Transplante de progenitores hematopoyéticos (TPH) alogénico no mieloablativo

El objetivo de este trabajo es investigar la toxicidad y demostrar la factibilidad y eficacia del injerto hematopoyético proveniente de un donante emparentado HLA-idéntico tras un acondicionamiento no mieloablativo en pacientes con enfermedades hematológicas de alto riesgo. Incluye 37 pacientes a los que se les realizó un TPH de sangre periférica procedente de un hermano HLA-idéntico. La mediana de células mononucleadas, CD3+ y CD34+ infundidas fue de 4,7 (1–9,7) x 108/Kg, 5,8 (1–36,3) x 107/Kg y 3,1 (1,3–9) x 106/Kg, respectivamente. La recuperación de neutrófilos se produjo en 17 días tras la infusión (7-39) y de plaquetas en 15 días (9-96). En la mayoría de pacientes se detectó un quimerismo mixto que pasó a completo a los 3 meses del trasplante; 9 pacientes precisaron la infusión de linfocitos del donante. Presentaron EICH aguda 16 pacientes (42%) (7 de ellos grados III-IV), 2 desarrollaron enfermedad venoclusiva hepática y 9 EICH crónica. Tras una mediana de seguimiento de 20 meses, 14 pacientes (38%) siguen vivos; 23 han fallecido (62%), 9 (24%) por progresión, 6 (16%) por EICH aguda y 8 (22%) por otras complicaciones. La supervivencia global actuarial a 2 años es del 32% (16-49 meses) y la supervivencia libre de progresión del 60% (43-77 meses). Se demuestra que la combinación de un acondicionamiento no mieloablativo con citostáticos y drogas inmunosupresoras produce una toxicidad moderada y permite el injerto con quimerismo total, en pacientes no candidatos a trasplante convencional por enfermedad de alto riesgo y presencia de comorbilidades asociadas.The aim of this paper is to investigate the toxicity and demonstrate the feasibility and efficacy of hematopoietic graft from an HLA-identical related donor after non-myeloablative conditioning in patients with high-risk hematological diseases. Includes 37 patients who underwent a peripheral blood HSCT from HLA-identical sibling. The median of infused mononuclear cells, CD 3 + cells and CD 34 + cells, was 4.7 (1-9.7) x 108/Kg, 5,8 (1-36.3) x 107/Kg and 3.1 (1 .3-9) x 106/Kg, respectively. Neutrophil recovery occurred at 17 days postinfusion (7-9) and platelets at 15 post-infusion. In most patients detected a mixed chimerism became a full three months after transplantation, nine patients required donor lymphocyte infusion. The majority of which became fully mixed at 3 months after transplantation, 9 patients required the infusion of donor lymphocytes. Sixteen patients presented acute GVHD (42%) (7 of them grade III-IV), 2 developed hepatic veno-occlusive disease and 9 chronic GVHD. After a median follow up of 20 months, 14 patients (38%) are alive, 23 have died (62%), 9 (24%) for progression, 6 (16%) for acute GVHD and 8 (22%) for further complications. Overall survival actuarial 2 years is 32% (16-49 months) and progression-free survival of 60% (43-77 months). It is shown that the combination of a non-myeloablative conditioning with cytostatic and immunosuppressive drugs produces a moderate toxicity and allows the graft with total chimerism in patients not candidates for conventional transplantation high-risk disease and presence of comorbidities

RT-PCR multiplex para la detección simultánea de las mutaciones FLT3-ITD/NPM-1/AML1-ETO asociadas a Leucemia Mieloide Aguda

La Leucemia Mieloide Aguda (LMA) representa un grupo de neoplasias muy heterogéneo. Las aberraciones citogenéticas detectadas en el momento del diagnóstico son el marcador pronóstico más comúnmente utilizado. Sin embargo, el 20% de los casos de LMA presentan un cariotipo normal. Dentro de este grupo de pacientes la presencia de mutaciones del tipo FLT3-ITD se considera de mal pronóstico. Sin embargo, la presencia de la mutación NMP1 o AML1-ETO se asocia a un mejor pronóstico. En este contexto, el objetivo de este trabajo es el desarrollo de una técnica de diagnóstico molecular hematológico, que permita la detección simultánea de mutaciones para estos tres genes. Hemos desarrollado un método basado en la reacción en cadena de la polimerasa (PCR) que permite amplificar y visualizar simultáneamente estos 3 marcadores tanto desde ARN (un paso) como desde ADNc (dos pasos). De las 28 muestras analizadas, 6 (21,42 %) muestras fueron positivas para FLT3-ITD, 7 para NPM-1 (25%) y otras 4 (14,28) para AML1-ETO. Al comparar ambos métodos (ADNc vs ARN) con métodos convencionales los resultados de las 28 muestras estudiadas fue equivalente en el 100% de los casos, demostrando la robustez de los mismos.Acute Myeloid Leukemia (AML) is a heterogeneous group of neoplasms. The cytogenetic aberrations detected at the time of diagnosis are most commonly used as prognostic marker. However, 20% of AML patients exhibit a normal karyotype. Within this group of patients the presence of FLT3 -ITD mutations type is considered of poor prognosis. However, the presence of AML1 –ETO or NMP-1 or mutation is associated with a better prognosis. In this context, the aim of this work is to develop a technique of molecular diagnostic in hematology, allowing the simultaneous detection of mutations for these three genes. We have developed a method based on PCR that simultaneously amplifies and visualizes these three molecular markers both from RNA (one- step) and from cDNA (step two). Of the 28 samples tested, 6 (21.42%) samples were positive for FLT3 -ITD, 7 for NPM- 1 (25% ) and 4 ( 14,28 ) for AML1 -ETO . When comparing the two methods (cDNA vs RNA) by conventional techniques the obtained results from the 28 samples tested was equivalent in 100% of cases, demonstrating the robustness of this development

A new tool to screen patients with severe obstructive sleep apnea in the primary care setting : a prospective multicenter study

Altres ajuts: Sociedad Española de Neumología y Cirugía Torácica (SEPAR), Societat Catalana de Pneumologia (SOCAP).The coordination between different levels of care is essential for the management of obstructive sleep apnea (OSA). The objective of this multicenter project was to develop a screening model for OSA in the primary care setting. Anthropometric data, clinical history, and symptoms of OSA were recorded in randomly selected primary care patients, who also underwent a home sleep apnea test (HSAT). Respiratory polygraphy or polysomnography were performed at the sleep unit to establish definite indication for continuous positive airway pressure (CPAP). By means of cross-validation, a logistic regression model (CPAP yes/no) was designed, and with the clinical variables included in the model, a scoring system was established using the β coefficients (PASHOS Test). In a second stage, results of HSAT were added, and the final accuracy of the model was assessed. 194 patients completed the study. The clinical test included the body mass index, neck circumference and observed apneas during sleep (AUC 0.824, 95% CI 0.763-0.886, P < 0.001). In a second stage, the oxygen desaturation index (ODI) of 3% (ODI3% ≥ 15%) from the HSAT was added (AUC 0.911, 95% CI 0.863-0.960, P < 0.001), with a sensitivity of 85.5% (95% CI 74.7-92.1) and specificity of 67.8% (95% CI 55.1-78.3). The use of this model would prevent referral to the sleep unit for 55.1% of the patients. The two-stage PASHOS model is a useful and practical screening tool for OSA in primary care for detecting candidates for CPAP treatment. Clinical Trial Registration Registry: ClinicalTrials.gov; Name: PASHOS Project: Advanced Platform for Sleep Apnea Syndrome Assessment; URL: ; Identifier: NCT02591979. Date of registration: October 30, 2015. The online version contains supplementary material available at 10.1186/s12890-022-01827-0

European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

The 2017 European LeukemiaNet (ELN 2017) guidelines for the diagnosis and management of acute myeloid leukemia (AML) have become fundamental guidelines to assess the prognosis and postremission therapy of patients. However, they have been retrospectively validated in few studies with patients included in different treatment protocols. We analyzed 861 patients included in the Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias-12 risk-adapted protocol, which indicates cytarabine-based consolidation for patients allocated to the ELN 2017 favorable-risk group, whereas it recommends allogeneic stem cell transplantation (alloSCT) as a postremission strategy for the ELN 2017 intermediateand adverse-risk groups. We retrospectively classified patients according to the ELN 2017, with 327 (48%), 109 (16%), and 245 (36%) patients allocated to the favorable-, intermediate-, and adverse-risk group, respectively. The 2- and 5-year overall survival (OS) rates were 77% and 70% for favorable-risk patients, 52% and 46% for intermediate-risk patients, and 33% and 23% for adverse-risk patients, respectively. Furthermore, we identified a subgroup of patients within the adverse group (inv(3)/t(3;3), complex karyotype, and/or TP53 mutation/17p abnormality) with a particularly poor outcome, with a 2-year OS of 15%. Our study validates the ELN 2017 risk stratification in a large cohort of patients treated with an ELN-2017 risk-adapted protocol based on alloSCT after remission for nonfavorable ELN subgroups and identifies a genetic subset with a very poor outcome that warrants investigation of novel strategies

Characterization of monoclonal gammopathy of undetermined significance by calorimetric analysis of blood serum proteome

© 2015 Barceló et al. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant proliferative disorder thatmay progress to multiplemyeloma, a malignant plasma cell neoplasia.We evaluated differential scanning calorimetry (DSC) as an experimental tool for differentiating serum samples of MGUS patients from healthy individuals. DSC thermograms can be used for monitoring changes in the serum proteome associated with MGUS. MGUS patients showed great variability in serum thermogram characteristics, which depended on the IgG, IgA or IgM isotypes and/or the κ or λ light chains. Thermogram feature parameters distinguished patients with MGUS from healthy people. Serum samples, named as non-MGUS, were also collected frompatients with subjacent immunological pathologies who were discarded of having MGUS through serum immunofixation. They were used to verify the sensitivity of DSC for discriminating MGUS from related blood dyscrasias. Only some DSC thermogram feature parameters differentiated, to a lesser extent, between MGUS and non-MGUS individuals.We contemplate DSC as a tool for early diagnosis and monitoring of MGUS.BFU2010-15518 from the Spanish Ministry of Science and InnovationPeer Reviewe

MALDI-TOF analysis of blood serum proteome can predict the presence of monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia that can progress to malignant multiple myeloma (MM). Specific molecular biomarkers to classify the MGUS status and discriminate the initial asymptomatic phase of MM have not been identified. We examined the serum peptidome profile of MGUS patients and healthy volunteers using MALDI-TOF mass spectrometry and developed a predictive model for classifying serum samples. The predictive model was built using a support vector machine (SVM) supervised learning method tuned by applying a 20-fold cross-validation scheme. Predicting class labels in a blinded test set containing randomly selected MGUS and healthy control serum samples validated the model. The generalization performance of the predictive model was evaluated by a double cross-validation method that showed 88% average model accuracy, 89% average sensitivity and 86% average specificity. Our model, which classifies unknown serum samples as belonging to either MGUS patients or healthy individuals, can be applied to clinical diagnosis. © 2018 Barceló et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.We are grateful to Dr. A. Gutierrez for his support and assistance in serum sample collection. We also thank C. Serret for helpful assistance in serum sample collection. We are indebted to Dr. N. Matamoros for valuable discussions on clinical issues and to Dr. J. Merino for his useful help in data analysis. The authors would like to acknowledge and thank HUSE (University Hospital Son Espases), Biobank HUSE and “Fundacio´ Banc de Sang i Teixits de les Illes Balears” (Balearic Islands Blood Bank) for providing serum samples used in this work, and the “Servicios Cientificote´cnicos” (UIB) for their assistance in providing the infrastructure to conduct the study.Peer reviewe

Avaluació de l’adquisició de procediments científics per alumnes de 4t d’ESO i 2n de batxillerat a les Illes Balears. La seva relació amb els requeriments d’estudis superiors

Resumen tomado de la publicaciónGrup de recerca: Formació inicial del Professorat de Secundària - Didàctica de les Ciències (FIPS) - Institut de Rercerca i Innovació Educativa de la Universitat de les Illes Balears.Fecha de realización del estudio: 2005-2008L’objectiu d’aquesta investigació és determinar el nivell d’adquisició d’alguns procediments científics per part dels alumnes de 4t de l’Educació Secundària Obligatòria (ESO) i de 2n de batxillerat de les Illes Balears, tenint com a referència els requisits necessaris que estableixen els currículums oficials de les dues etapes. No s’inclou en les pretensions de l’estudi fer comparacions amb els resultats obtinguts a altres comunitats de l’Estat o a altres països del nostre entorn, encara que la metodologia utilitzada sigui aplicable en investigacions similars d’altres comunitats o països.BalearesES

Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1

The negative prognostic impact of internal tandem duplication of FLT3 (FLT3- ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML- NPM1) is restricted to those with a higher FLT3 -ITD allelic ratio (FLT3 high ; ≥0.5) and considered negligible in those with a wild-type (FLT3 WT)/low ITD ratio (FLT3 low). Because the comutation of DNMT3A (DNMT3A mut) has been suggested to negatively influence prognosis in AML- NPM1, we analyzed the impact of DNMT3A mut in FLT3 -ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML- NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3A mut status did not have a prognostic impact, with comparable overall survival (P =.2). Prognostic stratification established by FLT3 -ITD (FLT3 WT = FLT3 low > FLT3 high) was independent of DNMT3A mut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3A mut was associated with a higher number of mutated NPM1 transcripts after induction (P =.012) and first consolidation (C1; P <.001). All DNMT3A mut patients were MRD + after C1 (P <.001) and exhibited significant MRD persistence after C2 and C3 (MRD + vs MRD − ; P =.027 and P =.001, respectively). Finally, DNMT3A mut patients exhibited a trend toward greater risk of molecular relapse (P =.054). In conclusion, DNMT3A mut did not modify the overall prognosis exerted by FLT3 -ITD in AML- NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention

Avaluació de l'adquisició de procediments científics per part de l'alumnat de 4t d'ESO i de 2n de batxillerat a les Illes Balears

El objeto de esta investigación es determinar el nivel de adquisición de procedimientos cientíi cos adquiridos por parte del alumnado de 4° de la ESO y de 2° de bachillerato de las Illes Balears, tomando como referencia los requerimientos necesarios que establecen los currículos oficiales y, también, las propuestas del profesorado de la universidad en cuanto a las metas que seria deseable alcanzar al respecto. No se incluye, en las pretensiones del estudio, realizar comparaciones con los resultados obtenidos en otras comunidades del estado o en otros países de nuestro entorno.L'objecte d'aquesta investigació és determinar el nivell d'adquisició de procediments científics per part dels alumnes de 4t d'ESO i de 2n de batxillerat de les Illes Balears. La referència són els requeriments necessaris que estableixen els currículums ofcials i també les propostes dels professors de la Universitat quant a les ftes que seria desitjable assolir al respecte. No pretenem fer comparacions amb els resultats obtinguts a altres comunitats de l'Estat espanyol o a altres països del nostre entorn

Anuari de l'educació de les Illes Balears

Resumen basado en el de la publicaciónGrupo FIPS: formado por profesores de los departamentos de Física y Química y de Biología y Geología de varios institutos de educación secundaria de Mallorca y del departamento de Biología de la UIB. Trabaja en el ICE/IRIE de la UIB desde el año 1992 sobre temas de currículum y de investigación relacionados con la didáctica de las ciencias.Se presenta la evolución de la educación secundaria obligatoria (ESO) durante el periodo comprendido entre los años 2001 y 2011 en las Illes Balears, a partir del análisis de una serie de datos que pueden resultar interesantes como indicadores de la situación actual de esta etapa de nuestro sistema educativo. Asimismo, el trabajo actualiza un estudio anterior que fue publicado en este mismo anuario en el año 2007 con el título «Estat actual i futur immediat del’educació secundària obligatòria a les Illes Balears».Es presenta l’evolució de l’educació secundària obligatòria (ESO) durant el període comprès entre els anys 2001 i 2011 a les Illes Balears, a partir de l’anàlisi d’una sèrie de dades que poden resultar interessants com a indicadors de la situació actual d’aquesta etapa del nostre sistema educatiu. Tanmateix, el treball actualitza un estudi anterior que fou publicat en aquest mateix anuari l’any 2007 amb el títol «Estat actual i futur immediat de l’educació secundària obligatòria a les Illes Balears».Universitat de les Illes Balears. Departament de Pedagogia i Did'actiques Específiques; Cra. de Valldemossa, km 7.5; Palma; Tel.: +34971 17 30 00; http://biblioteca.uib.cat/ES