Search

The FaSt-SWOT project is funded by the Spanish Research Agency and the European Regional Development Fund (AEI/FEDER, UE) under Grant Agreement (PID2021-122417NB-I00). The present research is conducted within the framework of the activities of the Spanish Government through the "María de Maeztu Centre of Excellence'' accreditation to IMEDEA (CSIC-UIB) (CEX2021-001198). The Spanish Ministry of Science and Innovation, the Regional Government of the Balearic Islands and the Spanish Research Council (CSIC) are acknowledged for their support to the ICTS SOCIB. A. P., B. M. and B. B. L. thank the European Union funding through the EuroSea project an Horizon 2020 research and innovation programme under grant agreement No 862626., With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001198).

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

The Catalonian Newborn Screening Program (CNSP) began in 1969, in Barcelona. It was promoted by Dr. Juan Sabater Tobella and supported by Barcelona Provincial Council and Juan March Foundation. That is how the Institute of Clinical Biochemistry was born, whose aims were diagnosis, research and teaching, along with the spirit of contributing to the prevention of mental retardation. The CNSP began with the detection of phenylketonuria (PKU), and, in 1982, the Program was expanded with the inclusion of congenital hypothyroidism detection. Towards 1990, the Program covered almost 100% of all newborns (NB) in Catalonia. In 1999, the CNSP was expanded with the incorporation of cystic fibrosis. It took fourteen years, until 2013, to make the largest expansion so far, with the incorporation of 19 metabolic diseases to the screening panel. The detection of sickle cell disease began in 2015 and in 2017 the detection of severe combined immunodeficiency was included. Currently, the CNSP includes 24 diseases in its main panel. Since 1969, 2,787,807 NBs have been screened, of whom 1,724 have been diagnosed with any of these diseases, and 252 of other disorders by differential diagnosis with those included in the main panel. The global prevalence is 1: 1,617 NBs affected by any of the diseases included in the CNSP and 1: 1,140 NBs if incidental findings diagnosed through the CNSP are included.

Refractoriness to induction therapy and relapse after complete remission are the leading causes of death in patients with acute myeloid leukaemia (AML). This study focussed on the prediction of response to standard induction therapy and outcome of patients with AML using a combined strategy of mutational profiling by next-generation sequencing (NGS, n = 190) and ex vivo PharmaFlow testing (n = 74) for the 10 most widely used drugs for AML induction therapy, in a cohort of adult patients uniformly treated according to Spanish PETHEMA guidelines. We identified an adverse mutational profile (EZH2, KMT2A, U2AF1 and/or TP53 mutations) that carries a greater risk of death [hazard ratio (HR): 3·29, P

The pathophysiology of restless legs syndrome (RLS) is complex. Secondary RLS with iron deficiency -which suggests disturbed iron homeostasis- remains to be elucidated.We report the findings from a unique blood donor family with RLS. Three blood donors family members were diagnosed with RLS defined by the International RLS Study Group and without history of neurologic diseases and RLS symptoms in the last 3-5 years (range of blood donation: 10-40 years). The neurological examination and electromyographies were normal. A polisomnography showed disturbed nocturnal sleep with a reduction in sleep efficiency and an increased periodic limbs movement index. The cranial MRI showed brain iron deposits in basal ganglia, substantia nigra, red nuclei and dentate nuclei. Phenotypic and genotypic studies rule out genetic haemochromatosis or iron overload.The abnormal iron accumulation in the basal ganglia indicated a complex iron metabolism disorder of the central nervous system. Further studies are warranted to confirm our findings and its role in the pathophysiology of RLS.Aumento de los depositos cerebrales de hierro en una familia de donantes de sangre con sindrome de piernas inquietas.Introduccion. La fisiopatologia del sindrome de piernas inquietas (SPI) es compleja. El mecanismo a traves del cual la ferropenia favorece el desarrollo del SPI no esta esclarecido, aunque se sugiere la presencia de una alteracion en la homeostasis cerebral del hierro. Casos clinicos. Se presentan los hallazgos inusuales en una familia de donantes de sangre con SPI. Tres miembros de la misma familia fueron diagnosticados de SPI, cumpliendo los criterios definidos por el grupo internacional para el estudio del SPI (International Restless Legs Syndrome Study Group). Todos eran donantes de sangre habituales (rango de donacion: 10-40 años) y los sintomas de SPI tenian un curso de 3-5 años. La exploracion general y neurologica fue normal en todos los casos, asi como los electromiogramas. El estudio fenotipico y genotipico descarto la presencia de hemocromatosis y otras causas geneticas de sobrecarga cerebral de hierro. Los estudios polisomnograficos mostraron sueño nocturno perturbado, con reduccion de su eficiencia, y un aumento del indice de movimientos periodicos de las piernas. La resonancia magnetica craneal evidencio un aumento de los depositos cerebrales de hierro en los ganglios basales, la sustancia negra, el nucleo rojo y los dentados. Conclusion. Este aumento patologico de los depositos cerebrales de hierro sugiere la presencia de un complejo trastorno del metabolismo cerebral del hierro en nuestros pacientes. Futuros estudios deben confirmar estos hallazgos y profundizar en el estudio de su relacion con la fisiopatologia del SPI.

The reason cancer pain remains prevalent and hard to classify may be partially explained by the failure to identify neuropathic mechanisms. The objective of this research was to identify the syndromes of cancer pain that may be particularly hard to manage due to their mixed pathophysiology.

Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients and has prognostic impact. Our purpose is to determine the correlation between the observed CR/CRi rate after idarubicin (IDA) and cytarabine (CYT) 3 + 7 induction and the leukemic chemosensitivity measured by an ex vivo test of drug activity. Bone marrow samples from adult patients with newly diagnosed AML were included in this study. Whole bone marrow samples were incubated for 48 h in well plates containing IDA, CYT, or their combination. Pharmacological response parameters were estimated using population pharmacodynamic models. Patients attaining a CR/CRi with up to two induction cycles of 3 + 7 were classified as responders and the remaining as resistant. A total of 123 patients fulfilled the inclusion criteria and were evaluable for correlation analyses. The strongest clinical predictors were the area under the curve of the concentration response curves of CYT and IDA. The overall accuracy achieved using MaxSpSe criteria to define positivity was 81%, predicting better responder (93%) than non-responder patients (60%). The ex vivo test provides better yet similar information than cytogenetics, but can be provided before treatment representing a valuable in-time addition. After validation in an external cohort, this novel ex vivo test could be useful to select AML patients for 3 + 7 regimen vs. alternative schedules., This study was supported by grants from the Spanish Ministry of Economy, Industry and Competitiveness, Enisa (Empresa Nacional de Innovación, S.A.) and Soprea (Sociedad para la Promoción y Reconversión Económica de Andalucía, S.A.U.).

Objetivos: Describir nuestra experiencia preliminar en el tratamiento de metástasis vertebrales mediante radiofrecuencia y cifoplastia combinadas en sesión única. Material y métodos: Se trataron cuatro pacientes con metástasis vertebral única confirmada histológicamente (mama, próstata, pulmón y mieloma en D12, L1, L5 y D12, respectivamente). La indicación en todos los casos fue el dolor con una mala respuesta al tratamiento médico habitual. Todos los pacientes presentaban dolor en el rango 6-7 de la escala visual analógica (EVA). En dos casos existía lesión lítica del muro posterior. Tras la obtención del consentimiento informado se realizó el procedimiento bajo sedación e infiltración anestésica local. Se efectuó abordaje transpedicular bilateral con sistemas de punción ósea 11G. Se insertaron de forma coaxial dos agujas de radiofrecuencia para efectuar un ciclo de ablación por cada pedículo. Durante el ciclo de ablación la punta del dispositivo correspondiente se situó en la unión del tercio medio con el tercio anterior del cuerpo vertebral, empleando la segunda aguja como sensor térmico, con su extremo a la altura del muro posterior. La duración de cada ciclo de ablación fue de 8 minutos, alcanzando temperaturas intratumorales de 70-80 ºC. A continuación se realizó cifoplastia transpedicular. Resultados: No se registraron complicaciones intra-periprocedimiento, con alta domiciliaria en las 24 horas siguientes. En todos los pacientes hubo una mejoría inmediata del dolor tras el procedimiento (con dolor de intensidad 1-2 de la EVA). En tres pacientes se retiró progresivamente la medicación analgésica, sin evidencia en ninguno de ellos de progresión local de la enfermedad ni recurrencia-aumento del dolor en el seguimiento (dolor de intensidad 1 de la EVA en un seguimiento en el rango de 8-14 meses). En un paciente no se pudo efectuar seguimiento clínico-radiológico posterior al alta. Conclusión: El empleo de radiofrecuencia asociada a cifoplastia en la enfermedad metastásica vertebral puede contribuir al manejo del dolor refractario al tratamiento médico y al control local de la enfermedad. Objectives: Describe our preliminary experience in the treatment of vertebral metastases by radiofrequency and Kyphoplasty combined in one single session. Material and methods: Four patients with histologically confirmed single spinal metastasis (breast, prostate, lung and myeloma in L1, L5, D12, D12, respectively) were treated. The indication in all cases was pain with a poor response to medical treatment. All patients had pain in the range 6-7 visual analogue scale (VAS). In two cases there was a lytic lesion of the spinal posterior wall. After obtaining informed consent, and under sedation and local anesthetic the procedure took place. The transpedicular approach took place with a 11 G bone puncture system. Two radiofrequency needles were coaxially inserted to carry out an ablation cycle through each pedicle. During the ablation cycle the tip of the ablation neddle stood between the anterior and middle third of the vertebral body, while the second needle was used as thermal sensor with its end to the height of the vertebral posterior wall. The duration of each cycle of ablation was 8 minutes reaching intratumoral temperatures of 70-80 ºC. Transpedicular Kyphoplasty was performed subsequently. Results: No complications were reported during or after the procedure and patients were discharged in the first 24 hours. There was an immediate improvement in pain after the procedure (with a VAS 1-2 intensity pain) in all patients. During follow up, analgesic medication was withdrawn in three patients, and there was no evidence of disease progression or recurrence of pain (pain intensity 1 (VAS) in a follow-up in the range of 8-14 months). Clinical and radiological follow-up after discharge could not be performed on a patient. Conclusion: The use of radio-frequency associated with Kyphoplasty in vertebral metastatic disease can contribute to the management of refractory pain to medical treatment.

Background: CoQ10 deficiencies are associated to mutations in genes of CoQ biosynthesis and respond to CoQ10 supplementation. Early treatment allows better outcome. Therefore, early diagnosis is desirable. Objectives: Developing a non-radioactive methodology for fibroblast CoQ10 biosynthesis quantification that enables discriminating primary deficiencies. Methods: Fibroblasts were incubated 72 h with 28 ?M 2 H3-mevalonate or 1.65 mM 13 C6-p-hydroxybenzoate. The labeled CoQ10 synthesized was analyzed by HPLC-MS/MS. Patients: A) To validate the method: one patient with confirmed primary deficiency (COQ2 mutation) and 6 patients with CoQ10 deficiency secondary to other inborn errors of metabolism (ETF, ETFDH, VLCAD, MELAS or Nieman-Pick Type C). B) 3 groups of CoQ10 deficiencies: 1) 3 Patients heterozygous for one COQ gene; 2) 5 without mutations in the genes studied but responsive to CoQ10, 3) 9 clearly deficient, without further genetic or therapeutical studies. Results and discussion: A) We have demonstrated that our method is suitable for discriminating between primary and secondary deficiencies. B) 10/17 patients' fibroblasts investigated showed significantly decreased CoQ10 synthesis (40-88 % of the lower control) and mutational study of COQ genes should be performed. In patients with normal rates the deficiency is probably secondary. Conclusions: Our method is a good tool for the diagnosis of these treatable diseases.