Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Data quality validation of the Spanish Incisional Hernia Surgery Registry (EVEREG): pilot study.

PURPOSE: The Spanish Incisional Hernia Surgery Registry (EVEREG) was promoted by the Abdominal Wall Section of the Spanish Association of Surgeons, starting data collection in July 2012 and currently has more than 14,000 cases. The objective of this study was to validate the data collected through a pilot audit process. METHODS: A sample of hospitals participating in the EVEREG registry since the beginning was selected. Patients registered in these centers in the 2012-2020 period were included. A stratified random sampling was carried out, with the inclusion of 10% of registered cases per center with a minimum of 20 cases per center. At each participating center, two researchers not belonging to the center undergoing the audit checked (on site or telematically) the concordance between the data in the registry and the data contained in the case history of each patient. RESULTS: 330 patients have been analyzed, out of a total of 2673 registered, in 9 participating centers. The average accuracy has been 95.7%. Incorrect data 1.5% and missing data 2.3% CONCLUSION: The group of pilot hospitals from this EVERG incisional hernia surgery registry shows a very high precision of 95.7%. The confirmation of these findings in all the centers participating in the registry will make it possible to guarantee the quality of the studies made and their comparability with other similar national registries. TRIAL REGISTRATION: nnTrial registration number: ClinicalTrials.gov ID:NCT03899012.

Neuropsychiatric phenotypes of anti-NMDAR encephalitis: a prospective study.

BACKGROUND: Patients with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis (ANMDARE) show a wide range of behavioral abnormalities and are often mistaken for primary psychiatric presentations. We aimed to determine the behavioral hallmarks of ANMDARE with the use of systematic neuropsychiatric and cognitive assessments. METHODS: A prospective study was conducted, with 160 patients admitted to the National Institute of Neurology and Neurosurgery of Mexico, who fulfilled criteria for possible autoimmune encephalitis and/or red flags along a time window of seven years. Cerebrospinal fluid (CSF) antibodies against the NR1 subunit of the NMDAR were processed with rat brain immunohistochemistry and cell-based assays with NMDA expressing cells. Systematic cognitive, neuropsychiatric, and functional assessments were conducted before knowing NMDAR antibodies results. A multivariate analysis was used to compare patients with and without definite ANMDARE according to antibodies in CSF. RESULTS: After obtaining the CSF antibodies results in 160 consecutive cases, 100 patients were positive and classified as having definite ANMDARE. The most frequent neuropsychiatric patterns were psychosis (81%), delirium (75%), catatonia (69%), anxiety-depression (65%), and mania (27%). Cognition was significantly impaired. A total of 34% of the patients had a predominantly neuropsychiatric presentation without seizures. After multivariate analysis, the clinical hallmarks of ANMDARE consisted of a catatonia-delirium comorbidity, tonic-clonic seizures, and orolingual dyskinesia. CONCLUSIONS: Our study supports the notion of a neurobehavioral phenotype of ANMDARE characterized by a fluctuating course with psychotic and affective symptoms, catatonic signs, and global cognitive dysfunction, often accompanied by seizures and dyskinesia. The catatonia-delirium comorbidity could be a distinctive neurobehavioral phenotype of ANMDARE.

Experiencia clínica en hipertensión arterial pulmonar en un hospital general de tercer nivel / Clinical experience in pulmonary arterial hypertension in a general tertiary hospital

Introducción: La hipertensión arterial pulmonar es una enfermedad rara. Cursa con aumento progresivo de la resistencia vascular pulmonar e insuficiencia ventricular derecha y muerte precoz. Los tratamientos específicos han mejorado la esperanza de vida aunque el pronóstico a largo plazo sigue siendo desfavorable con una mortalidad del 40% a los tres años.Materiales y métodos: El estudio es descriptivo observacional trasversal y retrospectivo realizado en un hospital general de tercer nivel entre mayo de 2004 y agosto de 2020. Se midió la capacidad funcional (CF), la presión arterial pulmonar media, el test de la marcha de los 6 minutos (PM6M) entre otras variables. Se recogieron variables de tratamiento farmacológico específico y efectos adversos, así como la adherencia farmacológica.Resultados: La población fue de 27 pacientes, la mayoría mujeres con edad media de 62 años. Más del 80% de los pacientes presentaban CF II-III y PM6M de riesgo intermedio. Los tratamientos en primera línea y monoterapia mayoritarios fueron el sildenafilo y bosentán con un grado de recomendación de Ia, seguidos de ambrisentán. Los otros grupos de fármacos fueron minoritarios en los pacientes. No se encontraron diferencias estadísticamente significativas en la variación del PM6M, sí hubo variación de PAPm de forma positiva. Conclusiones: Todos los pacientes llevaban en tratamiento específico más de tres años, aunque sería necesario ampliar el tamaño muestral. En cuanto a la seguridad los efectos adversos fueron de grado leve y la adherencia al tratamiento elevada. (AU)

Introduction: Pulmonary arterial hypertension is a rare disease. It results a progressive increase in pulmonary vascular resistance and in right ventricular failure and early death. Specific treatments have improved the life expectancy of patients but the long-term prognosis remains poor, resulting in a high mortality of 40% at 3 years. Materials and methods: The research conducted is descriptive, cross-sectional and retrospective. It was carried out in a third level general hospital between May 2004 and August 2020. The measured variables were functional capacity (CF), PAPm, 6-minute walk test (PM6M) and other clinical parameters. Variables related to specific pharmacological treatment and adverse effects, as well as pharmacological adherence were also collected. Results: The study population was 27 patients, most of them women, with an average age of 62 years. More than 80% of patients presented CF II-III and PM6M of moderate risk. First-line and monotherapy treatments were mainly sildenafil and bosentan, with an Ia recommendation level. Ambrisentan was also a first-line treatment. The other drug groups were in the minority among patients. On the other hand, no statistically significant differences in PM6M variation were found, although there was positive variation in PAPm. Conclusions: The patients had been on specific treatment for more than three years. In terms of safety, adverse effects were minor and adherence to treatment high. (AU)

Estudio del switch de adalimumab por su biosimilar en un hospital de tercer nivel / Study of adalimumab switch for its biosimilar in a tertiary hospital

Objetivos: Debido al aumento en el consumo de los medicamentos biológicos y al impacto que esto supone en el gasto hospitalario, los objetivos de este estudio son: calcular el ahorro económico anual generado por el switch a adalimumab biosimilar y analizar el porcentaje de pacientes que mantienen dicho tratamiento en un hospital de tercer nivel. Material y métodos: Estudio descriptivo, observacional, longitudinal, retrospectivo en el que se incluyeron un grupo de pacientes a los que se les realizó switch de adalimumab por su biosimilar cuando en la Comisión Asesora Técnica de medicamentos de la comunidad se autorizó dicho cambio. Resultados: De los 218 pacientes, nueve tuvieron que volver al medicamento original (4,13%). La motivación fue: pérdida de eficacia en cinco, reacción alérgica en tres y otro, un paciente pediátrico con dolor tras la inyección del medicamento biosimilar. El coste de adquisición en nuestro hospital de una unidad del medicamento original es de 195,6 €, mientras que del biosimilar es de 75 €. Si consideramos una posología cada dos semanas, ya que es la más frecuente en nuestros pacientes, el coste anual por paciente con el original sería de 5.085 € y con el biosimilar de 1.950 €. Por lo tanto, el ahorro anual que supone el cambio del medicamento original al biosimilar es de 683.560 €. Conclusiones: El switch de adalimumab original al biosimilar supone un importante ahorro económico sin que se reduzca la efectividad en el proceso de su enfermedad. Lo que contribuye a la eficiencia y sostenibilidad del sistema sanitario. En nuestra población, el 4,13% tuvo que volver al medicamento original. Sería conveniente realizar estudios en un número superior de pacientes y continuar su seguimiento a largo plazo para obtener conclusiones más firmes. (AU)

Objectives: Due to the increase in the consumption of biologic drugs and the impact this has on hospital spending, the objectives of this study are: to calculate the economic savings generated by switching to biosimilar adalimumab and to analyze the percentage of patients who maintain this treatment in a tertiary level hospital. Material and methods: Descriptive, observational, longitudinal, retrospective study that included a group of patients who were switched from adalimumab to its biosimilar, when the Technical Advisory Committee for Medicines of the community authorized the change. Results: Of the 218 patients, nine had to return to the original drug (4.13%). The motivation was: loss of efficacy in five, allergic reaction in three and the other was a pediatric patient with pain after injection of the biosimilar drug. The acquisition cost in our hospital of an unit of the original drug is €195.6, while that of the biosimilar is €75. If we consider a dosage every two weeks, since this is the most frequent in our patients, the annual cost per patient with the original drug would be €5,085 and with the biosimilar €1,950. Therefore, the annual savings from switching from the original drug to the biosimilar is €683,560. Conclusions: Switching from the original adalimumab to the biosimilar means significant economic savings without reducing the effectiveness of the disease process. This contributes to the efficiency and sustainability of the halthcare system. In our population, 4.13% had to return to the original drug. It would be advisable to carry out the study in a larger number of patients and to continue its long-term follow-up to obtain firmer conclusions. (AU)

Contribución de la inteligencia sanitaria a la formación / Contribution of medical intelligence to training

La inteligencia sanitaria contribuye de forma importante a la mejora de la práctica clínica y la formación del personal militar de sanidad como es a través del análisis de la información sanitaria y aplicación de los resultados de este análisis a la mejora de la atención del paciente traumático grave. Los registros de trauma recogen datos que son de utilidad para su posterior análisis colaborando en el desarrollo, mejora, actualización e implantación de programas de enseñanza para el personal de sanidad en los que tiene un papel fundamental la simulación clínica. Material y métodos:Se ha realizado una búsqueda no sistemática en distintas bases de datos como Medline, Revista Military Medicine o Google Académico.Resultados y discusión:En Europa existen distintos registros de trauma, tanto civiles como militares, que recogen datos de distintos aspectos de la atención al paciente politraumatizado.Conclusión:El análisis por parte de la inteligencia sanitaria de los datos registrados y una formación eficaz con la inclusión de simulación clínica, contribuirá a la mejora de la formación del personal sanitario, tanto civil como militar, y por lo tanto al aumento de la supervivencia del paciente con trauma grave. (AU)

Introduction: Medical Intelligence contributes significantly to the improvement of clinical practice and training of military health personnel, such as through health information analysis and application of the results of this analysis to the improvement of patient severe trauma care. Trauma registries collect data that are useful for further analysis by collaborating in the development, improvement, updating and implementation of education programmes for health personnel where clinical simulation plays a key role.Material and methods:An unsystematic review has been carried out on different databases such as Medline, Military Medicine Magazine or Google Scholar.Results and discussion:In Europe there are different trauma registries, both civilian and military, which collect data on different aspects of the care of the trauma patient.Conclusion:Analysis by the Medical Intelligence of the registered data and effective training, including clinical simulation, will contribute to the improvement of the training of health personnel, both civilian and military, and therefore to increase the patient survival with severe trauma. (AU)

[Effectiveness on adherence to biological drugs and experience of a pharmaceutical intervention based on CMO model in patients with rheumatic disease (AdhER-2 study)].

BACKGROUND: We aimed to assess the effectiveness on adherence to treatment with biologic disease modifying anti-rheumatic drugs (b-DMARD) and experience with providers of healthcare of a CMO pharmaceutical intervention care model in subjects with rheu-matoid arthritis, psoriatic arthritis, and ankylosing spondylitis stratified according to their needs. METHOD: Prospective, single-centre randomized controlled study. The study period was eleven months. Non-compliant patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondy-litis treated with b-DMARD were included. Patients were randomized to a control (CG) or intervention group (IG) who received regular or the CMO pharmaceutical intervention model treatment, respec-tively. Baseline and final adherence were determined using medication possession ratio, the Compliance Questionnaire on Rheu-matology, and Morisky Medication Adherence Scale. To assess baseline and final patient experience with providers of healthcare we applied the Chronic Patient Experience Assessment Instrument (IEXPAC). RESULTS: For the IG, one patient (5.6%) was categorized as priority 1, nine (50.0%) as priority 2, and eight (44.4%) as priority 3. Ninety pharmaceutical interventions were carried out (5.1±1.8 interventions / patient). At the end of the study, the IG showed higher fre-quency of patients who adhered to the pharmaceutical intervention (77.8 vs 18.8%; p=0.002) and higher mean IEXPAC score (7.6±1.3 vs 5.8±1.1; p <0.001) in comparison to the CG. Conclusion The CMO pharmaceutical intervention model significantly improves patient adherence to b-DMARD and their experience with the providers of healthcare.

Eficacia de una intervención farmacéutica basada en el modelo CMO sobre la adherencia a fármacos biológicos y la experiencia del pacientecon enfermedad reumática (Estudio ADhER-2) / Effectiveness on adherence to biological drugs and experience of a pharmaceutical intervention based on CMO model in patients with rheumatic disease (AdhER-2 study)

Fundamento: Analizar la eficacia de una intervención farmacéutica basada en el modelo CMO sobre la adherencia a fármacos biológicos modificadores de la enfermedad (FAME-b) y sobre la experiencia con los profesionales y servicios sanitarios de pacientescon artritis reumatoide, artritis psoriásica y espondilitis anquilosante estratificados según sus necesidades de atención. Material y métodos: Estudio experimental prospectivo, unicéntrico y controlado de once meses de duración. Se incluyeron pacientes con artritis reumatoide, artritis psoriásica y espondilitis anquilosante no adherentes a FAME-b. Se aleatorizaron en grupo control (GC) e intervención (GI), que recibieron atención farmacéutica habitual o basada en CMO, respectivamente. La adherencia basaly final se calculó mediante la ratio media de posesión de medicamentos y las puntuaciones obtenidas en Compliance Questionnaire on Rheumatology y en Morisky Medication Adherence Scale. Para valorar la experiencia basal y final de los pacientes con los profesionales y servicios sanitarios se utilizó el instrumento de Evaluaciónde la Experiencia del Paciente Crónico (IEXPAC). Resultados: En el GI (n=18), solo un paciente fue estratificado como prioridad 1 (5,6%), nueve se estratificaron como prioridad2 (50,0%) y ocho como prioridad 3 (44,4%). Se realizaron 90 intervenciones farmacéuticas (5,1±1,8 intervenciones por paciente). Al finalizar el estudio, el GI mostró respecto del GC más pacientes adherentes (77,8 vs 18,8%; p=0,002) y mayor puntuación IEXPAC (7,6±1,3 vs 5,8±1,1; p <0,001). Conclusiones: La intervención farmacéutica basada en el modelo CMO mejoró significativamente la adherencia a FAME-b y la experiencia de los pacientes con los profesionales y el sistema sanitario.(AU)

Background: We aimed to assess the effectiveness on adherence to treatment with biologic disease modifying antirheumatic drugs (b-DMARD) and experience with providers of healthcare of a CMO pharmaceutical intervention care model in subjects with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis stratified according to their needs. Method: Prospective, single centre randomized controlled study. The study period was eleven months. Non compliant patients withrheumatoid arthritis, psoriatic arthritis, and ankylosing spondy litis treated with b-DMARD were included. Patients were randomized to a control (CG) or intervention group (IG) who receivedregular or the CMO pharmaceutical intervention model treatment, respectively. Baseline and final adherence were determined using medication possession ratio, the Compliance Questionnaire onRheumatology, and Morisky Medication Adherence Scale. To assess baseline and final patient experience with providers of healthcare we applied the Chronic Patient Experience Assessment Instrument (IEXPAC). Results: For the IG, one patient (5.6%) was categorized as priority1, nine (50.0%) as priority 2, and eight (44.4%) as priority 3. Ninety pharmaceutical interventions were carried out (5.1±1.8 interventions / patient). At the end of the study, the IG showed higherfrequency of patients who adhered to the pharmaceutical intervention (77.8 vs 18.8%; p=0.002) and higher mean IEXPAC score (7.6±1.3 vs 5.8±1.1; p <0.001) in comparison to the CG. Conclusion: The CMO pharmaceutical intervention model significantly improves patient adherence to b-DMARD and their experience with the providers of healthcare.(AU)

Experiencia clínica con erenumab durante el primer año de tratamiento / Clinical experience with erenumab during the first year of treatment

Introducción: El erenumab, un antagonista del péptido relacionado con el gen de la calcitonina, ha sido autorizado para la profilaxis de la migraña. Se presenta como una alternativa para pacientes con múltiples fracasos terapéuticos, los cuales presentan baja calidad de vida y alta discapacidad asociada.Objetivo: Analizar la efectividad y la seguridad del erenumab durante el primer año de tratamiento y evaluar su impacto en la calidad de vida y la discapacidad. Pacientes y métodos: Estudio observacional prospectivo longitudinal realizado durante 15 meses. Se incluyó a los pacientes que cumplían los criterios de financiación del erenumab. Se recogieron años de enfermedad, días de migraña/mes, intensidad del dolor, tratamientos previos, dosis y efectos adversos. Además, se evaluaron la calidad de vida y la discapacidad mediante los cuestionarios Migraine-Specific Quality Of Life Questionnaire 2.1 y Migraine Disability Assessment Scale, que se repitieron a los tres y a los 12 meses. Resultados:Se incluyó a 43 pacientes, el 79,1% mujeres, el 95,3% con migraña crónica y con una edad media de 48,2 años. Previamente al erenumab presentaban 20 días de migraña/mes, intensidad de dolor 8,2, un 30,6% de calidad de vida y el 72,5% tenía discapacidad muy grave. Quince pacientes suspendieron el erenumab por ineficacia y uno por intolerancia. Trece recibieron erenumab durante un año y 14 continuaban en tratamiento. Las cuatro variables de efectividad mejoraron significativamente con el erenumab al tercer mes. Quince pacientes (34,9%) presentaron efectos adversos, en su mayoría leves. El estreñimiento fue el más frecuente. Conclusiones: El erenumab mostró efectividad en la mayoría de los pacientes para profilaxis de migraña en los tres primeros meses, reduciendo significativamente los días de migraña/mes, la intensidad del dolor y la discapacidad asociada. Además, mejoró significativamente la calidad de vida. Es un fármaco seguro.(AU)

Introduction: Erenumab, a calcitonin gene-related peptide antagonist, has been approved for migraine prophylaxis. It represents an alternative for patients with multiple treatment failures, who have a low quality of life and high associated disability. Aim: To analyse the effectiveness and safety of erenumab during the first year of treatment and to assess its impact on quality of life and disability. Patients and methods. It is a longitudinal prospective observational study conducted over 15 months. Patients who met the funding criteria for erenumab were included. Data concerning years of illness, migraine days/month, pain intensity, previous treatments, doses and adverse effects were collected. In addition, quality of life and disability were assessed using the Migraine-Specific Quality Of Life Questionnaire 2.1 and Migraine Disability Assessment Scale, repeated at three and 12 months. Results: Forty-three patients were included, 79.1% female, 95.3% with chronic migraine and with a mean age of 48.2 years. Prior to erenumab they had 20 migraine days/month, a pain intensity of 8.2 and a 30.6% quality of life, and 72.5% had very severe disability. Fifteen patients stopped taking erenumab due to inefficacy and one due to intolerance. Thirteen received erenumab for one year and 14 continued with the treatment. All four effectiveness variables were significantly improved with erenumab by the third month. Fifteen patients (34.9%) had adverse effects, most of which were mild. Constipation was the most frequent. Conclusions: Erenumab proved effective in most patients for migraine prophylaxis in the first three months, significantly reducing the number of migraine days/month, pain intensity and associated disability. Moreover, it significantly improved their quality of life . It is a safe drug.(AU)

[Clinical experience with erenumab during the first year of treatment]. / Experiencia clínica con erenumab durante el primer año de tratamiento.

INTRODUCTION: Erenumab, a calcitonin gene-related peptide antagonist, has been approved for migraine prophylaxis. It represents an alternative for patients with multiple treatment failures, who have a low quality of life and high associated disability. AIM: To analyse the effectiveness and safety of erenumab during the first year of treatment and to assess its impact on quality of life and disability. PATIENTS AND METHODS: It is a longitudinal prospective observational study conducted over 15 months. Patients who met the funding criteria for erenumab were included. Data concerning years of illness, migraine days/month, pain intensity, previous treatments, doses and adverse effects were collected. In addition, quality of life and disability were assessed using the Migraine-Specific Quality Of Life Questionnaire 2.1 and Migraine Disability Assessment Scale, repeated at three and 12 months. RESULTS: Forty-three patients were included, 79.1% female, 95.3% with chronic migraine and with a mean age of 48.2 years. Prior to erenumab they had 20 migraine days/month, a pain intensity of 8.2 and a 30.6% quality of life, and 72.5% had very severe disability. Fifteen patients stopped taking erenumab due to inefficacy and one due to intolerance. Thirteen received erenumab for one year and 14 continued with the treatment. All four effectiveness variables were significantly improved with erenumab by the third month. Fifteen patients (34.9%) had adverse effects, most of which were mild. Constipation was the most frequent. CONCLUSIONS: Erenumab proved effective in most patients for migraine prophylaxis in the first three months, significantly reducing the number of migraine days/month, pain intensity and associated disability. Moreover, it significantly improved their quality of life . It is a safe drug.

TITLE: Experiencia clínica con erenumab durante el primer año de tratamiento.Introducción. El erenumab, un antagonista del péptido relacionado con el gen de la calcitonina, ha sido autorizado para la profilaxis de la migraña. Se presenta como una alternativa para pacientes con múltiples fracasos terapéuticos, los cuales presentan baja calidad de vida y alta discapacidad asociada. Objetivo. Analizar la efectividad y la seguridad del erenumab durante el primer año de tratamiento y evaluar su impacto en la calidad de vida y la discapacidad. Pacientes y métodos. Estudio observacional prospectivo longitudinal realizado durante 15 meses. Se incluyó a los pacientes que cumplían los criterios de financiación del erenumab. Se recogieron años de enfermedad, días de migraña/mes, intensidad del dolor, tratamientos previos, dosis y efectos adversos. Además, se evaluaron la calidad de vida y la discapacidad mediante los cuestionarios Migraine-Specific Quality Of Life Questionnaire 2.1 y Migraine Disability Assessment Scale, que se repitieron a los tres y a los 12 meses. Resultados. Se incluyó a 43 pacientes, el 79,1% mujeres, el 95,3% con migraña crónica y con una edad media de 48,2 años. Previamente al erenumab presentaban 20 días de migraña/mes, intensidad de dolor 8,2, un 30,6% de calidad de vida y el 72,5% tenía discapacidad muy grave. Quince pacientes suspendieron el erenumab por ineficacia y uno por intolerancia. Trece recibieron erenumab durante un año y 14 continuaban en tratamiento. Las cuatro variables de efectividad mejoraron significativamente con el erenumab al tercer mes. Quince pacientes (34,9%) presentaron efectos adversos, en su mayoría leves. El estreñimiento fue el más frecuente. Conclusiones. El erenumab mostró efectividad en la mayoría de los pacientes para profilaxis de migraña en los tres primeros meses, reduciendo significativamente los días de migraña/mes, la intensidad del dolor y la discapacidad asociada. Además, mejoró significativamente la calidad de vida. Es un fármaco seguro.

Mutations in the John Cunningham virus VP1 gene could predispose to the development of progressive multifocal leukoencephalopathy in multiple sclerosis patients undergoing treatment with natalizumab.

BACKGROUND: Patients with Multiple Sclerosis (MS) undergoing treatment with natalizumab (NTZ) are at risk of developing progressive multifocal leukoencephalopathy (PML) due to the reactivation of John Cunningham (JC) virus. A relevant characteristic among PML cases is the development of single nucleotide mutations in the VP1 gene of the causal JC virus. The identification of such mutations in timely manner can provide valuable information for MS management. OBJECTIVE: To identify mutations along the JC virus VP1 gene in MS patients undergoing treatment with NTZ, and correlate them with anti-JC virus antibody index. METHODS: Eighty-eight MS patients, one hundred twenty controls, and six patients with diagnosis of Human Immunodeficiency Virus (HIV) with and without secondary PML were included. JC virus was identified in peripheral blood mononuclear cells and cerebrospinal fluid by PCR. Amplification and sequencing of the entire length of the VP1 gene were performed in all positive clinical samples. RESULTS: In MS cases no mutations were observed in the JC virus VP1 gene, but it was positive in HIV controls with PML. Interestingly, the JC virus VP1 gene sequence derived from the HIV patients exhibited a non-silent substitution in position 186 (G â†’ C), leading to an amino acid change (Lys â†’ Asp). We did not find correlation between anti-JC virus antibody index and DNA viral detection. CONCLUSIONS: . The identification of single nucleotide mutants in the JC virus VP1 gene might be an early predictive marker to PML for efficient patient treatment and follow-up.

Radiological and surgical management of bleeding pancreatic pseudocyst in a pediatric patient. / Manejo radiológico y quirúrgico del pseudoquiste pancreático hemorrágico en el paciente pediátrico.

INTRODUCTION: The pancreas is the fourth most frequently involved solid organ in pediatric abdominal trauma. We present the case of a giant pancreatic pseudocyst secondary to trauma and how it was radiologically and surgically managed. CLINICAL CASE: This is the case of a 13-year-old male patient admitted as a result of a grade IV pancreatic lesion, which turned into a 170x86x180 mm pancreatic pseudocyst. Intracystic bleeding required radiological embolization of the proximal gastroduodenal artery. Subsequent abdominal compartment syndrome, biliary leak, and chemical peritonitis required laparotomy and collection drainage. Pancreatitis and duct fistula had a slow but favorable progression. DISCUSSION: The presence of duct damage is a failure predictor in the conservative treatment of pancreatic trauma. Surgical management could be indicated in recurrent, multiple, or giant (> 200 mm) pseudocysts. Intracystic bleeding is rare but potentially fatal. Selective angiogram could be a useful tool for improved prognosis.

INTRODUCCION: El páncreas es el cuarto órgano sólido más afectado en el traumatismo abdominal infantil. Presentamos la complicación de un pseudoquiste pancreático gigante secundario a traumatismo y su manejo radiológico y quirúrgico. CASO CLINICO: Varón de 13 años que ingresa por lesión pancreática grado IV, que evoluciona desarrollando un pseudoquiste pancreático de 170x86x180 mm. Un sangrado intraquístico requirió embolización radiológica de la arteria gastroduodenal proximal. El posterior síndrome compartimental abdominal, fuga biliar y peritonitis química obligaron a realizar una laparotomía y drenaje de colecciones. La pancreatitis y fístula ductal tuvieron una progresión lenta pero favorable. COMENTARIOS: La presencia de daño ductal es un predictor de fracaso del tratamiento conservador en el traumatismo pancreático. El manejo quirúrgico podría indicarse en pseudoquistes recurrentes, múltiples o gigantes (> 200 mm). El sangrado intraquístico es raro pero potencialmente letal, pudiendo ser la angiografía selectiva una herramienta útil en la mejora del pronóstico.

Manejo radiológico y quirúrgico del pseudoquiste pancreático hemorrágico en el paciente pediátrico / Radiological and surgical management of bleeding pancreatic pseudocyst in a pediatric patient

Introducción: El páncreas es el cuarto órgano sólido más afectadoen el traumatismo abdominal infantil. Presentamos la complicación deun pseudoquiste pancreático gigante secundario a traumatismo y sumanejo radiológico y quirúrgico. Caso clínico: Varón de 13 años que ingresa por lesión pancreáticagrado IV, que evoluciona desarrollando un pseudoquiste pancreáticode 170x86x180 mm. Un sangrado intraquístico requirió embolizaciónradiológica de la arteria gastroduodenal proximal. El posterior síndromecompartimental abdominal, fuga biliar y peritonitis química obligarona realizar una laparotomía y drenaje de colecciones. La pancreatitis yfístula ductal tuvieron una progresión lenta pero favorable. Comentarios: La presencia de daño ductal es un predictor de fraca-so del tratamiento conservador en el traumatismo pancreático. El manejoquirúrgico podría indicarse en pseudoquistes recurrentes, múltiples ogigantes (> 200 mm). El sangrado intraquístico es raro pero potencial-mente letal, pudiendo ser la angiografía selectiva una herramienta útilen la mejora del pronóstico.(AU)

Introduction: The pancreas is the fourth most frequently in-volved solid organ in pediatric abdominal trauma. We present thecase of a giant pancreatic pseudocyst secondary to trauma and howit was radiologically and surgically managed. Clinical case: This is the case of a 13-year-old male patientadmitted as a result of a grade IV pancreatic lesion, which turned into a 170x86x180 mm pancreatic pseudocyst. Intracystic bleedingrequired radiological embolization of the proximal gastroduodenalartery. Subsequent abdominal compartment syndrome, biliary leak,and chemical peritonitis required laparotomy and collection drainage.Pancreatitis and duct fistula had a slow but favorable progression. Discussion: The presence of duct damage is a failure predictorin the conservative treatment of pancreatic trauma. Surgical mana-gement could be indicated in recurrent, multiple, or giant (> 200mm) pseudocysts. Intracystic bleeding is rare but potentially fatal.Selective angiogram could be a useful tool for improved prognosis.(AU)

Expiration Date Effect on Mechanical and Chemical Properties of Glass Ionomer Cements

ABSTRACT: The glass ionomer cements (GICs) is a generic name given to a group of materials widely used in clinical dentistry which if used after the specified expiration date, material properties may be affected. to evaluate the Vick ers microhardness, surface morphology and the energy dispersive X-ray microanalysis (EDX), of GICs with different expiration dates that were stored at room temperature. specimens of highly viscous glass ionomer cement (HVGIC) (Ketac Cem and Ketac Molar) and resin-modified glass ionomer cement (RMGIC) (Vitrebond) with different expiration dates (current, close to their expiration and expired) were prepared for Vickers microhardness test and scanning electronic microscopy (SEM) with EDX, measuring 5 mm in diameter and 2 mm length, per the manufacturer's instructions, in standard cylindrical teflon molds. For the comparison of obtained values, the ANOVA test was used, while Tukey test was used for the multiple comparisons. In all the GICs used, the microhardness decreased as the expiration date approached, finding a significant statistical differen ce (P<0.05) in Ketac Molar and Vitrebond. SEM sample analysis revealed similar cohesive cracks in all tested materials. The EDX analysis revealed the presence of the elements F, Al and Si in all GICs and Ca only in Ketac Molar and Ketac Cem. The elements were found in a higher atomic percentage in the GICs with an current date and in a lower percentage in those with an expired date. HVGIC and RMGIC with an expiration date finish and that were stored at room temperature, suffer significant physical and chemical changes, which could put doubts its clinical effectiveness.

RESUMEN: El cemento de ionómero de vidrio (CIV) es un nombre genérico que se le da a un grupo de materiales ampliamente utilizados en odontología clínica que si se usan después de la fecha de vencimiento especificada, las propiedades del material pueden verse afectadas. evaluar la microdureza Vickers, la morfología superficial y el microanálisis de energía dispersa de rayos X (EDX), de CIV con diferentes fechas de caducidad almacenados a temperatura ambiente. Muestras de cemento de ionómero de vidrio de alta viscosidad (CIVAV) (Ketac Cem y Ketac Molar) y cemento de ionómero de vidrio modificado con resina (CIVMR) (Vitrebond) con diferentes fechas de vencimiento (vigente, próximo a su vencimiento y vencido) de 5 x 2 mm, fueron preparadas para microscopía electrónica de barrido (MEB) con EDX y microdureza Vickers, según las instrucciones del fabricante, en moldes de teflón cilíndricos estándar. Para la comparación de los valores obtenidos se utilizó la prueba ANOVA, mientras que para las comparaciones múltiples se utilizó la prueba de Tukey. En todos los CIV utilizados, la microdureza disminuyó a medida que se acercaba la fecha de vencimiento, encontrándose una diferencia estadística significativa (P <0.05) en Ketac Molar y Vitrebond. El análisis de la muestra en MEB reveló grietas cohesivas similares en todos los materiales probados. El análisis EDX reveló la presencia de los elementos F, Al y Si en todos los GIC y Ca solo en Ketac Molar y Ketac Cem. Los elementos se encontraron en mayor porcentaje atómico en los GIC con fecha vigente y en menor porcentaje en aquellos con una fecha vencida. Los CIVAV y CIVMR con fecha de caducidad vencida y que fueron alma- cenados a temperatura ambiente, sufrieron cambios físicos y químicos importantes, lo que podría poner en duda su efectividad clínica.

Rapamicina oral: una alternativa en niños con anomalías vasculares complicadas / Oral rapamycin: an alternative in children with complicated vascular abnormalities

Objetivos: El uso del inhibidor mTOR sirolimus ha supuesto unavance en el tratamiento de pacientes con anomalías vasculares complicadas. El objetivo de este estudio es presentar nuestra serie de pacientespediátricos con anomalías vasculares tratados con sirolimus oral y haceruna revisión de la literatura al respecto. Material y métodos: Se realizó un análisis retrospectivo de lospacientes con anomalías vasculares complicadas tratados con sirolimusoral en nuestro centro desde el año 2016. La dosis inicial utilizada fuede 0,8 mg/m2 cada 12 horas y el rango terapéutico de 5-15 ng/ml. Todos los pacientes recibieron profilaxis con trimetoprim-sulfametoxazol. Resultados: Se incluyeron seis niños, tres varones y tres mujeres, con una edad media al inicio del tratamiento de 9,5 años. Trespresentaban una malformación linfática en cabeza y cuello, dos unamalformación venosa en miembro inferior y la última una malformación combinada linfática-venosa a nivel toracoabdominal. Todos habíanrecibido múltiples tratamientos previos sin mejoría. Tras el inicio desirolimus, cinco pacientes mejoraron clínicamente (tiempo medio 3,6meses) y cuatro radiológicamente (tiempo medio 6,6 meses). Se registraron efectos adversos leves y transitorios en tres casos. Actualmente,cinco pacientes continúan con el tratamiento. Conclusiones: El sirolimus oral es un tratamiento eficaz y seguroen pacientes con anomalías vasculares complicadas. Nuestros resultadosapoyan su uso en malformaciones linfáticas y venosas en las que hanfracasado otros tratamientos, presentando buenas respuestas sintomáticasy, en menor medida, radiológicas.(AU)

Objective: Sirolimus mTOR inhibitor represents a major advancein the treatment of patients with complicated vascular abnormalities.The objective of this study was to present our series of pediatric patientswith vascular abnormalities treated with oral sirolimus, and to conducta review of the relevant literature. Materials and methods: A retrospective analysis of patients withcomplicated vascular abnormalities treated with oral sirolimus in ourhealthcare facility from 2016 was carried out. Initial dosage was 0.8 mg/m 2 every 12 hours, and therapeutic range was 5-15 ng/ml. All patientsreceived trimethoprim-sulfamethoxazole prophylaxis. Results: 6 children –3 boys and 3 girls– with a mean age of 9.5years at treatment initiation were included. 3 of them had head and necklymphatic malformation, 2 had lower limb venous malformation, and 1had combined lymphatic-venous malformation at the thoracoabdominal level. They all had received multiple previous treatments withoutimprovement. Following sirolimus initiation, 5 patients had clinicalimprovement (mean time: 3.6 months) and 4 had radiological improvement (mean time: 6.6 months). Mild and transitory adverse effects werenoted in the 3 cases. Today, 5 patients remain under treatment. Conclusions: Oral sirolimus is an effective and safe treatment inpatients with complicated vascular abnormalities. Our results supportsirolimus use in lymphatic and venous malformations in which previoustreatments have failed, with a good symptomatic and, to a lesser extent,radiological response.(AU)

Empty bed contact time: The key for micropollutant removal in activated carbon filters.

The removal of micropollutants from wastewater is an emerging issue that currently concerns the wastewater sector the most. Granular Activated Carbon (GAC) has gained recognition as a suitable technology for dealing with this problem. This study assesses the performance of six GAC-filters for the removal of micropollutants installed as final treatment step at a municipal wastewater treatment plant. The influence of the GAC-type and the Empty Bed Contact Time (EBCT) on the filter performance was evaluated. The breakthrough behaviour of 13 selected micropollutants as well as the removal of the Dissolved Organic Carbon (DOC) and UV absorption at 254 nm were investigated. Besides, the adsorbed DOC (qDOC) was introduced as assessment parameter (adsorbed and biodegraded DOC), instead of the commonly used treated bed volume. Finally, Size Exclusion Chromatography (SEC) with online DOC and UV254nm detection was applied for a better understanding of the influent and effluent characteristics. The results showed that the pore size distribution is a crucial feature of the activated carbon. A balanced proportion of macro-, meso­ and micropores may play a role in the better removal of micropollutants in presence of DOC. Regardless of the GAC-type, a minimum EBCT between 20 - 30 min was necessary. We proved that a short EBCT would not fully use the sorption capacity, whereas a long EBCT would increase the carbon demand without improving of the removal. Lastly, according to the SEC results, after a short operation time no difference between the influent and effluent chromatographable fractions (DOC and UV254nm) was observed.

Practical management of pulmonary nodules in the most common pediatric tumors. / Manejo práctico de los nódulos pulmonares en las neoplasias pediátricas más frecuentes.

In pediatric patients with sarcomas, hepatoblastomas, or other types of primary tumors, lung metastases are often found at diagnosis or during follow-up. The wide variety of primary tumors and clinical situations makes management and follow-up of these patients challenging. Chest CT is the best way to detect the dissemination of disease to the lungs. Many pulmonary nodules are nonspecific, and many might not be pathological. Others have characteristics that make them suspicious. Although there are some general features that indicate that a pulmonary nodule is likely to be a metastasis, sometimes the meaning of these features depends on the primary tumor. Furthermore, metastases can develop during the course of the disease, and the protocols for follow-up are different for different primary tumors. We review the different protocols used at our hospital for the primary tumors that most often metastasize to the lungs, including the criteria for lung metastases and the follow-up for each primary tumor.

Perceived discrimination in patients with multiple sclerosis and depressive symptomatology.

BACKGROUND: Multiple Sclerosis is the central nervous system's most common demyelinating disease and the second leading cause of neurological disability in young adults. Its natural development involves physical and cognitive impairment. Patients commonly perceive discrimination against them, regardless of its occurrence, accepting it as an inherent part of the disease. OBJECTIVE: This study aimed to determine the association between perceived discrimination and the depressive symptoms and physical disability present in patients diagnosed with multiple sclerosis, treated at the Demyelinating Diseases Clinic of the National Institute of Neurology and Neurosurgery, Manuel Velasco Suárez. METHODS: A cross-sectional study was conducted in 98 patients diagnosed with multiple sclerosis. Demographic and clinical variables were obtained through clinical interviews. The severity of the disease was determined using the Extended Disability Status Scale (EDSS), depressive symptoms were assessed with the Beck Depression Inventory (BDI), and perceived discrimination was rated using the King Internalized Stigma Scale. RESULTS: The studied sample's mean age was 36.3 years, schooling 13.6 years, symptoms onset was at 26.2 years (with a delay in diagnosis of 3.2 years), and a disease evolution of 10.9 years. 71.4% were single; 52% had an unpaid work activity and 57.1% were women. The EDSS average was 3.5 points; 24.5% presented moderate to severe depressive symptoms and 53.1% referred perceived discrimination. CONCLUSIONS: Perceived discrimination in patients with multiple sclerosis was associated with earlier disease onset, depressive symptoms, and the lack of caregivers. Medical care and life quality improvement for this vulnerable group require greater education regarding the disease and the establishment of patient support programs.

Implications of biological activated carbon filters for micropollutant removal in wastewater treatment.

Granulated Activated Carbon (GAC) filtration is a common process for advanced wastewater treatment. In such filters, the removal of organic substances results from adsorptive as well as biological processes. This work investigated the potential of biological processes and their influence on GAC-filter performance. During 32 months, the removal of micropollutants,Dissolved Organic Carbon (DOC) and the spectral absorption coefficient was monitored in six GAC-filters. The effects of pre-treatment (cloth- and/or membrane-filtration), EBCT (from 6 - 35 min) and GAC-type were evaluated. Likewise, the impact of the influent´s fluctuations in temperature, flow and concentration (ammonia, nitrate, and soluble reactive phosphorus (sRP)) were analysed. Biological processes were tracked by the frequency of backwashing, oxygen consumption, removal of poorly absorbable micropollutants and production of transformation products. Pre-treatment influenced biofilm growth significantly. Membrane filtration delayed the first backwashing event by 122 d in comparison to cloth-filtration, where the first backwash was conducted after only 21 d. Removal of poorly absorbable substances was observed early on (40 - 50 d). Parallel operation contributed to a better utilisation of the GAC-capacity and the biological removal potential. Influent nitrogen species > 0.5 mg N/L promoted biofilm growth, whereas sRP seemed to have no effect. The developed biofilm and optimal operating conditions led to longer life spans of the GAC-filters, making carbon usage rates comparable to those from PAC applications. The results suggest that biological processes accounted for about 25 - 42% of the totally removed DOC at the end of the operation.

Oral rapamycin: an alternative in children with complicated vascular abnormalities. / Rapamicina oral: una alternativa en niños con anomalías vasculares complicadas.

OBJECTIVE: Sirolimus mTOR inhibitor represents a major advance in the treatment of patients with complicated vascular abnormalities. The objective of this study was to present our series of pediatric patients with vascular abnormalities treated with oral sirolimus, and to conduct a review of the relevant literature. MATERIAL AND METHODS: A retrospective analysis of patients with complicated vascular abnormalities treated with oral sirolimus in our healthcare facility from 2016 was carried out. Initial dosage was 0.8 mg/m2 every 12 hours, and therapeutic range was 5-15 ng/ml. All patients received trimethoprim-sulfamethoxazole prophylaxis. RESULTS: 6 children -3 boys and 3 girls- with a mean age of 9.5 years at treatment initiation were included. 3 of them had head and neck lymphatic malformation, 2 had lower limb venous malformation, and 1 had combined lymphatic-venous malformation at the thoracoabdominal level. They all had received multiple previous treatments without improvement. Following sirolimus initiation, 5 patients had clinical improvement (mean time: 3.6 months) and 4 had radiological improvement (mean time: 6.6 months). Mild and transitory adverse effects were noted in the 3 cases. Today, 5 patients remain under treatment. CONCLUSIONS: Oral sirolimus is an effective and safe treatment in patients with complicated vascular abnormalities. Our results support sirolimus use in lymphatic and venous malformations in which previous treatments have failed, with a good symptomatic and, to a lesser extent, radiological response.

OBJETIVOS: El uso del inhibidor mTOR sirolimus ha supuesto un avance en el tratamiento de pacientes con anomalías vasculares complicadas. El objetivo de este estudio es presentar nuestra serie de pacientes pediátricos con anomalías vasculares tratados con sirolimus oral y hacer una revisión de la literatura al respecto. MATERIAL Y METODOS: Se realizó un análisis retrospectivo de los pacientes con anomalías vasculares complicadas tratados con sirolimus oral en nuestro centro desde el año 2016. La dosis inicial utilizada fue de 0,8 mg/m2 cada 12 horas y el rango terapéutico de 5-15 ng/ml. Todos los pacientes recibieron profilaxis con trimetoprim-sulfametoxazol. RESULTADOS: Se incluyeron seis niños, tres varones y tres mujeres, con una edad media al inicio del tratamiento de 9,5 años. Tres presentaban una malformación linfática en cabeza y cuello, dos una malformación venosa en miembro inferior y la última una malformación combinada linfática-venosa a nivel toracoabdominal. Todos habían recibido múltiples tratamientos previos sin mejoría. Tras el inicio de sirolimus, cinco pacientes mejoraron clínicamente (tiempo medio 3,6 meses) y cuatro radiológicamente (tiempo medio 6,6 meses). Se registraron efectos adversos leves y transitorios en tres casos. Actualmente, cinco pacientes continúan con el tratamiento. CONCLUSIONES: El sirolimus oral es un tratamiento eficaz y seguro en pacientes con anomalías vasculares complicadas. Nuestros resultados apoyan su uso en malformaciones linfáticas y venosas en las que han fracasado otros tratamientos, presentando buenas respuestas sintomáticas y, en menor medida, radiológicas.