Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia.

BACKGROUND: Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5'-phosphate-PLP-and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. RESULTS: The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (-GT) of pathogenic ALPL variants: 40 +GT and 37 -GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP < 25 UI/L (model 1), the area under curve (AUC) and the 95% confidence intervals (CI) was 0.68 (95% CI 0.63-0.72) and it improved to 0.87 (95% CI 0.8-0.9), when PEA or PLP threshold levels were added (models 2 and 3), reaching 0.94 (0.91-0.97) when both substrates were included (model 4). The internal validation showed that the addition of serum PLP threshold levels to the model just including ALP improved significantly sensitivity (S) and negative predictive value (NPV) - 100%, respectively- with an accuracy (AC) of 93% in comparison to the inclusion of urinary PEA (S: 71%; NPV 75% and AC: 79%) and similar diagnostic utility measures as those observed in model 3 were detected when both substrates were added. CONCLUSIONS: In this study, we propose a biochemical predictive model based on the threshold levels of the main biochemical markers of HPP (ALP < 25 IU/L and PLP > 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variants.

Patología pulmonar intersticial / Interstitial lung disease

No disponible

Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia?

BACKGROUND: Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase-ALP-measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. RESULTS: Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9-30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9-13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p < 0.05) in this group. Regarding laboratory features, median ALP levels were lower in subjects with ALPL variants (26 vs 29 IU/L; p < 0.005). Interestingly, the threshold of ALP levels < 25 IU/L showed a specificity, positive predictive value and positive likelihood ratio of 97.8, 94.4% and 19.8 to detect a positive ALPL test, respectively. CONCLUSIONS: In subjects with persistent hypophosphatasaemia -secondary causes excluded- one out of two presented ALPL variants. Musculoskeletal pain and ALP levels < 25 IU/L are associated with this variant(s). In this scenario, ALP levels < 25 IU/L seem to be very useful to identify individuals with the presence of an ALPL variant.

Osteoporosis y psoriasis / Osteoporosis and Psoriasis

La psoriasis es un proceso inflamatorio crónico que se ha asociado con múltiples comorbilidades, especialmente las formas más graves y asociadas a artritis. El estado de inflamación sistémica es, probablemente, la conexión entre todas estas enfermedades concomitantes. Algunos trabajos recientes indican que los pacientes con psoriasis pueden tener mayor riesgo de fracturas patológicas y osteoporosis. Las guías actuales de abordaje de las comorbilidades de la psoriasis no incluyen valoración de la salud del hueso. Por eso, en este artículo nos proponemos revisar la evidencia disponible sobre la relación entre psoriasis y osteoporosis. Repasaremos primero el concepto de osteoporosis, abordaremos también el papel de la vitamina D en el hueso y, por último, proponemos un algoritmo de manejo y tratamiento de la osteoporosis en el paciente con psoriasis

Psoriasis is a chronic inflammatory disease associated with multiple comorbidities, particularly in patients with arthritis or more severe forms of the disease. The link between all these comorbidities is probably systemic inflammation. Several recent studies have indicated that patients with psoriasis may be at an increased risk of pathologic fractures and osteoporosis. Current guidelines on comorbidities in psoriasis do not recommend assessment of bone health. In this article, we review the available evidence on the association between psoriasis and osteoporosis. We first examine the concept of osteoporosis and the role of vitamin D in bone health and then propose an algorithm for managing and treating this condition in patients with psoriasis

Osteoporosis and Psoriasis. / Osteoporosis y psoriasis.

Psoriasis is a chronic inflammatory disease associated with multiple comorbidities, particularly in patients with arthritis or more severe forms of the disease. The link between all these comorbidities is probably systemic inflammation. Several recent studies have indicated that patients with psoriasis may be at an increased risk of pathologic fractures and osteoporosis. Current guidelines on comorbidities in psoriasis do not recommend assessment of bone health. In this article, we review the available evidence on the association between psoriasis and osteoporosis. We first examine the concept of osteoporosis and the role of vitaminD in bone health and then propose an algorithm for managing and treating this condition in patients with psoriasis.

Alendronate after denosumab discontinuation in women previously exposed to bisphosphonates was not effective in preventing the risk of spontaneous multiple vertebral fractures: two case reports.

At denosumab discontinuation, an antiresorptive agent is indicated to reduce the high bone turnover, the rapid bone loss, and the risk of spontaneous vertebral fractures. We report two cases of postmenopausal women, previously exposed to bisphosphonates, treated with alendronate at denosumab discontinuation. Alendronate was ineffective to avoid spontaneous clinical vertebral fractures. They presented three and nine spontaneous vertebral fractures 8 and 12 months after denosumab discontinuation, respectively. Ineffectiveness of alendronate was attributed to insufficient control of the rebound as assessed by B-crosslaps measures in the first case, and partially to the high risk of fractures in the later. In both situations, the increased fracture risk may have favoured these new fractures. It is urgent to define effective therapeutic strategies to avoid spontaneous vertebral fractures after denosumab discontinuation.

Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells.

PURPOSE: Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia; however, no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters. METHODS/PATIENTS: Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were analyzed by RT-qPCR. RESULTS: Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocytic leukemia patients statistically correlate with a blocked autophagic flux. CONCLUSION: Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.

Spatial characterization of landscapes through multifractal analysis of DEM.

Landscape evolution is driven by abiotic, biotic, and anthropic factors. The interactions among these factors and their influence at different scales create a complex dynamic. Landscapes have been shown to exhibit numerous scaling laws, from Horton's laws to more sophisticated scaling of heights in topography and river network topology. This scaling and multiscaling analysis has the potential to characterise the landscape in terms of the statistical signature of the measure selected. The study zone is a matrix obtained from a digital elevation model (DEM) (map 10 × 10 m, and height 1 m) that corresponds to homogeneous region with respect to soil characteristics and climatology known as "Monte El Pardo" although the water level of a reservoir and the topography play a main role on its organization and evolution. We have investigated whether the multifractal analysis of a DEM shows common features that can be used to reveal the underlying patterns and information associated with the landscape of the DEM mapping and studied the influence of the water level of the reservoir on the applied analysis. The results show that the use of the multifractal approach with mean absolute gradient data is a useful tool for analysing the topography represented by the DEM.

First experience of enzyme replacement therapy with idursulfase in Spanish patients with Hunter syndrome under 5 years of age: case observations from the Hunter Outcome Survey (HOS).

Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans (GAGs), multisystem organ failure and early death. Enzyme replacement therapy (ERT) with idursulfase is commercially available since 2007. Early access programs were established since 2005. However, limited information on the effects of ERT in young children is available to date. The aim of this analysis was therefore to determine the effects of ERT on patients younger than 5 years of age. We report data from six Spanish patients with confirmed Hunter syndrome who were younger than 5 years at the start of ERT, and had been treated with weekly intravenous infusions of idursulfase between 6 and 14 months. Baseline and treatment data were obtained from the Hunter Outcome Survey (HOS). HOS is an international database of MPS II patients on ERT or candidates to be treated, that collects data in a registry manner. HOS is supported by Shire Human Genetic Therapies, Inc. (Cambridge, MA, USA). At baseline, all patients showed neurological abnormalities, including ventriculomegaly, hydrocephaly, cerebral atrophy, perivascular changes and white matter lesions. Other signs and symptoms included thoracic deformity, otitis media, joint stiffness and hepatosplenomegaly, demonstrating that children under 5 years old can also be severely affected. ERT reduced urinary GAG levels, and reduced spleen (n = 2) and liver size (n = 1) after only 8 months. Height growth was maintained within the normal range during ERT. Joint mobility either stabilized or improved during ERT. In conclusion, this case series confirms the early onset of signs and symptoms of Hunter syndrome and provides the first evidence of ERT beneficial effects in patients less than 5 years of age. Similar efficacy and safety profiles to those seen in older children can be suggested, although further studies including a direct comparison with older patients would still be required.

Third cycle university studies in Europe in the field of agricultural engineering and in the emerging discipline of biosystems engineering.

The main objectives of European Thematic Network entitled 'Education and Research in Agricultural for Biosystems Engineering in Europe (ERABEE-TN)' is to initiate and contribute to the structural development and the assurance of the quality assessment of the emerging discipline of Biosystems Engineering in Europe. ERABEE is co-financed by the European Community in the framework of the LLP Programme. The partnership consists of 35 participants from 27 Erasmus countries, out of which 33 are Higher Education Area Institutions (EDU) and 2 are Student Associations (ASS). 13 Erasmus participants (e.g. Thematic Networks, Professional Associations, and Institutions from Brazil, Croatia, Russia and Serbia) are also involved in the Thematic Network through synergies. To date, very few Biosystems Engineering programs exist in Europe and those that are initiated are at a very primitive stage of development. The innovative and novel goal of the Thematic Network is to promote this critical transition, which requires major restructuring in Europe, exploiting along this direction the outcomes accomplished by its predecessor; the USAEE-TN (University Studies in Agricultural Engineering in Europe). It also aims at enhancing the compatibility among the new programmes of Biosystems Engineering, aiding their recognition and accreditation at European and International level and facilitating greater mobility of skilled personnel, researchers and students. One of the technical objectives of ERABEE is dealing with mapping and promoting the third cycle studies (including European PhDs) and supporting the integration of research at the 1st and 2nd cycle regarding European Biosystems Engineering university studies. During the winter 2008 - spring 2009 period, members of ERABEE conducted a survey on the contemporary status of doctoral studies in Europe, and on a possible scheme for promotion of cooperation and synergies in the framework of the third cycle of studies and the European Doctorate in Biosystems Engineering in Europe. This paper presents the results of the survey. The legal regulations and their extent on the different countries concerning the third cycle are presented, along with the current structure of third cycle studies. The evolution and adaptation to the new EHEA in each country is also considered. Information was also gathered on the emerging topics of the Biosystems Engineering field and how these topics could be addressed by the new doctoral programmes at the European level.

El riesgo de gractura en mujeres con osteoporosis. Subestudio OSSO (Estudio observacional de osteoporosis grave) / Clinical characteristics that may ncrease the fracture risk in women with osteoporosis. OSSO sub-study (Observational study of severe osteoporosis)

Las mujeres con osteoporosis establecida presentan un mayor riesgo de fracturas y un deterioro de su calidad de vida. El objetivo del estudio es determinar las características clínicas que pueden alertar a los médicos a la hora del diagnóstico. En el subestudio que aquí se presenta se obtuvieron grupos emparejados: uno con características asociadas al aumento del riesgo de fractura y un grupo control sin dichas características. Se compararon los factores de riesgo y la calidad de vida. En los 104 pares relacionados encontrados no se observaron diferencias en la mayoría de factores de riesgo de osteoporosis. Las escalas empleadas mostraron una reducción significativa de la calidad de vida en el grupo que presentaba cualquiera de los criterios de riesgo elevado de fracturas (p < 0,05). La presencia de fracturas múltiples o de antecedentes de respuesta inadecuada a fármacos para la osteoporosis está asociada con una peor calidad de vida

Established osteoporosis in women is associated with a higher risk of fractures and poor quality of life. The objective of this study was to determine clinical features that could alert clinicians during diagnosis. Risk factors and quality of life were compared in paired groups. The first group presented clinical features related to increased risk of fracture, while the second, the control group, did not. Although 104 pairs were studied, no differences were found for the majority of osteoporosis risk factors. Nevertheless, the scales used showed a significant reduction in quality of life in the group that presented a higher fracture risk (P < 0.05). The existence of multiple fractures or a history of inadequate response to osteoporosis treatment is related to poorer quality of life

[Parapneumonic effussion. A review of 33 cases over 6 years]. / Derrame pleural paraneumónico. Revision de 33 casos en 6 años.

UNLABELLED: The incidence of empyema thoracis in children seems to be increasing. The objective [corrected] of this study is to propose a rational initial treatment of parapneumonic effusions in order to reduce hospital stay and late-stage empyema complications. Medical records of 33 children presenting parapneumonic effusions who required any surgical therapy between 1997 and 2002 were reviewed. They were grouped as (I) successful management with chest tube, (II) successful management with intrapleural instillation of urokinase and (III) successful surgical treatment: (IIIa) thoracoscopy or (IIIb) thoracotomy. CONCLUSION: Early sonographic evaluation of parapneumonic effusions is usefull to evaluate the severity of disease and the need for surgical intervention. Thoracoscopic-assisted surgery is an effective treatment for pediatric early-stage empyema. Thoracotomy is indicated for most children with established empyema.

Derrame pleural paraneumónico. Revisión de 33 casos en 6 años / Parapneumonic effusion. A review of 33 cases over 6 years

La incidencia de derrames paraneumónicos complicados está aumentando en pediatría. El objetivo de este trabajo es establecer una pauta de manejo precoz de los niños con derrame paraneumónico desde el momento del diagnóstico, con el fin de disminuir la estancia hospitalaria y evitar las complicaciones derivadas del empiema organizado. Para ello se revisaron las historias clínicas de 33 niños con derrame paraneumónico que precisó tratamiento específico para su resolución, atendidos entre 1997 y 2000. Se dividieron en los siguientes grupos de tratamiento: (I) drenaje del derrame mediante tubo de tórax; (II) desbridamiento de la cavidad pleural con urokinasa; (III) procedimientos quirúrgicos: (IIIa) toracoscopia y (IIIb) toracotomía. Conclusiones: la ecografía torácica precoz es útil en la evaluación de la severidad del derrame y la necesidad de tratamientos más agresivos. La toracoscopia es una técnica segura y eficaz en el manejo precoz del empiema en los niños. La toracotomía está indicada para el tratamiento del empiema organizado (AU)

The incidence of empyema thoracis in children seems to be increasing. The objetive of this study is to propose a rational initial treatment of parapneumonic effusions in order to reduce hospital stay and late-stage empyema complications. Medical records of 33 children presenting parapneumonic effusions who required any surgical therapy between 1997 and 2002 were reviewed. They were grouped as (I) successful management with chest tube, (II) successful management with intrapleural instillation of urokinase and (III) successful surgical treatment: (IIIa) thoracoscopy or (IIIb) thoracotomy. CONCLUSION: Early sonographic evaluation of parapneumonic effusions is usefull to evaluate the severity of disease and the need for surgical intervention. Thoracoscopic –assisted surgery is an effective treatment for pediatric early-stage empyema. Thoracotomy is indicated for most children with established empiema (AU)

Algunos aspectos de la anorexia nerviosa / Some aspects of the nervous anorexia

La anorexia nerviosa es un trastorno de origen psíquico que afecta a la conducta alimentaria y constituye un complejisimo cuadro compuesto de múltiples factores de todo orden que interactúan entre sí condicionándose o potenciándose. Estos pacientes presentan una serie de rasgos comunes, como son una baja autoestima, una valoración negativa de su aspecto personal, una actitud muy crítica en relación con su ingesta, una arraigada creencia en la falta de control sobre su peso y, sobre todo, la equiparación entre autocontrol y adelgazamiento. Se revisa la etipatogenia, los aspectos epidemiológicos, el cuadro clínico, el diagnóstico, las fases de la anorexia y los aspectos socioculturales y familiares. Por tanto, la anorexia nerviosa es un trastorno de la esfera oroalimenticia que afecta en la etapa adolescente fundamentalmente a las mujeres. Aunque la causa de esta patología es desconocida existe un nutrido grupo de factores que desencadenan y mantienen la enfermedad. El cuadro clínico afecta a numerosas funciones orgánicas entre las que destacamos la amenorrea. En cuanto a la recuperación de la enfermedad, destacamos la separación ambiental del paciente y así poder crear una situación de individuación (AU)

Urticaria crónica por parasitación intestinal: a propósito de un caso / Concerning a case of chronic urticaria due to intestinal parasites

No disponible

Incidencia de la diabetes mellitus tipo 1 en la población de 0-14 años de edad, de la provincia de Jaén (1995-2000) / No disponible

Antecedentes. Los estudios de incidencia de diabetes tipo 1 son prioritarios para establecer tendencias y diferencias geográficas que ayuden a clarificar los factores ambientales que pueden intervenir. Y a un mejor conocimiento de la enfermedad. Objetivo. Conocer la incidencia de diabetes tipo 1, en la población de 0-14 años de edad, de la provincia de Jaén, durante el periodo 1995-2000. Pacientes y métodos. Diseño observacional, longitudinal y retropectivo. Los criterios de definición de casos fueron: criterios diagnósticos (normas del “NDDG” y “ADA”, edad de 0-14 años, y residencia de Jaén de forma habitual. La fuente de identificación fueron las historias clínicas de la red hospitalaria provincial. La población de rieso se estableció según datos y estimaciones censales. Se calculó la densidad de incidencia por años yla incidencia media para los seis años de estudio. Resultados. La incidencia media observada en Jaén es de 15.24 casos/105 niños-año; apreciándose, desde el año 1996 a 2000 una ligerísima tendencia a la disminución de las incidencias anuales (20,2 casos /105 niños a 12,1 casos/105). Se observó un ligero predominio de incidencia entre los varones, muy marcado en el grupo de 0-4 años de edad, donde el cociente de incidencias varón: mujer alcanza una cifra de cuatro. El grupo de edad de 5-9 años es el de mayor incidencia de diabetes, siendo llamativa la baja incidencia observada en niñas de 0-4 años de edad. Conclusiones. La incidencia de diabetes tipo 1 en Jaén en menor de la esperada y se observa una relativa estabilidad o ligero descenso en el peiodo de 1996-2000 (AU)

Introduction. The studies about incidence of diabetes mellitus type 1 (DM-1) are very important in order to establish geographical differences and to clarify the role of environment factors in the pathogenesis of the illness. Objedtive. Knowing the incidence of DM_1 in children younger than 14 years old in Jaén from 1995-2000. Patients and methods. We notice a slight tendency for annual incidence to go dow (from 20,2 cases/105 children to 12,1 cases/105). There was a slightly greater incidence in males than in females, specially in children 0 to 4 years of age. The highest incidence was observed among children 5 to 9 years of age and the lowest one in children diagnosed within the first year of live. Conclusions. The incidence of DM_1 in Jaén is lower than we expected and there is an very slight tendency to lower form 1996 to 2000 (AU)

[Continuing education in primary care: the educational needs of its professionals]. / Formación continuada en atención primaria: necesidades formativas de sus profesionales.

OBJECTIVES: To find professionals' suggestions for training contents, the value they place on various options, the difficulties they detect for attending activities and their preferences for time-table and format of courses. DESIGN: Cross-sectional, descriptive study. SETTING: Primary Care Area 7 in Madrid. PARTICIPANTS: Medical and office workers from the area (n=1,053). MAIN MEASUREMENTS: An anonymous self-filled questionnaire. RESULTS: 39% replied (46% nurses; 42% administrative assistants, and 40% doctors). The subjects for courses most often requested by doctors were dermatology, minor surgery and radiology; by nurses, emergency, functional bandages and computer skills; and by administrative assistants, computers, management of health service delivery and Internet. The continuing education options valued most highly were courses/workshops in the area's continuing education programme, self-training sessions and rotations. The main difficulties for attending courses were the lack of budget for cover and time-tables outside working hours. 42% preferred mornings; and 35%, courses lasting more than 20 hours. CONCLUSIONS: The training needs expressed by doctors and nurses are mainly clinical in content, whereas those of office staff are mainly computer-related. The most highly valued training options are the courses/workshops in the area's continuing education programme. The main difficulty for attending courses is the lack of cover for their job.

Formación continuada en atención primaria: necesidades formativas de sus profesionales / Continuing education in primary care: the educational needs of its professionals

Objetivo. Conocer las sugerencias en contenidos formativos expresadas por los profesionales, el valor que asignan a las diferentes opciones, las dificultades detectadas para la asistencia a las actividades presenciales y sus preferencias en cuanto a horario y formato de los cursos. Diseño. Estudio descriptivo transversal. Emplazamiento. Área 7 de Atención Primaria de Madrid. Participantes. Profesionales sanitarios y no sanitarios del área (n = 1.053). Mediciones principales. Encuesta autocumplimentada y anónima. Resultados. Porcentaje de respuestas: 39 per cent (enfermeras 46 per cent; auxiliares administrativos 42 per cent, y médicos 40 per cent). Las áreas temáticas que más solicitan los médicos son dermatología, cirugía menor y radiología; las enfermeras: urgencias, vendajes funcionales e informática, y los administrativos: informática, gestión de prestaciones del servicio sanitario y aplicaciones en Internet. Las opciones de formación continuada a las que asignan un mayor valor son cursos/talleres del programa de formación continuada del área, sesiones autoformativas y rotaciones. Las principales dificultades expresadas para la asistencia a los cursos son la falta de presupuesto de suplencias y horarios fuera de la jornada laboral. El 42 per cent prefiere el horario de mañana y el 35 per cent los cursos de más de 20 h. Conclusiones. Las necesidades formativas expresadas por los médicos y enfermeras son mayoritariamente de contenido clínico, y las de los administrativos están relacionadas con la informática. Las opciones formativas más valoradas son los cursos/talleres del programa de formación continuada del área y la principal dificultad expresada para la asistencia a cursos es la no suplencia del puesto de trabajo. (AU)