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1. Digitized microimmunoassays with nuclear antigens for multiplexquantification of human specific IgE to B-lactam antibiotics

Author: Universitat Politècnica de València. Departamento de Química - Departament de Química, AGENCIA ESTATAL DE INVESTIGACION, COMISION DE LAS COMUNIDADES EUROPEA, Universitat Politècnica de València, Hospital Universitari i Politècnic La Fe, Juárez-Rodríguez, María José, Morais, Sergi, Maquieira Catala, Angel, Universitat Politècnica de València. Departamento de Química - Departament de Química, AGENCIA ESTATAL DE INVESTIGACION, COMISION DE LAS COMUNIDADES EUROPEA, Universitat Politècnica de València, Hospital Universitari i Politècnic La Fe, Juárez-Rodríguez, María José, Morais, Sergi, and Maquieira Catala, Angel
Abstract: [EN] Microanalytical systems have huge potential for prognosis and diagnosis of diseases where the quantification of biomarkers is the critical factor. Immunoglobulin E (IgE)-associated allergy is the most common immune disorder and reliable multiplex quantification of specific IgE antibodies is of key importance for in vitro allergy diagnosis. Here, we report an unprecedented highly sensitive multiplex colorimetric microanalytical system for reliable quantification of ß-lactam-specific IgE. The biosensor microsystem includes a regular digital versatile surface where nuclear antigens are immobilized in microarray format to determine simultaneously specific IgEs to amoxicillin, penicillin G, piperacillin and aztreonam, using a hacked disc drive as the optoelectrical sensor. The analytical microsystem was successfully tested in a cohort of 101 human serum samples, showing a limit of detection of 0.06 IU/mL (144¿pg IgE/mL), a clinical sensitivity of 42.3 % for amoxicillin, and an excellent specificity (100 %). The analytical performances were good as compared and validated with both in vivo and in vitro reference clinical immunofluorescence assay, settling a good correlation between the techniques. The compact microanalytical system can be easily implemented in primary care laboratory settings without the need for any additional instrumentation, facilitating massive drug allergy screening and delabeling campaigns to better define drug sensitization profiles.
Published: 2021

2. Wideband Electromagnetic Body Phantoms for the Evaluation of Wireless Communications in the Microwave Spectrum

Author: Cardona Marcet, Narciso, García Pardo, Concepción, Vallés Lluch, Ana, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Universitat Politècnica de València, Hospital Universitari i Politècnic La Fe, Castelló Palacios, Sergio, Cardona Marcet, Narciso, García Pardo, Concepción, Vallés Lluch, Ana, Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica, Universitat Politècnica de València, Hospital Universitari i Politècnic La Fe, and Castelló Palacios, Sergio
Abstract: [ES] La constante evolución de la tecnología y la búsqueda de nuevas aplicaciones que mejoren la vida de las personas ha llevado a la incorporación de estas tecnologías en el organismo. Las redes inalámbricas de área corporal (WBAN) son un buen ejemplo de esto, que consisten en redes de comunicaciones ubicadas en el propio cuerpo, tanto en la superficie como implantadas en su interior mediante el uso de dispositivos inalámbricos. Estas redes utilizan el cuerpo humano como medio de transmisión, por lo que debe evaluarse la influencia del mismo sobre la propagación. Además, las nuevas generaciones de comunicaciones móviles se están moviendo hacia el uso de frecuencias cada vez más altas, como las ondas milimétricas, que son más sensibles a la presencia de cualquier objeto en el entorno, incluidos los humanos. La investigación y el diseño de antenas y dispositivos que tengan en cuenta el cuerpo humano requiere pruebas en el entorno donde se supone que deben usarse. Los fantomas se convierten en una herramienta para evaluar la transmisión de señales electromagnéticas en un medio equivalente al cuerpo para evitar la experimentación en humanos o animales. Además de eso, se puede estudiar la influencia de estas ondas electromagnéticas sobre los propios tejidos en cuanto a la tasa de absorción específica (SAR)., [CA] L'evolució constant de la tecnologia i la recerca de noves aplicacions que milloren la vida de les persones ha portat a la incorporació d'aquestes tecnologies en l'organisme. Les xarxes sense fils d'àrea corporal (WBAN) són un bon exemple d'açò, que consisteixen en xarxes de comunicacions ubicades al propi cos, tant en la superfície com implantades en el seu interior mitjançant l'ús de dispositius sense fils. Aquestes xarxes empren el cos humà com a medi de transmissió, per la qual cosa se n'ha d'avaluar la influència sobre la propagació. A més, les noves generacions de comunicacions mòbils s'estan movent cap a l'ús de freqüències cada vegada més altes, com les ones mil·limètriques, que són més sensibles a la presència de qualsevol objecte en l'entorn, incloent-hi els humans. La investigació i el disseny d'antenes i dispositius que tinguen en compte el cos humà requereix proves en l'entorn on se suposa que han d'usar-se. Els fantomes esdevenen una eina per a avaluar la transmissió de senyals electromagnètics en un medi equivalent al cos per tal d'evitar l'experimentació en humans o animals. A més d'això, es pot estudiar la influència d'aquestes ones electromagnètiques sobre els teixits mateixos en relació amb la taxa d'absorció específica (SAR)., [EN] The constant evolution of technology and the search for new applications that improve people's lives has led to the arrival of the incorporation of these technologies in the organism. Wireless body area networks (WBANs) are a good example of this, consisting of communications networks located in the body itself, both on the surface and implanted inside it through the use of wireless devices. These networks use the human body as the transmitting medium, so its influence over the propagation has to be assessed. Besides, new generations of mobile communications are moving towards the use of higher frequencies, as the millimetre waves, which are more sensitive to the presence of any object in the environment, including humans. The research and design of antennas and devices that take into account the human body requires testing in the environment where these are supposed to be used. Phantoms become a tool for evaluating the transmission of electromagnetic signals in a body-equivalent medium in order to avoid experimentation on humans or animals. In addition to that, the influence of these electromagnetic waves over the tissues themselves can be studied with regard to the specific absorption rate (SAR).
Published: 2019

3. Analysis of the Possible Persistent Genotoxic Damage in Workers Linked to the Ardystil Syndrome

Author: Universitat Politècnica de València. Departamento de Ingeniería Química y Nuclear - Departament d'Enginyeria Química i Nuclear, Universitat Politècnica de València. Instituto de Seguridad Industrial, Radiofísica y Medioambiental - Institut de Seguretat Industrial, Radiofísica i Mediambiental, Hospital Universitari i Politècnic La Fe, Generalitat Valenciana, Montoro Pastor, Alegría, Sebastià, N., Hervás, D., Esteban, V., Bonafont, J., Barquinero, J.F., Almonacid, M., Cervera, J., Such, E., Verdú Martín, Gumersindo Jesús, Soriano, J.M., Villaescusa Blanca, Juan Ignacio, Universitat Politècnica de València. Departamento de Ingeniería Química y Nuclear - Departament d'Enginyeria Química i Nuclear, Universitat Politècnica de València. Instituto de Seguridad Industrial, Radiofísica y Medioambiental - Institut de Seguretat Industrial, Radiofísica i Mediambiental, Hospital Universitari i Politècnic La Fe, Generalitat Valenciana, Montoro Pastor, Alegría, Sebastià, N., Hervás, D., Esteban, V., Bonafont, J., Barquinero, J.F., Almonacid, M., Cervera, J., Such, E., Verdú Martín, Gumersindo Jesús, Soriano, J.M., and Villaescusa Blanca, Juan Ignacio
Abstract: [EN] Background: A combination of several factors including a change in the paint application system; a lack of proper hygiene; and inadequate safety measures caused a severe health impact in the workers of some textile painting factories. This outbreak, mainly characterized by respiratory disorders, caused the death of six people and it has been classified as Ardystil syndrome. Materials and Methods: Fifty-two workers involved in the outbreak and 48 healthy subjects not known to have exposed to the potentially mutagenic agents participated in the study. The program evaluated possible genotoxic damage through the sister chromatid exchange (SCE) cytogenetic biomarker assay. We determined the frequency of SCE, high-frequency cells (HFCs), and a ratio, which can be considered as a new parameter, allowing for the study of the SCE distribution pattern among the chromosomes. Results: There was no statistically significant difference in the SCE frequency and in the mean number of HFCs between the control and the Ardystil-affected groups. However, smoking increased the incidence of all parameters studied in both the case and control groups. Conclusions: This study shows that workers involved in the Ardystil syndrome did not suffer genotoxic damage as measured by SCE and HFCs when compared with the control group.
Published: 2016

4. UV protection from cotton fabrics dyed with different tea extracts

Author: Universitat Politècnica de València. Escuela Politécnica Superior de Alcoy - Escola Politècnica Superior d'Alcoi, Universitat Politècnica de València; Instituto de Investigación Sanitaria La Fe, Hospital Universitari i Politècnic La Fe, Bonet Aracil, María Angeles, Díaz-García, Pablo, Bou-Belda, Eva, Sebastiá, Natividad, Montoro, Alegría, Rodrigo, Regina, Universitat Politècnica de València. Escuela Politécnica Superior de Alcoy - Escola Politècnica Superior d'Alcoi, Universitat Politècnica de València; Instituto de Investigación Sanitaria La Fe, Hospital Universitari i Politècnic La Fe, Bonet Aracil, María Angeles, Díaz-García, Pablo, Bou-Belda, Eva, Sebastiá, Natividad, Montoro, Alegría, and Rodrigo, Regina
Abstract: [EN] Recently, natural dyes are becoming more important because they are considered environmentally friendly. However, the reduction in pollution is not only the main aspect that makes them interesting. New properties such antibacterial, sun protection, etc., can be added to the material dyed with them. In this work we consider different teas, the red one, the black and the green tea. Tea is commonly known all over the world ant they are considerably appreciated by their antioxidant properties. In this work the antioxidant effect of tea extracts has been determined and cotton fabrics were dyed. Previously, fabrics were treated with chitosan as a natural and not pollutant mordant. The effectiveness of dyeing cotton with tea extracts has been objectively studied by the K/S value and the chromatic values CIELab. Furthermore, the ultra violet (UV) protection has been determined as the Ultraviolet Protection Factor (UPF). Having dyed cotton with the tea extracts and analysing the results, no relationship was found between antioxidant effect and the dyeing yield nor the UPF. The same kind of tea offered fabrics with different colours depending on the extraction method. Some samples showed reddish hue and others a greenish one but it was not directly related to red or green tea. We could conclude that the final colour is more influenced by the way the extraction has been performed than by the kind of tea used. Regarding the UPF, it has been demonstrated that the effectiveness depends on the method used and the level of protection is considerably increased although there are two kinds of tea which show higher results. © 2016 Elsevier Ltd. All rights reserved.
Published: 2016

5. Tintura de tejidos de algodón con té. Influencia del tipo de té y del proceso de extracción de color

Author: Universitat Politècnica de València. Departamento de Ingeniería Textil y Papelera - Departament d'Enginyeria Tèxtil i Paperera, Universitat Politècnica de València. Escuela Politécnica Superior de Alcoy - Escola Politècnica Superior d'Alcoi, Hospital Universitari i Politècnic La Fe, Universitat Politècnica de València, Bonet Aracil, María Angeles, Díaz-García, Pablo, Bou-Belda, Eva, Monllor Pérez, Pablo, Universitat Politècnica de València. Departamento de Ingeniería Textil y Papelera - Departament d'Enginyeria Tèxtil i Paperera, Universitat Politècnica de València. Escuela Politécnica Superior de Alcoy - Escola Politècnica Superior d'Alcoi, Hospital Universitari i Politècnic La Fe, Universitat Politècnica de València, Bonet Aracil, María Angeles, Díaz-García, Pablo, Bou-Belda, Eva, and Monllor Pérez, Pablo
Abstract: [EN] The study is focused on the use of natural dyes and mordants in order to dye cotton fabrics. In this paper we have used four dyes based on tea, red tea, black tea, Green tea and White one. In order to extract thedye, two procedures were carried on. One extraction process was carried on in a cold treatment and the other one was performed with boiling water. Samples died were tested with a colorimetric spectrophotometer, getting L*a*b* values and K/S according to Kubelka Munk. Results showed that both the extraction procedure and the nature of the tea influence the final result., [ES] El presente estudio se centra en el uso de colorantes y mordientes naturales para tintar tejido de algodón. Se han utilizado cuatro especies tintóreas, té negro, blanco, verde y rojo. Para llevar a cabo la tintura se realizó primeramente el proceso de extracción siguiendo dos procedimientos distintos, con y sin temperatura, para cada uno de los tés. Para poder valorar y comparar objetivamente los resultados obtenidos, se analizan las muestras tintadas en un espectrofotómetro de reflexión, por el que se obtienen las coordenadas cromáticas en el espacio CIELAB y la fuerza de color (K/S) según la ecuación de Kubelka-Munk. Los resultados mostraron que influyen tanto el té utilizado como el método de extracción realizado.
Published: 2015

6. Quantitative approach to assist neuroblastoma assessment by measuring I-123 mIBG uptake in scintigraphic images

Author: Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Geodésica, Cartográfica y Topográfica - Escola Tècnica Superior d'Enginyeria Geodèsica, Cartogràfica i Topogràfica, Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería del Diseño - Escola Tècnica Superior d'Enginyeria del Disseny, Hospital Universitari i Politècnic La Fe, Universitat Poltècnica de València, Martínez Díaz, Rafael, Balaguer Guill, Julia, Sánchez Ruiz, Luis Manuel, Bello Arques, Pilar, Castel, Victoria, Rivas Sanchez, Antonio, Cañete Nieto, Adela, Falgás Lacueva, Marina, Loaiza Gongora, Jose Luis, Peris Fajarnes, Guillermo, Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Geodésica, Cartográfica y Topográfica - Escola Tècnica Superior d'Enginyeria Geodèsica, Cartogràfica i Topogràfica, Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería del Diseño - Escola Tècnica Superior d'Enginyeria del Disseny, Hospital Universitari i Politècnic La Fe, Universitat Poltècnica de València, Martínez Díaz, Rafael, Balaguer Guill, Julia, Sánchez Ruiz, Luis Manuel, Bello Arques, Pilar, Castel, Victoria, Rivas Sanchez, Antonio, Cañete Nieto, Adela, Falgás Lacueva, Marina, Loaiza Gongora, Jose Luis, and Peris Fajarnes, Guillermo
Abstract: Whole-body 123I-Metaiodobenzylguanidine (mIBG) scintigraphy is used as the primary image modality in neuroblastoma detection. It is the most sensitive and specific method for staging and response evaluation. Validated semi-quantitative scoring methods with low interobserver variability and high reproducibility have shown to be indispensable for the evaluation of response to therapy. However, low resolution, noise and acquisition difficulties, specially in children, make low definition scans. These facts increase observer dependent interpretations that limit assessment and complicate to put a scoring method succesfully into practice. It is essential to have an objective and reliable measure of response to test the activity of therapies. In this paper we propose the use of a quantitative observer-independent measurement of the strength of uptake to be used as an additional tool for assisting the International Society of Paediatric Oncology Europe Neuroblastoma Group (SIOPEN) semi-quantitative scoring method. This is the scoring method recommended by the SIOPEN Nuclear Medicine and Physics Committee, in collaborative work with the Children’s Oncology Group, as the standard one for acquiring and reporting diagnostic paediatric mIBG scans across Europe. Our proposed method is based on the ratio between the amount of specific uptake at tumours and the amount of non-specific uptake at SIOPEN anatomical sectors which has shown to be constant in all the scans of the patients.
Published: 2015

7. Nuisance tripping of residual current circuit breakers: A practical case

Author: Universitat Politècnica de València. Instituto de Ingeniería Energética - Institut d'Enginyeria Energètica, Universitat Politècnica de València. Departamento de Ingeniería Eléctrica - Departament d'Enginyeria Elèctrica, Universitat Politècnica de València. Departamento de Construcciones Arquitectónicas - Departament de Construccions Arquitectòniques, Universitat Politècnica de València, Hospital Universitari i Politècnic La Fe, Roldán Porta, Carlos, Escrivá Escrivá, Guillermo, Cárcel Carrasco, Francisco Javier, Roldán Blay, Carlos, Universitat Politècnica de València. Instituto de Ingeniería Energética - Institut d'Enginyeria Energètica, Universitat Politècnica de València. Departamento de Ingeniería Eléctrica - Departament d'Enginyeria Elèctrica, Universitat Politècnica de València. Departamento de Construcciones Arquitectónicas - Departament de Construccions Arquitectòniques, Universitat Politècnica de València, Hospital Universitari i Politècnic La Fe, Roldán Porta, Carlos, Escrivá Escrivá, Guillermo, Cárcel Carrasco, Francisco Javier, and Roldán Blay, Carlos
Abstract: Residual current circuit breakers (RCCBs) are often used to provide protection against indirect contacts in a grounded electrical installation. However, there are situations where the use of RCCBs presents certain problems. In some installations, tripping may occur for no apparent reason. Furthermore, it is very laborious and difficult to find the cause of such nuisance tripping in RCCBs. This article presents a case studied by the authors in the La Fe Hospital in Valencia (Spain), where the nuisance tripping of RCCBs became a serious problem. The methodology followed to find the causes and the solutions adopted are described.
Published: 2014

8. A glimpse into relapsed refractory multiple myeloma treatment in real-world practice in Spain: the GeminiS study

Author: Soler, Alfons, Garcia Sanchez, Ricarda, Pérez Persona, Ernesto, Arnao Herraiz, Mario, García-Guiñón, Antoni, Domingo, Abel, González Pardo, Miriam, de la Rubia, Javier, Mateos, María-Victoria, Ríos-Tamayo, Rafael, [Ríos-Tamayo R] Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. [Soler JA] Department of Hematology, HospitalUniversitari Parc Taulí de Sabadell, Catalonia, Spain. [García-Sánchez R] Department of Hematology, Hospital Virgen de la Victoria, Málaga, Spain. [Pérez Persona E] Department of Hematology, Hospital Universitario de Navarra, Pamplona, Spain. [Arnao M] Department of Hematology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [García-Guiñón A] Department of Hematology, Hospital Universitari Arnau de Vilanova, Lleida, Spain. [Domingo A] Department of Hematology, Hospital General de Granollers, Granollers, Spain. [González-Pardo M] Medical Department, Janssen-Cilag España, Spain. [de la Rubia J] Hospital Universitari i Politècnic La Fe, Valencia, Spain. Hematology Department, Universidad Católica'San Vicente Mártir', Valencia, Spain. CIBERONC CB16/12/00284,Valencia, Spain. [Mateos MV] Instituto de Investigación Biomédica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Hospital Universitario de Salamanca, Salamanca, Spain, and Hospital General de Granollers
Subjects: Mieloma múltiple, Medicaments - Eficàcia, Neoplasms::Neoplasms by Histologic Type::Neoplasms, Plasma Cell::Multiple Myeloma [DISEASES], neoplasias::neoplasias por tipo histológico::neoplasias de células plasmáticas::mieloma múltiple [ENFERMEDADES], Hematology, Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal [CHEMICALS AND DRUGS], características del estudio::estudio multicéntrico [CARACTERÍSTICAS DE PUBLICACIONES], Anticossos monoclonals, aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales [COMPUESTOS QUÍMICOS Y DROGAS], Study Characteristics::Multicenter Study [PUBLICATION CHARACTERISTICS]
Abstract: Relapsed-refractory multiple mieloma; Monoclonal antibodies; Observational multicenter study Mieloma múltiple recidivant-refractari; Anticossos monoclonals; Estudi observacional multicèntric Mieloma múltiple recidivante-refractario; Anticuerpos monoclonales; Estudio multicéntrico observacional Objectives: To describe the incorporation of monoclonal antibodies (mAb) in real-world (RW) practice for the treatment of patients with relapsed refractory multiple myeloma (RRMM) in a setting with other treatment alternatives. Methods: This was an observational, multicenter, ambispective study of RRMM treated with or without a mAb. Results: A total of 171 patients were included. For the group treated without mAb, the median (95% CI) progression-free survival (PFS) to relapse was 22.4 (17.8-27.0) months; partial response or better (≥PR) and complete response or better (≥CR) was observed in 74.1% and 24.1% of patients, respectively; and median time to first response in first relapse was 2.0 months and in second relapse was 2.5 months. For the group of patients treated with mAb in first or second relapse, the median PFS was 20.9 (95% CI, could not be evaluated) months; the ≥ PR and ≥ CR rates were 76,2% and 28.6%, respectively; and the median time to first response in first relapse was 1.2 month and in second relapse was 1.0 months. The safety profiles for the combinations were consistent with those expected. Conclusions: The incorporation of mAb in RW practice for the treatment of RRMM has shown good quality and speed of response with a similar safety profile shown in randomized clinical trials. Keywords: Relapsed-refractory multiple myeloma; daratumumab; monoclonal antibodies; real-world; standard of care.
Published: 2023

9. An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology

Author: Rut Ann Thomassen, Jernej Dolinsek, Carmen Ribes-Koninckx, Erasmo Miele, Christos Tzivinikos, Corina Pienar, Javier Martín-de-Carpi, Emmanuel Mas, Marc A. Benninga, Osvaldo Borrelli, Ilse Broekaert, Mike Thomson, University Hospital of Cologne [Cologne], Great Ormond Street Hospital for Children [London] (GOSH), University medical centre Maribor (UKC Maribor), Hospital Sant Joan de Déu [Barcelona], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, VU University Medical Center [Amsterdam], SEGUIN, Nathalie, Broekaert, Ilse Julia, Borrelli, Osvaldo, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut, Thomson, Mike, Tzivinikos, Christo, Benninga, Marc, and Hospital Universitari i Politècnic La Fe
Subjects: medicine.medical_specialty, Malabsorption, Consensus, Carbohydrate malabsorption, 030309 nutrition & dietetics, MEDLINE, carbohydrate malabsorption, small intestinal bacterial overgrowth, Helicobacter pylori infection, Helicobacter Infections, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, children, Internal medicine, Small intestinal bacterial overgrowth, medicine, breath testing, Humans, Intensive care medicine, Exocrine pancreatic insufficiency, Child, Children, 0303 health sciences, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Hepatology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Fat malabsorption, Breath testing, Systematic review, Breath Tests, Pediatrics, Perinatology and Child Health, Position paper, 030211 gastroenterology & hepatology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Systematic Reviews as Topic
Abstract: International audience; Objectives: Given a lack of a systematic approach to the use of breath testing in paediatric patients, the aim of this position paper is to provide expert guidance regarding the indications for its use and practical considerations to optimise its utility and safety. Methods: Nine clinical questions regarding methodology, interpretation, and specific indications of breath testing and treatment of carbohydrate malabsorption were addressed by members of the Gastroenterology Committee (GIC) of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN). A systematic literature search was performed from 1983 to 2020 using PubMed, the MEDLINE and Cochrane Database of Systematic Reviews. Grading of Recommendations, Assessment, Development, and Evaluation was applied to evaluate the outcomes. During a consensus meeting, all recommendations were discussed and finalised. In the absence of evidence from randomised controlled trials, recommendations reflect the expert opinion of the authors. Results: A total of 22 recommendations were voted on using the nominal voting technique. At first, recommendations on prerequisites and preparation for as well as on interpretation of breath tests are given. Then, recommendations on the usefulness of H2-lactose breath testing, H2-fructose breath testing as well as of breath tests for other types of carbohydrate malabsorption are provided. Furthermore, breath testing is recommended to diagnose small intestinal bacterial overgrowth (SIBO), to control for success of Helicobacter pylori eradication therapy and to diagnose and monitor therapy of exocrine pancreatic insufficiency, but not to estimate oro-caecal transit time (OCTT) or to diagnose and follow-up on celiac disease. Conclusions: Breath tests are frequently used in paediatric gastroenterology mainly assessing carbohydrate malabsorption, but also in the diagnosis of small intestinal overgrowth, fat malabsorption, H. pylori infection as well as for measuring gastrointestinal transit times. Interpretation of the results can be challenging and in addition, pertinent symptoms should be considered to evaluate clinical tolerance.
Published: 2021

10. Deciphering Multiple Sclerosis Progression

Author: Virginia Meca-Lallana, Leticia Berenguer-Ruiz, Joan Carreres-Polo, Sara Eichau-Madueño, Jaime Ferrer-Lozano, Lucía Forero, Yolanda Higueras, Nieves Téllez Lara, Angela Vidal-Jordana, Francisco Carlos Pérez-Miralles, Institut Català de la Salut, [Meca-Lallana V] Multiple Sclerosis Unit, Neurology Department, Fundación de Investigación Biomédica, Hospital Universitario de la Princesa, Madrid, Spain. [Berenguer-Ruiz L] Neurology Department, Hospital Marina Baixa, Alicante, Spain. [Carreres-Polo J] Neuroradiology Section, Radiology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Eichau-Madueño S] Multiple Sclerosis CSUR Unit, Neurology Department, Hospital Universitario Virgen Macarena, Seville, Spain. [Ferrer-Lozano J] Department of Pathology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Forero L] Neurology Department, Hospital Puerta del Mar, Cádiz, Spain. [Vidal-Jordana A] Servei de Neurologia/Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Oncology, medicine.medical_specialty, Other subheadings::Other subheadings::/physiopathology [Other subheadings], Otros calificadores::Otros calificadores::/fisiopatología [Otros calificadores], Esclerosi múltiple - Propensió, Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], Review, Disease, neurofilament, Esclerosi múltiple - Fisiologia patològica, multiple sclerosis, lcsh:RC346-429, Sistema nerviós - Degeneració, 03 medical and health sciences, 0302 clinical medicine, Degenerative disease, Internal medicine, medicine, In patient, 030212 general & internal medicine, enfermedades del sistema nervioso::enfermedades neurodegenerativas [ENFERMEDADES], lcsh:Neurology. Diseases of the nervous system, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], Expanded Disability Status Scale, business.industry, Multiple sclerosis, Neurodegeneration, Disease progression, neurodegeneration, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], medicine.disease, Clinical trial, progressive multiple sclerosis, Neurology, Nervous System Diseases::Neurodegenerative Diseases [DISEASES], enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Neurology (clinical), business, 030217 neurology & neurosurgery, MRI
Abstract: Esclerosi múltiple; Neurodegeneració Esclerosis múltiple; Neurodegeneración Multiple sclerosis; Nneurodegeneration Multiple sclerosis (MS) is primarily an inflammatory and degenerative disease of the central nervous system, triggered by unknown environmental factors in patients with predisposing genetic risk profiles. The prevention of neurological disability is one of the essential goals to be achieved in a patient with MS. However, the pathogenic mechanisms driving the progressive phase of the disease remain unknown. It was described that the pathophysiological mechanisms associated with disease progression are present from disease onset. In daily practice, there is a lack of clinical, radiological, or biological markers that favor an early detection of the disease's progression. Different definitions of disability progression were used in clinical trials. According to the most descriptive, progression was defined as a minimum increase in the Expanded Disability Status Scale (EDSS) of 1.5, 1.0, or 0.5 from a baseline level of 0, 1.0–5.0, and 5.5, respectively. Nevertheless, the EDSS is not the most sensitive scale to assess progression, and there is no consensus regarding any specific diagnostic criteria for disability progression. This review document discusses the current pathophysiological concepts associated with MS progression, the different measurement strategies, the biomarkers associated with disability progression, and the available pharmacologic therapeutic approaches.
Published: 2021

11. Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

Author: F. Le Calvez-Kelm, John K. Field, Nicolas Girard, Ernst-Jan M. Speel, Marie Brevet, Lynnette Fernandez-Cuesta, Jean-François Deleuze, Nicolas Lemaitre, Noémie Leblay, Sandrine Boyault, Marius Lund-Iversen, Gabriella Sozzi, Véronique Hofman, Sylvie Lantuejoul, Lucia Anna Muscarella, Paolo Graziano, Alex Soltermann, Matthieu Foll, Amelie Chabrier, Robert Olaso, A. Ferrari, Anne Boland, Paul Hofman, Luca Roz, Behnoush Abedi-Ardekani, Janine Altmüller, Tiffany M. Delhomme, Akram Ghantous, Christophe Caux, Jules L. Derks, Giuseppe Pelosi, Vincent Meyer, Anne-Marie C. Dingemans, Juan Sandoval, Jean-Michel Vignaud, Jelena Stojsic, Catherine Voegele, Geoffroy Durand, James D. McKay, Peter Nuernberg, Cyrille Cuenin, Nicolas Alcala, L. Moonen, Hector Hernandez-Vargas, Ugo Pastorino, Theo Giffon, O.T. Brustugun, L. Mangiante, Mauro Papotti, Philippe Lorimier, Anne-Claire Toffart, Prudence A. Russell, Aurélie A G Gabriel, Zdenko Herceg, A. S. Sertier, Joachim H. Clement, M. Milione, Joerg Saenger, Luka Brcic, Stéphanie Lacomme, V. Thomas de Montpreville, A. Viari, Marco Volante, Elisabeth Brambilla, Gavin M. Wright, Cécile Blanc-Fournier, David Hervás, N. Le Stang, H. Popper, Françoise Galateau-Sallé, Centre international de Recherche sur le Cancer (CIRC), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Fondation Synergie Lyon Cancer [Lyon], Centre Léon Bérard [Lyon], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cologne Center for Genomics [Cologne] (CCG), University of Cologne, Centre for Molecular Medicine Cologne [Cologne] (CMMC), University Hospital of Cologne [Cologne], School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de pneumologie [Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Institute of Pathology and Molecular Pathology [Zurich], Department Hematology and Medical Oncology [Jena], Jena University Hospital [Jena], Central Clinic Bad Berka, Department of Molecular and Clinical Cancer Medicine [Liverpool], University of Liverpool, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), University of Melbourne, IRCCS Istituto Nazionale dei Tumori [Milano], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Oslo University Hospital [Oslo], Centre Chirurgical Marie Lannelongue (CCML), Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), University Hospital Graz, Clinical Center of Serbia (KCS), Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Università degli Studi di Milano = University of Milan (UNIMI), Università degli studi di Torino = University of Turin (UNITO), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospital Universitari i Politècnic La Fe, Synergie Lyon Cancer [Lyon], UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre chirurgical Marie Lannelongue, University of Milan, University of Turin, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Promovendi ODB, Pulmonologie, RS: GROW - R2 - Basic and Translational Cancer Biology, MUMC+: MA Med Staf Spec Longziekten (9), and Pathologie
Subjects: 0301 basic medicine, Oncology, Male, Lung Neoplasms, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Datasets as Topic, 02 engineering and technology, Neuroendocrine tumors, Machine Learning, PATHWAY, Cancer genomics, lcsh:Science, Lung, Aged, 80 and over, Comparative Genomic Hybridization, Multidisciplinary, Intracellular Signaling Peptides and Proteins, Genomics, Middle Aged, 021001 nanoscience & nanotechnology, Prognosis, 3. Good health, Neuroendocrine Carcinomas, Survival Rate, medicine.anatomical_structure, Female, Non small cell, HEALTH, Technology Platforms, 0210 nano-technology, Adult, EXPRESSION, medicine.medical_specialty, Adolescent, Science, CELL LUNG-CANCER, Nerve Tissue Proteins, Carcinoid Tumor, DENDRITIC CELLS, General Biochemistry, Genetics and Molecular Biology, Article, Small-cell lung cancer, CLASSIFICATION, 03 medical and health sciences, Young Adult, Internal medicine, Overall survival, medicine, Carcinoma, Biomarkers, Tumor, Humans, Survival rate, Aged, Homeodomain Proteins, IDENTIFICATION, business.industry, MUTATIONS, Membrane Proteins, General Chemistry, medicine.disease, Small Cell Lung Carcinoma, 030104 developmental biology, DISCOVERY, Carcinoma, Large Cell, lcsh:Q, business, NEUROENDOCRINE TUMORS, Comparative genomic hybridization
Abstract: The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms., The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Here, Alcala and colleagues present a multi-omics analysis of these tumours, revealing distinct molecular and prognostic subgroups.
Published: 2019

12. Detection of plasmid-mediated colistin resistance, mcr-1 gene, in Escherichia coli isolated from high-risk patients with acute leukemia in Spain

Author: Miguel A. Sanz, Laurent Debrauwer, Ana Djukovic, Rym Lalaoui, Jaime Sanz, Eva María González-Barberá, Carles Ubeda, Sofiane Bakour, Karina B. Xavier, Jose Luis López-Hontangas, Jean-Marc Rolain, Bernhard Kuster, Miguel Salavert, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Hospital Universitari i Politècnic La Fe, Universidad Carlos III de Madrid [Madrid] (UC3M), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Technical University of Munich (TUM), Technische Universität München [München] (TUM), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CIBER de Epidemiología y Salud Pública (CIBERESP), ANR FloraStopInfectMRE project, InfecERA-ERANET-Acciones complementarias [PCIN-2015-094], IHU Mediterranee Infection, Marseille, France, French Government [10-IAHU-03], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.drug_class, 030106 microbiology, Antibiotics, Colistin resistance, Microbial Sensitivity Tests, Biology, medicine.disease_cause, beta-Lactamases, Microbiology, Leukemic patients, 03 medical and health sciences, Minimum inhibitory concentration, 0302 clinical medicine, Plasmid, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Bacterial, medicine, Escherichia coli, Humans, Pharmacology (medical), [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, 030212 general & internal medicine, Escherichia coli Infections, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Leukemia, Colistin, Escherichia coli Proteins, Middle Aged, biology.organism_classification, Enterobacteriaceae, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Spain, Colistin resistance, Escherichia coli, Leukemic patients, Spain, mcr-1 gene, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Multilocus sequence typing, mcr-1 gene, MCR-1, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Plasmids
Abstract: Background: Bacterial infections in immunocompromised patients are associated with a high mortality and morbidity rate. In this high-risk group, the presence of multidrug-resistant (MDR) bacteria, particularly bacteria that harbor a transferable antibiotic resistance gene, complicates the management of bacterial infections. In this study, we investigated the presence of the transferable colistin resistance mcr genes in patients with leukemia in Spain. Methods: 217 fecal samples collected in 2013-2015 from 56 patients with acute leukemia and colonized with MDR Enterobacteriaceae strains, were screened on September 2017 for the presence of the colistin resistance mcr genes (mcr-1 to -5) by multiplex PCR. mcr positive strains selected on LBJMR and Mac-Conkey supplemented with colistin (2 mu g/ml) media were phenotypically and molecularly characterized by antimicrobial susceptibility testing, minimum inhibitory concentration, multilocus sequence typing and plasmid characterization. Results: Among 217 fecal samples, 5 samples collected from 3 patients were positive for the presence of the mcr-1 colistin-resistance gene. Four Escherichia coli strains were isolated and exhibited resistance to colistin with MIC = 4 mu g/ml. Other genes conferring the resistance to beta-lactam antibiotics have also been identified in mcr-1 positive strains, including bla(TEM-206) and bla(TEM-98). Three different sequence types were identified, including ST1196, ST140 and ST10. Plasmid characterization allowed us to detect the mcr-1 colistin resistance gene on conjugative IncP plasmid type. Conclusion: To the best of our knowledge, we have identified the mcr-1 gene for the first time in leukemia patients in Spain. In light of these results, strictmeasures have been implemented to prevent its dissemination. (c) 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Published: 2019

13. Challenges in Clinical Metaproteomics Highlighted by the Analysis of Acute Leukemia Patients with Gut Colonization by Multidrug-Resistant Enterobacteriaceae

Author: Rechenberger, Julia, Samaras, Patroklos, Jarzab, Anna, Behr, Juergen, Frejno, Martin, Djukovic, Ana, Sanz, Jaime, González-Barberá, Eva, Salavert, Miguel, López-Hontangas, Jose Luis, Xavier, Karina, Debrauwer, Laurent, Rolain, Jean-Marc, Sanz, Miguel, Garcia-Garcerà, Marc, Wilhelm, Mathias, Ubeda, Carles, Kuster, Bernhard, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), Hospital Universitari i Politècnic La Fe, Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Université de Lausanne (UNIL), CIBER in Epidemiology and Public Health, BMBF FloraStopMRE grant [031L0089], Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Lausanne = University of Lausanne (UNIL)
Subjects: [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, human gut microbiome, data analysis, lcsh:QR1-502, multi-omics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, lcsh:Microbiology, Article, proteomics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, clinical proteomics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, mass spectrometry, metaproteome, multidrug-resistant Enterobacteriaceae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology
Abstract: International audience; The microbiome has a strong impact on human health and disease and is, therefore, increasingly studied in a clinical context. Metaproteomics is also attracting considerable attention, and such data can be efficiently generated today owing to improvements in mass spectrometry-based proteomics. As we will discuss in this study, there are still major challenges notably in data analysis that need to be overcome. Here, we analyzed 212 fecal samples from 56 hospitalized acute leukemia patients with multidrug-resistant Enterobactericeae (MRE) gut colonization using metagenomics and metaproteomics. This is one of the largest clinical metaproteomic studies to date, and the first metaproteomic study addressing the gut microbiome in MRE colonized acute leukemia patients. Based on this substantial data set, we discuss major current limitations in clinical metaproteomic data analysis to provide guidance to researchers in the field. Notably, the results show that public metagenome databases are incomplete and that sample-specific metagenomes improve results. Furthermore, biological variation is tremendous which challenges clinical study designs and argues that longitudinal measurements of individual patients are a valuable future addition to the analysis of patient cohorts.
Published: 2019

14. J Acquir Immune Defic Syndr

Author: Daniel Gillor, Lars P. Ryder, Rodolphe Thiébaut, Luuk Gras, Santiago Moreno, Marie Helleberg, Peter Reiss, Michael S. Saag, Margaret T May, Jonathan A C Sterne, Ferdinand W. N. M. Wit, Janet Tate, Niels Obel, Frank de Wolf, Ronald B. Geskus, Colette Smith, José M. Miró, Jodie L. Guest, Dominique Costagliola, Suzanne M Ingle, Matthias Cavassini, Antonella dʼArminio Monforte, Heidi M. Crane, Marta Montero, Timothy R. Sterling, Leah Shepherd, Viviane D. Lima, Christoph Stephan, Adam Trickey, Armin Rieger, John Gill, Antiretroviral Therapy Cohort Collaboration (ART-CC), Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Bristol [Bristol], University of Copenhagen = Københavns Universitet (KU), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Emory University School of Medicine, Emory University [Atlanta, GA], University of Calgary, University of Washington [Seattle], British Columbia Centre for Excellence in HIV/AIDS [Vancouver], University of British Columbia (UBC), University of Milan, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), University of Barcelona, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Universitätsklinikum Frankfurt, Goethe-University Frankfurt am Main, University College of London [London] (UCL), Yale University School of Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), University of Vienna [Vienna], Universität zu Köln, Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Hospital Universitari i Politècnic La Fe, University of Amsterdam [Amsterdam] (UvA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Amsterdam Institute for Global Health & Development [Amsterdam, The Netherlands], Imperial College London, Public Health Service of Amsterdam, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano = University of Milan (UNIMI), Yale School of Medicine [New Haven, Connecticut] (YSM), Universität zu Köln = University of Cologne, Université de Lausanne = University of Lausanne (UNIL), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Oxford, Gestionnaire, Hal Sorbonne Université, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Université de Bordeaux (UB), Graduate School, AII - Infectious diseases, APH - Global Health, APH - Methodology, Global Health, and APH - Aging & Later Life
Subjects: CD8 ratio [CD4], Male, Oncology, Cross-sectional study, CD4:CD8 ratio, [SDV]Life Sciences [q-bio], Cell, Human immunodeficiency virus (HIV), CD4-CD8 Ratio, CD4 cell count, HIV Infections, CD8-Positive T-Lymphocytes, 030312 virology, medicine.disease_cause, MORPH3Eus, Pharmacology (medical), Longitudinal Studies, Young adult, Cd4 cell count, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Clinical Science, Middle Aged, Viral Load, SISTM, 3. Good health, Antiretroviral therapy, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.anatomical_structure, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Coll_IDLIC, Adult, medicine.medical_specialty, Adolescent, Anti-HIV Agents, CD8 cell count, antiretroviral therapy, Young Adult, 03 medical and health sciences, Age, Internal medicine, medicine, Coll_ART-CC, Humans, Lymphocyte Count, Anti-HIV Agents/therapeutic use, CD4 Lymphocyte Count, Cross-Sectional Studies, HIV Infections/drug therapy, HIV-1, Viral Load/drug effects, business.industry, HIV, age, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Supplemental Digital Content is Available in the Text., Background: An increasing number of HIV-positive individuals now start antiretroviral therapy (ART) with high CD4 cell counts. We investigated whether this makes restoration of CD4 and CD8 cell counts and the CD4:CD8 ratio during virologically suppressive ART to median levels seen in HIV-uninfected individuals more likely and whether restoration depends on gender, age, and other individual characteristics. Methods: We determined median and quartile reference values for CD4 and CD8 cell counts and their ratio using cross-sectional data from 2309 HIV-negative individuals. We used longitudinal measurements of 60,997 HIV-positive individuals from the Antiretroviral Therapy Cohort Collaboration in linear mixed-effects models. Results: When baseline CD4 cell counts were higher, higher long-term CD4 cell counts and CD4:CD8 ratios were reached. Highest long-term CD4 cell counts were observed in middle-aged individuals. During the first 2 years, median CD8 cell counts converged toward median reference values. However, changes were small thereafter and long-term CD8 cell count levels were higher than median reference values. Median 8-year CD8 cell counts were higher when ART was started with
Published: 2018

15. Comparative outcomes of extracorporeal membrane oxygenation for COVID-19 delivered in experienced European centres during successive SARS-CoV-2 variant outbreaks (ECMO-SURGES): an international, multicentre, retrospective cohort study

Author: Matthieu Schmidt, David Hajage, Micha Landoll, Benjamin Pequignot, Elise Langouet, Matthieu Amalric, Armand Mekontso-Dessap, Luis Chiscano-Camon, Katy Surman, Dylan Finnerty, Patricia Santa-Teresa, Antonio Arcadipane, Pablo Millán, Roberto Roncon-Albuquerque, Aaron Blandino-Ortiz, Pablo Blanco-Schweizer, Pilar Ricart, Ricardo Gimeno-Costa, Carlos Luis Albacete, Philip Fortuna, Peter Schellongowski, Dieter Dauwe, Hadrien Winiszewski, Antoine Kimmoun, Bruno Levy, Greet Hermans, Giacomo Grasselli, Guillaume Lebreton, Christophe Guervilly, Gennaro Martucci, Christian Karagiannidis, Jordi Riera, Alain Combes, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pharmacoépidémiologie et évaluation des soins [iPLesp] (PEPITES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Universität Witten Herdecke, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Marseille, IMRB - 'Biomechanics and Respiratory Apparatus' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Groupe de recherche clinique CARMAS (Cardiovascular and Respiratory Manifestations of Acute lung injury and Sepsis) (CARMAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-CHU Henri Mondor [Créteil], Vall d'Hebron University Hospital [Barcelona], Royal Papworth Hospital [Cambridge, UK] (RPH), Hospital General Universitario 'Gregorio Marañón' [Madrid], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Universidad Loyola Andalucía = Loyola University Andalucía, Hospital de São João [Porto], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Rio Hortega University Hospital (Hospital Universitario Río Hortega) [Valladolid, Spain] (RHUH), Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Clínico Universitario Virgen de la Arrixaca = University Hospital Virgen de la Arrixaca [Murcia], Centro Hospitalar de Lisboa Central E.P.E, Medizinische Universität Wien = Medical University of Vienna, University Hospitals Leuven [Leuven], Service d'anesthésie et soins intensifs [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), and Vall d’Hebron Research Institute (VHIR)
Subjects: Pulmonary and Respiratory Medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract: International audience
Published: 2023

16. Single- or double-unit UCBT following RIC in adults with AL: a report from Eurocord, the ALWP and the CTIWP of the EBMT

Author: Annalisa Ruggeri, Jan J. Cornelissen, Eliane Gluckman, Patrice Chevallier, Mohamad Mohty, Bipin N. Savani, Guillermo Sanz, Frédéric Baron, Didier Blaise, Myriam Labopin, Eefke Petersen, Arnon Nagler, Eric Beohou, Department of Hematology [Liege, Belgium], CHU Sart Tilman [Liege, Belgium]-Université de Liège, Eurocord [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie [Marseille], Centre de Lutte contre le Cancer-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Servicio de Hematologia [Valencia, Spain], Hospital Universitari i Politècnic La Fe, Department of Hematology [Utrecht, The Netherlands] (UMCU), University Medical Center [Utrecht], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], France Monacord [Monaco], Centre Scientifique de Monaco (CSM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Division of Hematology and Bone Marrow Transplantation [Ramat-Gan, Israel], The Chaim Sheba Medical Center at Tel hashomer, no source, Université de Liège-CHU Sart Tilman [Liege, Belgium], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Centre de Lutte contre le Cancer, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, BMC, BMC, and Hematology
Subjects: Oncology, Male, Cancer Research, Transplantation Conditioning, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Single, Graft vs Host Disease, Hematopoietic stem cell transplantation, 0302 clinical medicine, AML, Medicine, 10. No inequality, Reduced-intensity, Univariate analysis, Hematology, Incidence (epidemiology), Hematopoietic Stem Cell Transplantation, lcsh:Diseases of the blood and blood-forming organs, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Fetal Blood, 3. Good health, [SDV] Life Sciences [q-bio], Leukemia, Myeloid, Acute, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, Double, lcsh:RC254-282, 03 medical and health sciences, Young Adult, Unrelated cord blood, Internal medicine, Humans, Molecular Biology, Aged, Retrospective Studies, Transplantation, Neutrophil Engraftment, business.industry, lcsh:RC633-647.5, Research, Retrospective cohort study, Surgery, UCB, Neoplasm Recurrence, Local, business, ALL, 030215 immunology
Abstract: Background The feasibility of cord blood transplantation (CBT) in adults is limited by the relatively low number of hematopoietic stem/progenitor cells contained in one single CB unit. The infusion of two CB units from different partially HLA-matched donors (double CBT) is frequently performed in patients who lack a sufficiently rich single CB unit. Methods We compared CBT outcomes in patients given single or double CBT following reduced-intensity conditioning (RIC) in a retrospective multicenter registry-based study. Inclusion criteria included adult (≥18 years) patients, acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), complete remission (CR) at the time of transplantation, first single (with a cryopreserved TNC ≥ 2.5 × 107/kg) or double CBT between 2004 and 2014, and RIC conditioning. Results Data from 534 patients with AML (n = 408) or ALL (n = 126) receiving a first single (n = 172) or double (n = 362) CBT were included in the analyses. In univariate analysis, in comparison to patients transplanted with a single CB, double CB recipients had a similar incidence of neutrophil engraftment but a suggestion for a higher incidence of grade II–IV acute GVHD (36 versus 28%, P = 0.08). In multivariate analyses, in comparison to single CBT recipients, double CBT patients had a comparable incidence of relapse (HR = 0.9, P = 0.5) and of nonrelapse mortality (HR = 0.8, P = 0.3), as well as comparable overall (HR = 0.8, P = 0.17), leukemia-free (HR = 0.8, P = 0.2) and GVHD-free, relapse-free (HR = 1.0, P = 0.3) survival. Conclusions These data failed to demonstrate better transplantation outcomes in adult patients receiving double CBT in comparison to those receiving single CBT with adequate TNC after RIC. Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0497-9) contains supplementary material, which is available to authorized users.
Published: 2017

17. Intermittent inotropic support with levosimendan in advanced heart failure as destination therapy: The LEVO-D registry

Author: David Dobarro, Víctor Donoso‐Trenado, Eduard Solé‐González, Carlos Moliner‐Abós, José Manuel Garcia‐Pinilla, Silvia Lopez‐Fernandez, Sonia Ruiz‐Bustillo, Carles Diez‐Lopez, Javier Castrodeza, Ana B. Méndez‐Fernández, David Vaqueriza‐Cubillo, Marta Cobo‐Marcos, Javier Tobar, Igor Sagasti‐Aboitiz, Miguel Rodriguez, Vanessa Escolar, Ana Abecia, Pau Codina, Inés Gómez‐Otero, Francisco Pastor, Raquel Marzoa‐Rivas, Eva González‐Babarro, Javier de Juan‐Baguda, María Melendo‐Viu, Fernando de Frutos, José Gonzalez‐Costello, Institut Català de la Salut, [Dobarro D] Hospital Álvaro Cunqueiro, Complexo Hospitalario Universitario de Vigo, Vigo, Spain. [Donoso-Trenado V] Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Solé González E] Hospital Clinic i Provincial, Barcelona, Spain. [Moliner-Abós C] Hospital de la Santa Creu i Sant Pau, IIB SANT PAU, Barcelona, Spain. [Garcia-Pinilla JM] Hospital Universitario Virgen de la Victoria, IBIMA, Málaga, Ciber-Cardiovascular, Instituto de Salud Carlos III, Departamento de Medicina y Dermatología, Universidad de Málaga, Malaga, Spain. [Lopez-Fernandez S] Hospital Universitario Virgen de las Nieves, ibs. GRANADA, Granada, Spain. [Méndez-Fernández AB] Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Cardiovascular Agents::Cardiotonic Agents [CHEMICALS AND DRUGS], Cardiovascular Diseases::Heart Diseases::Heart Failure [DISEASES], Insuficiència cardíaca - Tractament, Farmacologia cardiovascular, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos cardiovasculares::cardiotónicos [COMPUESTOS QUÍMICOS Y DROGAS], Cardiology and Cardiovascular Medicine, enfermedades cardiovasculares::enfermedades cardíacas::insuficiencia cardíaca [ENFERMEDADES]
Abstract: Advanced heart failure; Inotropes; Palliative care Insuficiencia cardiaca avanzada; Inotropos; Cuidados paliativos Insuficiència cardíaca avançada; Inòtrops; Cures pal·liatives Aim Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. Methods and results Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4–26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (−1.5) HF visit 1 year before levosimendan (−1.5) and heart rate >70 b.p.m. (−2). Patients with a score less than −1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. Conclusion In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.
Published: 2023

18. Unrelated cord blood transplantation for adult patients with acute myeloid leukemia: higher incidence of acute graft-versus-host disease and lower survival in male patients transplanted with female unrelated cord blood--a report from Eurocord, the Acute Leukemia Working Party, and the Cord Blood Committee of the Cellular Therapy and Immunobiology Working Party of the European Group for Blood and Marrow Transplantation

Author: Baron, Frédéric, Labopin, Myriam, Ruggeri, Annalisa, Mohty, Mohamad, Sanz, Guillermo, Milpied, Noel, Bacigalupo, Andrea, Rambaldi, Alessandro, Bonifazi, Francesca, Bosi, Alberto, Sierra, Jorge, Yakoub-Agha, Ibrahim, Ribera, Jose-Maria, Gluckman, Eliane, Nagler, Arnon, Universitat Autònoma de Barcelona, Service d'Hématologie, Université de Liège-CHU Sart-Tilman, Centre International des greffes [CHU Saint-Antoine] (EBMT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Servicio de Hematologia, Hospital Universitari i Politècnic La Fe, Service d'Hématologie et Thérapie Cellulaire, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Department of Haematology II, Ospedale San Martino, Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Institute of Hematology and Medical, Oncology L and A Seràgnoli, Policlinico S. Orsola - Malpighi, Bone Marrow Transplant Unit (BMT), Azienda Ospedaliera Careggi, Hematology Department, Hospital de la Santa Creu i Sant Pau, Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Jose Carreras Research Institute, Hospital Universitari Germans Trias i Pujol, France Monacord, Centre Scientifique de Monaco (CSM), Division of Hematology and Bone Marrow Transplantation, The Chaim Sheba Medical Center at Tel hashomer, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, BMC, BMC, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut Universitaire d'Hématologie (IUH), and Hôpital Claude Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, Cancer Research, [SDV]Life Sciences [q-bio], GVHD, Graft vs Host Disease, Blood Donors, 0302 clinical medicine, AML, Risk Factors, hemic and lymphatic diseases, Medicine, 0303 health sciences, Acute leukemia, Hematology, Incidence, Hazard ratio, Middle Aged, 3. Good health, Europe, Survival Rate, [SDV] Life Sciences [q-bio], Leukemia, surgical procedures, operative, Oncology, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Cord blood, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Young Adult, Sex Factors, Unrelated cord blood, Sang fetal, Internal medicine, Humans, Survival rate, Molecular Biology, 030304 developmental biology, Aged, Retrospective Studies, Transplantation, business.industry, Research, medicine.disease, Survival Analysis, Surgery, Multivariate Analysis, business
Abstract: Background In the setting of allogeneic human leukocyte antigen (HLA)-matched bone marrow transplantation, transplanting male patients with grafts from female donors has been associated with a higher incidence of graft-versus-host disease (GVHD) and of nonrelapse mortality (NRM). The aim of the current analysis was to compare transplantation outcomes in male patients given female unrelated cord blood (UCB) versus other gender combinations. Patients and methods Data from 552 consecutive patients with acute myeloid leukemia (AML) given a single UCB transplantation between 2000 and 2014 were included. Results In comparison with other gender combination, male patients given female UCB (n = 131) had a trend for a higher incidence of grades II–IV acute GVHD (33 versus 25 %, P = 0.08), a trend for a higher incidence of NRM (41 versus 33 %, P = 0.06), and a lower leukemia-free (LFS, 30 versus 41 %, P = 0.01) and overall survival (OS, 33 versus 45 %, P = 0.008). In multivariate analyses, taking into consideration all patients for which data on HLA-matching and cell dose transplanted were fully available (n = 363), male patients transplanted with a female UCB had a trend for a higher incidence of grade III–IV acute GVHD (hazard ratio (HR) = 2.0, P = 0.06), a trend for a higher NRM (HR = 1.5, P = 0.06), and a worse LFS (HR = 1.4, P = 0.04) and OS (HR = 1.3, P = 0.06). Conclusions Our data suggest that male patients transplanted with female UCB might have higher risk of acute GVHD and of NRM leading to worse LFS and OS. These results should be confirmed in other large cohorts of patients before used for determining the choice of an UCB unit. Electronic supplementary material The online version of this article (doi:10.1186/s13045-015-0207-4) contains supplementary material, which is available to authorized users.
Published: 2015

19. PECATI: A Multicentric, Open-Label, Single-Arm Phase II Study to Evaluate the Efficacy and Safety of Pembrolizumab and Lenvatinib in Pretreated B3-Thymoma and Thymic Carcinoma Patients

Author: Laurence Bigay-Game, Miguel Sampayo, Nicolas Girard, Laurent Greillier, Benjamin Besse, Javier de Castro, Jordi Remon, Sophie Cousin, R. Bernabé, Oscar Juan, Joaquin Mosquera, Silvia Novello, Centro Integral Oncologico Clara Campal, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut Curie [Paris], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Università degli studi di Torino = University of Turin (UNITO), Hospital Universitario La Paz, Service de pneumologie [Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hospital Universitario Virgen del Rocío [Sevilla], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Nord [CHU - APHM], Institut Bergonié [Bordeaux], UNICANCER, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Institut Gustave Roussy (IGR), and Université Paris-Saclay
Subjects: Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Thymoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Second-line, Pembrolizumab, Antibodies, Monoclonal, Humanized, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Immunotherapy, Lenvatinib, Pembrolizumab, Second-line, Thymic epithelial tumors, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Lenvatinib, Humans, Medicine, Thymic epithelial tumors, Lung cancer, Survival rate, Thymic carcinoma, business.industry, Phenylurea Compounds, Standard treatment, Cancer, Thymus Neoplasms, medicine.disease, chemistry, Quinolines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, business
Abstract: International audience; Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival.
Published: 2022

20. Malnutrition management of hospitalized patients with diabetes/hyperglycemia in the perioperative setting

Author: Palma, Samara, García Malpartida, Katherine, García-Almeida, José Manuel, Matía‑Martín, Pilar, Sanz París, Alejandro, Burgos Peláez, Rosa, Institut Català de la Salut, [Palma Milla S] Unidad de Nutrición Clínica y Dietética, Servicio de Endocrinología y Nutrición, Hospital Universitario La Paz, Madrid, Spain. [García Malpartida K] Servicio de Endocrinología y Nutrición, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Burgos Peláez R] Unitat de Suport Nutricional, Servei d’Endocrinologia i Nutrició, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [García Almeida JM] Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Matía Martín P] Departamento de Endocrinología y Nutrición, Hospital Clínico San Carlos, Madrid, Spain. [Sanz Paris A] Servicio de Nutrición, Hospital Universitario Miguel Servet, Zaragoza, Spain. Instituto de Investigación Sanitaria (IIS) Aragón, Zaragoza, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo de la glucosa::hiperglucemia [ENFERMEDADES], Diabetis, Surgical Procedures, Operative [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperglycemia [DISEASES], enfermedades nutricionales y metabólicas::trastornos nutricionales::desnutrición [ENFERMEDADES], Hiperglucèmia, Operacions quirúrgiques, enfermedades del sistema endocrino::diabetes mellitus [ENFERMEDADES], intervenciones quirúrgicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Nutritional and Metabolic Diseases::Nutrition Disorders::Malnutrition [DISEASES], Malnutrició, Endocrine System Diseases::Diabetes Mellitus [DISEASES]
Abstract: Diabetes; Surgery; Perioperative setting Diabetes; Cirugía; Periodo perioperatorio Diabetis; Cirurgia; Període perioperatori Las personas con diabetes tienen un riesgo elevado de requerir una intervención quirúrgica a lo largo de su vida y de tener complicaciones perioperatorias en caso de un control metabólico deficiente. La hospitalización representa un evento estresante que, unido a otros factores asociados a procedimientos diagnósticos y terapéuticos, conlleva un deterioro del estado nutricional de los pacientes. Se ha observado una asociación entre un estado nutricional deficiente y resultados adversos en pacientes quirúrgicos. El presente artículo describe los resultados del consenso de expertos y las respuestas de los panelistas sobre el manejo nutricional en la práctica clínica habitual de los pacientes con diabetes/hiperglucemia hospitalizados en planta (no críticos) en el periodo perioperatorio. People with diabetes are at high risk of requiring surgical intervention throughout their lives, and of perioperative complications in case of poor metabolic control. Hospitalization represents a stressful event that, together with other factors associated with diagnostic and therapeutic procedures, leads to a deterioration in the nutritional status of the patients. An association between poor nutritional status and adverse outcomes in surgical patients has been observed. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) in the perioperative setting.
Published: 2022

21. Number needed to treat and associated cost analysis of cenobamate versus third-generation anti-seizure medications for the treatment of focal-onset seizures in patients with drug-resistant epilepsy in Spain

Author: Vicente Villanueva, José M. Serratosa, Manuel Toledo, Miguel Ángel Calleja, Andrés Navarro, Joel Sabaniego, Paloma Pérez-Domper, Elena Álvarez-Barón, Silvia Subías, Alicia Gil, Institut Català de la Salut, [Villanueva V] Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Serratosa JM] Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Toledo M] Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Ángel Calleja M] Hospital Universitario Virgen Macarena, Sevilla, Spain. [Navarro A] Hospital General Universitario de Elche, Alicante, Spain. [Sabaniego J] Angelini Pharma, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Epilèpsia, Behavioral Neuroscience, Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Epilepsy::Drug Resistant Epilepsy [DISEASES], economía y organizaciones para la atención de la salud::economía::costes y análisis de costes [ATENCIÓN DE SALUD], Neurology, Health Care Economics and Organizations::Economics::Costs and Cost Analysis [HEALTH CARE], Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Anticonvulsants [CHEMICALS AND DRUGS], Anticonvulsius, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos del sistema nervioso central::anticonvulsivantes [COMPUESTOS QUÍMICOS Y DROGAS], Cost-eficàcia, Neurology (clinical), enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades cerebrales::epilepsia::epilepsia resistente a los medicamentos [ENFERMEDADES], Resistència als medicaments
Abstract: Medicamentos anticonvulsivos; Cenobamato; Eficiencia Medicaments anticonvulsius; Cenobamat; Eficiència Anti-seizure medications; Cenobamate; Efficiency Introduction Epilepsy is a serious neurological disease, ranking high in the top causes of disability. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, approximately 40% of patients suffer from Drug-Resistant Epilepsy (DRE) despite the availability of the latest options called third-generation Anti-Seizure Medications(ASMs). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. The introduction of a new drug increases the number of therapeutic options available, making it important to compare it with existing alternatives in terms of clinical benefit and efficiency. Purpose This study aimed to compare the clinical benefit, in terms of the Number Needed to Treat (NNT), and the efficiency, in terms of Cost per NNT (CNT), associated with cenobamate versus third-generation ASMs used in Spain for the adjunctive treatment of FOS in patients with DRE. Methods The Number Needed to Treat data was calculated based on the ≥50% responder rate and seizure freedom endpoints (defined as the percentage of patients achieving 50% and 100% reduction in seizure frequency, respectively), obtained from pivotal clinical trials performed with cenobamate, brivaracetam, perampanel, lacosamide, and eslicarbazepine acetate. The NNT was established as the inverse of the treatment responder rate minus the placebo responder rate and was calculated based on the minimum, mid-range Daily Defined Dose (DDD), and maximum doses studied in the pivotal clinical trials of each ASM. CNT was calculated by multiplying the annual treatment cost by NNT values for each treatment option. Results In terms of NNT, cenobamate was the ASM associated with the lowest values at all doses for both ≥50% responder rate and seizure freedom compared with the alternatives. In terms of CNT, for ≥50% responder rate, cenobamate was the ASM associated with the lowest CNT values at DDD and lacosamide and eslicarbazepine acetate at the minimum and maximum dose, respectively. For seizure freedom, cenobamate was associated with the lowest CNT value at DDD and the maximum dose and lacosamide at the minimum dose. Conclusions Cenobamate could represent the most effective ASM in all doses studied compared to the third-generation ASMs and the most efficient option at DDD for both ≥50% responder rate and seizure freedom. This study could represent an important contribution towards informed decision-making regarding the selection of the most appropriate therapy for FOS in adult patients with DRE from a clinical and economical perspective in Spain. This study was sponsored by Angelini Pharma España, S.L.U.
Published: 2022

22. Systematic review and meta‐analysis: the incidence and prevalence of paediatric coeliac disease across Europe

Author: Osvaldo Borrelli, Christos Tzivinikos, Corina Pienar, Carmen Ribes-Koninckx, John Williams, Kym Thorne, Ilse Broekaert, Stephen E. Roberts, Javier Martín-de-Carpi, Ann John, Emmanuel Mas, Nikhil Thapar, Marc A. Benninga, Rut Anne Thomassen, Mike Thomson, Jernej Dolinsek, Sian Morrison-Rees, Erasmo Miele, Roberts, Stephen E, Morrison-Rees, Sian, Thapar, Nikhil, Benninga, Marc A, Borrelli, Osvaldo, Broekaert, Ilse, Dolinsek, Jernej, Martin-de-Carpi, Javier, Mas, Emmanuel, Miele, Erasmo, Pienar, Corina, Ribes-Koninckx, Carmen, Thomassen, Rut A, Thomson, Mike, Tzivinikos, Christo, Thorne, Kymberley, John, Ann, Williams, John G, Swansea University, Great Ormond Street Hospital for Children [London] (GOSH), University College of London [London] (UCL), Children’s Health Queensland [Brisbane] (CHQ), University of Amsterdam [Amsterdam] (UvA), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], University of Sheffield [Sheffield], Al Jalila Children's Specialty Hospital, and European Society for Paediatric Gastroenterology Hepatology and Nutrition
Subjects: Pediatrics, medicine.medical_specialty, MEDLINE, Age at diagnosis, Cochrane Library, Asymptomatic, Coeliac disease, Serology, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Prevalence, medicine, Humans, Pharmacology (medical), Child, Aged, Autoantibodies, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Hepatology, business.industry, Incidence, Incidence (epidemiology), Gastroenterology, Infant, medicine.disease, 3. Good health, Europe, Celiac Disease, Child, Preschool, Meta-analysis, 030211 gastroenterology & hepatology, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background: Coeliac disease is one of the most prevalent immune-mediated gastrointestinal disorders in children. Aim: To review the incidence and prevalence of paediatric coeliac disease, and their trends, regionally across Europe, overall and according to age at diagnosis. Methods: Systematic review and meta-analysis from January 1, 1950 to December 31, 2019, based on PubMed, CINAHL and the Cochrane Library, searches of grey literature and websites and hand searching of reference lists. A total of 127 eligible studies were included. Results: The prevalence of previously undiagnosed coeliac disease from screening surveys (histology based) ranged from 0.10% to 3.03% (median = 0.70%), with a significantly increasing annual trend (P = 0.029). Prevalence since 2000 was significantly higher in northern Europe (1.60%) than in eastern (0.98%), southern (0.69%) and western (0.60%) Europe. Large increases in the incidence of diagnosed coeliac disease across Europe have reached 50 per 100 000 person-years in Scandinavia, Finland and Spain. The median age at diagnosis increased from 1.9 years before 1990 to 7.6 since 2000. Larger increases in incidence were found in older age groups than in infants and ages
Published: 2021

23. Safety of Thiopurine Use in Paediatric Gastrointestinal Disease

Author: Jernej Dolinsek, Christos Tzivinikos, Rut Ann Thomassen, Erasmo Miele, Carmen Ribes-Koninckx, Nikhil Thapar, Rok Orel, Corina Pienar, Ilse Broekaert, Mike Thomson, Emmanuel Mas, Marc A. Benninga, 'Federico II' University of Naples Medical School, University of Amsterdam [Amsterdam] (UvA), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Victor Babeş University of Medicine and Pharmacy (UMFT), Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], NHS Foundation Trust [London], The Royal Marsden, Al Jalila Children's Specialty Hospital, University College of London [London] (UCL), Queensland Paediatric Infectious Diseases Laboratory [Australia], University of Queensland [Brisbane]-Children's Health Research Centre, Paediatric Gastroenterology, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, ARD - Amsterdam Reproduction and Development, Miele, E., Benninga, M. A., Broekaert, I., Dolinsek, J., Mas, E., Orel, R., Pienar, C., Ribes-Koninckx, C., Thomassen, R. A., Thomson, M., Tzivinikos, C., and Thapar, N.
Subjects: Infliximab therapy, medicine.medical_specialty, Autoimmune hepatitis, Inflammatory bowel disease, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Gastrointestinal Agents, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Recurrence, inflammatory bowel disease, 030225 pediatrics, Steroid sparing, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Immunologic Factors, 6-mercaptopurine, Adverse effect, Intensive care medicine, Child, azathioprine, Thiopurine methyltransferase, biology, autoimmune hepatitis, Crohn disease, business.industry, Mercaptopurine, thiopurines, Gastroenterology, medicine.disease, Inflammatory Bowel Diseases, 3. Good health, Gastrointestinal disease, Pediatrics, Perinatology and Child Health, biology.protein, adverse effects, 030211 gastroenterology & hepatology, business, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Thiopurines, alone or in combination with other agents, have a pivotal role in the treatment of specific gastrointestinal and hepatological disorders. In inflammatory bowel disease and autoimmune hepatitis thiopurines have proven their value as steroid sparing agents for the maintenance of remission and may be considered for preventing postoperative Crohn disease recurrence where there is moderate risk of this occurring. Their use with infliximab therapy reduces antibody formation and increases biologic drug levels. The routine clinical use of thiopurines has, however, been questioned due to a number of potential adverse effects. The aim of this article is to provide information regarding the use, and in particular, safety of these agents in clinical practice in the light of such potentially severe, albeit rare, effects.
Published: 2020

24. Delphi consensus on recommendations for the treatment of spinal muscular atrophy in Spain (RET-AME consensus)

Author: I. Pitarch Castellano, M. Cabrera-Serrano, R. Calvo Medina, M.G. Cattinari, S. Espinosa García, J.A. Fernández-Ramos, O. García Campos, D. Gómez-Andrés, M.A. Grimalt Calatayud, A.J. Gutiérrez Martínez, E. Ibáñez Albert, S. Kapetanovic García, M. Madruga-Garrido, M. Martínez-Moreno, J. Medina Cantillo, A.I. Melián Suárez, A. Moreno Escribano, F. Munell, A. Nascimento Osorio, S.I. Pascual-Pascual, M. Povedano, I.M. Santana Casiano, J.F. Vázquez-Costa, Institut Català de la Salut, [Pitarch Castellano I] Sección de Neurología Pediátrica, Unidad de Enfermedades Neuromusculares, Servicio de Pediatría, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Cabrera-Serrano M] Servicio de Neurología y Neurofisiología, Hospital Virgen del Rocío, Sevilla, Spain. [Calvo Medina R] Sección de Neurología Pediátrica, Servicio de Pediatría, Hospital Materno-Infantil Regional Universitario de Málaga, Spain. [Cattinari MG] Fundación Atrofia Muscular Espinal (FundAME), Madrid, Spain. [Espinosa García S] Sección de Rehabilitación Infantil, Hospital Universitario La Paz, Madrid, Spain. [Fernández-Ramos JA] Sección de Neurología Pediátrica, Servicio de Pediatría, Hospital Universitario Reina Sofía, Córdoba, Spain. [Gómez-Andrés D, Munell F] Secció de Neurologia Pediàtrica, Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Consensus, Delphi Technique, Infant, Newborn, Presa de decisions, enfermedades del sistema nervioso::enfermedades del sistema nervioso central::enfermedades de la médula espinal::atrofia muscular espinal [ENFERMEDADES], Neurodegenerative Diseases, Atròfia muscular espinal - Tractament, Other subheadings::/therapy [Other subheadings], Atrofia muscular espinal (AME), Delphi, Spinal muscular atrophy (SMA), Psychological Phenomena::Mental Processes::Thinking::Decision Making::Consensus [PSYCHIATRY AND PSYCHOLOGY], Treatment, Muscular Atrophy, Spinal, Spain, Neuromuscular, Materials Chemistry, Tratamiento, Humans, Nervous System Diseases::Central Nervous System Diseases::Spinal Cord Diseases::Muscular Atrophy, Spinal [DISEASES], fenómenos psicológicos::procesos mentales::pensamiento::toma de decisión::consenso [PSIQUIATRÍA Y PSICOLOGÍA], Child, Otros calificadores::/terapia [Otros calificadores]
Abstract: Atrofia muscular espinal; Tratamiento; Delphi Atròfia muscular espinal; Tractament; Delphi Spinal muscular atrophy; Treatment; Delphi Introduction Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a biallelic mutation of the SMN1 gene, located on the long arm of chromosome 5, and predominantly affects the motor neurons of the anterior horn of the spinal cord, causing progressive muscle weakness and atrophy. The development of disease-modifying treatments is significantly changing the natural history of SMA, but uncertainty remains about which patients can benefit from these treatments and how that benefit should be measured. Methodology A group of experts specialised in neurology, neuropediatrics, and rehabilitation and representatives of the Spanish association of patients with SMA followed the Delphi method to reach a consensus on 5 issues related to the use of these new treatments: general aspects, treatment objectives, outcome assessment tools, requirements of the treating centres, and regulation of their use. Consensus was considered to be achieved when a response received at least 80% of votes. Results Treatment protocols are useful for regulating the use of high-impact medications and should guide treatment, but should be updated regularly to take into account the most recent evidence available, and their implementation should be assessed on an individual basis. Age, baseline functional status, and, in the case of children, the type of SMA and the number of copies of SMN2 are characteristics that should be considered when establishing therapeutic objectives, assessment tools, and the use of such treatments. The cost-effectiveness of these treatments in paediatric patients is mainly influenced by early treatment onset; therefore, the implementation of neonatal screening is recommended. Conclusions The RET-AME consensus recommendations provide a frame of reference for the appropriate use of disease-modifying treatments in patients with SMA. Introducción La atrofia muscular espinal (AME) es una enfermedad neurodegenerativa, causada por una mutación bialélica del gen 5q SMN1, que afecta predominantemente a las neuronas motoras de la asta anterior medular causando una progresiva debilidad y atrofia muscular. La aparición de tratamientos modificadores del curso de la enfermedad está cambiando considerablemente la historia natural de la AME, pero existe todavía incertidumbre sobre qué pacientes se pueden beneficiar de estos tratamientos y cómo se debería medir ese beneficio. Metodología Un grupo de expertos especialistas en neurología, neuropediatría, rehabilitación y de la asociación de pacientes FundAME analizaron, siguiendo la metodología Delphi, 5 apartados relacionados con el uso de los nuevos tratamientos: aspectos generales; objetivos del tratamiento; herramientas de medición de resultados; requisitos de los centros tratantes; y regulación de su uso. Se definió como consenso cuando una respuesta recibió al menos el 80% de los votos. Resultados Los protocolos de tratamiento son útiles para regular el uso de medicamentos de alto impacto y deben constituir una guía para el tratamiento, pero se deben actualizar regularmente para recoger la evidencia más reciente disponible y su implementación se debe valorar de forma individualizada. La edad, la funcionalidad basal y, en el caso de los niños, el tipo de AME y el número de copias de SMN2 son características que se deben tener en cuenta a la hora de establecer los objetivos terapéuticos, las herramientas de medición y el uso de dichos tratamientos. El aspecto más determinante del coste-efectividad de estos tratamientos en la edad pediátrica es su inicio precoz, por lo que se recomienda la instauración de un cribado neonatal. Conclusiones Las recomendaciones del consenso RET-AME proporcionan un marco de referencia para el uso adecuado de tratamientos modificadores de la enfermedad en pacientes con AME.
Published: 2022

25. An ESPGHAN Position Paper on the Use of Low-FODMAP Diet in Pediatric Gastroenterology

Author: Thomassen, R A, Luque, V, Assa, A, Borrelli, O, Broekaert, I, Dolinsek, J, Martin-de-Carpi, J, Mas, E, Miele, E, Norsa, L, Ribes-Koninckx, C, Saccomani, M Deganello, Thomson, M, Tzivinikos, C, Verduci, E, Bronsky, J, Haiden, N, Köglmeier, J, de Koning, B, Benninga, M A, Pediatrics, Paediatric Gastroenterology, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam Reproduction & Development (AR&D), Oslo University Hospital [Oslo], Universitat Rovira i Virgili, The Hebrew University of Jerusalem (HUJ), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University of Maribor, University of Barcelona, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Naples Federico II = Università degli studi di Napoli Federico II, ASST Papa Giovanni XXIII [Bergamo, Italy], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Inst Invest Sanitaria La FE, Sheffield Children's NHS Foundation Trust, Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Università degli Studi di Milano = University of Milan (UNIMI), University Hospital Motol [Prague], Medizinische Universität Wien = Medical University of Vienna, Erasmus University Rotterdam, University of Amsterdam [Amsterdam] (UvA), SEGUIN, Nathalie, Thomassen, R A, Luque, V, Assa, A, Borrelli, O, Broekaert, I, Dolinsek, J, Martin-de-Carpi, J, Mas, E, Miele, E, Norsa, L, Ribes-Koninckx, C, Saccomani, M Deganello, Thomson, M, Tzivinikos, C, Verduci, E, Bronsky, J, Haiden, N, Köglmeier, J, de Koning, B, and Benninga, M A
Subjects: IRRITABLE-BOWEL-SYNDROME, Oligosaccharides, CHILDREN, Disaccharides, POLYOLS DIET, CLINICAL-TRIAL, Irritable Bowel Syndrome, Diet, Carbohydrate-Restricted, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, QUALITY-OF-LIFE, MANAGEMENT, Humans, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, REDUCES SYMPTOMS, Child, Settore MED/38 - Pediatria Generale e Specialistica, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Monosaccharides, Gastroenterology, RANDOMIZED CONTROLLED-TRIAL, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Fermentation, Pediatrics, Perinatology and Child Health, LOW FERMENTABLE OLIGOSACCHARIDES, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CELIAC GLUTEN SENSITIVITY, Systematic Reviews as Topic
Abstract: OBJECTIVES: Excluding oligo-, di-, monosaccharides and polyols (FODMAPs) from the diet is increasingly being used to treat children with gastrointestinal complaints. The aim of this position paper is to review the available evidence on the safety and efficacy of its use in children and provide expert guidance regarding practical aspects in case its use is considered. METHODS: Members of the Gastroenterology Committee, the Nutrition Committee and the Allied Health Professionals Committee of the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Clinical questions regarding initiation, introduction, duration, weaning, monitoring, professional guidance, safety and risks of the diet are addressed. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. RESULTS: The systematic literature search revealed that the low-FODMAP diet has not been comprehensively studied in children. Indications and contraindications of the use of the diet in different pediatric gastroenterological conditions are discussed and practical recommendations are formulated. CONCLUSIONS: There is scarce evidence to support the use of a low-FODMAP diet in children with Irritable Bowel Syndrome and no evidence to recommend its use in other gastrointestinal diseases and complaints in children. Awareness of how and when to use the diet is crucial, as a restrictive diet may impact nutritional adequacy and/or promote distorted eating in vulnerable subjects. The present manuscript provides practical safety tips to be applied when the low-FODMAP diet is considered in children.
Published: 2022

26. Clinical Implications of the Genetic Background in Pediatric Pulmonary Arterial Hypertension: Data from the Spanish REHIPED Registry

Author: Alejandro Cruz-Utrilla, Natalia Gallego-Zazo, Jair Antonio Tenorio-Castaño, Inmaculada Guillén, Alba Torrent-Vernetta, Amparo Moya-Bonora, Carlos Labrandero, María Elvira Garrido-Lestache Rodríguez-Monte, Alejandro Rodríguez-Ogando, María del Mar Rodríguez Vázquez Del Rey, Juana Espín, Beatriz Plata-Izquierdo, María Álvarez-Fuente, Antonio Moreno-Galdó, Pilar Escribano-Subias, María Jesús Del Cerro Marín, Institut Català de la Salut, [Cruz-Utrilla A] Pulmonary Hypertension Unit, ERN-Lung, Cardiology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. [Gallego-Zazo N, Tenorio-Castaño JA] Instituto de Genética Médica y Molecular (INGEMM), Hospital Universitario La Paz, Madrid, Spain. CIBERER, Centro de Investigación en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. ITHACA, European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability, Brussels, Belgium. [Guillén I] Pediatric Cardiology Unit, Department of Pediatrics, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Torrent-Vernetta A, Moreno-Galdó A] CIBERER, Centro de Investigación en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain. Unitat de Pneumologia Pediàtrica i Fibrosi Quística, Servei de Pediatria, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Moya-Bonora A] Pediatric Cardiology, Department of Pediatrics, Hospital Universitari i Politècnic La Fe, Valencia, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: enfermedades respiratorias::enfermedades pulmonares::hipertensión pulmonar [ENFERMEDADES], Catalysis, técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Inorganic Chemistry, Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary [DISEASES], Hipertensió pulmonar - Aspectes genètics, Other subheadings::Other subheadings::/genetics [Other subheadings], Humans, genetics, Familial Primary Pulmonary Hypertension, Registries, Physical and Theoretical Chemistry, Child, Molecular Biology, Spectroscopy, Pulmonary Arterial Hypertension, Otros calificadores::Otros calificadores::/genética [Otros calificadores], Organic Chemistry, heritable pulmonary arterial hypertension, General Medicine, Investigative Techniques::Epidemiologic Methods::Data Collection::Registries [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Computer Science Applications, Registres mèdics, pediatric pulmonary hypertension, pulmonary veno-occlusive disease, Pulmonary Veno-Occlusive Disease, Genetic Background
Abstract: Genetics; Heritable pulmonary arterial hypertension; Pediatric pulmonary hypertension Genética; Hipertensión arterial pulmonar hereditaria; Hipertensión pulmonar pediátrica Genètica; Hipertensió arterial pulmonar hereditària; Hipertensió pulmonar pediàtrica Background: Pulmonary arterial hypertension (PAH) is a severe and rare disease with an important genetic background. The influence of genetic testing in the clinical classification of pediatric PAH is not well known and genetics could influence management and prognosis. Objectives: The aim of this work was to identify the molecular fingerprint of PH children in the REgistro de pacientes con HIpertensión Pulmonar PEDiátrica (REHIPED), and to investigate if genetics could have an impact in clinical reclassification and prognosis. Methods: We included pediatric patients with a genetic analysis from REHIPED. From 2011 onward, successive genetic techniques have been carried out. Before genetic diagnosis, patients were classified according to their clinical and hemodynamic data in five groups. After genetic analysis, the patients were reclassified. The impact of genetics in survival free of lung transplantation was estimated by Kaplan–Meier curves. Results: Ninety-eight patients were included for the analysis. Before the genetic diagnoses, there were idiopathic PAH forms in 53.1%, PAH associated with congenital heart disease in 30.6%, pulmonary veno-occlusive disease—PVOD—in 6.1%, familial PAH in 5.1%, and associated forms with multisystemic disorders—MSD—in 5.1% of the patients. Pathogenic or likely pathogenic variants were found in 44 patients (44.9%). After a genetic analysis, 28.6% of the cohort was “reclassified”, with the groups of heritable PAH, heritable PVOD, TBX4, and MSD increasing up to 18.4%, 8.2%, 4.1%, and 12.2%, respectively. The MSD forms had the worst survival rates, followed by PVOD. Conclusions: Genetic testing changed the clinical classification of a significant proportion of patients. This reclassification showed relevant prognostic implications. This project was funded by project “Bases Genético-Moleculares de la Medicina de Precisión en la Hipertensión Arterial Pulmonar”. Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Gobierno de España. Co-funded by “Fondo Europeo de Desarrollo Regional, Programa Operativo Crecimiento Inteligente 2014–2020” (Award number: PI 18/01233). A.C.-U. holds a research-training contract “Rio Hortega” (CM20/00164) from the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III). REHIPED is supported by unrestricted grants of Janssen and Ferrer.
Published: 2022

27. Randomized phase II trial of FOLFIRI-panitumumab compared with FOLFIRI alone in patients with RAS wild-type circulating tumor DNA metastatic colorectal cancer beyond progression to first-line FOLFOX-panitumumab: the BEYOND study (GEMCAD 17-01)

Author: Jorge Aparicio, Anna C. Virgili Manrique, Jaume Capdevila, Félix Muñoz Boza, Patricia Galván, Paula Richart, Helena Oliveres, David Páez, Jorge Hernando, Sara Serrano, Ruth Vera, Xavier Hernandez-Yagüe, Rafael Álvarez Gallego, M. Carmen Riesco-Martinez, Xavier García de Albeniz, Joan Maurel, Institut Català de la Salut, [Aparicio J, Richart P] Medical Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Virgili Manrique AC] Medical Oncology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Capdevila J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IOB-Teknon, Barcelona, Spain. [Muñoz Boza F] Medical Oncology Department, Hospital Universitari Sant Joan de Reus, Reus, Spain. [Galván P] Translational Genomics and Targeted Therapies in Solid Tumors, Medical Oncology Department, Hospital Clínic de Barcelona, Barcelona, Spain. [Hernando J] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Proto-Oncogene Proteins B-raf, Cancer Research, Prognosi, Leucovorin, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Second line therapy, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Circulating Tumor DNA, nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ácidos nucleicos libres de células::ADN tumoral circulante [COMPUESTOS QUÍMICOS Y DROGAS], Còlon - Càncer - Tractament, Metastatic disease, Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [DISEASES], Recte - Càncer - Tractament, Antineoplastic Combined Chemotherapy Protocols, Humans, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [DISEASES], Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Cell-Free Nucleic Acids::Circulating Tumor DNA [CHEMICALS AND DRUGS], Liquid biopsy, Rectal Neoplasms, Panitumumab, Antibodies, Monoclonal, General Medicine, neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales [ENFERMEDADES], Colorectal cancer, afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::progresión de la enfermedad [ENFERMEDADES], Oncology, Colonic Neoplasms, Disease Progression, Camptothecin, Fluorouracil, Colorectal Neoplasms
Abstract: Purpose Panitumumab plus FOLFOX (P-FOLFOX) is standard first-line treatment for RAS wild-type (WT) metastatic colorectal cancer. The value of panitumumab rechallenge is currently unknown. We assessed addition of panitumumab to FOLFIRI (P-FOLFIRI) beyond progression to P-FOLFOX in patients with no RAS mutations in liquid biopsy (LB). Methods In this randomized phase II trial, patients were assigned (3:2 ratio) to second-line P-FOLFIRI (arm A) or FOLFIRI alone (arm B). LB for circulating tumor DNA analysis was collected at study entry and at disease progression. Primary endpoint was 6-month progression-free survival. Two-stage Simon design required 85 patients to be included (EudraCT 2017-004519-38). Results Between February 2019 and November 2020, 49 patients were screened (16 RAS mutations in LB detected) and 31 included (18 assigned to arm A and 13 to arm B). The study was prematurely closed due to inadequate recruitment. Serious adverse events were more frequent in arm A (44% vs. 23%). Overall response rate was 33% (arm A) vs. 7.7% (arm B). Six-month progression-free survival rate was 66.7% (arm A) and 38.5% (arm B). Median progression-free survival was 11.0 months (arm A) and 4.0 months (arm B) (hazard ratio, 0.58). At disease progression, RAS or BRAF mutations in LB were found in 4/11 patients (36%) in arm A and 2/10 (20%) in arm B. Conclusions The BEYOND study suggests a meaningful benefit of P-FOLFIRI beyond progression to P-FOLFOX in metastatic colorectal cancer patients with WT RAS status selected by LB. This strategy deserves further investigation.
Published: 2022

28. Cognitive impairment in multiple sclerosis: diagnosis and monitoring

Author: Angela Vidal-Jordana, Ricardo C Ginestal-López, Virginia Meca-Lallana, Francisco Pérez-Miralles, Joan Carreres-Polo, Francisco Gascón-Giménez, Nieves Téllez-Lara, Yolanda Higueras, Jesús Romero-Imbroda, Sara Eichau-Madueño, Institut Català de la Salut, [Meca-Lallana V] Unidad de Enfermedades Desmielinizantes, Servicio de Neurología, Hospital Universitario de La Princesa, Madrid, Spain. [Gascón-Giménez F] Unidad de Esclerosis Múltiple, Servicio de Neurología, Hospital Clínico Universitario, Valencia, Spain. [Ginestal-López RC] Servicio de Neurología, Hospital Clínico San Carlos, Madrid, Spain. [Higueras Y] Instituto de Investigación Sanitaria del Gregorio Marañón, Hospital Gregorio Marañón, Madrid, Spain. [Téllez-Lara N] Servicio de Neurología, Hospital Clínico Universitario, Valladolid, Spain. [Carreres-Polo J] Servicio de Radiología, Hospital Universitari i Politècnic La Fe de Valencia, Valencia, Spain. [Vidal-Jordana Á] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Esclerosi múltiple - Complicacions, medicine.medical_specialty, Neurology, Otros calificadores::/diagnóstico [Otros calificadores], Dermatology, Cognitive dysfunction, Multiple sclerosis, Neurophysiological monitoring, Neuropsychological tests, Multiple sclerosis, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], Physical medicine and rehabilitation, Quality of life (healthcare), Cognitive dysfunction, Multidisciplinary approach, Neuropsychology, Other subheadings::/diagnosis [Other subheadings], Medicine, Humans, Neuropsychological assessment, Cognitive rehabilitation therapy, Tests neuropsicològics, Cognitive evaluation theory, medicine.diagnostic_test, business.industry, Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis [DISEASES], Cognition, General Medicine, Psychiatry and Mental health, Neuropsychological tests, Mental Disorders::Neurocognitive Disorders::Cognition Disorders::Cognitive Dysfunction [PSYCHIATRY AND PSYCHOLOGY], enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple [ENFERMEDADES], Quality of Life, Original Article, Neurology (clinical), Neurophysiological monitoring, business, Trastorns de la cognició - Diagnòstic, trastornos mentales::trastornos neurocognitivos::trastornos cognitivos::disfunción cognitiva [PSIQUIATRÍA Y PSICOLOGÍA], Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract: Introduction Cognitive impairment (CI) has a prevalence of 45–70% in people with multiple sclerosis (MS), producing a negative impact on their quality of life, personal life, and work. Early detection of CI has become an important aspect to be considered for an adequate follow-up, to optimize social adaptation and to implement specific cognitive rehabilitation strategies. The aim of this work is to propose a suitable cognitive evaluation of patients with MS based on available and efficient tools for diagnosis and monitoring purposes well supported by literature review and clinical experience. Methods A multidisciplinary panel of professionals from the field of neurology, neuropsychology, and neuroimaging performed a literature review of the topic of cognitive impairment assessment. This was combined and completed with their clinical experience to produce a set of recommendations. Results Some limitations to cognitive evaluation are described: shortage of time and resources during the neurology consultation, scarceness or absence of specialized professionals’ availability, importance of tests adaptation, and doubts about its use to define therapeutic efficiency. We recommend a baseline and annual screening evaluation, and we suggest a baseline and periodic neuropsychological assessment. The latter ought to change to a recommendation with the presence of either positive screening test, or subjective to cognitive complaints, screening-test results and patient or family report mismatch, or in specific social/work situations. Conclusions Cognitive evaluation should be performed on all patients diagnosed with MS and throughout follow-up. It is necessary to support the creation of multidisciplinary MS teams to optimize the evaluation and follow-up of MS patients.
Published: 2021

29. First-line Nivolumab + Ipilimumab + Chemo in Patients With Advanced NSCLC and Brain Metastases: Results From CheckMate 9LA

Author: Carbone, D., Ciuleanu, T., Cobo, M., Schenker, M., Zurawski, B., Menezes, J., Richardet, E., Bennouna, J., Felip, E., Juan-Vidal, O., Alexandru, A., Sakai, H., de La Mora Jimenez, E., Paz-Ares, L., Reck, M., John, T., Hu, N., Zhang, X., Tran, P., Grootendorst, D.J., Lu, S., The Ohio State University Press, The Oncology Institute 'Prof. Dr. Ion Chiricuţă' [Cluj-Napoca, Romania] (TOI), Virgen de la Victoria University Hospital, SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Institute of Oncology Prof. Dr. Alexandru Trestioreanu (IOB), Saitama Cancer Center [Saitama, Japan] (S2C), Universidad de Guadalajara, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), German Center for Lung Research, Austin Hospital [Melbourne], Austin Health, Bristol-Myers Squibb [Princeton], Shanghai Jiaotong University, and Bernardo, Elizabeth
Subjects: [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

30. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update

Author: X. Zhang, Michael Schenker, Shunyuan Lu, Arnaud Scherpereel, Maurice Pérol, A. Lingua, Manuel Cobo, S. Marimuthu, Tudor-Eliade Ciuleanu, Arteid Memaj, Eduardo Richardet, O. Juan-Vidal, F. Reyes, David P. Carbone, B. Zurawski, A. Alexandru, Phuong Tran, Hiroshi Sakai, Jaafar Bennouna, Martin Reck, Enriqueta Felip, Thomas John, Juliana Janoski de Menezes, Pierre-Jean Souquet, C. Martin, Luis Paz-Ares, P. De Marchi, German Center for Lung Research, Institutul oncologic Prof Dr Ion Chiricuta [Cluj-Napoca, Romania], Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), Instituto Medico Rio Cuarto SA [Córdoba, Argentina] (IMRC), Fundacion Arturo Lopez Perez [Santiago, Metropolitana, Chile] (FALP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Barretos Cancer Hospital [São Paulo, Brazil] (BCH), Instituto Alexander Fleming [Buenos Aires, Argentina] (IAF), Centre Léon Bérard [Lyon], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Shanghai Jiaotong University, Hospital Universitario 12 de Octubre [Madrid], Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], Austin Hospital [Melbourne], Austin Health, Bernardo, Elizabeth, Institut Català de la Salut, [Reck M] Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany. [Ciuleanu TE] Department of Oncology, Institutul Oncologic Prof Dr Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca, Romania. [Cobo M] Department of Medical Oncology, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. [Schenker M] Department of Oncology, SF Nectarie Oncology Center, Craiova, Romania. [Zurawski B] Department of Clinical Oncology, Ambulatorium Chemioterapii, Bydgoszcz, Poland. [Menezes J] Department of Oncology, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil. [Felip E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Other subheadings::Other subheadings::/drug therapy [Other subheadings], NSCLC, Quimioteràpia combinada, nivolumab, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Non-Small-Cell Lung, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, first-line, ipilimumab, Lung cancer, Adverse effect, NSCLC, dual immunotherapy, first-line, ipilimumab, nivolumab, Original Research, Chemotherapy, business.industry, Hazard ratio, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung [DISEASES], neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas [ENFERMEDADES], medicine.disease, Confidence interval, Discontinuation, Nivolumab, dual immunotherapy, Neoplasm Recurrence, Local, business, Corrigendum, Pulmons - Càncer - Tractament, medicine.drug
Abstract: Background To further characterize survival benefit with first-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone, we report updated data from the phase III CheckMate 9LA trial with a 2-year minimum follow-up. Patients and methods Adult patients were treatment naïve, with stage IV/recurrent non-small-cell lung cancer, no known sensitizing EGFR/ALK alterations, and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized 1 : 1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with two cycles of chemotherapy, or four cycles of chemotherapy. Updated efficacy and safety outcomes are reported, along with progression-free survival (PFS) after next line of treatment (PFS2), treatment-related adverse events (TRAEs) by treatment cycle, and efficacy outcomes in patients who discontinued all treatment components in the experimental arm due to TRAEs. Results With a median follow-up of 30.7 months, nivolumab plus ipilimumab with chemotherapy continued to prolong overall survival (OS) versus chemotherapy. Median OS was 15.8 versus 11.0 months [hazard ratio 0.72 (95% confidence interval 0.61-0.86)]; 2-year OS rate was 38% versus 26%. Two-year PFS rate was 20% versus 8%. ORR was 38% versus 25%, respectively; 34% versus 12% of all responses were ongoing at 2 years. Median PFS2 was 13.9 versus 8.7 months. Improved efficacy outcomes in the experimental versus control arm were observed across most subgroups, including by programmed death-ligand 1 and histology. No new safety signals were observed; onset of grade 3/4 TRAEs was mostly observed during the first two treatment cycles in the experimental arm. In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy treatment due to TRAEs (n = 61) median OS was 27.5 months; 56% of responders had an ongoing response ≥1 year after discontinuation. Conclusions With a 2-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy provided durable efficacy benefits over chemotherapy with a manageable safety profile and remains an efficacious first-line treatment of advanced non-small-cell lung cancer., Highlights • Nivolumab + ipilimumab + two cycles of chemotherapy (chemo) significantly prolonged survival versus chemo in first-line advanced NSCLC. • At 2 years, overall survival benefits were durable with nivolumab + ipilimumab + chemo versus chemo. • Benefits of nivolumab + ipilimumab + chemo were seen across most patient subgroups, including by PD-L1 and histology. • Discontinuing nivolumab + ipilimumab + chemo due to treatment-related AEs did not negatively impact long-term benefits. • Nivolumab + ipilimumab + two cycles of chemo is an efficacious first-line treatment option for advanced non-oncogene-driven NSCLC.
Published: 2021

31. Drugs in Focus: Octreotide Use in Children With Gastrointestinal Disorders

Author: Osvaldo Borrelli, Erasmo Miele, C Ribes Koninckx, Rut Ann Thomassen, J Martin de-Carpi, Marc A. Benninga, Ilse Broekaert, Jernej Dolinsek, Christo Tzivinikos, Corina Pienar, Emmanuel Mas, Mike Thomson, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Great Ormond Street Hospital for Children [London] (GOSH), University Hospital of Cologne [Cologne], University medical centre Maribor (UKC Maribor), 'Federico II' University of Naples Medical School, Victor Babeş University of Medicine and Pharmacy (UMFT), University of Amsterdam [Amsterdam] (UvA), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe, Oslo University Hospital [Oslo], Sheffield Children's NHS Foundation Trust, Al Jalila Children's Specialty Hospital, and VU University Medical Center [Amsterdam]
Subjects: medicine.medical_specialty, Gastrointestinal bleeding, Gastrointestinal Diseases, Octreotide, Lymphangiectasia, somatostatin, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Gastrointestinal Agents, children, Chylous ascites, Internal medicine, chylous ascites, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Child, business.industry, Chylothorax, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, bleeding, 3. Good health, Clinical trial, diarrhoea, Pancreatitis, Pharmaceutical Preparations, ocreotide, 030220 oncology & carcinogenesis, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Acute Disease, Pediatrics, Perinatology and Child Health, Acute pancreatitis, 030211 gastroenterology & hepatology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; Octreotide, a somatostatin analogue, has been used for more than 20 years in children with gastrointestinal bleeding, chylothorax or chylous ascites, intestinal lymphangiectasia, pancreatitis, intestinal dysmotility, and severe diarrhoea; however, until now, there is a lack of randomised clinical trials evaluating the efficacy of this compound in childhood. Hence, we aimed to review the literature in order to determine the evidence of its use and safety in children, using PubMed from 2000 to 2021 with the search terms "octreotide" and "children" and "bleeding or chylous ascites or chylothorax or acute pancreatitis or lymphangiectasia or diarrhoea or intestinal dysmotility".
Published: 2021

32. Liver transplantation for patients with acute-on-chronic liver failure (ACLF) in Europe: Results of the ELITA/EF-CLIF collaborative study (ECLIS)

Author: Luca S. Belli, Christophe Duvoux, Thierry Artzner, William Bernal, Sara Conti, Paolo A. Cortesi, Sophie-Caroline Sacleux, George-Philippe Pageaux, Sylvie Radenne, Jonel Trebicka, Javier Fernandez, Giovanni Perricone, Salvatore Piano, Silvio Nadalin, Maria C. Morelli, Silvia Martini, Wojciech G. Polak, Krzysztof Zieniewicz, Christian Toso, Marina Berenguer, Claudia Iegri, Federica Invernizzi, Riccardo Volpes, Vincent Karam, René Adam, François Faitot, Liane Rabinovich, Faouzi Saliba, Lucy Meunier, Mickael Lesurtel, Frank E. Uschner, Costantino Fondevila, Baptiste Michard, Audrey Coilly, Magdalena Meszaros, Domitille Poinsot, Andreas Schnitzbauer, Luciano G. De Carlis, Roberto Fumagalli, Paolo Angeli, Vincente Arroyo, Rajiv Jalan, Raffaella Viganò, Chiara Mazzarelli, Andrea Lauterio, Alessandro Giacomoni, Francesca Donato, Pietro Lampertico, Luisa Pasulo, Stefano Fagiuoli, Michele Colledan, Maria Cristina Morelli, Giovanni Vitale, Damiano Patrono, Renato Romagnoli, Antonio Ottobrelli, Ioannis Petridis, Umberto Cillo, Giacomo Germani, Patrizia Burra, Philippe Bachellier, Pietro Addeo, Camille Besch, Francoise Faitot, Sophie Caroline Sacleux, Saliba Faouzi, Rene Adam, Didier Samuel, Celine Guichon, Stéfanie Faure, Josè Ursic-Bedoya, Jorde Colmenero, David Toapanta, María Hernández-Tejero, Carmen Vinaixa, Caroline den Hoed, Jubi E. de Haan, Andrea Della Penna, Frank Erhard Uschner, Martin Welker, Stefan Zeuzem, Wolf Bechstein, Nicolas Goossens, Joanna Raszeja-Wyszomirska, Dev Katarey, Banwari Agarwal, Surgery, Internal Medicine, Gastroenterology & Hepatology, Intensive Care, ASST Great Metropolitan Niguarda / ASST Grande Ospedale Metropolitano Niguarda [Milan, Italia], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de Hautepierre [Strasbourg], King‘s College London, Ospedale Multimedica Sesto San Giovanni, Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Goethe-University Frankfurt am Main, European Foundation for Study of Chronic Liver Failure [Barcelona] (EF CLIF), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Azienda Ospedaliero-Universitaria di Bologna, Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Medical University of Warsaw - Poland, Geneva University Hospitals and Geneva University, Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Hospital Papa Giovanni XXIII (Hosp P Giovanni XXIII), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), Pôle des Pathologies Digestives Hépatiques et Transplantation [Hôpital Hautepierre-Strasbourg], Department of Physiopatology and Transplantation, University of Milan (DEPT), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale S. Giovanni Battista-Molinette, Azienda Ospedaliera di Padova, Università degli Studi di Padova = University of Padua (Unipd), Hospital Clinic i Provincial de Barcelona (SCReN), University College London Hospitals (UCLH), Belli, L, Duvoux, C, Artzner, T, Bernal, W, Conti, S, Cortesi, P, Sacleux, S, Pageaux, G, Radenne, S, Trebicka, J, Fernandez, J, Perricone, G, Piano, S, Nadalin, S, Morelli, M, Martini, S, Polak, W, Zieniewicz, K, Toso, C, Berenguer, M, Iegri, C, Invernizzi, F, Volpes, R, Karam, V, Adam, R, Faitot, F, Rabinovich, L, Saliba, F, Meunier, L, Lesurtel, M, Uschner, F, Fondevila, C, Michard, B, Coilly, A, Meszaros, M, Poinsot, D, Schnitzbauer, A, De Carlis, L, Fumagalli, R, Angeli, P, Arroyo, V, Jalan, R, Fagiuoli, S, Goossens, Nicolas, and Salvy-Córdoba, Nathalie
Subjects: Male, 0301 basic medicine, Multi-drug resistant organisms, medicine.medical_treatment, Waiting list, Salvage therapy, Liver transplantation, Severity of Illness Index, MESH: Proportional Hazards Models, Cohort Studies, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Medicine, MESH: Cohort Studies, Acute-on-Chronic Liver Failure, MESH: Aged, High rate, MESH: Middle Aged, ddc:617, Hazard ratio, MESH: Acute-On-Chronic Liver Failure, Middle Aged, Prognosis, Predictive factors, Italy, Female, 030211 gastroenterology & hepatology, Adult, MESH: Liver Transplantation, medicine.medical_specialty, MESH: Prognosis, 03 medical and health sciences, MESH: Severity of Illness Index, Internal medicine, Humans, Acute on chronic liver failure, Renal replacement therapy, Aged, Proportional Hazards Models, Retrospective Studies, MESH: Humans, Hepatology, business.industry, MESH: Italy, MESH: Adult, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Retrospective cohort study, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Multi-drug resistant organism, MESH: Male, 030104 developmental biology, Predictive factor, business, MESH: Female
Abstract: Background & Aims: Liver transplantation (LT) has been proposed as an effective salvage therapy even for the sickest patients with acute-on-chronic liver failure (ACLF). This large collaborative study was designed to assess the current clinical practice and outcomes of patients with ACLF who are wait-listed for LT in Europe. Methods: This was a retrospective study including 308 consecutive patients with ACLF, listed in 20 centres across 8 European countries, from January 2018 to June 2019. Results: A total of 2,677 patients received a LT: 1,216 (45.4%) for decompensated cirrhosis. Of these, 234 (19.2%) had ACLF at LT: 58 (4.8%) had ACLF-1, 78 (6.4%) had ACLF-2, and 98 (8.1%) had ACLF-3. Wide variations were observed amongst countries: France and Germany had high rates of ACLF-2/3 (27-41%); Italy, Switzerland, Poland and the Netherlands had medium rates (9-15%); and the United Kingdom and Spain had low rates (3-5%) (p 4 mmol/L (hazard ratio [HR] 3.14; 95% CI 1.37-7.19), recent infection from multidrug resistant organisms (HR 3.67; 95% CI 1.63-8.28), and renal replacement therapy (HR 2.74; 95% CI 1.37-5.51) were independent predictors of post-LT mortality. During the same period, 74 patients with ACLF died on the waiting list. In an intention-to-treat analysis, 1-year survival of patients with ACLF on the LT waiting list was 73% for ACLF-1 or-2 and 50% for ACLF-3. Conclusion: The results reveal wide variations in the listing of patients with ACLF in Europe despite favourable post-LT survival. Risk factors for mortality were identified, enabling a more pre-cise prognostic assessment of patients with ACLF. Lay summary: Acute-on-chronic liver failure (ACLF) is a severe clinical condition for which liver transplantation is an effective therapeutic option. This study has demonstrated that in Europe, referral and access to liver transplantation (LT) for patients with ACLF needs to be harmonised to avoid inequities. Post-LT survival for patients with ACLF was >80% after 1 year and some factors have been identified to help select patients with favourable outcomes. (C) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All reserved.
Published: 2021

33. Lactobacillus supports Clostridiales to restrict gut colonization by multidrug-resistant Enterobacteriaceae

Author: Ana Djukovic, María José Garzón, Cécile Canlet, Vitor Cabral, Rym Lalaoui, Marc García-Garcerá, Julia Rechenberger, Marie Tremblay-Franco, Iván Peñaranda, Leonor Puchades-Carrasco, Antonio Pineda-Lucena, Eva María González-Barberá, Miguel Salavert, José Luis López-Hontangas, Miguel Á. Sanz, Jaime Sanz, Bernhard Kuster, Jean-Marc Rolain, Laurent Debrauwer, Karina B. Xavier, Joao B. Xavier, Carles Ubeda, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana [Espagne] (FISABIO), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Instituto Gulbenkian de Ciência [Oeiras] (IGC), Fundação Calouste Gulbenkian, Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Université de Lausanne = University of Lausanne (UNIL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Instituto de Investigación Sanitaria de Aragón [Zaragoza] (IIS Aragón), Universidad de Navarra [Pamplona] (UNAV), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Instituto de Salud Carlos III [Madrid] (ISC), Memorial Sloan-Kettering Cancer Institute, Memorial Sloane Kettering Cancer Center [New York], C.U. was supported by the InfectERA-ERANET-Acciones complementarias grant [PCIN-2015-094] from the Spanish Ministerio de Economia y Competitividad and the 7th Research framework program from EU, grants from Conselleria d'Innovacio, Universitats, Ciencia i Societat Digital [AICO/2019/266, CIPROM/2021/053] and a grant from the Spanish MICINN [PID2020-120292RB-I00]. A.D. was supported by a Boehringer Ingelheim Fonds travel grant, and with J.B.X. by grant R01 AI137269/AI/NIAID from the US National Institutes of Health. B.K. was supported by the BMBF FloraStopMRE grant [031L0089]. V.C. was supported by an European Commission grant [MSCA-IF-2018-843183]. J.S. was supported by an InfectERA-ERANET-Acciones complementarias de programacion conjunta internacional grant (AC15/00070) and Proyectos de Investigacion en Salud del Instituto Carlos III (PI18/00280). K.B.X. was supported by FundacAo para a Ciencia e a Tecnologia grant (InfectERA/0004/2015). J.M.R. was supported by ANR FloraStopInfectMRE project., Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and LESUR, Hélène
Subjects: Clostridiales, Multidisciplinary, [SDV]Life Sciences [q-bio], General Physics and Astronomy, General Chemistry, General Biochemistry, Genetics and Molecular Biology, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Butyrates, Lactobacillus, Mice, Enterobacteriaceae, Animals, Prospective Studies
Abstract: Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of hospitalized patients combined with mice experiments, we find that Lactobacillus is key, though not sufficient, to restrict MRE gut colonization. Lactobacillus rhamnosus and murinus increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth through increased butyrate levels and reduced nutrient sources. This mechanism of colonization resistance, an interaction between Lactobacillus spp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions for developing effective probiotics that prevent infections in hospitalized patients.
Published: 2021

34. Hereditary angioedema due to C1 inhibitor deficiency: real-world experience from the Icatibant Outcome Survey in Spain

Author: Mar Guilarte, Anna Sala-Cunill, María Luisa Baeza, Rosario Cabañas, María Dolores Hernández, Ethel Ibañez, Carlos Hernando de Larramendi, Ramon Lleonart, Teófilo Lobera, Luis Marqués, Blanca Sáenz de San Pedro, Jaco Botha, Irmgard Andresen, Teresa Caballero, for the IOS Study Group, Institut Català de la Salut, [Guilarte M, Sala-Cunill A] Secció d’Al•lèrgia, Servei de Medicina, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Research Network on Allergy (National Allergy Network ARADyAL: Asma, Reacciones Adversas y Alérgicas), Instituto de Salud Carlos III, Madrid, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Baeza ML] Allergy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain. Biomedical Research Network on Rare Diseases, CIBERER-U761, Gregorio Marañón Health Research Institute, Madrid, Spain. [Cabañas R] Allergy Department, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research (IdiPaz), Madrid, Spain. Biomedical Research Network on Rare Diseases, CIBERER-U754, Madrid, Spain. [Hernández MD, Ibañez E] Allergy Department, IIS-Hospital Universitari I Politècnic La Fe, Valencia, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Hereditary angioedema, Therapeutics::Patient Care::Time-to-Treatment [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Research, Malalties congènites - Tractament, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], técnicas de investigación::métodos epidemiológicos::recopilación de datos::encuestas y cuestionarios [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], enfermedades del sistema inmune::hipersensibilidad::hipersensibilidad inmediata::urticaria::angioedema::angioedemas hereditarios [ENFERMEDADES], General Medicine, RC581-607, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Bradykinin, Inflamació, Immune System Diseases::Hypersensitivity::Hypersensitivity, Immediate::Urticaria::Angioedema::Angioedemas, Hereditary [DISEASES], Spain, terapéutica::asistencia al paciente::tiempo hasta el tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Proteïna C - Deficiència, Icatibant, Bradykinin B2 receptor antagonists, On-demand treatment, Registries, Immunologic diseases. Allergy
Abstract: Bradykinin; Hereditary angioedema; Icatibant Bradicinina; Angioedema hereditario; Icatibant Bradicinina; Angioedema hereditari; Icatibant Background The Icatibant Outcome Survey (IOS) is an international registry monitoring the use of icatibant, a bradykinin B2 receptor antagonist indicated for the acute treatment of hereditary angioedema (HAE) attacks. Our goal was to assess disease characteristics and icatibant treatment outcomes in patients with HAE due to C1 inhibitor deficiency (HAE type 1 or 2 (HAE-1/2)) from Spain relative to other countries participating in IOS. Methods Descriptive retrospective analyses of data are reported from 10 centers in Spain vs 51 centers in 12 other participating countries (July 2009 to January 2019). Results No meaningful differences were identified between patients in Spain (n = 119) and patients across other countries (n = 907) regarding median age at symptom onset (15.0 vs 12.0 years) or diagnosis (22.3 vs 20.5 years). Overall HAE attack rates (total attacks/total years of follow-up) were 2.66 in Spain and 1.46 across other countries. Patients in Spain reported fewer severe/very severe HAE attacks before treatment (41.0% vs 45.9%; P
Published: 2021

35. Drugs in Focus: The Use of Racecadotril in Paediatric Gastrointestinal Disease

Author: Emmanuel Mas, Ilse Broekaert, Erasmo Miele, Christos Tzivinikos, Jernej Dolinsek, Carmen Ribes-Koninckx, Marc A. Benninga, Corina Pienar, Rut Anne Thomassen, Nikhil Thapar, Rok Orel, Mike Thomson, Victor Babeş University of Medicine and Pharmacy (UMFT), Emma Children’s Hospital Academic Medical Centre, University Hospital of Cologne, University medical centre Maribor (UKC Maribor), Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli studi di Napoli Federico II, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Hospital Universitario y Politécnico La Fe, Oslo University Hospital [Oslo], NHS Foundation Trust, Al Jalila Children's Specialty Hospital, UCL Great Ormond Street Institute of Child Health [London, UK], Great Ormond Street Hospital, Partenaires INRAE, Queensland Children's Hospital, Pienar, Corina, Benninga, Marc A, Broekaert, Ilse J, Dolinsek, Jernej, Mas, Emmanuel, Miele, Erasmo, Orel, Rok, Ribes-Koninckx, Carmen, Thomassen, Rut-Anne, Thomson, Mike, Tzivinikos, Christo, Thapar, Nikhil, Paediatric Gastroenterology, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, Amsterdam Reproduction & Development (AR&D), ProdInra, Migration, University of Naples Federico II = Università degli studi di Napoli Federico II, and Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
Subjects: Diarrhea, Drug, Thiorphan, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Gastrointestinal Diseases, medicine.drug_class, media_common.quotation_subject, medicine.medical_treatment, Pharmacology, Racecadotril, 03 medical and health sciences, 0302 clinical medicine, adjuvant, 030225 pediatrics, Antidiarrhoeal, medicine, Humans, Antidiarrheals, Child, Adverse effect, Neprilysin, media_common, racecadotril, business.industry, digestive, oral, and skin physiology, Gastroenterology, medicine.disease, Small intestine, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, Pharmaceutical Preparations, Gastrointestinal disease, Pediatrics, Perinatology and Child Health, 030211 gastroenterology & hepatology, business, gastroenteritis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Adjuvant, medicine.drug
Abstract: International audience; Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant anti-diarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant anti-diarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.
Published: 2020

36. Drug clearance in neonates : a combination of population pharmacokinetic modelling and machine learning approaches to improve individual prediction

Author: Yue-E Wu, Alison H. Thomson, Yi Zheng, José Esteban Peris, Lo Yl, Bernd Meibohm, Edmund V. Capparelli, Wei Zhao, John N. van den Anker, Irja Lutsar, Hai-Yan Shi, Hai-Yan Xu, Xiao Li, Stéphanie Leroux, Karel Allegaert, Evelyne Jacqz-Aigrain, Bo Hao Tang, Yue Zhou, Xin Huang, Xiaoling Wang, Bao-Ping Xu, Bu-Fan Yao, Jacobus Burggraaf, Nicolas Simon, A.-Dong Shen, Chen Kou, Guo-Xiang Hao, Efthymios Manolis, Tian-You Wang, Remedios Marques, Valérie Biran, Jumpei Saito, Zheng Guan, Wen-Qi Wang, Shandong University, Leiden University Medical Center (LUMC), Universiteit Leiden, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), European Medicines Agency [Amsterdam, Pays-Bas] (EMA), Hôpital Sud [CHU Rennes], CHU Pontchaillou [Rennes], Shandong Jiaotong University [Jinan], Capital University of Medical Sciences [Beijing] (CUMS), University of Strathclyde [Glasgow], University of California [San Diego] (UC San Diego), University of California (UC), Hôpital Robert Debré, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), The University of Tennessee Health Science Center [Memphis] (UTHSC), University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Universitat de València (UV), University of Tartu, National Center for Child Health and Development [Tokyo], Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Georgetown University [Washington] (GU), University Children's Hospital [Basel, Switzerland]], and Malbec, Odile
Subjects: SELECTION, 0301 basic medicine, RM, BIG DATA, AZLOCILLIN, Metabolic Clearance Rate, [SDV]Life Sciences [q-bio], education, 030106 microbiology, Population, Drug Elimination Routes, Body weight, Machine learning, computer.software_genre, Models, Biological, 030226 pharmacology & pharmacy, CLASSIFICATION, Machine Learning, 03 medical and health sciences, 0302 clinical medicine, Text mining, Pharmacokinetics, Vancomycin, REGRESSION, Covariate, Humans, Medicine, Pharmacology (medical), CROSS-VALIDATION, Combined method, Pharmacology, education.field_of_study, PRETERM, business.industry, Infant, Newborn, CEFEPIME, DOSING OPTIMIZATION, [SDV] Life Sciences [q-bio], YOUNG, Artificial intelligence, business, computer, Clearance, Predictive methods
Abstract: International audience; Background Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data. Objective The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates. Methods Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods. Results The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods. Conclusion A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data. Bo-Hao Tang and Zheng Guan contributed equally to this work.
Published: 2021

37. Sucrosomial Iron Supplementation for the Treatment of Iron Deficiency Anemia in Inflammatory Bowel Disease Patients Refractory to Oral Iron Treatment

Author: V. Robles, Pilar Nos, Claudia Herrera-de Guise, Alicia Algaba, Yolanda Ber Nieto, Guillermo Bastida, Esteban Sáez-González, Fernando Gomollón, Jose Manuel Soares, Fernando Bermejo, Institut Català de la Salut, [Bastida G] Department of Gastroenterology, CIBEREHD, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain. [Herrera-de Guise C, Robles V] Unitat d'Atenció a la Colitis de Crohn, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Algaba A] Department of Gastroenterology, Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), Hospital Universitario de Fuenlabrada, 28046 Madrid, Spain. [Ber Nieto Y] Department of Gastroenterology, Hospital Universitario San Jorge, 22004 Huesca, Spain. [Soares JM] Department of Gastroenterology, Hospital Pedro Hispano, 4454-509 Matosinhos, Portugal, Vall d'Hebron Barcelona Hospital Campus, and Servicio de Digestivo. Hospital Universitario de Fuenlabrada
Subjects: enfermedades nutricionales y metabólicas::enfermedades metabólicas::trastornos del metabolismo del hierro::anemia ferropénica [ENFERMEDADES], Male, Inorganic Chemicals::Elements::Metals, Heavy::Iron [CHEMICALS AND DRUGS], Administration, Oral, Gastroenterology, Inflammatory bowel disease, Ferric Compounds, Intestins - Inflamació - Tractament, enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::enfermedad inflamatoria intestinal [ENFERMEDADES], Hemoglobins, Enfermedades Inflamatorias del Intestino, 0302 clinical medicine, iron deficiency, Quality of life, Surveys and Questionnaires, Compuestos de Hierro, Anèmia ferropènica - Tractament, TX341-641, Prospective Studies, Prospective cohort study, Depression (differential diagnoses), Aged, 80 and over, Nutrition and Dietetics, Anemia, Iron-Deficiency, sucrosomial iron, Iron deficiency, Middle Aged, anemia, humanities, compuestos inorgánicos::elementos::metales pesados::hierro [COMPUESTOS QUÍMICOS Y DROGAS], Anemia Ferropénica, Treatment Outcome, Tolerability, 030220 oncology & carcinogenesis, Other subheadings::Other subheadings::/administration & dosage [Other subheadings], 030211 gastroenterology & hepatology, Female, Adult, medicine.medical_specialty, Anemia, Iron, Article, 03 medical and health sciences, Young Adult, inflammatory bowel disease, Internal medicine, medicine, Humans, Ferro - Metabolisme - Ús terapèutic, Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Inflammatory Bowel Diseases [DISEASES], Aged, Otros calificadores::Otros calificadores::/administración & dosificación [Otros calificadores], Nutrition. Foods and food supply, business.industry, iron supplementation, Nutritional and Metabolic Diseases::Metabolic Diseases::Iron Metabolism Disorders::Anemia, Iron-Deficiency [DISEASES], medicine.disease, Inflammatory Bowel Diseases, Trace Elements, Iron-deficiency anemia, Dietary Supplements, Quality of Life, business, Iron Compounds, Food Science
Abstract: Iron deficiency anemia (IDA) is a common manifestation of Inflammatory Bowel Disease (IBD). Oral iron supplements are the treatment of choice, but are not always well tolerated. Sucrosomial® iron (SI) may represent an alternative. This prospective study assessed the tolerability and effectiveness of SI, and quality of life (QoL) of IDA-IBD patients who were intolerant to oral iron salts. The study included 52 individuals treated with 1 capsule/day for 12 weeks. Tolerability was assessed through a gastrointestinal symptom severity questionnaire. Hemoglobin (Hb) levels and clinical symptoms of IDA were analyzed. QoL was assessed using IBDQ-9 and EuroQoL questionnaires. The percentage of patients with excellent/good health increased from 42.9% to 94.3%. Mean Hb concentration significantly increased at all follow-up visits (p &lt, 0.05). Almost all participants (96.9%) were adherent to the study medication. Patients’ QoL improved (IBDQ-9: from 60.9 to 65.5). Patients also improved in mobility (71.8% to 78.1%), usual activities (51.3% to 68.7%), pain/discomfort (41.0% to 53.1%), and extreme depression/anxiety problems (7.7% to 3.2%), they worsened in self-care (100% to 90.6%), but perceived an enhancement in their global health [EQ-VAS score: 61.9 (±26.1) to 66.9 (±20.3)]. SI was well tolerated and improved IDA symptoms, IBD activity, and patients’ QoL. In conclusion, SI should be considered in IDA–IBD patients.
Published: 2021
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38. First-line nivolumab (NIVO) plus ipilimumab (IPI) plus two cycles of chemotherapy (chemo) versus chemo alone (4 cycles) in patients with advanced non-small cell lung cancer (NSCLC): Two-year update from CheckMate 9LA

Author: Phuong Tran, Aurella Alexandru, S. Marimuthu, Tudor-Eliade Ciuleanu, Hiroshi Sakai, Manuel Cobo, Luis Paz-Ares, Michael Schenker, Jaafar Bennouna, Arnaud Scherpereel, Arteid Memaj, Enriqueta Felip, O. Juan-Vidal, David P. Carbone, B. Zurawski, Thomas John, Eduardo Richardet, Juliana Janoski de Menezes, Shun Lu, Martin Reck, German Center for Lung Research, Institutul oncologic Prof Dr Ion Chiricuta [Cluj-Napoca, Romania], Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron University Hospital [Barcelona], Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Shanghai Jiaotong University, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], Bristol Myers Squibb [Springfield, PA, USA] (BMS), Austin Hospital [Melbourne], Austin Health, and Bernardo, Elizabeth
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, First line, Checkmate, non-small cell lung cancer (NSCLC), Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, medicine.disease, stomatognathic diseases, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, hemic and lymphatic diseases, medicine, Overall survival, In patient, Nivolumab, business, neoplasms, medicine.drug
Abstract: 9000 Background: In the randomized phase 3 CheckMate 9LA trial (NCT03215706), first-line NIVO + IPI combined with 2 cycles of chemo significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs chemo alone (4 cycles). Clinical benefit was observed regardless of programmed death ligand 1 (PD-L1) expression level and histology. Here we report data with 2 years’ minimum follow-up from this study. Methods: Adult patients (pts) with stage IV / recurrent NSCLC, ECOG performance status ≤ 1, and no known sensitizing EGFR/ALK alterations were stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous) and were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles; n = 361) or chemo alone (4 cycles; n = 358). Pts with non-squamous NSCLC in the chemo-alone arm could receive pemetrexed maintenance. The primary endpoint was OS. Secondary endpoints included PFS and ORR by blinded independent central review, and efficacy by different PD-L1 levels. Safety was exploratory. Results: At a minimum follow-up of 24.4 months for OS (database lock: Feb 18, 2021), pts treated with NIVO + IPI + chemo continued to derive OS benefit vs chemo, with a median OS of 15.8 months vs 11.0 months, respectively (HR, 0.72 [95% CI, 0.61–0.86]); 2-year OS rates were 38% vs 26%. Median PFS with NIVO + IPI + chemo vs chemo was 6.7 months vs 5.3 months (HR, 0.67 [95% CI, 0.56–0.79]); 8% and 37% of pts who had disease progression received subsequent immunotherapy, respectively. ORR was 38% with NIVO + IPI + chemo vs 25% with chemo. Similar clinical benefit with NIVO + IPI + chemo vs chemo was observed in all randomized pts and across the majority of subgroups, including by PD-L1 expression level (Table) or histology. Any grade and grade 3–4 treatment-related adverse events were reported in 92% and 48% of pts in the NIVO + IPI + chemo arm vs 88% and 38% in the chemo arm, respectively. Conclusion: With 2 years’ minimum follow-up, first-line NIVO + IPI + chemo demonstrated durable survival and benefit versus chemo in pts with advanced NSCLC; no new safety signals were identified. Clinical trial information: NCT03215706. [Table: see text]
Published: 2021

39. Spanish guide for neonatal stabilization and resuscitation 2021: Analysis, adaptation and consensus on international recommendations

Author: Gonzalo, Zeballos Sarrato, Alejandro, Avila-Alvarez, Raquel, Escrig Fernández, Montserrat, Izquierdo Renau, César W, Ruiz Campillo, Celia, Gómez Robles, Martín, Iriondo Sanz, Institut Català de la Salut, [Zeballos Sarrato G] Servicio de Neonatología, Hospital Universitario Gregorio Marañón, Madrid, Spain. [Avila-Alvarez A] Unidad de Neonatología, Servicio de Pediatría, Complexo Hospitalario Universitario, A Coruña (CHUAC), Sergas, A Coruña, Spain. [Escrig Fernández R] Servicio de Neonatología, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Izquierdo Renau M] Servicio de Neonatología, Sant Joan de Déu, BCNatal, Hospital Sant Joan de Déu-Hospital Clínic, Universidad de Barcelona, Barcelona, Spain. [Ruiz Campillo CW] Servei de Neonatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gómez Robles C] Servicio de Neonatología, Hospital Regional Universitario de Málaga, Málaga, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Medicina intensiva neonatal, Medicina - Presa de decisions, Consensus, terapéutica::asistencia al paciente::asistencia del enfermo crítico::cuidados intensivos neonatales [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Management of Technology and Innovation, Resuscitation, Infants nadons, Therapeutics::Patient Care::Critical Care::Intensive Care, Neonatal [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract: Reanimación; Estabilización; Recién nacido Reanimació; Estabilització; Nounat Resuscitation; Stabilization; Newborn After the publication of the recommendations, agreed by all the scientific societies through the ILCOR, at the end of 2020, the GRN-SENeo began a process of analysis and review of the main changes since the last guidelines, to which a specific consensus positioning on controversial issues, trying to avoid ambiguities and trying to adapt the evidence to our environment. This text summarizes the main conclusions of this work and reflects the positioning of that group. Tras la publicación de las recomendaciones, consensuadas por todas las sociedades científicas a través del ILCOR, a finales del año 2020, el GRN-SENeo inició un proceso de análisis y revisión de los principales cambios desde las últimas guías, a los que se añadió un posicionamiento específico de consenso en temas controvertidos, tratando de evitar ambigüedades, y procurando adaptar la evidencia a nuestro medio. El presente texto, resume las principales conclusiones de este trabajo y refleja el posicionamiento de dicho grupo.
Published: 2021

40. Brain region volumes and their relationship with disability progression and cognitive function in primary progressive multiple sclerosis

Author: Guillermo Izquierdo, Jorge Maurino, Lluís Ramió-Torrentà, Bonaventura Casanova, Daniel Prefasi, Jose R. Ara, Francisco Pérez-Miralles, Lucienne Costa-Frossard, Oscar Fernandez, Virginia Meca-Lallana, Antonio García-Merino, María L Martínez-Ginés, Sara Moreno-García, Francisco Gascón-Giménez, Joan Carreres-Polo, Institut Català de la Salut, [Pérez-Miralles FC] Neuroimmunology Unit, Department of Neurology, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Prefasi D] Department of Medical, Roche Farma S.A, Madrid, Spain. [García-Merino A] Department of Neurology, Hospital Universitario Puerta de Hierro, Majadahonda, Spain. [Ara JR] Department of Neurology, Hospital Universitario Miguel Servet, Zaragoza, Spain.[Izquierdo G] Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain. [Meca-Lallana V] Department of Neurology, Hospital Universitario La Princesa, Madrid, Spain. [Ramió-Torrentà L] Unitat de Neuroimmunologia i Esclerosi Múltiple, Departament de Neurologia, Hospital Universitari de Girona Dr. Josep Trueta, Institut Català de la Salut (ICS), Girona, Spain. Institut d’Assistència Sanitària, Salt, Spain. Institut d’Investigació Biomèdica de Girona (IDIBGI), Salt, Spain. Departament de Ciències Mèdiques, Facultat de Medicina, Universitat de Girona, Girona, Spain, and Hospital Universitari de Girona Dr Josep Trueta
Subjects: primary progressive multiple sclerosis, Esclerosi múltiple, enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple::esclerosis múltiple crónica progresiva [ENFERMEDADES], brain volume, Audiology, Esclerosi múltiple -- Tractament, Cohort Studies, Behavioral Neuroscience, 0302 clinical medicine, Cognition, fenómenos psicológicos::procesos mentales::cognición [PSIQUIATRÍA Y PSICOLOGÍA], magnetic resonance imaging, Prospective Studies, Gray Matter, Cervell, Original Research, medicine.diagnostic_test, 05 social sciences, Psychological Phenomena::Mental Processes::Cognition [PSYCHIATRY AND PSYCHOLOGY], Brain, brain volume, cognitive function, disability progression, magnetic resonance imaging, primary progressive multiple sclerosis, Multiple Sclerosis, Chronic Progressive, Magnetic Resonance Imaging, Straight gyrus, medicine.anatomical_structure, disability progression, Brain size, medicine.medical_specialty, Multiple Sclerosis, 050105 experimental psychology, lcsh:RC321-571, White matter, 03 medical and health sciences, Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Tomography::Magnetic Resonance Imaging [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis::Multiple Sclerosis, Chronic Progressive [DISEASES], medicine, Humans, 0501 psychology and cognitive sciences, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::tomografía::imagen por resonancia magnética [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Effects of sleep deprivation on cognitive performance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, cognitive function, business.industry, Magnetic resonance imaging, Lobe, Cerebellar tonsil, Imatgeria per ressonància magnètica, business, 030217 neurology & neurosurgery, Multiple sclerosis -- Treatment
Abstract: Background and purpose Evidence on regional changes resulting from neurodegenerative processes underlying primary progressive multiple sclerosis (PPMS) is still limited. We assessed brain region volumes and their relationship with disability progression and cognitive function in PPMS patients. Methods This was an MRI analysis of 43 patients from the prospective Understanding Primary Progressive Multiple Sclerosis (UPPMS) cohort study. MRI scans were performed within 3 months before enrollment and at month 12. Results Gray matter volume of declive and white matter volumes adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus significantly decreased from baseline to month 12. Baseline white matter volumes adjacent to right amygdala and left cuneus significantly differed between patients with and without disability progression, as well as baseline gray matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Baseline gray matter volumes of right cuneus and right superior temporal gyrus positively correlated with 12‐month Selective Reminding Test and Word List Generation performance, respectively. Gray matter changes in right superior semilunar lobe and white matter adjacent to left declive and right cerebellar tonsil also positively correlated with Word List Generation scores, while white matter change in left inferior semilunar lobe positively correlated with Symbol Digit Modalities Test performance after 12 months. Conclusions White and gray matter volumes of specific brain regions could predict disability progression and cognitive performance of PPMS patients after one year., The data described in the present manuscript provide a detailed description of region volume changes exhibited by primary progressive multiple sclerosis patients over one year, including decreases in gray matter declive and white matter adjacent to left straight gyrus, right calcarine sulcus, and right inferior occipital gyrus. In addition, baseline volumes of white matter adjacent to right amygdala and left cuneus could also predict 1‐year disability progression in patients with primary progressive multiple sclerosis, as well as baseline grey matter volumes of left cuneus, right parahippocampal gyrus, right insula, left superior frontal gyrus, declive, right inferior temporal gyrus, right superior temporal gyrus (pole), and right calcarine sulcus. Furthermore, baseline volumes of certain regions such as grey matter of right cuneus and right superior temporal gyrus could also predict cognitive performance after one year, as well as volume changes in grey matter of right superior semilunar lobe and white matter of left inferior semilunar lobe and adjacent to left declive and right cerebellar tonsil were correlates of cognitive performance.
Published: 2021

41. Impaired Binding to Junctophilin-2 and Nanostructural Alteration in CPVT Mutation

Author: Yuriana Aguilar-Sanchez, Olivier Villejoubert, Feliciano Protasi, Liheng Yin, Camille Rabesahala de Meritens, Julio L. Álvarez, Pascale Gerbaud, Ernst Niggli, Romain Perrier, Pierre Joanne, Héctor H. Valdivia, F. Anthony Lai, Spyros Zissimopoulos, Riccardo Rizzetto, Esther Zorio, Elena Marques-Sule, Linwei Li, Yue Yi Wang, Yadan Zhang, Alexandra Zahradnikova Jr, Carmen R. Valdivia, Simona Boncompagni, Jean-Pierre Benitah, Valérie Nicolas, Ana Maria Gomez, Josefina Ramos-Franco, Philippe Mateo, Miguel Fernandez-Tenorio, Signalisation et physiopathologie cardiovasculaire (CARPAT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Università degli studi 'G. d'Annunzio' Chieti-Pescara [Chieti-Pescara] (Ud'A), Institute of Life Science [Swansea], Swansea University, Rush University Medical Center [Chicago], University of Bern, Ingénierie et Plateformes au Service de l'Innovation Thérapeutique (IPSIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Qatar University, University of Wisconsin-Madison, Hospital Universitari i Politècnic La Fe, and Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV)
Subjects: Ile de france, Physiology, CPVT, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, action potential, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Political science, junctophilin, ryanodine receptor, media_common.cataloged_instance, Humans, European union, 610 Medicine & health, 030304 developmental biology, media_common, 0303 health sciences, calcium, Ryanodine Receptor Calcium Release Channel, RyR2, musculoskeletal system, Sarcoplasmic Reticulum, Death, Sudden, Cardiac, calcium induced calcium release, Gain of Function Mutation, cardiomyocyte calcium handling, cardiovascular system, ventricular tachycardia, mutation, Cardiology and Cardiovascular Medicine, Humanities
Abstract: Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare disease, manifested by syncope or sudden death in children or young adults under stress conditions. Mutations in the Ca 2+ release channel/RyR2 (type 2 ryanodine receptor) gene account for about 60% of the identified mutations. Recently, we found and described a mutation in RyR2 N-terminal domain, RyR2 R420Q . Objective: To determine the arrhythmogenic mechanisms of this mutation. Methods and Results: Ventricular tachycardias under stress conditions were observed in both patients with catecholaminergic polymorphic ventricular tachycardia and knock-in mice. During action potential recording (by patch-clamp in knock-in mouse cardiomyocytes and by microelectrodes in mutant human induced pluripotent stem cell-derived cardiomyocytes), we observed an increased occurrence of delayed afterdepolarizations under isoproterenol stimulation, associated with increased Ca 2+ waves during confocal Ca 2+ recording in both mouse and human RyR2 R420Q cardiomyocytes. In addition, Ca 2+ -induced Ca 2+ -release, as well as a rough indicator of fractional Ca 2+ release, were higher and Ca 2+ sparks longer in the RyR2 R420Q -expressing cells. At the ultrastructural nanodomain level, we observed smaller RyR2 clusters and widened junctional sarcoplasmic reticulum measured by gated stimulated emission depletion super-resolution and electron microscopy, respectively. The increase in junctional sarcoplasmic reticulum width might be due to the impairment of RyR2 R420Q binding to JPH2 (junctophilin-2), as there were less junctophilin-2 coimmunoprecipitated with RyR2 R420Q . At the single current level, the RyR2 R420Q channel dwells longer in the open state at low intracellular Ca 2+ ([Ca 2+ ] i ), but there is predominance of a subconductance state. The latter might be correlated with an enhanced interaction between the N terminus and the core solenoid, a RyR2 interdomain association that has not been previously implicated in the pathogenesis of arrhythmias and sudden cardiac death. Conclusions: The RyR2 R420Q catecholaminergic polymorphic ventricular tachycardia mutation modifies the interdomain interaction of the channel and weakens its association with JPH2. These defects may underlie both nanoscale disarrangement of the dyad and channel dysfunction.
Published: 2021

42. A brain atlas of axonal and synaptic delays based on modelling of cortico-cortical evoked potentials

Author: Jean-Didier, Lemaréchal, Maciej, Jedynak, Lena, Trebaul, Anthony, Boyer, François, Tadel, Manik, Bhattacharjee, Pierre, Deman, Viateur, Tuyisenge, Leila, Ayoubian, Etienne, Hugues, Blandine, Chanteloup-Forêt, Carole, Saubat, Raouf, Zouglech, Gina Catalina, Reyes Mejia, Sébastien, Tourbier, Patric, Hagmann, Claude, Adam, Carmen, Barba, Fabrice, Bartolomei, Thomas, Blauwblomme, Jonathan, Curot, François, Dubeau, Stefano, Francione, Mercedes, Garcés, Edouard, Hirsch, Elizabeth, Landré, Sinclair, Liu, Louis, Maillard, Eeva-Liisa, Metsähonkala, Ioana, Mindruta, Anca, Nica, Martin, Pail, Ana Maria, Petrescu, Sylvain, Rheims, Rodrigo, Rocamora, Andreas, Schulze-Bonhage, William, Szurhaj, Delphine, Taussig, Antonio, Valentin, Haixiang, Wang, Philippe, Kahane, Nathalie, George, Olivier, David, Elisa, Nacci, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Le Centre de Magnétoencéphalographie et d'Electroencéphalographie [CHU Pitié-Salpêtrière] (MEG-EEG), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Service de neurochirurgie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], Hospital Universitario y Politécnico La Fe [Valencia, Spain], CHU Strasbourg, Centre Hospitalier Sainte Anne [Paris], Jinan University [Guangzhou], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), University Emergency Hospital [Bucharest], Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University Hospital Brno, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IMIM-Hospital del Mar, Generalitat de Catalunya, Freiburg University Medical Center, CHU Lille, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Tsinghua University [Beijing] (THU), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Firenze = University of Florence (UniFI), Centre de recherche cerveau et cognition (CERCO UMR5549), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), The research leading to these results has received funding from the European Research Councilunder the European Union's Seventh Framework Programme (FP/2007-2013)/ERC GrantAgreement no. 616268 F-TRACT, the European Union’s Horizon 2020 FrameworkProgramme for Research and Innovation under Specific Grant Agreement No. 785907 and945539 (Human Brain Project SGA2 and SGA3), and from the French 'Investissementsd’avenir' programme under grant numbers ANR-11-INBS-0006 and ANR-10-IAIHU-06. PHwas supported by Swiss National Science Foundation grant #CRSII5_170873, ANR-11-INBS-0006,FLI,France Life Imaging(2011), European Project: 616268,EC:FP7:ERC,ERC-2013-CoG,F-TRACT(2014), European Project: 785907,H2020,HBP SGA2(2018), European Project: 945539,H2020,H2020-SGA-FETFLAG-HBP-2019,HBP SGA3(2020), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Toulouse Mind & Brain Institut (TMBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Gestionnaire, Hal Sorbonne Université, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, Functional Brain Tractography - F-TRACT - - EC:FP7:ERC2014-08-01 - 2019-07-31 - 616268 - VALID, Human Brain Project Specific Grant Agreement 2 - HBP SGA2 - - H20202018-04-01 - 2020-03-31 - 785907 - VALID, and Human Brain Project Specific Grant Agreement 3 - HBP SGA3 - - H20202020-01-01 - 2023-09-30 - 945539 - VALID
Subjects: neural mass models, 0303 health sciences, Brain Mapping, Epilepsy, cortico-cortical evoked potential, Brain, Bayes Theorem, Electric Stimulation, dynamic causal modelling, 03 medical and health sciences, 0302 clinical medicine, axonal conduction delay, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], synaptic time constant, Evoked Potentials, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (
Published: 2021

43. Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

Author: Yener Koc, Jaime Sanz, Johanna Tischer, Emanuele Angelucci, Montserrat Rovira, Mahmoud Aljurf, Arnon Nagler, Annalisa Ruggeri, Nicolaus Kröger, Myriam Labopin, Bipin N. Savani, J. L. Diez-Martin, Fabio Ciceri, Jacques Emmanuel Galimard, Simona Sica, Mutlu Arat, Mohamad Mohty, Moiseev Ivan Sergeevich, Boris V. Afanasyev, Sanz, J., Galimard, J. -E., Labopin, M., Afanasyev, B., Sergeevich, M. I., Angelucci, E., Kroger, N., Koc, Y., Ciceri, F., Diez-Martin, J. L., Arat, M., Sica, S., Rovira, M., Aljurf, M., Tischer, J., Savani, B., Ruggeri, A., Nagler, A., Mohty, M., Hospital Universitari i Politècnic La Fe, Instituto de Salud Carlos III [Madrid] (ISC), Pathologies biliaires, fibrose et cancer du foie [CHU Saint-Antoine], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Hématologie et d'Immunologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Pavlov First Saint Petersburg State Medical University [St. Petersburg], Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS), University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Medicana International [Istanbul, Turkey], Ospedale San Raffaele, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Sisli Florence Nightingale Hospital [Istanbul, Turkey], Università cattolica del Sacro Cuore [Roma] (Unicatt), King Faisal University (KFU), University-Hospital Munich-Großhadern [München], Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], and The Chaim Sheba Medical Center [Tel Hashomer, Israel]
Subjects: Male, Cancer Research, medicine.medical_treatment, Lymphoblastic Leukemia, Graft vs Host Disease, Hematopoietic stem cell transplantation, Acute lymphoblastic leukemia, 0302 clinical medicine, Cumulative incidence, RC254-282, Hematology, Hematopoietic Stem Cell Transplantation, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, 3. Good health, Allogeneic stem cell transplant, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, Post-transplant cyclophosphamide, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Transplantation, Homologous, In patient, Diseases of the blood and blood-forming organs, Sibling, Molecular Biology, Antineoplastic Agents, Alkylating, Aged, Retrospective Studies, Alternative donor transplants, Haploidentical transplant, business.industry, Research, Transplantation, Haploidentical, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, RC633-647.5, business, 030215 immunology
Abstract: Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.
Published: 2021

44. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial

Author: Pierre-Jean Souquet, David P. Carbone, Michael Schenker, Shun Lu, S. Meadows-Shropshire, A. Alexandru, Pamela Salman, Hiroshi Sakai, Jaafar Bennouna, Maurice Pérol, Enriqueta Felip, Alejo Lingua, J. Yan, Juliana Janoski de Menezes, B. Zurawski, Martin Reck, Arnaud Scherpereel, C. Martin, Eduardo Richardet, Abderrahim Oukessou, Tudor-Eliade Ciuleanu, Manuel Cobo, O. Juan-Vidal, Pedro Rafael Martins De Marchi, Thomas John, Luis Paz-Ares, Shruti Agrawal, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), The Oncology Institute 'Prof. Dr. Ion Chiricuţă' [Cluj-Napoca, Romania] (TOI), Instituto de Investigación Biomédica [Malaga, Spain] (IBIMA), SF Nectarie Oncology Center [Craiova, Romania], Ambulatorium Chemioterapii [Bydgoszcz, Poland] (AC), Hospital Nossa Senhora Da Conceição [Porto Alegre, Brazil] (HNSDC), Instituto Oncológico De Córdoba [Córdoba, Argentina] (IODC), Immunogenic Cell Death and Mesothelioma Therapy (CRCINA-ÉQUIPE 4), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes), Vall d'Hebron Institute of Oncology [Barcelone] (VHIO), Vall d'Hebron University Hospital [Barcelona], Hospital Universitario La Fe [Valencia, Spain] (HU), Oncology Institute of Bucharest Professor Doctor Alexandru Trestioreanu [Bucharest, Romania] (OIB), Saitama Cancer Center [Saitama, Japan] (S2C), Instituto Medico Rio Cuarto SA [Córdoba, Argentina] (IMRC), Fundacion Arturo Lopez Perez [Santiago, Metropolitana, Chile] (FALP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Barretos Cancer Hospital [São Paulo, Brazil], Instituto Alexander Fleming [Buenos Aires, Argentina] (IAF), Centre Léon Bérard [Lyon], Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Lille, CHU Lille, Shanghai Jiao Tong University [Shanghai], Austin Hospital [Melbourne], Austin Health, Ohio State University [Columbus] (OSU), Bristol-Myers Squibb [Princeton], German Center for Lung Research, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, and Bernardo, Elizabeth
Subjects: Male, medicine.medical_specialty, Ipilimumab, [SDV.CAN]Life Sciences [q-bio]/Cancer, Neutropenia, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, medicine, Clinical endpoint, Humans, 030212 general & internal medicine, Aged, Neoplasm Staging, business.industry, Hazard ratio, Middle Aged, medicine.disease, Interim analysis, 3. Good health, respiratory tract diseases, Regimen, Nivolumab, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, Febrile neutropenia, medicine.drug
Abstract: Erratum in Correction to Lancet Oncol 2021; 22: 198-211. [No authors listed] Lancet Oncol. 2021 Mar;22(3):e92. doi: 10.1016/S1470-2045(21)00082-6. PMID: 33662299 No abstract available.; International audience; Background: First-line nivolumab plus ipilimumab has shown improved overall survival in patients with advanced non-small-cell lung cancer (NSCLC). We aimed to investigate whether the addition of a limited course (two cycles) of chemotherapy to this combination would further enhance the clinical benefit.Methods: This randomised, open-label, phase 3 trial was done at 103 hospitals in 19 countries. Eligible patients were aged 18 years or older with treatment-naive, histologically confirmed stage IV or recurrent NSCLC, and an Eastern Cooperative Oncology Group performance status of 0-1. Patients were randomly assigned (1:1) by an interactive web response system via permuted blocks (block size of four) to nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) combined with histology-based, platinum doublet chemotherapy (intravenously every 3 weeks for two cycles; experimental group), or chemotherapy alone (every 3 weeks for four cycles; control group). Randomisation was stratified by tumour histology, sex, and PD-L1 expression. The primary endpoint was overall survival in all randomly assigned patients. Safety was analysed in all treated patients. Results reported here are from a pre-planned interim analysis (when the study met its primary endpoint) and an exploratory longer-term follow-up analysis. This study is active but no longer recruiting patients, and is registered with ClinicalTrials.gov, number NCT03215706.Findings: Between Aug 24, 2017, and Jan 30, 2019, 1150 patients were enrolled and 719 (62·5%) randomly assigned to nivolumab plus ipilimumab with two cycles of chemotherapy (n=361 [50%]) or four cycles of chemotherapy alone (n=358 [50%]). At the pre-planned interim analysis (median follow-up 9·7 months [IQR 6·4-12·8]), overall survival in all randomly assigned patients was significantly longer in the experimental group than in the control group (median 14·1 months [95% CI 13·2-16·2] vs 10·7 months [9·5-12·4]; hazard ratio [HR] 0·69 [96·71% CI 0·55-0·87]; p=0·00065). With 3·5 months longer median follow-up (median 13·2 months [IQR 6·4-17·0]), median overall survival was 15·6 months (95% CI 13·9-20·0) in the experimental group versus 10·9 months (9·5-12·6) in the control group (HR 0·66 [95% CI 0·55-0·80]). The most common grade 3-4 treatment-related adverse events were neutropenia (in 24 [7%] patients in the experimental group vs 32 [9%] in the control group), anaemia (21 [6%] vs 50 [14%]), diarrhoea (14 [4%] vs two [1%]), increased lipase (22 [6%] vs three [1%]), and asthenia (tjree [1%] vs eight [2%]). Serious treatment-related adverse events of any grade occurred in 106 (30%) patients in the experimental group and 62 (18%) in the control group. Seven (2%) deaths in the experimental group (acute kidney failure, diarrhoea, hepatotoxicity, hepatitis, pneumonitis, sepsis with acute renal insufficiency, and thrombocytopenia; one patient each) and six (2%) deaths in the control group (anaemia, febrile neutropenia, pancytopenia, pulmonary sepsis, respiratory failure, and sepsis; one patient each) were treatment related.Interpretation: Nivolumab plus ipilimumab with two cycles of chemotherapy provided a significant improvement in overall survival versus chemotherapy alone and had a favourable risk-benefit profile. These data support this regimen as a new first-line treatment option for patients with advanced NSCLC.Funding: Bristol Myers Squibb.
Published: 2021

45. Haploinsufficiency of the Sin3/HDAC corepressor complex member SIN3B causes a syndromic intellectual disability/autism spectrum disorder

Author: Erica E. Davis, Xenia Latypova, Damien Lederer, LaDonna Immken, Bertrand Isidor, Carmen Orellana, Nicolette S. den Hollander, Shannon Bell, Francisco Martínez, Alice Molle, Oluwadamilare A. Adebambo, Thomas Besnard, Dmitriy Niyazov, Anne Claude Tabet, Marie Deprez, Kamran Moradkhani, Alfonso Caro, Sandra Mercier, Solène Conrad, Philippe M. Campeau, Xiang-Jiao Yang, Christelle Retière, Nicholas Katsanis, Marie Vincent, Kirsty McWalter, Jill A. Rosenfeld, Raymond J. Louie, Stéphane Bézieau, Cynthia Fourgeux, Sharon F. Suchy, Jagdeep S. Walia, Mónica Roselló, Cédric Le Caignec, Emmelien Aten, Jeremie Poschmann, Benjamin Cogné, Peter Kannu, Miranda Splitt, Pawel Stankiewicz, Yline Capri, Catherine Willem, Tahir N. Khan, Justine Rousseau, Sébastien Küry, Jonathan I. Levy, Roger E. Stevenson, Centre hospitalier universitaire de Nantes (CHU Nantes), Duke University Medical Center, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hospital Universitario y Politécnico La Fe [Valencia, Spain], Ochsner Medical Center [New Orleans, Louisiana, USA], Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Hôpital Robert Debré, The Hospital for sick children [Toronto] (SickKids), Leiden University Medical Center (LUMC), Institute of Genetic Medicine [Newcastle], Newcastle University [Newcastle], Kingston General Health Research Institute [Kingston, ON, Canada] (KGHRI), Dell Children's Medical Group [Austin, TX, USA] (DCMG), Baylor College of Medicine (BCM), Baylor University, GeneDx [Gaithersburg, MD, USA], The Greenwood Genetic Center, Centre Hospitalier Universitaire Sainte-Justine [Montréal, QC, Canada] (CHU Sainte-Justine), EFS Centre-Pays de la Loire [Nantes], Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications (CRCINA-ÉQUIPE 1), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), LabEX IGO Immunothérapie Grand Ouest, McGill University = Université McGill [Montréal, Canada], Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Medical School [Chicago], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe, CHU Sainte Justine [Montréal], Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nantes Université (Nantes Univ), and RETIERE, Christelle
Subjects: Male, Models, Molecular, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Haploinsufficiency, medicine.disease_cause, Histones, 0302 clinical medicine, HDAC, Intellectual disability, Child, Zebrafish, Genetics (clinical), Exome sequencing, Genetics, 0303 health sciences, Mutation, HDAC, SIN3A, SINB, acetylation, autism, epigenetics, intellectual disability, mutation, transcription, zebrafish, Syndrome, Middle Aged, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], intellectual disability, Child, Preschool, Larva, Female, transcription, Adolescent, DNA Copy Number Variations, autism, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Histone Deacetylases, Frameshift mutation, Young Adult, 03 medical and health sciences, Report, medicine, Animals, Humans, Epigenetics, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, SIN3A, acetylation, epigenetics, Infant, Zebrafish Proteins, SINB, biology.organism_classification, medicine.disease, zebrafish, Repressor Proteins, Histone deacetylase, mutation, 030217 neurology & neurosurgery
Abstract: International audience; Proteins involved in transcriptional regulation harbor a demonstrated enrichment of mutations in neurodevelopmental disorders. The Sin3 (Swi-independent 3)/histone deacetylase (HDAC) complex plays a central role in histone deacetylation and transcriptional repression. Among the two vertebrate paralogs encoding the Sin3 complex, SIN3A variants cause syndromic intellectual disability, but the clinical consequences of SIN3B haploinsufficiency in humans are uncharacterized. Here, we describe a syndrome hallmarked by intellectual disability, developmental delay, and dysmorphic facial features with variably penetrant autism spectrum disorder, congenital malformations, corpus callosum defects, and impaired growth caused by disruptive SIN3B variants. Using chromosomal microarray or exome sequencing, and through international data sharing efforts, we identified nine individuals with heterozygous SIN3B deletion or single-nucleotide variants. Five individuals harbor heterozygous deletions encompassing SIN3B that reside within a $230 kb minimal region of overlap on 19p13.11, two individuals have a rare nonsynonymous substitution, and two individuals have a single-nucleotide deletion that results in a frameshift and predicted premature termination codon. To test the relevance of SIN3B impairment to measurable aspects of the human phenotype, we disrupted the orthologous zebrafish locus by genome editing and transient suppression. The mutant and morphant larvae display altered craniofacial patterning, commissural axon defects, and reduced body length supportive of an essential role for Sin3 function in growth and patterning of anterior structures. To investigate further the molecular consequences of SIN3B variants, we quantified genome-wide enhancer and promoter activity states by using H3K27ac ChIP-seq. We show that, similar to SIN3A mutations, SIN3B disruption causes hyperacetylation of a subset of enhancers and promoters in peripheral blood mononuclear cells. Together, these data demonstrate that SIN3B haploinsufficiency leads to a hitherto unknown intellectual disability/autism syndrome, uncover a crucial role of SIN3B in the central nervous system, and define the epigenetic landscape associated with Sin3 complex impairment.
Published: 2021

46. Echocardiographic Left Ventricular Mass Estimation: Two-Dimensional Area-Length Method is Superior to M-Mode Linear Method in Swine Models of Cardiac Diseases

Author: Jaume Aguero, Roger J. Hajjar, Kelly P. Yamada, Kenneth Fish, Koichi Nomoto, Taro Kariya, Satoshi Miyashita, Shin Watanabe, Kiyotake Ishikawa, Nadjib Hammoudi, Olympia Bikou, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro Nacional de Investigaciones Cardiovasculares Carlos III [Madrid, Spain] (CNIC), Instituto de Salud Carlos III [Madrid] (ISC), Hospital Universitari i Politècnic La Fe, and Phospholamban Foundation
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Sus scrofa, Population, Myocardial Infarction, Pharmaceutical Science, Infarction, 030204 cardiovascular system & hematology, Linear methods, Ventricular Function, Left, Article, Muscle hypertrophy, Left ventricular mass, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, Genetics, Animals, Medicine, In patient, education, Genetics (clinical), Observer Variation, education.field_of_study, Ventricular Remodeling, business.industry, Reproducibility of Results, medicine.disease, Disease Models, Animal, Area length method, 030104 developmental biology, Linear relationship, Echocardiography, Cardiology, Molecular Medicine, Female, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Echocardiography offers rapid and cost-effective estimations of left ventricular (LV) mass, but its accuracy in patients with cardiac disease remains unclear. LV mass was measured by M-mode-based linear method and two-dimensional echocardiography (2DE)-based area-length method in pig models and correlation with actual LV weight was assessed. Twenty-six normal, 195 ischemic heart disease (IHD), and 33 non-IHD HF pigs were included. A strong positive linear relationship to the actual LV weight was found with 2DE-based area-length method (r = 0.82, p
Published: 2020

47. Bronchoscopist's perception of the quality of the single-use bronchoscope (Ambu aScope4™) in selected bronchoscopies: a multicenter study in 21 Spanish pulmonology services

Author: Flandes, Javier, Giraldo-Cadavid, Luís Fernando, Alfayate, Javier, Fernández-Navamuel, Iker, Agusti, Carlos, Lucena, Carmen M., Rosell, Antoni, Andreo, Felipe, Centeno, Carmen, Montero, C., Vidal, Iria, García-Alfonso, Lucía, Bango, Antonio, Ariza, Miguel, Gallego, Rocío, Orta, Marta, Bello, Salvador, Mincholé, Elisa, Torrego, Alfons, Pajares, Virginia, González, Héctor, Wangüemert, Aurelio Luís, Pérez-Izquierdo, Julio, Disdier, Carlos, de Vega Sanchez, Blanca, Cordovilla, Rosa, Cascón, Juan, Cruz, Antonio, García-López, J.Javier, Puente, Luis, Benedetti, Paola, García-Gallo, Cristina L., Díaz Nuevo, Gema, Aguado, Silvia, Partida, Concepción, Díaz-Agero, Prudencio, Luque Crespo, Estefania, Pavón, María, Páez, Francisco, Cases, Eenrique, Martínez, Raquel, Briones, Andrés, Fernández, Cleofe, Martín Serrano, Concepción, Uribe-Hernández, Ana María, Robles, Jose, Universitat Autònoma de Barcelona, [Flandes,J, Alfayate,J, Fernández‑Navamuel,I] Pneumology Service, Bronchoscopy and Interventional Pulmonology Unit, University Hospital 'Fundación Jiménez Díaz', ISS-FJD CIBERES, Madrid, Spain.[Giraldo‑Cadavid,LF] Interventional Pulmonology, Fundación Neumológica Colombiana, Profesor Titular Universidad de La Sabana, Bogotá, DC, Colombia. [Agusti,C, Lucena,CM] Department of Epidemiology and Biostatistics, School of Medicine, Universidad de La Sabana, La Caro, Chía, Colombia. [Rosell,A] Pneumology Service, Hospital Clínic Universitari, Barcelona, Spain. [Andreo,F, Centeno,C] Pneumology Service, Hospital Universitari de Bellvitge, Barcelona, Spain. [Montero,C, Vidal,I, García-Alfonso,L] Pneumology Service, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain. [Bango,A, Ariza,M] Pulmonology Service, Complexo Hospitalario Universitario, A Coruña, Spain. [Gallego,R, Orta,M] Pneumology Service, Central University Hospital of Asturias, Oviedo Asturias, Spain. [Bello,S, incholé,E] Pneumology Service, Hospital San Pedro de Alcántara, Cáceres, Spain. [Torrego, Pajares,V] Pneumology Service, Miguel Servet University Hospital, Zaragoza, Spain. [González,H] Pneumology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Wangüemert,AL] Pneumology Service, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain. [Pérez‑Izquierdo,J] Pneumology Service, Hospital San Juan de Dios, Santa Cruz de Tenerife, Spain. [Disdier,C, de Vega Sanchez,B] Pneumology Service, Galdakao University Hospital, Bilbao Vizcaya, Spain. [Cordovilla,R, Cascón,J, Cruz,A] Pneumology Service, Hospital Clínico Universitario, Valladolid, Spain. [García‑López,JJ, Puente,L, Benedetti,P] Pneumology Service, University Assistance Complex, Salamanca, Spain. [García‑Gallo,CL, Díaz Nuevo,G, Aguado,G] Pneumology Service, Hospital Universitario Gregorio Marañón, Madrid, Spain. [Partida,C, Díaz‑Agero,P]Pneumology Service, Puerta de Hierro University Hospital, Madrid, Spain. [Luque Crespo,E, Pavón,M]Thoracic Surgery Service, Hospital Universitario La Paz, Madrid, Spain. [Páez,F] Pneumology Service, Virgen de Macarena University Hospital, Seville, Spain. [Cases,E, Martínez,R, Briones,A] Pneumology Service, Carlos Hay Regional University Hospital, Malaga, Spain. [Fernández,C, and Martín Serrano,C] Respiratory Endoscopy Unit, Hospital Universitari i Politècnic La Fe, Valencia, Spain. [Uribe‑Hernández,AM] Pneumology Service, General University Hospital, Alicante, Spain. [Robles,J] Fundación Neumológica Colombiana, Bogotá, DC, Colombia. [Giraldo‑Cadavid,LF] Industrial Electronic Engineering, GHS SL, Madrid, Spain.
Subjects: Bronchoscopist, Health Knowledge, Attitudes, Practice, aScope4™, CUSUM, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Bronchoscopy, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Equipment Design [Medical Subject Headings], Broncoscòpia, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Attitude::Attitude to Health::Health Knowledge, Attitudes, Practice [Medical Subject Headings], Medicine, 030212 general & internal medicine, Prospective Studies, aScope4&#8482, Disposable Equipment, media_common, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Thoracic Surgical Procedures::Pulmonary Surgical Procedures::Bronchoscopy [Medical Subject Headings], medicine.diagnostic_test, Equipment Design, Quality, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies [Medical Subject Headings], Pulmonology, Bronchoscopes, Pulmonologists, Clinical Competence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Disposable Equipment [Medical Subject Headings], Learning Curve, Bronchoalveolar lavage, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Attitude of Health Personnel, media_common.quotation_subject, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Equipment and Supplies::Diagnostic Equipment::Endoscopes::Bronchoscopes [Medical Subject Headings], Bronchoscopies, CUSUM analysis, 03 medical and health sciences, Internal medicine, Humans, Quality (business), Medical physics, lcsh:RC705-779, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, SARS-CoV-2, Research, COVID-19, lcsh:Diseases of the respiratory system, Cross-Sectional Studies, 030228 respiratory system, Multicenter study, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Care Surveys [Medical Subject Headings], Health Care Surveys, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Attitude::Attitude of Health Personnel [Medical Subject Headings], Health Care::Health Services Administration::Quality of Health Care::Clinical Competence [Medical Subject Headings], business, Psychiatry and Psychology::Psychological Phenomena and Processes::Psychology, Applied::Psychology, Educational::Learning::Learning Curve [Medical Subject Headings]
Abstract: Background The disposable bronchoscope is an excellent alternative to face the problem of SARS-CoV-2 and other cross infections, but the bronchoscopist's perception of its quality has not been evaluated. Methods To evaluate the quality of the Ambu-aScope4 disposable bronchoscope, we carried out a cross-sectional study in 21 Spanish pulmonology services. We use a standardized questionnaire completed by the bronchoscopists at the end of each bronchoscopy. The variables were described with absolute and relative frequencies, measures of central tendency and dispersion depending on their nature. The existence of learning curves was evaluated by CUSUM analysis. Results The most frequent indications in 300 included bronchoscopies was bronchial aspiration in 69.3% and the median duration of these was 9.1 min. The route of entry was nasal in 47.2% and oral in 34.1%. The average score for ease of use, image, and aspiration quality was 80/100. All the planned techniques were performed in 94.9% and the bronchoscopist was satisfied in 96.6% of the bronchoscopies. They highlighted the portability and immediacy of the aScope4TM to start the procedure in 99.3%, the possibility of taking and storing images in 99.3%. The CUSUM analysis showed average scores > 70/100 from the first procedure and from the 9th procedure more than 80% of the scores exceeded the 80/100 score. Conclusions The aScope4™ scored well for ease of use, imaging, and aspiration. We found a learning curve with excellent scores from the 9th procedure. Bronchoscopists highlighted its portability, immediacy of use and the possibility of taking and storing images.
Published: 2020

48. Management of chronic liver disease-associated severe thrombocytopenia in Spain: a view from the experts

Author: Manuel Romero-Gómez, Alicia Gil Aguirre, José Luis Calleja-Panero, Raúl J. Andrade, Rafael Esteban, Maria Eva Mingot-Castellano, Rocío Muñoz-Peñín, Rafael Bañares, Javier Crespo, Roy Bentley, John Shepherd, Isidro Jarque, Shionogi, and [Calleja-Panero,JL] Department of Hepatology. Hospital Universitario Puerta de Hierro Majadahonda. Madrid, Spain. [Andrade,RJ] Digestive Diseases Clinical Management Unit. Instituto de Investigación Biomédica de Málaga-IBIMA. Hospital Universitario Virgen de la Victoria. Universidad de Málaga. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd. Málaga, Spain. [Bañares,J] Department of Hepatology. Hospital General Universitario Gregorio Marañón. Madrid, Spain. [Crespo,J] Department of Hepatology. Hospital Universitario Marqués de Valdecilla. Santander, Spain. [Esteban,R] Department of Hepatology. Hospital Universitario Vall d’Hebron. Barcelona, Spain. [Jarque,I] Department of Hematology. Hospital Universitari i Politècnic La Fe. Valencia, Spain. [Mingot-Castellano,EM] Department of Hematology. Hospital Universitario Virgen del Rocío. Sevilla, Spain. [Romero-Gómez,M] Department of Hepatology. Hospital Universitario Virgen del Rocío. Sevilla, Spain. [Muñoz-Peñín,R] Shionogi Inc. Madrid, Spain. [Bentley,R] Shionogi Inc. Florham Park. New Jersey, USA. [Gil,A] Omakase Consulting S.L. Barcelona, Spain.
Subjects: medicine.medical_specialty, Epidemiology, Terapéutica, MEDLINE, Delphi method, Platelet Transfusion, Lung injury, Chronic liver disease, Técnica Delfos, Delphi, Thrombo-poietin receptor agonists, Thrombopoietin receptor agonists, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Health care, medicine, Epidemiología, Humans, Intensive care medicine, Adverse effect, Platelet transfusion, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], business.industry, Transfusión de plaquetas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Biological Therapy::Blood Transfusion::Blood Component Transfusion::Platelet Transfusion [Medical Subject Headings], Liver Diseases, Gastroenterology, Anemia, General Medicine, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Platelet Disorders::Thrombocytopenia [Medical Subject Headings], medicine.disease, Trombocitopenia, Thrombocytopenia, Severe thrombocytopenia, Treatment, Plate-let transfusion, Diseases::Digestive System Diseases::Liver Diseases [Medical Subject Headings], Spain, business, Diseases::Hemic and Lymphatic Diseases::Hematologic Diseases::Anemia [Medical Subject Headings]
Abstract: [Background] chronic liver disease (CLD) patients often present thrombocytopenia (TCP) and when severe, it may prevent them from undergoing necessary invasive procedures due to an increased bleeding risk. The lack of scientific evidence makes it impossible to determine key aspects of the current management and associated healthcare burden of these patients in Spain., [Purpose] to gain insight into the current situation of patients with CLD-associated severe TCP undergoing invasive procedures in Spain, based on the experience of clinical experts. Methods: national Delphi study involving 32 medical experts., [Results] the estimated prevalence of CLD-associated severe TCP is approximately 5,967, with an annual incidence of 1,148 new patients. Patients undergo a median of 1 (0-3) invasive procedures/year. Platelet transfusions (PTs) are the standard option to raise platelet counts and are associated with significant burden. The achievement of target platelet levels (≥ 50 x 109/l) after a transfusion is not routinely measured. The lack of effectiveness and short life span of transfused platelets can lead to procedure cancellations and bleeding events, which potentially affect patient outcomes. Adverse events occur in 1-25 % of patients, including mild (febrile and allergic reactions) and severe events (e.g., transfusion-related acute lung injury). Between 5-15 % of patients are unfit to receive PTs and approximately 3 % are treated off-label with thrombopoietin receptor agonists., [Conclusions] this study provides a snapshot of the current situation in Spain, highlighting that the current management is poorly standardized and suboptimal in some cases. The results suggest the benefit of developing a consensus document to address some of these shortcomings and to advance in the search for alternatives to PTs., This study was funded by Shionogi Inc.
Published: 2020

49. A pediatric regimen for adolescents and young adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: Results of the ALLRE08 PETHEMA trial

Author: Ribera, Josep Maria, Morgades, Mireia, Montesinos, Pau, Tormo, Mar, Martínez Carballeira, Daniel, González Campos, José, Gil, Cristina, Barba, Pere, García Boyero, Raimundo, Coll, Rosa, Pedreño, María, Ribera, Jordi, Mercadal, Santiago, Vives, Susana, Novo, Andrés, Genescà, Eulàlia, Hernández Rivas, Jesús María, Bergua, Juan, Amigo, María Luz, Vall Llovera, Ferran, Martínez Sánchez, Pilar, Calbacho, María, García Cadenas, Irene, Garcia Guiñon, Antonio, Sánchez Sánchez, María José, Cervera, Marta, Feliu, Evarist, Orfao, Alberto, PETHEMA Group, Josep Carreras Leukemia Foundation, Universidad Autónoma de Barcelona, CSIC-USAL - Instituto de Biología Molecular y Celular del Cancer de Salamanca (IBMCC), Institut Català de la Salut, [Ribera JM, Morgades M] Departments of Clinical Hematology, ICO-Hospital Germans Trias i Pujol. Josep Carreras Research Institute, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Montesinos P] Departments of Clinical Hematology, Hospital Universitari i Politècnic La Fe, CIBERONC, Instituto Carlos III, Valencia, Spain, Madrid, Spain. [Tormo M] Departments of Clinical Hematology, Hospital Clínico Valencia, Valencia, Spain. [Martínez-Carballeira D] Hospital Central de Asturias, Oviedo, Spain. [González-Campos J] Departments of Clinical Hematology, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Barba P] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Male, 0301 basic medicine, Cancer Research, Neoplasm, Residual, Lymphoblastic Leukemia, Adolescents, 0302 clinical medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, neoplasias::neoplasias por tipo histológico::leucemia::leucemia linfoide::leucemia-linfoma linfoblástico de células precursoras [ENFERMEDADES], Medicine, Philadelphia Chromosome, Cumulative incidence, Other subheadings::/therapeutic use [Other subheadings], Young adult, Complete response, health care economics and organizations, Original Research, Clinical Trials as Topic, Remission Induction, terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], hemic and immune systems, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, humanities, Survival Rate, Oncology, 030220 oncology & carcinogenesis, behavior and behavior mechanisms, Female, Adult, acute lymphoblastic leukemia, adolescents and young adults, pediatric treatment, medicine.medical_specialty, Adolescent, Philadelphia Chromosome Negative, education, acute lymphoblastic leukemia, lcsh:RC254-282, Teenagers, Young Adult, 03 medical and health sciences, Internal medicine, Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Overall survival, Humans, Radiology, Nuclear Medicine and imaging, In patient, Leucèmia limfocítica crònica, Neoplasms::Neoplasms by Histologic Type::Leukemia::Leukemia, Lymphoid::Precursor Cell Lymphoblastic Leukemia-Lymphoma [DISEASES], business.industry, Otros calificadores::/uso terapéutico [Otros calificadores], Clinical Cancer Research, social sciences, personas::Grupos de Edad::adolescente [DENOMINACIONES DE GRUPOS], Persons::Age Groups::Adolescent [NAMED GROUPS], Regimen, 030104 developmental biology, Leucèmia limfoblàstica - Quimioteràpia, pediatric treatment, Chronic lymphocytic leukemia, Neoplasm Recurrence, Local, business, adolescents and young adults, Follow-Up Studies
Abstract: On behalf of the PETHEMA Group, Spanish Society of Hematology., [Background]: Pediatric‐based or ‐inspired trials have improved the prognosis of adolescents and young adults (AYA) with Philadelphia chromosome‐negative (Ph‐neg) acute lymphoblastic leukemia (ALL)., [Methods]: This study reports the results of treatment of the ALLRE08 trial, a full pediatric trial for AYA aged 15‐30 years with standard‐risk (SR) ALL., [Results]: From 2008 to 2018, 89 patients (38 adolescents [15‐18 years] and 51 young adults [YA, 19‐30 years], median age: 20 [15‐29] years) were enrolled in the ALLRE08 trial. The complete response (CR) was 95%. Twenty‐two patients were transferred to a high‐risk (HR) protocol because of poor marrow response on day 14 (n = 20) or high‐level of end‐induction minimal residual response (MRD ≥ 0.25%, n = 2). Cumulative incidence of relapse (CIR) at 5 years was 35% (95%CI: 23%‐47%), with significant differences between adolescents and YA: 13% (4%‐28%) vs 52% (34%‐67%), P = .012. No treatment‐related mortality was observed in 66/66 patients following the ALLRE08 trial vs 3/23 patients moved to a HR trial. The estimated 5‐year overall survival (OS) was 74% (95%CI: 63%‐85%), with significantly higher rates for adolescents vs YA: 87% (95%CI: 74%‐100%) vs 63% (46%‐80%), P = .021. Although CIR or OS were lower in patients who were transferred to a HR trial, the differences were not statistically significant (CIR: 34% [21%‐47%] vs 37% [14%‐61%]; OS: 78% [66%‐90%] vs 61% [31%;91%])., [Conclusion]: A full pediatric trial is feasible and effective for AYA with Ph‐neg, SR‐ALL, with better results for adolescents than for YA. Outcome of patients with poor early response rescued with a HR trial was not significantly inferior., We thanks to the following institutions from Spain their support for this paper: ICO‐Hospital Germans Trias i Pujol. Josep Carreras Research Institute. Universitat Autònoma de Barcelona. Hospital Universitari i Politècnic La Fe, Valencia. Hospital Clínico Valencia. Hospital Central de Asturias, Oviedo. Hospital Universitario Virgen del Rocío, Sevilla. Hospital General Universitario de Alicante. Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona. Hospital General Universitario de Castellón. ICO‐Hospital Josep Trueta, Girona. Hospital Dr Peset, Valencia. ICO‐Hospital Duran i Reynals, L'Hospitalet de Llobregat. Hospital Son Espases, Palma de Mallorca. Hospital Clínico Universitario, Cancer Research Center (IBMCC‐CSIC/USAL), Cytometry Service, Salamanca. Hospital San Pedro de Alcántara, Cáceres. Hospital Morales Meseguer, Murcia. Hospital Mútua de Terrassa, Terrassa. Hospital Doce de Octubre, Madrid. Hospital Ramón y Cajal, Madrid. Hospital de Sant Pau, Barcelona. Hospital Arnau de Vilanova, Lleida. Hospital Lucus Augusti, Lugo. ICO‐Hospital Joan XXIII, Tarragona.
Published: 2020

50. Guía española de estabilización y reanimación neonatal 2021. Análisis, adaptación y consenso sobre las recomendaciones internacionales

Author: Gonzalo Zeballos Sarrato, Alejandro Avila-Alvarez, César W. Ruiz Campillo, Raquel Escrig Fernández, Montserrat Izquierdo Renau, Celia Gómez Robles, Martín Iriondo Sanz, Institut Català de la Salut, [Zeballos Sarrato G] Servicio de Neonatología, Hospital Universitario Gregorio Marañón, Madrid, España. [Avila-Alvarez A] Unidad de Neonatología, Servicio de Pediatría, Complexo Hospitalario Universitario, A Coruña (CHUAC), Sergas, A Coruña, España. [Escrig Fernández R] Servicio de Neonatología, Hospital Universitari i Politècnic La Fe, Valencia, España. [Izquierdo Renau M] Servicio de Neonatología, Sant Joan de Déu, BCNatal, Hospital Sant Joan de Déu-Hospital Clínic, Universidad de Barcelona, Barcelona, España. [Ruiz Campillo CW] Servei de Neonatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gómez Robles C] Servicio de Neonatología, Hospital Regional Universitario de Málaga, Málaga, España, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Medicina intensiva neonatal, Medicina - Presa de decisions, terapéutica::asistencia al paciente::asistencia del enfermo crítico::cuidados intensivos neonatales [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Recien nacido, Political science, Pediatrics, Perinatology and Child Health, Infants nadons, Therapeutics::Patient Care::Critical Care::Intensive Care, Neonatal [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Humanities
Abstract: Reanimación; Estabilización; Recién nacido Resuscitation; Stabilization; Newborn Reanimació; Estabilització; Nounat Tras la publicación de las recomendaciones, consensuadas por todas las sociedades científicas a través del ILCOR, a finales del año 2020, el GRN-SENeo inició un proceso de análisis y revisión de los principales cambios desde las últimas guías, a los que se añadió un posicionamiento específico de consenso en temas controvertidos, tratando de evitar ambigüedades, y procurando adaptar la evidencia a nuestro medio. El presente texto, resume las principales conclusiones de este trabajo y refleja el posicionamiento de dicho grupo. After the publication of the recommendations, agreed by all the scientific societies through the ILCOR, at the end of 2020, the GRN-SENeo began a process of analysis and review of the main changes since the last guidelines, to which a specific consensus positioning on controversial issues, trying to avoid ambiguities and trying to adapt the evidence to our environment. This text summarizes the main conclusions of this work and reflects the positioning of that group.
Published: 2022

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