective study to assess the impact of a novel CFTR therapy combination on body composition in patients with cystic fibrosis with F508del mutation.

BACKGROUND & AIM: Malnutrition is a prevalent condition in Cystic Fibrosis (CF) and can result in worsening of pulmonary function and other comorbidities. Cystic fibrosis transmembrane regulator (CFTR) modulator therapies are improving the CF-related care and outcomes. Body Mass Index (BMI) is the most commonly used parameter to assess nutritional status, albeit it is a very unspecific indicator. Hence, current guidelines recommend body composition analysis as a part of nutritional assessment. The aim of our study was to evaluate the impact of elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) treatment on body composition and respiratory function. METHODS: We recruited patients with CF from University Hospital La Princesa, with follow-up in the Adult Cystic Fibrosis Unit. All patients were eligible to initiate ELX/TEZ/IVA therapy. Body composition was assessed with a Bioelectrical Impedance Analysis (BIA) and spirometry data were obtained before and after 6 months of treatment. RESULTS: Our study sample was composed of 36 patients with CF. We observed a significant increase in BMI after 6 months of treatment (p < 0.001), as well as an increase in fat mass (p = 0.008) and visceral fat area (p = 0.026). The other body composition parameters did not yield significant changes. Overall, %FEV1 increased from 72.67 % (±17.39) to 84.74 % (±18.18) after 6 months of treatment. Interestingly, we found an inverse correlation between %FEV1 and fat mass (r = -0,476; p = 0,0058), %FEV1 and age (r = -0,411; p = 0,0196) and between %FEV1 and visceral fat area (r = -0,515; p = 0,0025). On the contrary, we found a direct correlation between %FEV1 and body cell mass (r = 0,367; p = 0,038). CONCLUSIONS: Novel CFTR modulators are emerging for the treatment of CF. Specifically, triple combination with ELX/TEZ/IVA has shown to effectively improve both pulmonary and nutritional status in patients with CF with F508del mutation. Body composition should be a part of the routine assessment for patients with CF.

Alpelisib-Induced Diabetes Mellitus: Case Report, Pharmacodynamics and Management Considerations.

Introduction: Alpelisib is an orally selective PI3K alpha inhibitor recently available for the treatment of advanced breast cancer. PI3K pathway is an intracellular signaling pathway that plays an important role in regulating glucose metabolism. Hyperglycemia is the most common adverse event associated. Methods: We describe the case of a severe hyperglycemia associated with alpelisib treatment in a patient with metastatic breast cancer and previously near-normal glycemia. We analyze the clinical presentation, PI3K inhibitor pharmacodynamic aspects, its influence in glycemic control and the required treatment approach. Results: An important impairment of glycemic control was observed after initiation of alpelisib. In addition to insulin sensitizers drugs, intensive insulin regimen was necessary. Flash glucose monitoring (FGM) information has been helpful in understanding the pharmacodynamic aspects of alpelisib and insulin titration. Development of hyperglycemia is fast, already observed 24 hours after initiation of therapy. FGM shows severe and persistent hyperglycemia during most of the day, with a significant downward effect in the 4 hours after each daily intake, which evidences the strong but transitory effect of the drug enzyme blockade. C-peptide level is remarkable in accordance with drug pharmacodynamics, consistent with a significant insulin resistance. Conclusions: Glucose monitoring should always be performed in patients treated with alpelisib, especially in patients with diabetes and prediabetes. It is crucial to anticipate in these patients. Any delay can lead to a worsening in metabolic control resulting in the discontinuation or reduction of alpelisib, which would lead to a decrease in its effectiveness, and consequently would deny patients an effective treatment with an impact on survival.

Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid. / Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid.

OBJECTIVE: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. METHODS: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. RESULTS: Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. CONCLUSIONS: Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications.

Perfil clínico y metabólico de pacientes con diabetes tipo LADA atendidos en atención especializada en la comunidad de Madrid / Clinical and metabolic profile of patients with latent autoimmune diabetes in adults in specialized care in Madrid

Objetivo: Definir las características clínicas de los pacientes con diabetes autoinmune latente del adulto (LADA), conocer su control metabólico y las complicaciones crónicas asociadas que presentan. Métodos: Seleccionamos pacientes con DM seguidos en las consultas de endocrinología de hospitales públicos de la Comunidad de Madrid que reunían los siguientes criterios: edad al diagnóstico de DM >30años, independencia inicial de insulina durante al menos 6meses y positividad de anticuerpos antiGAD. Analizamos datos clínicos relativos al diagnóstico de LADA, autoinmunidad asociada, niveles de péptidoC, pauta terapéutica, control metabólico y presencia de complicaciones crónicas. Resultados: Número de pacientes: 193. Mujeres: 56%. Antecedentes familiares de DM: 62%. Edad al diagnóstico de DM: 49años. Retraso en confirmación LADA: 3,5años. Tiempo de insulino-independencia: 12meses. PéptidoC basal suero: 0,66ng/ml (0,22nmol/l). Pauta de insulina basal-bolus: 76,7%. Dosis total diaria: 35,1U/día, correspondiente a 0,51U/kg. Sin fármacos orales asociados: 33,5%. Presencia de otras patologías autoinmunes: 57%. Glucemia en ayunas: 160,5mg/dl (8,91mmol/l). HbA1c: 7,7%. IMC: 25,4kg/m2 (sobrepeso: 31,5%; obesidad: 8%). Presión arterial: 128/75. Colesterol HDL: 65mg/dl (16,9mmol/l). Colesterol LDL: 96mg/dl (24,96mmol/l). Triglicéridos: 89mg/dl (1,01mmol/l). Complicaciones crónicas: 28%; microangiopatía: 23,1%; macroangiopatía: 4,9%. Conclusiones: El reconocimiento de LADA puede retrasarse varios años. La reserva pancreática de insulina de los pacientes es heterogénea y el grado medio de control glucémico deficiente a pesar de utilizar mayoritariamente insulinoterapia intensiva. Con frecuencia presentan sobrepeso, aunque tienen un control adecuado de la presión arterial y perfil lipídico y baja incidencia de complicaciones macroangiopáticas (AU)

Objective: To report the clinical characteristics of patients with latent autoimmune diabetes in adults (LADA), and to ascertain their metabolic control and associated chronic complications. Methods: Patients with DM attending specialized medical care in Madrid who met the following criteria: age at diagnosis of DM >30years, initial insulin independence for at least 6months and positive GAD antibodies were enrolled. Clinical profiles, data on LADA diagnosis, associated autoimmunity, C-peptide levels, therapeutic regimen, metabolic control, and presence of chronic complications were analyzed. Results: Number of patients; 193; 56% females. Family history of DM: 62%. Age at DM diagnosis: 49years. Delay in confirmation of LADA: 3.5years. Insulin-independence time: 12months. Baseline serum C-peptide levels: 0.66ng/ml. Basal-bolus regimen: 76.7%. Total daily dose: 35.1U/day, corresponding to 0.51U/Kg. With no associated oral antidiabetic drugs: 33.5%. Other autoimmune diseases: 57%. Fasting plasma glucose: 160.5mg/dL. HbA1c: 7.7%. BMI: 25.4kg/m2 (overweight, 31.5%; obesity, 8%). Blood pressure: 128/75. HDL cholesterol: 65mg/dL. LDL cholesterol: 96mg/dL. Triglycerides: 89mg/dL. Known chronic complications: 28%. Conclusions: Recognition of LADA may be delayed by several years. There is a heterogeneous pancreatic insulin reserve which is negative related to glycemic parameters. Most patients are poorly controlled despite intensive insulin therapy. They often have overweight, but have adequate control of BP and lipid profile and a low incidence of macrovascular complications (AU)

Estado actual de los sistemas de infusión subcutánea continua de insulina y monitorización continua de glucosa en la Comunidad de Madrid / Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid

OBJETIVO: Analizar la información disponible sobre el estado de los sistemas de infusión subcutánea continua de insulina (ISCI) y de monitorización continua de glucosa (MCG) en la red pública sanitaria de la Comunidad Autónoma de Madrid (CAM). MATERIAL Y MÉTODOS: Se remitió una encuesta a los 28 servicios de endocrinología de los hospitales públicos de la CAM con 31 preguntas sobre los sistemas ISCI y MCG, que incluían registros de pacientes y aspectos asistenciales, administrativos y logísticos. Entre marzo y mayo de 2014 se recibieron respuestas de los centros y se recabó la información de los 20 servicios que realizaban este tipo de procedimientos en nuestra comunidad. Los datos sobre pacientes pediátricos se recibieron mayoritariamente a través de los servicios de adultos, con la excepción de 2 servicios de pediatría de los que la información se recibió directamente. RESULTADOS: En la CAM hay contabilizados un total de 1.256 sistemas ISCI en la población diabética. Los usuarios son mayoritariamente adultos (1.089 pacientes), mientras que 167 corresponden a pacientes pediátricos. Durante 2013 se instauraron 151 nuevos tratamientos (12% del total) mientras que se retiraron un total de 14 bombas. La disponibilidad de recursos asistenciales y la proporción de facultativos de plantilla encargados de estos tratamientos son muy desiguales entre distintos centros. Un 85% de los hospitales incluye entre sus prestaciones sistemas MCG retrospectivos, y un 40% los utiliza habitualmente al inicio de los tratamientos ISCI. Trece centros (65%) utilizan MCG a tiempo real (MCG-TR) a largo plazo en casos seleccionados, contabilizándose un registro acumulado de 67 pacientes. CONCLUSIONES: La implantación de las tecnologías en diabetes en la CAM es desigual en los distintos centros madrileños, y continúa siendo inferior a otros países de nuestro entorno, aunque parece observarse una discreta tendencia a recortar esas diferencias

OBJECTIVE: To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. MATERIAL AND METHODS: A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. RESULTS: A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). CONCLUSIONS: Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use

[Current status of continuous subcutaneous insulin infusion and continuous glucose monitoring systems in the Community of Madrid]. / Estado actual de los sistemas de infusión subcutánea continua de insulina y monitorización continua de glucosa en la Comunidad de Madrid.

OBJECTIVE: To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid. MATERIAL AND METHODS: A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information. RESULTS: A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients). CONCLUSIONS: Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use.

[Low-dose cinacalcet reduces serum calcium in patients with primary hyperparathyroidism not eligible for surgery]. / Dosis bajas de cinacalcet reducen el calcio sérico en pacientes con hiperparatiroidismo primario no subsidiario de tratamiento quirúrgico.

We present our experience with low-dose cinacalcet to normalize serum calcium in patients with primary hyperparathyroidism (PHPT) not eligible for surgery. We analyzed the impact of this drug on various parameters of calcium-phosphorus metabolism and its tolerability profile. We recruited 17 patients diagnosed with PHPT who had hypercalcemia and also met one or more of the following inclusion criteria: elevated risk for parathyroidectomy, persistent/recurrent PHPT after previous parathyroid surgery or refusal to undergo surgery. The starting dose of cinacalcet was 30 or 60 mg/day, which was adjusted depending on the degree of calcemia reduction and tolerance to the drug. We observed a reduction in serum calcium that was already evident in the first post-treatment test. Appropriate dose adjustment was performed when required and normal serum calcium levels were achieved in most patients, remaining stable during follow-up. Parathyroid hormone was reduced but not normalized in most patients. Calciuria decreased while serum phosphate and alkaline phosphatase levels increased. Cinacalcet tolerance was generally good at the doses used. The most common adverse effects were weakness, dizziness and asthenia, leading to treatment withdrawal in only one patient. We conclude that low-dose cinacalcet reduces serum calcium efficiently, normalizes calcium levels in most patients with PHPT not eligible for surgical treatment and has a good tolerability profile.

Dosis bajas de cinacalcet reducen el calcio sérico en pacientes con hiperparatiroidismo primario no subsidiario de tratamiento quirúrgico / Low-dose cinacalcet reduces serum calcium in patients with primary hyperparathyroidism not eligible for surgery

Presentamos nuestra experiencia con cinacalcet a dosis bajas, en pacientes con hiperparatiroidismo primario (HPTP) no subsidiario de tratamiento quirúrgico con el objetivo principal de normalizar la calcemia. Analizamos el impacto del fármaco sobre diversos parámetros del metabolismo calcio-fósforo y su perfil de tolerancia. Reclutamos un total de 17 pacientes diagnosticados de HPTP que presentaban hipercalcemia y que reunían además alguno de los siguientes criterios de inclusión: riesgo elevado para paratiroidectomía, HPTP persistente/recurrente tras cirugía paratiroidea previa o rechazo del paciente a la intervención quirúrgica. La dosis inicial de cinacalcet fue de 30 o 60mg/día, la cual se ajustó en función del grado de reducción de la calcemia y la tolerancia al fármaco. Observamos una reducción del calcio sérico que ya resultaba evidente en el primer control postratamiento. Tras el ajuste pertinente de dosis cuando fue preciso, se consiguió normalizar la calcemia en una mayoría de los pacientes, la cual se mantuvo estable a lo largo del seguimiento. La PTH se redujo, aunque no se normalizó en la mayor parte de los pacientes. La calciuria descendió mientras que la fosforemia y la fosfatasa alcalina sérica aumentaron. La tolerancia a cinacalcet fue buena en general a las dosis utilizadas. Los efectos secundarios más frecuentes fueron debilidad, mareos y astenia, y solamente en un paciente motivaron la suspensión del tratamiento. Concluimos que cinacalcet a dosis bajas reduce la calcemia de forma eficaz y consigue una normalización de la misma en una mayoría de pacientes con HPTP no subsidiarios de tratamiento quirúrgico con un buen perfil de tolerancia al fármaco (AU)

We present our experience with low-dose cinacalcet to normalize serum calcium in patients with primary hyperparathyroidism (PHPT) not eligible for surgery. We analyzed the impact of this drug on various parameters of calcium-phosphorus metabolism and its tolerability profile We recruited 17 patients diagnosed with PHPT who had hypercalcemia and also met one or more of the following inclusion criteria: elevated risk for parathyroidectomy, persistent/recurrent PHPT after previous parathyroid surgery or refusal to undergo surgery. The starting dose of cinacalcet was 30 or 60mg/day, which was adjusted depending on the degree of calcemia reduction and tolerance to the drug.We observed a reduction in serum calcium that was already evident in the first post-treatment test. Appropriate dose adjustment was performed when required and normal serum calcium levels were achieved in most patients, remaining stable during follow-up. Parathyroid hormone was reduced but not normalized in most patients. Calciuria decreased while serum phosphate and alkaline phosphatase levels increased. Cinacalcet tolerance was generally good at the doses used. The most common adverse effects were weakness, dizziness and asthenia, leading to treatment withdrawal in only one patient. We conclude that low-dose cinacalcet reduces serum calcium efficiently, normalizes calcium levels in most patients with PHPT not eligible for surgical treatment and has a good tolerability profile (AU)

Rabdomiólisis por antitiroideos / Rhabdomiolysis secondary to antithyroid drugs

No disponible