Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)

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Improved Functionality of Integration-Deficient Lentiviral Vectors (IDLVs) by the Inclusion of IS2 Protein Docks.
(2021-08-06) Cortijo-Gutiérrez, Marina; Sánchez-Hernández, Sabina; Tristán-Manzano, María; Maldonado-Pérez, Noelia; Lopez-Onieva, Lourdes; Real, Pedro J; Herrera, Concha; Marchal, Juan Antonio; Martin, Francisco; Benabdellah, Karim
Integration-deficient lentiviral vectors (IDLVs) have recently generated increasing interest, not only as a tool for transient gene delivery, but also as a technique for detecting off-target cleavage in gene-editing methodologies which rely on customized endonucleases (ENs). Despite their broad potential applications, the efficacy of IDLVs has historically been limited by low transgene expression and by the reduced sensitivity to detect low-frequency off-target events. We have previously reported that the incorporation of the chimeric sequence element IS2 into the long terminal repeat (LTR) of IDLVs increases gene expression levels, while also reducing the episome yield inside transduced cells. Our study demonstrates that the effectiveness of IDLVs relies on the balance between two parameters which can be modulated by the inclusion of IS2 sequences. In the present study, we explore new IDLV configurations harboring several elements based on IS2 modifications engineered to mediate more efficient transgene expression without affecting the targeted cell load. Of all the insulators and configurations analysed, the insertion of the IS2 into the 3'LTR produced the best results. After demonstrating a DAPI-low nuclear gene repositioning of IS2-containing episomes, we determined whether, in addition to a positive effect on transcription, the IS2 could improve the capture of IDLVs on double strand breaks (DSBs). Thus, DSBs were randomly generated, using the etoposide or locus-specific CRISPR-Cas9. Our results show that the IS2 element improved the efficacy of IDLV DSB detection. Altogether, our data indicate that the insertion of IS2 into the LTR of IDLVs improved, not only their transgene expression levels, but also their ability to be inserted into existing DSBs. This could have significant implications for the development of an unbiased detection tool for off-target cleavage sites from different specific nucleases.
Nrf2 and Heme Oxygenase-1 Involvement in Atherosclerosis Related Oxidative Stress.
(MDPI, 2021-09-14) Alonso-Piñeiro, Jose Angel; Gonzalez-Rovira, Almudena; Sánchez-Gomar, Ismael; Moreno, Juan Antonio; Durán-Ruiz, Ma Carmen; Institute of Health Carlos III; Spanish Biomedical Research Center in Cardiovascular Diseases; Spanish Ministry of Science and Innovation; Spanish Society of Nephrology; Consejería de Salud y Familias-FEDER; Programa Operativo de Andalucia-FEDER
Atherosclerosis remains the underlying process responsible for cardiovascular diseases and the high mortality rates associated. This chronic inflammatory disease progresses with the formation of occlusive atherosclerotic plaques over the inner walls of vascular vessels, with oxidative stress being an important element of this pathology. Oxidation of low-density lipoproteins (ox-LDL) induces endothelial dysfunction, foam cell activation, and inflammatory response, resulting in the formation of fatty streaks in the atherosclerotic wall. With this in mind, different approaches aim to reduce oxidative damage as a strategy to tackle the progression of atherosclerosis. Special attention has been paid in recent years to the transcription factor Nrf2 and its downstream-regulated protein heme oxygenase-1 (HO-1), both known to provide protection against atherosclerotic injury. In the current review, we summarize the involvement of oxidative stress in atherosclerosis, focusing on the role that these antioxidant molecules exert, as well as the potential therapeutic strategies applied to enhance their antioxidant and antiatherogenic properties.
The role of bronchoscopy in patients with SARS-CoV-2 pneumonia.
(2021-07-12) Arenas-De Larriva, Marisol; Martín-DeLeon, Roberto; Urrutia Royo, Blanca; Fernández-Navamuel, Iker; Gimenez Velando, Andrés; Nuñez García, Laura; Centeno Clemente, Carmen; Andreo García, Felipe; Rafecas Codern, Albert; Fernández-Arias, Carmen; Pajares Ruiz, Virginia; Torrego Fernández, Alfons; Rajas, Olga; Iturricastillo, Gorane; Garcia Lujan, Ricardo; Comeche Casanova, Lorena; Sánchez-Font, Albert; Aguilar-Colindres, Ricardo; Larrosa-Barrero, Roberto; García García, Ruth; Cordovilla, Rosa; Núñez-Ares, Ana; Briones-Gómez, Andrés; Cases Viedma, Enrique; Franco, José; Cosano Povedano, Javier; Rodríguez-Perálvarez, Manuel Luis; Cebrian Gallardo, Jose Joaquin; Nuñez Delgado, Manuel; Pavón-Masa, María; Valdivia Salas, Maria Del Mar; Flandes, Javier
The role of bronchoscopy in coronavirus disease 2019 (COVID-19) is a matter of debate. This observational multicentre study aimed to analyse the prognostic impact of bronchoscopic findings in a consecutive cohort of patients with suspected or confirmed COVID-19. Patients were enrolled at 17 hospitals from February to June 2020. Predictors of in-hospital mortality were assessed by multivariate logistic regression. A total of 1027 bronchoscopies were performed in 515 patients (age 61.5±11.2 years; 73% men), stratified into a clinical suspicion cohort (n=30) and a COVID-19 confirmed cohort (n=485). In the clinical suspicion cohort, the diagnostic yield was 36.7%. In the COVID-19 confirmed cohort, bronchoscopies were predominantly performed in the intensive care unit (n=961; 96.4%) and major indications were: difficult mechanical ventilation (43.7%), mucus plugs (39%) and persistence of radiological infiltrates (23.4%). 147 bronchoscopies were performed to rule out superinfection, and diagnostic yield was 42.9%. There were abnormalities in 91.6% of bronchoscopies, the most frequent being mucus secretions (82.4%), haematic secretions (17.7%), mucus plugs (17.6%), and diffuse mucosal hyperaemia (11.4%). The independent predictors of in-hospital mortality were: older age (OR 1.06; p Bronchoscopy may be indicated in carefully selected patients with COVID-19 to rule out superinfection and solve complications related to mechanical ventilation. The presence of haematic secretions in the distal bronchial tract may be considered a poor prognostic feature in COVID-19.
The economic burden of metastatic breast cancer in Spain.
(2018-07-30) Bermejo de Las Heras, Begoña; Cortes Ramon Y Cajal, Javier; Galve Calvo, Elena; de la Haba Rodriguez, Juan; Garcia Mata, Jesus; Moreno Anton, Fernando; Pelaez Fernandez, Ignacio; Rodriguez-Lescure, Alvaro; Rodriguez Sanchez, Cesar A; Ruiz-Borrego, Manuel; Remak, Edit; Barra, Magdolna; Rivero, Maria; Soto Alvarez, Javier
The study aimed to estimate the burden of metastatic breast cancer (mBC) in Spain over 5 years. An incidence-based cost-of-illness model was developed in which a cohort of patients with mBC was followed from the diagnosis of metastatic disease over 5 years or death. Resource use data were collected through a physician survey conducted with 10 clinical experts in Spain. The model distinguished patients according to HER2 and hormonal receptor (HR) status, and followed the patient cohort in monthly cycles. The incident cohort was estimated to be 2,923 patients with mBC, consisting of 1,575 HER2-/HR+, 520 HER2+/HR+, 324 HER2+/HR-, and 503 triple negative patients. The estimated mean survival over the 5-year time period was 2.51 years, on average, with longer survival of 3.36 years for HER2+/HR+, 2.41 years for HER2-/HR+, 2.82 years for HER2+/HR- and shortest mean survival of 1.74 years for triple negative patients. The total costs were €469,92,731 for the overall population, €190,079,787 for the HER2-/HR+, €151,045,260 for the HER2+/HR+, €80,827,171 for the HER2+/HR- and €47,540,512 for the triple negative subgroups over 5 years. Per patient total costs were €160,642 on average, €120,664 for HER2-/HR+, €290,346 for HER2+/HR+, €249,152 for HER2+/HR-and €94,572 for triple negative patients over 5 years. The economic burden of mBC in Spain is significant, but differs by HER2 and HR status. HER2-/HR +patients account for the highest burden due to the prevalence of this category, but HER2+/HR +patients have the highest per patient costs.
The age again in the eye of the COVID-19 storm: evidence-based decision making.
(2021-05-20) Martín, María C; Jurado, Aurora; Abad-Molina, Cristina; Orduña, Antonio; Yarce, Oscar; Navas, Ana M; Cunill, Vanesa; Escobar, Danilo; Boix, Francisco; Burillo-Sanz, Sergio; Vegas-Sánchez, María C; Jiménez-de Las Pozas, Yesenia; Melero, Josefa; Aguilar, Marta; Sobieschi, Oana Irina; López-Hoyos, Marcos; Ocejo-Vinyals, Gonzalo; San Segundo, David; Almeida, Delia; Medina, Silvia; Fernández, Luis; Vergara, Esther; Quirant, Bibiana; Martínez-Cáceres, Eva; Boiges, Marc; Alonso, Marta; Esparcia-Pinedo, Laura; López-Sanz, Celia; Muñoz-Vico, Javier; López-Palmero, Serafín; Trujillo, Antonio; Álvarez, Paula; Prada, Álvaro; Monzón, David; Ontañón, Jesús; Marco, Francisco M; Mora, Sergio; Rojo, Ricardo; González-Martínez, Gema; Martínez-Saavedra, María T; Gil-Herrera, Juana; Cantenys-Molina, Sergi; Hernández, Manuel; Perurena-Prieto, Janire; Rodríguez-Bayona, Beatriz; Martínez, Alba; Ocaña, Esther; Molina, Juan
One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/μL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.
Insulin-Regulated Aminopeptidase in Women with Breast Cancer: A Role beyond the Regulation of Oxytocin and Vasopressin.
(2020-11-04) Ramírez-Expósito, María Jesús; Dueñas-Rodríguez, Basilio; Carrera-González, María Pilar; Navarro-Cecilia, Joaquín; Martínez-Martos, Jose Manuel
Insulin-regulated aminopeptidase (IRAP) is the only enzyme known to cleave oxytocin and vasopressin; however, it is also the high-affinity binding site for angiotensin IV (AngIV) receptor type 4 (AT4) ligands and it is related to insulin-dependent glucose transporters through the translocation of the glucose transporter type 4 (GLUT4). Previous studies have demonstrated an association between IRAP activity and the number and size of mammary tumors in an animal model of breast cancer (BC). Also, a highly significant increase in IRAP activity has been found in BC tissue from women patients. Here, we found no changes in circulating IRAP in premenopausal (preMP) women, but it increased significantly in postmenopausal (postMP) women not treated with neoadjuvant chemotherapy (NACH). However, in women treated with NACH, IRAP activity increased in both preMP and postMP women. Two years of follow-up indicated lower levels of IRAP activity in untreated preMP women, but a return to control levels in untreated postMP women, while IRAP activity returned to control levels in women treated with NACH. Circulating oxytocin decreased in both preMP and postMP women during the follow-up period. Differences in Oxytocin appeared between preMP and postMP women treated with NACH, but not in women who were not treated with NACH. On the contrary, circulating vasopressin increased in untreated and treated preMP and postMP women, with most of the differences related to the hormonal status as well as the neoadjuvant treatment during the two year follow-up We propose that IRAP is involved in mechanisms related not only to oxytocin and/or vasopressin regulation, but also to the local mammary RAS through AngIV and its role in glucose transportation through the IRAP/GLUT4 system.
Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens.
(Nature Publishing Group, 2021-10-20) Castaño-Bonilla, Tamara; Alonso-Dominguez, Juan M; Barragan, Eva; Rodriguez-Veiga, Rebeca; Sargas, Claudia; Gil, Cristina; Chillon, Carmen; Vidriales, Maria B; Garcia, Raimundo; Martinez-Lopez, Joaquin; Ayala, Rosa; Larrayoz, Maria J; Anguita, Eduardo; Cuello, Rebeca; Cantalapiedra, Alberto; Carrillo, Estrella; Soria-Saldise, Elena; Labrador, Jorge; Recio, Isabel; Algarra, Lorenzo; Rodriguez-Medina, Carlos; Bilbao-Syeiro, Cristina; Lopez-Lopez, Juan A; Serrano, Josefina; De-Cabo, Erik; Sayas, Maria J; Olave, Maria T; Sanchez-Garcia, Joaquin; Mateos, Mamen; Blas, Carlos; Lopez-Lorenzo, Jose L; Lainez-Gonzalez, Daniel; Serrano, Juana; Martinez-Cuadron, David; Sanz, Miguel A; Montesinos, Pau
FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.
Sandwich-Type Electrochemical Paper-Based Immunosensor for Claudin 7 and CD81 Dual Determination on Extracellular Vesicles from Breast Cancer Patients.
(2020-12-10) Ortega, Francisco G; Regiart, Matías D; Rodríguez-Martínez, Alba; de Miguel-Pérez, Diego; Serrano, María J; Lorente, José A; Tortella, Gonzalo; Rubilar, Olga; Sapag, Karim; Bertotti, Mauro; Fernández-Baldo, Martín A
This study is focused on identifying novel epithelial markers in circulating extracellular vesicles (EVs) through the development of a dual sandwich-type electrochemical paper-based immunosensor for Claudin 7 and CD81 determination, as well as its validation in breast cancer (BC) patients. This immunosensor allows for rapid, sensitive, and label-free detection of these two relevant BC biomarkers. Under optimum conditions, the limit of detection for Claudin 7 was 0.4 pg mL-1, with a wide linear range of 2 to 1000 pg mL-1, while for CD81, the limit of detection was 3 pg mL-1, with a wide linear range of 0.01 to 10 ng mL-1. Finally, we validated Claudin 7 and CD81 determination in EVs from 60 BC patients and 20 healthy volunteers, reporting higher diagnostic accuracy than the one observed with classical diagnostic markers. This analysis provides a low-cost, specific, versatile, and user-friendly strategy as a robust and reliable tool for early BC diagnosis.
Phase II study of high-sensitivity genotyping of KRAS, NRAS, BRAF and PIK3CA to ultra-select metastatic colorectal cancer patients for panitumumab plus FOLFIRI: the ULTRA trial.
(2019) Santos, C; Azuara, D; Viéitez, J M; Páez, D; Falcó, E; Élez, E; López-López, C; Valladares, M; Robles-Díaz, L; García-Alfonso, P; Bugés, C; Durán, G; Salud, A; Navarro, V; Capellá, G; Aranda, E; Salazar, R
Several studies show the importance of accurately quantifying not only KRAS and other low-abundant mutations because benefits of anti-EGFR therapies may depend on certain sensitivity thresholds. We assessed whether ultra-selection of patients using a high-sensitive digital PCR (dPCR) to determine KRAS, NRAS, BRAF and PIK3CA status can improve clinical outcomes of panitumumab plus FOLFIRI. This was a single-arm phase II trial that analysed 38 KRAS, NRAS, BRAF and PIK3CA hotspots in tumour tissues of irinotecan-resistant metastatic colorectal cancer patients who received panitumumab plus FOLFIRI until disease progression or early withdrawal. Mutation profiles were identified by nanofluidic dPCR and correlated with clinical outcomes (ORR, overall response rate; PFS, progression-free survival; OS, overall survival) using cut-offs from 0% to 5%. A quantitative PCR (qPCR) analysis was also performed. Seventy-two evaluable patients were enrolled. RAS (KRAS/NRAS) mutations were detected in 23 (32%) patients and RAS/BRAF mutations in 25 (35%) by dPCR, while they were detected in 7 (10%) and 11 (15%) patients, respectively, by qPCR. PIK3CA mutations were not considered in the analyses as they were only detected in 2 (3%) patients by dPCR and in 1 (1%) patient by qPCR. The use of different dPCR cut-offs for RAS (KRAS/NRAS) and RAS/BRAF analyses translated into differential clinical outcomes. The highest ORR, PFS and OS in wild-type patients with their lowest values in patients with mutations were achieved with a 5% cut-off. We observed similar outcomes in RAS/BRAF wild-type and mutant patients defined by qPCR. High-sensitive dPCR accurately identified patients with KRAS, NRAS, BRAF and PIK3CA mutations. The optimal RAS/BRAF mutational cut-off for outcome prediction is 5%, which explains that the predictive performance of qPCR was not improved by dPCR. The biological and clinical implications of low-frequent mutated alleles warrant further investigations. NCT01704703. 2012-001955-38.
Management of Primary Obstructive Megaureter by Endoscopic High-Pressure Balloon Dilatation. IDEAL Framework Model as a New Tool for Systematic Review.
(2019-04-16) Romero, Rosa M
Introduction: Therapeutic management of primary obstructive megaureter (POM) requiring surgery has been under debate for the last 15 years especially regarding the outcomes of endoscopic techniques compared to most traditional approaches. This review aims to analyze endoscopic High-Pressure Balloon Dilatation (HPBD) using the IDEAL model, a five-stage framework that describes surgical innovations (Idea, Development, Exploration, Assessment, and Long-term Study) and provides recommendations for a rigorous stepwise surgical research pathway. This model has been developed and demonstrated its value in evaluating surgical innovations assessing data quality and providing relevant information for the optimal design and feasibility of research in surgery. Materials and Methods: A systematic review of the published series of endoscopic HPBD in patients with POM was done using the IDEAL model as a tool to assess evidence quality. Reported clinical outcomes are also analyzed and reviewed. Results: The analysis of the results of the systematic assessment of the reported cohort of patients treated with HPBD for POM that the technique up to date is in stage 2a and stage 2b, or development. Evidence quality among the reported cohorts of patients with POM treated with HPBD is adequate, although systematization and standardization should be improved. Clinical outcomes of HPBD in the management of POM consistently show a 87.7% success rate with a negligible operative complication rate once "learning curve" has been surpassed. Symptomatic vesicoureteral reflux (VUR) is the main reason for ureteric reimplantation, but asymptomatic VUR does not seem to influence clinical outcome. Conclusions: The IDEAL framework and recommendations have allowed a systematic analysis of the evidence quality of the reported experience in the management of children with POM with HPBD of the vesicoureteral junction. The available evidence demonstrates that HPBD is an effective treatment for patients with POM, with a long-term success rate of 87.7% with very low morbidity. Future research mandates a standardization of data reporting, "ideally" following IDEAL recommendations, that would be required for any intervention and facilitate comparative analysis.
POLYMORPHISMS IN PHASE I-METABOLISING ENZYME AND HORMONE RECEPTOR GENES INFLUENCE THE RESPONSE TO ANTI-TNF THERAPY
(Bmj publishing group, 2018-06-01) Canet, L. M.; Sanchez-Maldonado, J. M.; Rodriguez-Ramos, A.; Lupianez, C. B.; Canhao, H.; Martinez-Bueno, M.; Escudero, A.; Segura-Catena, J.; Sorensen, S. B.; Hetland, M. L.; Soto-Pino, M. J.; Ferrer, M. A.; Garcia, A.; Glintborg, B.; Filipescu, I.; Perez-Pampin, E.; Gonzalez-Utrilla, A.; Lopez-Nevot, M. A.; Conesa-Zamora, P.; den Broeder, A. A.; da Vita, S.; Jacobsen, S. E. Hove; Collantes, E.; Quartuccio, L.; Fonseca, J. E.; Coenen, M. J.; Andersen, V.; Caliz-Caliz, R.; Sainz, J.; [Canet, L. M.] Univ Granada, Genom Oncol, Ctr Genom & Oncol Res Pfizer, GENYO,Andalusian Reg Govt,PTS Granada, Granada, Spain; [Sanchez-Maldonado, J. M.] Univ Granada, Genom Oncol, Ctr Genom & Oncol Res Pfizer, GENYO,Andalusian Reg Govt,PTS Granada, Granada, Spain; [Rodriguez-Ramos, A.] Univ Granada, Genom Oncol, Ctr Genom & Oncol Res Pfizer, GENYO,Andalusian Reg Govt,PTS Granada, Granada, Spain; [Lupianez, C. B.] Univ Granada, Genom Oncol, Ctr Genom & Oncol Res Pfizer, GENYO,Andalusian Reg Govt,PTS Granada, Granada, Spain; [Segura-Catena, J.] Univ Granada, Genom Oncol, Ctr Genom & Oncol Res Pfizer, GENYO,Andalusian Reg Govt,PTS Granada, Granada, Spain; [Sainz, J.] Univ Granada, Genom Oncol, Ctr Genom & Oncol Res Pfizer, GENYO,Andalusian Reg Govt,PTS Granada, Granada, Spain; [Canhao, H.] Univ Nova Lisboa, CEDOC, EpiDoC Unit, NOVA Med Sch, Lisbon, Portugal; [Canhao, H.] Univ Nova Lisboa, Natl Sch Publ Hlth, Lisbon, Portugal; [Martinez-Bueno, M.] Univ Granada, Area Genom Med, Ctr Genom & Ontol Res Pfizer, Andalusian Reg Govt,PTS Granada,GENYO, Granada, Spain; [Escudero, A.] Univ Cordoba, Dept Rheumatol, Reina Sofia Hosp, IMIBIC, Cordoba, Spain; [Collantes, E.] Univ Cordoba, Dept Rheumatol, Reina Sofia Hosp, IMIBIC, Cordoba, Spain; [Sorensen, S. B.] Rigshosp, Danish Rheumatol Biobank, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark; [Hetland, M. L.] Rigshosp, Danish Rheumatol Biobank, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark; [Glintborg, B.] Rigshosp, Danish Rheumatol Biobank, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark; [Sorensen, S. B.] Rigshosp, DANBIO Registry, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark; [Hetland, M. L.] Rigshosp, DANBIO Registry, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark; [Glintborg, B.] Rigshosp, DANBIO Registry, Copenhagen Ctr Arthrit Res COPECARE, Ctr Rheumatol & Spine Dis,Ctr Head & Orthopaed, Glostrup, Denmark; [Sorensen, S. B.] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark; [Hetland, M. L.] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark; [Soto-Pino, M. J.] Virgen de las Nieves Univ Hosp, Dept Rheumatol, Granada, Spain; [Ferrer, M. A.] Virgen de las Nieves Univ Hosp, Dept Rheumatol, Granada, Spain; [Garcia, A.] Virgen de las Nieves Univ Hosp, Dept Rheumatol, Granada, Spain; [Gonzalez-Utrilla, A.] Virgen de las Nieves Univ Hosp, Dept Rheumatol, Granada, Spain; [Caliz-Caliz, R.] Virgen de las Nieves Univ Hosp, Dept Rheumatol, Granada, Spain; [Sainz, J.] Virgen de las Nieves Univ Hosp, Dept Rheumatol, Granada, Spain; [Glintborg, B.] Copenhagen Univ Hosp, Gentofte & Herlev Hosp, Dept Rheumatol, Copenhagen, Denmark; [Filipescu, I.] Univ Med & Pharm Iuliu Hatieganu Cluj Napoca, Dept Rheumatol, Cluj Napoca, Romania; [Perez-Pampin, E.] Univ Hosp Santiago de Compostela, Rheumatol Unit, Santiago De Compostela, Spain; [Lopez-Nevot, M. A.] Virgen de las Nieves Univ Hosp, Immunol Dept, Granada, Spain; [Conesa-Zamora, P.] Santa Lucia Univ Hosp, Clin Anal Dept, Cartagena, Spain; [den Broeder, A. A.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands; [Coenen, M. J.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands; [da Vita, S.] Univ Udine, Dept Med & Biol Sci, Clin Rheumatol, Udine, Italy; [Quartuccio, L.] Univ Udine, Dept Med & Biol Sci, Clin Rheumatol, Udine, Italy; [Jacobsen, S. E. Hove] Hosp Southern Jutland, Dept Biochem & Immunol, Jutland, Denmark; [Fonseca, J. E.] Hosp Santa Maria, Rheumatol & Metab Bone Dis Dept, CHLN, Lisbon, Portugal; [Fonseca, J. E.] Univ Lisbon, Lisbon Acad Med Ctr, Fac Med, Rheumatol Res Unit,Inst Med Mol, Lisbon, Portugal; [Andersen, V.] Hosp Southern Jutland, IRS Ctr Sonderjylland, Focused Res Unit Mol Diagnost & Clin Res, Aabenraa, Denmark; [Andersen, V.] Univ Southern Denmark, Inst Mol Med, Fac Hlth Sci, Odense, Denmark; MSD (Merck); Janssen
Time trend in transcatheter aortic valve implantation: an analysis of the Spanish TAVI registry
(Permanyer publ, 2020-04-01) Jimenez-Quevedo, Pilar; Munoz-Garcia, Antonio; Trillo-Nouche, Ramiro; del Valle, Raquel; de la Torre Hernandez, Jose Maria; Salido, Luisa; Gutierrez, Enrique; Pan, Manuel; Sanchez-Gila, Joaquin; Garcia del Blanco, Bruno; Moreno, Raul; Blanco Mata, Roberto; Francisco Oteo, Juan; Amat-Santos, Ignacio; Regueiro, Ander; Ten, Francisco; Manuel Nogales, Juan; Fernandez-Nofrerias, Eduard; Andraka, Leire; Cruz Ferrer, Maria; Pinar, Eduardo; Romaguera, Rafael; Cuellas Ramon, Carlos; Alfonso, Fernando; Garcia-Blas, Sergio; Pinero, Antonio; Ignasi, Julia; Diaz Mendez, Rocio; Bordes, Pascual; Meseguer, Juan; Nombela-Franco, Luis; Spanish TAVI Registry; [Jimenez-Quevedo, Pilar] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Serv Cardiol, Madrid, Spain; [Nombela-Franco, Luis] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos IdISSC, Serv Cardiol, Madrid, Spain; [Munoz-Garcia, Antonio] Hosp Univ Virgen de la Victoria, Serv Cardiol, Malaga, Spain; [Trillo-Nouche, Ramiro] Complejo Hosp Univ Santiago de Compostela, Serv Cardiol, Santiago De Compostela, A Coruna, Spain; [del Valle, Raquel] Hosp Cent Asturias, Serv Cardiol, Oviedo, Asturias, Spain; [de la Torre Hernandez, Jose Maria] Hosp Univ Marques de Valdecilla, Serv Cardiol, IDIVAL, Santander, Cantabria, Spain; [Salido, Luisa] Hosp Ramon & Cajal, Serv Cardiol, Madrid, Spain; [Gutierrez, Enrique] Univ Carlos III, Hosp Gregorio Maranon, Serv Cardiol, CIBERCV, Madrid, Spain; [Pan, Manuel] Univ Cordoba, Hosp Univ Reina Sofia, Inst Maimonides Invest Biomed Cordoba IMIBIC, Serv Cardiol, Cordoba, Spain; [Sanchez-Gila, Joaquin] Hosp Univ Virgen de las Nieves, Serv Cardiol, Granada, Spain; [Garcia del Blanco, Bruno] Hosp Univ Vall dHebron, Serv Cardiol, Barcelona, Spain; [Moreno, Raul] Hosp Univ La Paz, Serv Cardiol, Madrid, Spain; [Blanco Mata, Roberto] Hosp Gen Univ Valencia, Serv Cardiol, Valencia, Spain; [Francisco Oteo, Juan] Hosp Puerta de Hierro, Serv Cardiol, Madrid, Spain; [Amat-Santos, Ignacio] Hosp Clin Univ Valladolid, Serv Cardiol, Valladolid, Spain; [Regueiro, Ander] Hosp Clin Barcelona, Serv Cardiol, Barcelona, Spain; [Ten, Francisco] Hosp Univ & Politecn La Fe, Serv Cardiol, Valencia, Spain; [Manuel Nogales, Juan] Hosp Univ Badajoz, Serv Cardiol, Badajoz, Spain; [Fernandez-Nofrerias, Eduard] Hosp Germans Trias i Pujol, Serv Cardiol, Barcelona, Spain; [Andraka, Leire] Hosp Univ Basurto, Serv Cardiol, Bilbao, Bizkaia, Spain; [Cruz Ferrer, Maria] Hosp Univ Miguel Servet, Serv Cardiol, Zaragoza, Spain; [Pinar, Eduardo] Hosp Clin Univ Virgen de la Arrixaca, Serv Cardiol, Murcia, Spain; [Romaguera, Rafael] Hosp Univ Bellvitge, Serv Cardiol, Barcelona, Spain; [Cuellas Ramon, Carlos] Hosp Univ Leon, Serv Cardiol, Leon, Spain; [Alfonso, Fernando] Hosp Univ La Princesa, Serv Cardiol, Madrid, Spain; [Garcia-Blas, Sergio] Hosp Clin Univ Valencia, Serv Cardiol, Valencia, Spain; [Pinero, Antonio] Hosp Univ Fdn Jimenez Diaz, Serv Cardiol, Madrid, Spain; [Ignasi, Julia] Hosp Germans Trias i Pujol, Serv Cirug Cardiaca, Barcelona, Spain; [Diaz Mendez, Rocio] Hosp Cent Asturias, Serv Cirug Cardiaca, Oviedo, Asturias, Spain; [Bordes, Pascual] Hosp Gen Univ Alicante, Serv Cardiol & Cirug Cardiaca, Alicante, Spain; [Meseguer, Juan] Hosp Gen Univ Alicante, Serv Cardiol & Cirug Cardiaca, Alicante, Spain; Section of Hemodynamics and Interventional Cardiology of the Spanish Society of Cardiology
Introduction and objectives: This study primary endpoint was to present the in-hospital all-cause mortality of the Spanish TAVI registry from its inception until 2018. Secondary endpoints included other in-hospital clinical events, 30-day all-cause mortality, and an assessment of the time trend of this registry. Methods: All consecutive patients included in the Spanish TAVI registry were analyzed. In this time-based analysis, the population was been divided into patients treated before 2014 (cohort A: 2009-2013) and patients treated between 2014 and 2018 (cohort B). Results: From August 2007 to June 2018, 7180 patients were included. The mean age was 81.2 +/- 6.5 years and 53% were women. The logistic EuroSCORE was 12% (8-20). Transfemoral access was used in 89%. In-hospital and 30-day all-cause mortality was 4.7% and 5.7%, respectively. On the time-based analyses during the hospital stay, the rate of myocardial infarction, stroke, need for pacemakers, tamponade, coronary obstruction, and vascular complications was similar between both groups. However, cohort B showed less need for conversion to surgery and malapposition of the valve. Also, the implant success rate increased from 93% to 96% (P
OXA-48 Carbapenemase-Producing Enterobacterales in Spanish Hospitals: An Updated Comprehensive Review on a Rising Antimicrobial Resistance.
(2021-01-18) Rivera-Izquierdo, Mario; Láinez-Ramos-Bossini, Antonio Jesús; Rivera-Izquierdo, Carlos; López-Gómez, Jairo; Fernández-Martínez, Nicolás Francisco; Redruello-Guerrero, Pablo; Martín-delosReyes, Luis Miguel; Martínez-Ruiz, Virginia; Moreno-Roldán, Elena; Jiménez-Mejías, Eladio
Carbapenemase-producing Enterobacterales (CPE) are significant contributors to the global public health threat of antimicrobial resistance. OXA-48-like enzymes and their variants are unique carbapenemases with low or null hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. CPEs have been classified by the WHO as high-priority pathogens given their association with morbidity and mortality and the scarce number of effective antibiotic treatments. In Spain, the frequency of OXA-48 CPE outbreaks is higher than in other European countries, representing the major resistance mechanism of CPEs. Horizontal transfer of plasmids and poor effective antibiotic treatment are additional threats to the correct prevention and control of these hospital outbreaks. One of the most important risk factors is antibiotic pressure, specifically carbapenem overuse. We explored the use of these antibiotics in Spain and analyzed the frequency, characteristics and prevention of CPE outbreaks. Future antibiotic stewardship programs along with specific preventive measures in hospitalized patients must be reinforced and updated in Spain.
Altered expression of the spliceosome components in leukocytes subsets from patients with ankylosing spondylitis: association to disease pathogenesis and therapeutic response
(BMJ publishing group, 2022-01-09) Ladehesa, L.; Castro, M. G.; Lopez-Pedrera, C.; Ortega, R.; Pedraza, S.; del Rio, M.; Abalos-Aguilera, M. C.; Ruiz-Limon, P.; Perez-Sanchez, C.; Ibanez-Costa, A.; Parra-Manso, Y.; Barbarroja, N.; Arias-de la Rosa, I.; Font, P.; Escudero, A.; Castano, J. P.; Luque, R. M.; Collantes, E.; Jimenez-Gomez, Y.; [Ladehesa, L.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Castro, M. G.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Lopez-Pedrera, C.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Ortega, R.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Abalos-Aguilera, M. C.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Ruiz-Limon, P.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Perez-Sanchez, C.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Ibanez-Costa, A.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Parra-Manso, Y.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Barbarroja, N.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Arias-de la Rosa, I.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Font, P.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Escudero, A.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Collantes, E.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Jimenez-Gomez, Y.] Cordoba Univ, Reina Sofia Univ Hosp, Rheumatol Serv, IMIBIC, Cordoba, Spain; [Pedraza, S.] Univ Cordoba, IMIBIC, Dept Biol Celular Fisiol & Inmunol, Hosp Reina Sofia, Cordoba, Spain; [del Rio, M.] Univ Cordoba, IMIBIC, Dept Biol Celular Fisiol & Inmunol, Hosp Reina Sofia, Cordoba, Spain; [Castano, J. P.] Univ Cordoba, IMIBIC, Dept Biol Celular Fisiol & Inmunol, Hosp Reina Sofia, Cordoba, Spain; [Luque, R. M.] Univ Cordoba, IMIBIC, Dept Biol Celular Fisiol & Inmunol, Hosp Reina Sofia, Cordoba, Spain; [Pedraza, S.] CIBERobn, Cordoba, Spain; [del Rio, M.] CIBERobn, Cordoba, Spain; [Castano, J. P.] CIBERobn, Cordoba, Spain; [Luque, R. M.] CIBERobn, Cordoba, Spain; [Pedraza, S.] CeiA3, Cordoba, Spain; [del Rio, M.] CeiA3, Cordoba, Spain; [Castano, J. P.] CeiA3, Cordoba, Spain; [Luque, R. M.] CeiA3, Cordoba, Spain; ISCIII
Ankylosing spondylitis (AS) is a chronic inflammatory disease whose etiopathogenesis remains incompletely understood. Splicing, a posttranscriptional process essential for RNA maturation, has recently been implicated in several human diseases through pathological deregulation of the spliceosome; however, alterations of the spliceosome and their modulation by therapeutic responses have not yet been described in AS. The objectives of this study were: (1) to evaluate the potential deregulation of the spliceosome in leukocytes from AS patients and its involvement in disease pathophysiology, and (2) to analyze the in vivo effects of anti-TNF drugs on spliceosome components in these cells. A cross-sectional study was conducted with 32 AS patients and 29 healthy donors (HDs), and a three-month longitudinal study was performed in eight AS patients undergoing anti-TNFα therapy. Disease activity was assessed using the BASDAI index, along with CRP and ESR levels; physical function was measured by BASFI, spinal mobility by BASMI, and structural damage by mSASSS. The expression of selected components of the major (n=12) and minor (n=4) spliceosomes, as well as splicing factors (n=28), was evaluated in purified leukocytes using Fluidigm technology, while inflammatory marker expression was assessed in parallel by RT-PCR.
GENETICALLY PREDISPOSITION AND PRO-INFLAMMATORY DYSREGULATIONS - CONNECTING RHEUMATOID ARTHRITIS AND MENTAL DISORDERS
(Bmj publishing group, 2018-06-01) Filipescu, I. C.; Ghib, L.; Juan Sainz, P.; Perez-Sanchez, C.; Lopez-Pedrera, C.; Escudero, A.; Damian, L.; Muntean, L.; Collantes-Estevez, E.; Rednic, S.; [Filipescu, I. C.] Univ Med & Pharm, Rheumatol Clin, Cluj Napoca, Romania; [Ghib, L.] Univ Med & Pharm, Rheumatol Clin, Cluj Napoca, Romania; [Damian, L.] Univ Med & Pharm, Rheumatol Clin, Cluj Napoca, Romania; [Muntean, L.] Univ Med & Pharm, Rheumatol Clin, Cluj Napoca, Romania; [Rednic, S.] Univ Med & Pharm, Rheumatol Clin, Cluj Napoca, Romania; [Juan Sainz, P.] Univ Granada, Ctr Genom & Oncol Res 3GENYO, Granada, Spain; [Perez-Sanchez, C.] Univ Cordoba, Inst Res Biomed Cordoba IMIBIC 4Maimonides, Cordoba, Spain; [Lopez-Pedrera, C.] 4Maimonides Inst Res Biomed Cordoba IMIBIC, Cordoba, Spain; [Escudero, A.] Univ Cordoba, Reina Sofia Univ Hosp, Cordoba, Spain
Patients with Axial Spondyloarthritis Show an Altered Flexion/Relaxation Phenomenon
(Mdpi, 2021-05-01) Aranda-Valera, I. Concepcion; Garrido-Castro, Juan Luis; Martinez-Galisteo, Alfonso; Pena-Amaro, Jose; Gonzalez-Navas, Cristina; Cuesta-Vargas, Antonio; Jimenez-Reina, Luis; Collantes-Estevez, Eduardo; Lopez-Medina, Clementina; [Aranda-Valera, I. Concepcion] Reina Sofia Univ Hosp, Rheumatol Dept, Cordoba 14004, Spain; [Collantes-Estevez, Eduardo] Reina Sofia Univ Hosp, Rheumatol Dept, Cordoba 14004, Spain; [Lopez-Medina, Clementina] Reina Sofia Univ Hosp, Rheumatol Dept, Cordoba 14004, Spain; [Aranda-Valera, I. Concepcion] Maimonides Inst Biomed Res Cordoba IMIBIC, G05 Grp, Cordoba 14004, Spain; [Garrido-Castro, Juan Luis] Maimonides Inst Biomed Res Cordoba IMIBIC, G05 Grp, Cordoba 14004, Spain; [Gonzalez-Navas, Cristina] Maimonides Inst Biomed Res Cordoba IMIBIC, G05 Grp, Cordoba 14004, Spain; [Collantes-Estevez, Eduardo] Maimonides Inst Biomed Res Cordoba IMIBIC, G05 Grp, Cordoba 14004, Spain; [Lopez-Medina, Clementina] Maimonides Inst Biomed Res Cordoba IMIBIC, G05 Grp, Cordoba 14004, Spain; [Aranda-Valera, I. Concepcion] Univ Cordoba, Cordoba 14004, Spain; [Garrido-Castro, Juan Luis] Univ Cordoba, Cordoba 14004, Spain; [Martinez-Galisteo, Alfonso] Univ Cordoba, Cordoba 14004, Spain; [Pena-Amaro, Jose] Univ Cordoba, Cordoba 14004, Spain; [Jimenez-Reina, Luis] Univ Cordoba, Cordoba 14004, Spain; [Collantes-Estevez, Eduardo] Univ Cordoba, Cordoba 14004, Spain; [Lopez-Medina, Clementina] Univ Cordoba, Cordoba 14004, Spain; [Cuesta-Vargas, Antonio] Univ Malaga, Malaga Inst Biomed Res IBIMA, Malaga 29016, Spain; Health Innovation Projects of Junta de Andalucia; University of Cordoba
Axial spondyloarthritis (axSpA) is a chronic rheumatic disease characterized by the presence of inflammatory back pain. In patients with chronic low back pain, the lumbar flexion relaxation phenomenon measured by surface electromyography (sEMG) differs from that in healthy individuals. However, sEMG activity in axSpA patients has not been studied. The purpose of this study was to analyze the flexion relaxation phenomenon in axSpA patients. A study evaluating 39 axSpA patients and 35 healthy controls was conducted. sEMG activity at the erector spinae muscles was measured during lumbar full flexion movements. sEMG activity was compared between axSpA patients and the controls, as well as between active (BASDAI >= 4) and non-active (BASDAI = 4) and non-active (BASDAI 0.8 for 1/FRR) and criterion validity. ROC analysis showed good discriminant validity for axSpA patients (AUC = 0.835) vs. the control group using 1/FRR. An abnormal flexion/relaxation phenomenon exists in axSpA patients compared with controls. sEMG could be an additional objective tool in the evaluation of patient function and disease activity status.
Optimization of Collagen Chemical Crosslinking to Restore Biocompatibility of Tissue-Engineered Scaffolds.
(2021-06-03) Islam, Mohammad Mirazul; AbuSamra, Dina B; Chivu, Alexandru; Argüeso, Pablo; Dohlman, Claes H; Patra, Hirak K; Chodosh, James; González-Andrades, Miguel
Collagen scaffolds, one of the most used biomaterials in corneal tissue engineering, are frequently crosslinked to improve mechanical properties, enzyme tolerance, and thermal stability. Crosslinkers such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) are compatible with tissues but provide low crosslinking density and reduced mechanical properties. Conversely, crosslinkers such as glutaraldehyde (GTA) can generate mechanically more robust scaffolds; however, they can also induce greater toxicity. Herein, we evaluated the effectivity of double-crosslinking with both EDC and GTA together with the capability of sodium metabisulfite (SM) and sodium borohydride (SB) to neutralize the toxicity and restore biocompatibility after crosslinking. The EDC-crosslinked collagen scaffolds were treated with different concentrations of GTA. To neutralize the free unreacted aldehyde groups, scaffolds were treated with SM or SB. The chemistry involved in these reactions together with the mechanical and functional properties of the collagen scaffolds was evaluated. The viability of the cells grown on the scaffolds was studied using different corneal cell types. The effect of each type of scaffold treatment on human monocyte differentiation was evaluated. One-way ANOVA was used for statistical analysis. The addition of GTA as a double-crosslinking agent significantly improved the mechanical properties and enzymatic stability of the EDC crosslinked collagen scaffold. GTA decreased cell biocompatibility but this effect was reversed by treatment with SB or SM. These agents did not affect the mechanical properties, enzymatic stability, or transparency of the double-crosslinked scaffold. Contact of monocytes with the different scaffolds did not trigger their differentiation into activated macrophages. Our results demonstrate that GTA improves the mechanical properties of EDC crosslinked scaffolds in a dose-dependent manner, and that subsequent treatment with SB or SM partially restores biocompatibility. This novel manufacturing approach would facilitate the translation of collagen-based artificial corneas to the clinical setting.
The Role of Emotional Regulation and Affective Balance on Health Perception in Cardiovascular Disease Patients According to Sex Differences.
(2020-09-30) Luque, Bárbara; Castillo-Mayén, Rosario; Cuadrado, Esther; Gutiérrez-Domingo, Tamara; Rubio, Sebastián J; Arenas, Alicia; Delgado-Lista, Javier; Pérez Martínez, Pablo; Tabernero, Carmen
One of the challenges of aging is the increase of people with chronic diseases, such as cardiovascular disease (CVD). Men and women experience the disease differently. Therefore, it has an impact on how CVD is treated and its outcomes. This research analyzed the relationship between psychosocial variables and health promotion among cardiovascular patients, paying special attention to sex differences. A longitudinal study with cardiovascular patients (747 in phase 1 (122 women) and 586 in phase 2 (83 women)) was carried out. Participants were evaluated based on their sociodemographic characteristics, affective balance, regulatory negative affect self-efficacy, stress and anxiety regulation strategies, and perceived global health. Results showed that men presented significantly higher scores in positive affect, affective balance, and self-efficacy to regulate negative emotions, while women presented significantly higher scores in negative affect and the use of passive strategies to cope with stressful situations. Regression analyses showed that all psychological variables studied in phase 1 were significant predictors of health perception in phase 2. According to the results, it is necessary to include strategies to improve cardiovascular health through education and emotional regulation, with a gender focus.
Hematuria Is Associated with More Severe Acute Tubulointerstitial Nephritis.
(MDPI, 2020-07-07) Esteras, Raquel; Fox, Jonathan G; Geddes, Colin C; Mackinnon, Bruce; Ortiz, Alberto; Moreno, Juan Antonio; FIS/FEDER; Spanish Ministry of Science and Innovation; Sociedad Española de Nefrología; Fundacion Renal Iñigo Álvarez de Toledo (FRIAT); ISCIII-RETIC REDinREN; Comunidad de Madrid
Acute tubulointerstitial nephritis (ATIN) is a common cause of acute kidney injury. Although haematuria is a risk factor for the development of renal disease, no previous study has analyzed the significance of haematuria in ATIN. Retrospective, observational analysis of 110 patients with biopsy-proven ATIN was conducted. Results: Haematuria was present in 66 (60%) ATIN patients. A higher percentage of ATIN patients with haematuria had proteinuria than patients without haematuria (89.4% vs. 59.1%, p = 0.001) with significantly higher levels of proteinuria (median (interquartile range) protein:creatinine ratio 902.70 (513-1492) vs. 341.00 (177-734) mg/g, pp <0.001). Moreover, those patients with more haematuria intensity had a higher urinary protein:creatinine ratio (1352.65 (665–2292) vs. 849.60 (562–1155) mg/g, p = 0.02). Those patients with higher proteinuria were more likely to need renal replacement therapy (22.7 vs. 0%, p = 0.03) and to suffer relapse (4 vs. 0%, p = 0.03). At the end of follow up, haematuric ATIN patients had higher serum creatinine levels (3.19 ± 2.91 vs. 1.91 ± 1.17 mg/dL, p = 0.007), and a trend towards a higher need for acute dialysis (7 vs. 1%, p = 0.09) and renal replacement therapy (12.1 vs. 2.3%, p = 0.12). Haematuria is common in ATIN and it is associated with worse renal function outcomes.
A Multiplex Test Assessing MiR663ame and VIMme in Urine Accurately Discriminates Bladder Cancer from Inflammatory Conditions.
(MDPI, 2020-02-24) Monteiro-Reis, Sara; Blanca, Ana; Tedim-Moreira, Joana; Carneiro, Isa; Montezuma, Diana; Monteiro, Paula; Oliveira, Jorge; Antunes, Luis; Henrique, Rui; Lopez-Beltran, António; Jeronimo, Carmen; Research Center of Portuguese Institute of Porto; Fundação para a Ciência e Tecnologia
Bladder cancer (BlCa) is a common malignancy with significant morbidity and mortality. Current diagnostic methods are invasive and costly, showing the need for newer biomarkers. Although several epigenetic-based biomarkers have been proposed, their ability to discriminate BlCa from common benign conditions of the urinary tract, especially inflammatory diseases, has not been adequately explored. Herein, we sought to determine whether VIMme and miR663ame might accurately discriminate those two conditions, using a multiplex test. Performance of VIMme and miR663ame in tissue samples and urines in testing set confirmed previous results (96.3% sensitivity, 88.2% specificity, area under de curve (AUC) 0.98 and 92.6% sensitivity, 75% specificity, AUC 0.83, respectively). In the validation sets, VIMme-miR663ame multiplex test in urine discriminated BlCa patients from healthy donors or patients with inflammatory conditions, with 87% sensitivity, 86% specificity and 80% sensitivity, 75% specificity, respectively. Furthermore, positive likelihood ratio (LR) of 2.41 and negative LR of 0.21 were also disclosed. Compared to urinary cytology, VIMme-miR663ame multiplex panel correctly detected 87% of the analysed cases, whereas cytology only forecasted 41%. Furthermore, high miR663ame independently predicted worse clinical outcome, especially in patients with invasive BlCa. We concluded that the implementation of this panel might better stratify patients for confirmatory, invasive examinations, ultimately improving the cost-effectiveness of BlCa diagnosis and management. Moreover, miR663ame analysis might provide relevant information for patient monitoring, identifying patients at higher risk for cancer progression.

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