International Physical Activity Questionnaire Short Form and accelerometer-assessed physical activity: concurrent validity using six cut-points in HF patients

Aims Physical activity (PA) is an important target for improving clinical outcomes in heart failure (HF) patients. Nonetheless, assessing the daily PA profile in this population is a challenging task, traditionally performed using self-report questionnaires such as the International PA Questionnaire Short Form (IPAQ-SF). This study aimed to evaluate the concurrent validity of the IPAQ-SF and accelerometer-assessed PA using six published cut-points in patients with HF and reduced or mildly reduced ejection fraction. Methods and results The concordance between the IPAQ-SF and a hip-worn accelerometer regarding daily time spent performing moderate to vigorous PA in bouts of at least 10 min was assessed in 53 participants for seven consecutive days using six different cut-points (Barnett, Dibben, Mark, Sanders, Troiano, and Vaha-Ypya). Spearman’s correlation and Bland–Altman plots were used to evaluate concurrent validity between methods. Regressions were used to study the association between patient variables, wear protocol (waking hour or 24 h), and absolute bias. The kappa index was used to evaluate the concordance between IPAQ-SF and accelerometry for classifying patients as active or non-active. All analyses were re-run using non-bouted metrics to investigate the effect of bouted versus non-bouted analysis. The IPAQ-SF and accelerometry showed low to negligible correlation (ρ = 0.12 to 0.37), depending on the cut-point used. The regression analysis showed that the absolute bias was higher in participants following the waking-hour protocol at all cut-points except Dibben’s (P ≤ 0.007). The concordance between the two methods to classify patients as active and non-active was low when using Mark (κ = 0.23) and Barnett (κ = 0.34) cut-points and poor for the remaining cut-points (κ = 0.03 to 0.18). The results of the sensitivity analysis showed negligible to low correlation using non-bouted metrics (ρ = 0.27 to 0.33). Conclusions Moderate to vigorous PA measures using IPAQ-SF and accelerometers are not equivalent, and we do not encourage researchers to use IPAQ-SF alone when assessing PA in HF patients. Moreover, applying personalized collection and processing criteria is important when assessing PA in HF patients. We recommend following the 24 h protocol and selecting cut-points calibrated in patients with cardiovascular diseases. Finally, it is necessary to develop a new tailored questionnaire that considers walking intensity and is adjusted to the current World Health Organisation recommendations, which use non-bouted metrics

Bifunctional acid-base ionic liquid for the one-pot synthesis of fine chemicals: thioethers, 2H-chromenes and 2H-quinoline derivatives

A bifunctional organocatalyst with ionic liquid properties and with an optimized distance between the acid and basic sites efficiently activates electron deficient olefins for 1,4 conjugated addition, which can be incorporated in different one-pot transformations for the preparation of cyclic and acyclic compounds of biological and synthetic interest. More specifically, the catalyst can be successfully applied for different carbon–carbon (Csingle bondC) and carbon–heteroatom (Csingle bondN, Csingle bondO, Csingle bondS) bond forming reactions integrated in a cascade sequence. The activity of the organocatalyst has been compared with that of structurally related monofunctional and bifunctional catalysts. The most attractive features of this procedure are the high atom economy and the use of inexpensive starting materials as well as the use of an environmentally friendly catalyst that can be easily recovered due to its ionic liquid properties.Financial support by Consolider-Ingenio 2010 (project MULTICAT), Spanish MICINN (Projects MAT2011-28009 and CTQ-201127550) and Program Severo Ochoa are gratefully acknowledged.Climent Olmedo, MJ.; Iborra Chornet, S.; Sabater Picot, MJ.; Vidal Castro, JD. (2014). Bifunctional acid-base ionic liquid for the one-pot synthesis of fine chemicals: thioethers, 2H-chromenes and 2H-quinoline derivatives. Applied Catalysis A: General. 481:27-38. https://doi.org/10.1016/j.apcata.2014.05.004S273848

La càrrega futura de l'excés de casos de diabetis mellitus de tipus 1 durant la pandèmia de COVID a Catalunya: avaluació econòmica

Diabetis mellitus de tipus 1; COVID-19; Avaluació econòmicaDiabetes mellitus de tipo 1; COVID-19; Evaluación económicaType 1 diabetes mellitus; COVID-19; Economic evaluationThis paper aims to provide a comprehensive assessment of the impact of the excess cases of DM1 during the first two years of the COVID-19 pandemic on health outcomes and health spending in Catalonia.Este documento pretende proporcionar una evaluación exhaustiva del impacto del exceso de casos de DM1 durante los dos primeros años de la pandemia COVID-19 en resultados de salud y gasto sanitario en Cataluña.Aquest document pretén proporcionar una avaluació exhaustiva de l'impacte de l'excés de casos de DM1 durant els dos primers anys de la pandèmia COVID-19 en els resultats de salut i la despesa sanitària a Catalunya

Abnormalities on 1q and 7q are associated with poor outcome in sporadic Burkitt's lymphoma. A cytogenetic and comparative genomic hybridization study

Comparative genomic hybridization (CGH) studies have demonstrated a high incidence of chromosomal imbalances in non-Hodgkin's lymphoma. However, the information on the genomic imbalances in Burkitt's Lymphoma (BL) is scanty. Conventional cytogenetics was performed in 34 cases, and long-distance PCR for t(8;14) was performed in 18 cases. A total of 170 changes were present with a median of four changes per case (range 1-22). Gains of chromosomal material (143) were more frequent than amplifications (5) or losses (22). The most frequent aberrations were gains on chromosomes 12q (26%), Xq (22%), 22q (20%), 20q (17%) and 9q (15%). Losses predominantly involved chromosomes 13q (17%) and 4q (9%). High-level amplifications were present in the regions 1q23-31 (three cases), 6p12-p25 and 8p22-p23. Upon comparing BL vs Burkitt's cell leukemia (BCL), the latter had more changes (mean 4.3 +/- 2.2) than BL (mean 2.7 +/- 3.2). In addition, BCL cases showed more frequently gains on 8q, 9q, 14q, 20q, and 20q, 9q, 8q and 14q, as well as losses on 13q and 4q. Concerning outcome, the presence of abnormalities on 1q (ascertained either by cytogenetics or by CGH), and imbalances on 7q (P=0.01) were associated with a short survival

Artificial Intelligence on FDG PET Images Identifies Mild Cognitive Impairment Patients with Neurodegenerative Disease

[EN] The purpose of this project is to develop and validate a Deep Learning (DL) FDG PET imaging algorithm able to identify patients with any neurodegenerative diseases (Alzheimer's Disease (AD), Frontotemporal Degeneration (FTD) or Dementia with Lewy Bodies (DLB)) among patients with Mild Cognitive Impairment (MCI). A 3D Convolutional neural network was trained using images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The ADNI dataset used for the model training and testing consisted of 822 subjects (472 AD and 350 MCI). The validation was performed on an independent dataset from La Fe University and Polytechnic Hospital. This dataset contained 90 subjects with MCI, 71 of them developed a neurodegenerative disease (64 AD, 4 FTD and 3 DLB) while 19 did not associate any neurodegenerative disease. The model had 79% accuracy, 88% sensitivity and 71% specificity in the identification of patients with neurodegenerative diseases tested on the 10% ADNI dataset, achieving an area under the receiver operating characteristic curve (AUC) of 0.90. On the external validation, the model preserved 80% balanced accuracy, 75% sensitivity, 84% specificity and 0.86 AUC. This binary classifier model based on FDG PET images allows the early prediction of neurodegenerative diseases in MCI patients in standard clinical settings with an overall 80% classification balanced accuracy.This work was financially supported by INBIO 2019 (DEEPBRAIN), INNVA1/2020/83(DEEPPET) funded by Generalitat Valenciana, and PID2019-107790RB-C22 funded by MCIN/AEI/10.13039/501100011033/. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org).The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.Prats-Climent, J.; Gandia-Ferrero, MT.; Torres-Espallardo, I.; Álvarez-Sanchez, L.; Martinez-Sanchis, B.; Cháfer-Pericás, C.; Gómez-Rico, I.... (2022). Artificial Intelligence on FDG PET Images Identifies Mild Cognitive Impairment Patients with Neurodegenerative Disease. Journal of Medical Systems. 46(8):1-13. https://doi.org/10.1007/s10916-022-01836-w11346

Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma

In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can be circumvented remain undetermined. We previously reported the frequent inactivation of the proapoptotic BIM gene in B-cell lymphomas. Here we show that BIM epigenetic silencing by concurrent promoter hypermethylation and deacetylation occurs frequently in primary BL samples and BL-derived cell lines. Remarkably, patients with BL with hypermethylated BIM presented lower complete remission rate (24% vs 79%; P = .002) and shorter overall survival (P = .007) than those with BIM-expressing lymphomas, indicating that BIM transcriptional repression may mediate tumor chemoresistance. Accordingly, by combining in vitro and in vivo studies of human BL-xenografts grown in immunodeficient RAG2(-/-)γc(-/-) mice and of murine B220(+)IgM(+) B-cell lymphomas generated in Eμ-MYC and Eμ-MYC-BIM(+/-) transgenes, we demonstrate that lymphoma chemoresistance is dictated by BIM gene dosage and is reversible on BIM reactivation by genetic manipulation or after treatment with histone-deacetylase inhibitors. We suggest that the combination of histone-deacetylase inhibitors and high-dose chemotherapy may overcome chemoresistance, achieve durable remission, and improve survival of patients with BL

La incidència de diabetis mellitus de tipus 1 durant la pandèmia de COVID-19 a Catalunya

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Diabetis mellitus de tipus 1; Malaltia crònicaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Diabetes mellitus de tipo 1; Enfermedad crónicaCoronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Type 1 diabetes mellitus; Chronic diseaseIntroducció: la diabetis de tipus 1 és una malaltia crònica que es caracteritza per la falta de producció d’insulina per part del pàncrees, el que provoca un augment dels nivells de glucosa en sang. En alguns països s’ha reportat un increment en la incidència de diabetis de tipus 1 durant la pandèmia de COVID-19. Objectiu: comprovar si ha augmentat la incidència de diabetis de tipus 1 durant la pandèmia de COVID-19 a Catalunya. Mètodes: estimació de la incidència esperada de diabetis de tipus 1 per als anys 2020-2021 a través d’una regressió Poisson, i comparació amb la incidència observada. La incidència observada es va obtenir a partir del registre poblacional de diabetis de tipus 1 del programa PADRIS d’analítica de dades d’AQuAS. Resultats: de forma agregada, l’any 2020 la incidència no va augmentar significativament respecte a l’any anterior, però per a l’any 2021 va augmentar significativament en un 28 %. Els majors augments, en tots dos anys, es van donar entre les persones menors de 18 anys i les dones. Conclusions i discussió: durant la pandèmia de COVID-19 es va produir un augment notable i estadísticament significatiu de la incidència de casos de DM1 a Catalunya, encara que no és possible establir una relació de causalitat entre la pandèmia i la diabetis. Es requereixen més estudis per investigar els possibles mecanismes biològics o socials que podrien explicar aquest fenomen i les seves implicacions clíniques i sanitàries.Introducción: la diabetes tipo 1 es una enfermedad crónica que se caracteriza por la falta de producción de insulina por parte del páncreas, lo que provoca un aumento de los niveles de glucosa en sangre. En algunos países se ha reportado un incremento en la incidencia de diabetes tipo 1 durante la pandemia de COVID-19. Objetivo: comprobar si ha aumentado la incidencia de diabetes tipo 1 durante la pandemia de COVID-19 en Cataluña. Métodos: estimación de la incidencia esperada de diabetes tipo 1 para los años 2020-2021 a través de una regresión Poisson, y comparación con la incidencia observada. La incidencia observada se obtuvo a partir del registro poblacional de diabetes tipo 1 del programa PADRIS de analítica de datos de AQuAS. Resultados: de forma agregada, en el año 2020 la incidencia no aumentó significativamente respecto al año anterior, pero para el año 2021 aumentó significativamente en un 28%. Los mayores aumentos, en ambos años, se dieron entre las personas menores de 18 años y las mujeres. Conclusiones y discusión: durante la pandemia de COVID-19 se produjo un aumento notable y estadísticamente significativo de la incidencia de casos de DM1 en Cataluña, aunque no es posible establecer una relación de causalidad entre la pandemia y la diabetes. Se requieren más estudios para investigar los posibles mecanismos biológicos o sociales que podrían explicar este fenómeno y sus implicaciones clínicas y sanitarias.Introduction: Type 1 diabetes (T1D) is a chronic disease characterized by insufficient insulin production by the pancreas, leading to high blood glucose levels. Some countries have reported an increase in the incidence of T1D during the COVID-19 pandemic. Objective: To examine whether the incidence of T1D has increased during the COVID-19 pandemic in Catalonia. Methods: We estimated the expected incidence of T1D for 2020-2021 using a Poisson regression model based on historical data from 2010 to 2019. We compared the expected incidence with the observed incidence obtained from the population-based T1D registry of the PADRIS data analysis program of AQuAS. Results: In 2020, there was no significant increase in incidence compared to 2019, but in 2021 there was a significant increase of 28%. The largest increases occurred among people under 18 years old and women. Conclusions and discussion: There was a notable and statistically significant increase in T1D cases in Catalonia during the COVID-19 pandemic, although a causal relationship between the pandemic and diabetes cannot be established. Further studies are needed to explore the possible biological or social mechanisms that could explain this phenomenon and its clinical and health implications

Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma

The historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK-MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials

Electrophysiological characteristics of permanent atrial fibrillation: insights from research models of cardiac remodeling

[EN] Atrial fibrillation (AF) results in a remodeling of the electrical and structural characteristics of the cardiac tissue which dramatically reduces the efficacy of pharmacological and catheter-based ablation therapies. Recent experimental and clinical results have demonstrated that the complexity of the fibrillatory process significantly differs in paroxysmal versus persistent AF; however, the lack of appropriate research models of remodeled atrial tissue precludes the elucidation of the underlying AF mechanisms and the identification of appropriated therapeutic targets. Here, we summarize the different research models used to date, highlighting the lessons learned from them and pointing to the new doors that should be open for the development of innovative treatments for AF.The authors were supported by grants from the Spanish Ministry of Science and Innovation (PLE2009-0152), the Instituto de Salud Carlos III (Ministry of Economy and Competitiveness, Spain: PI13-01882 and PI13-00903) the Red de Investigacion Cardiovacular (RIC) from Instituto de Salud Carlos III (Ministry of Economy and Competitiveness, Spain). F Atienza served on the advisory board of Medtronic and has received research funding from St. Jude Medical Spain. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Climent, A.; Guillem Sánchez, MS.; Atienza Fernández, F.; Fernandez-Aviles, F. (2014). Electrophysiological characteristics of permanent atrial fibrillation: insights from research models of cardiac remodeling. Expert Review of Cardiovascular Therapy. 13(1):1-3. https://doi.org/10.1586/14779072.2015.986465S1313

A Novel Framework for Phenotyping Children With Suspected or Confirmed Infection for Future Biomarker Studies

Copyright © 2021 Nijman, Oostenbrink, Moll, Casals-Pascual, von Both, Cunnington, De, Eleftheriou, Emonts, Fink, van der Flier, de Groot, Kaforou, Kohlmaier, Kuijpers, Lim, Maconochie, Paulus, Martinon-Torres, Pokorn, Romaine, Calle, Schlapbach, Smit, Tsolia, Usuf, Wright, Yeung, Zavadska, Zenz, Levin, Herberg, Carrol and the PERFORM consortium (Personalized Risk assessment in febrile children to optimize Real-life Management across the European Union).Background: The limited diagnostic accuracy of biomarkers in children at risk of a serious bacterial infection (SBI) might be due to the imperfect reference standard of SBI. We aimed to evaluate the diagnostic performance of a new classification algorithm for biomarker discovery in children at risk of SBI. Methods: We used data from five previously published, prospective observational biomarker discovery studies, which included patients aged 0– <16 years: the Alder Hey emergency department (n = 1,120), Alder Hey pediatric intensive care unit (n = 355), Erasmus emergency department (n = 1,993), Maasstad emergency department (n = 714) and St. Mary's hospital (n = 200) cohorts. Biomarkers including procalcitonin (PCT) (4 cohorts), neutrophil gelatinase-associated lipocalin-2 (NGAL) (3 cohorts) and resistin (2 cohorts) were compared for their ability to classify patients according to current standards (dichotomous classification of SBI vs. non-SBI), vs. a proposed PERFORM classification algorithm that assign patients to one of eleven categories. These categories were based on clinical phenotype, test outcomes and C-reactive protein level and accounted for the uncertainty of final diagnosis in many febrile children. The success of the biomarkers was measured by the Area under the receiver operating Curves (AUCs) when they were used individually or in combination. Results: Using the new PERFORM classification system, patients with clinically confident bacterial diagnosis (“definite bacterial” category) had significantly higher levels of PCT, NGAL and resistin compared with those with a clinically confident viral diagnosis (“definite viral” category). Patients with diagnostic uncertainty had biomarker concentrations that varied across the spectrum. AUCs were higher for classification of “definite bacterial” vs. “definite viral” following the PERFORM algorithm than using the “SBI” vs. “non-SBI” classification; summary AUC for PCT was 0.77 (95% CI 0.72–0.82) vs. 0.70 (95% CI 0.65–0.75); for NGAL this was 0.80 (95% CI 0.69–0.91) vs. 0.70 (95% CI 0.58–0.81); for resistin this was 0.68 (95% CI 0.61–0.75) vs. 0.64 (0.58–0.69) The three biomarkers combined had summary AUC of 0.83 (0.77–0.89) for “definite bacterial” vs. “definite viral” infections and 0.71 (0.67–0.74) for “SBI” vs. “non-SBI.” Conclusion: Biomarkers of bacterial infection were strongly associated with the diagnostic categories using the PERFORM classification system in five independent cohorts. Our proposed algorithm provides a novel framework for phenotyping children with suspected or confirmed infection for future biomarker studies.publishersversionPeer reviewe