IDIS - Instituto de Investigación Sanitaria de Santiago de Compostela (Galicia)

Permanent URI for this collection

https://hdl.handle.net/20.500.12105/16966

El Instituto de Investigación Sanitaria de Santiago (IDIS) Se constituyó el 31 de enero de 2008, mediante un convenio de colaboración entre la Consellería de Sanidade, el Servizo Galego de Saúde y la Universidad de Santiago de Compostela. Es un centro de investigación biomédica de marcado carácter traslacional que aprovecha las sinergias del Complejo Hospitalario Universitario de Santiago de Compostela (CHUS) y de la Universidad de Santiago de Compostela (USC) para impulsar, promover y fomentar la investigación de excelencia, el conocimiento científico y tecnológico y su posterior traslación al sector productivo, así como la docencia y la formación y siempre con un objetivo claro: mejorar la salud de la población. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2010, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

Browse

Now showing 1 - 20 of 49

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial
(Oxford University Press, 2021-05-01) Pujol, Miquel; Miro, Jose-Maria; Shaw, Evelyn; Aguado, Jose-Maria; San-Juan, Rafael; Puig-Asensio, Mireia; Pigrau, Carles; Calbo, Esther; Montejo, Miguel; Rodriguez-Alvarez, Regino; Garcia-Pais, Maria-Jose; Pintado, Vicente; Escudero-Sanchez, Rosa; Lopez-Contreras, Joaquin; Morata, Laura; Montero, Milagros; Andres, Marta; Pasquau, Juan; Arenas, Maria-del-Mar; Padilla, Belen; Murillas, Javier; Jover-Saenz, Alfredo; Lopez-Cortes, Luis Eduardo; Garcia-Pardo, Graciano; Gasch, Oriol; Videla, Sebastian; Hereu, Pilar; Tebe, Cristian; Pallares, Natalia; Sanllorente, Mireia; Dominguez, Maria-Angeles; Camara, Jordi; Ferrer, Ana; Padulles, Ariadna; Cuervo, Guillermo; Carratala, Jordi; MRSA Bacteremia (BACSARM) Trial Investigators
Background. We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. Methods. A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. Results. of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). Conclusions. Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events.
RP11-362K2.2:RP11-767I20.1 Genetic Variation Is Associated with Post-Reperfusion Therapy Parenchymal Hematoma. A GWAS Meta-Analysis
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-07) Muiño, Elena; Carcel-Marquez, Jara; Carrera, Caty; Llucia-Carol, Laia; Gallego-Fabrega, Cristina; Cullell, Natalia; Lledos, Miquel; Castillo, Jose; Sobrino, Tomas; Campos, Francisco; Rodriguez-Castro, Emilio; Millan, Monica; Muñoz-Narbona, Lucia; Bustamante, Alejandro; Lopez-Cancio, Elena; Ribo, Marc; Alvarez-Sabin, Jose; Jimenez-Conde, Jordi; Roquer, Jaume; Giralt-Steinhauer, Eva; Soriano-Tarraga, Carolina; Vives-Bauza, Cristofol; Diaz Navarro, Rosa; Tur Campos, Silvia; Obach, Victor; Arenillas, Juan Francisco; Segura, Tomas; Serrano-Heras, Gemma; Marti-Fabregas, Joan; Delgado-Mederos, Raquel; Camps-Renom, Pol; Prats-Sanchez, Luis; Guisado, Daniel; Guasch, Marina; Marin, Rebeca; Martinez-Domeno, Alejandro; Freijo Guerrero, Maria del Mar; Moniche, Francisco; Cabezas, Juan Antonio; Castellanos, Mar; Krupinsky, Jerzy; Strbian, Daniel; Tatlisumak, Turgut; Thijs, Vincent; Lemmens, Robin; Slowik, Agnieszka; Pera, Joanna; Heitsch, Laura; Ibañez, Laura; Cruchaga, Carlos; Dhar, Rajat; Lee, Jin-Moo; Montaner, Joan; Fernandez-Cadenas, Israel; International Stroke Genetic Consortium; Spanish Stroke Genetic Consortium
Stroke is one of the most common causes of death and disability. Reperfusion therapies are the only treatment available during the acute phase of stroke. Due to recent clinical trials, these therapies may increase their frequency of use by extending the time-window administration, which may lead to an increase in complications such as hemorrhagic transformation, with parenchymal hematoma (PH) being the more severe subtype, associated with higher mortality and disability rates. Our aim was to find genetic risk factors associated with PH, as that could provide molecular targets/pathways for their prevention/treatment and study its genetic correlations to find traits sharing genetic background. We performed a GWAS and meta-analysis, following standard quality controls and association analysis (fastGWAS), adjusting age, NIHSS, and principal components. FUMA was used to annotate, prioritize, visualize, and interpret the meta-analysis results. The total number of patients in the meta-analysis was 2034 (216 cases and 1818 controls). We found rs79770152 having a genome-wide significant association (beta 0.09, p-value 3.90 x 10(-8)) located in the RP11-362K2.2:RP11-767I20.1 gene and a suggestive variant (rs13297983: beta 0.07, p-value 6.10 x 10(-8)) located in PCSK5 associated with PH occurrence. The genetic correlation showed a shared genetic background of PH with Alzheimer's disease and white matter hyperintensities. In addition, genes containing the ten most significant associations have been related to aggregated amyloid-beta, tau protein, white matter microstructure, inflammation, and matrix metalloproteinases.
Effectiveness of a Multicomponent Intervention in Primary Care That Addresses Patients with Diabetes Mellitus with Two or More Unhealthy Habits, Such as Diet, Physical Activity or Smoking: Multicenter Randomized Cluster Trial (EIRA Study)
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-06) Represas-Carrera, Francisco; Couso-Viana, Sabela; Mendez-Lopez, Fatima; Masluk, Barbara; Magallon-Botaya, Rosa; Recio-Rodriguez, Jose I; Pombo, Haizea; Leiva Rus, Alfonso; Gil-Girbau, Montserrat; Motrico, Emma; Marti-Lluch, Ruth; Gude, Francisco; Claveria, Ana
Introduction: We evaluated the effectiveness of an individual, group and community intervention to improve the glycemic control of patients with diabetes mellitus aged 45-75 years with two or three unhealthy life habits. As secondary endpoints, we evaluated the inverventions' effectiveness on adhering to Mediterranean diet, physical activity, sedentary lifestyle, smoking and quality of life. Method: A randomized clinical cluster (health centers) trial with two parallel groups in Spain from January 2016 to December 2019 was used. Patients with diabetes mellitus aged 45-75 years with two unhealthy life habits or more (smoking, not adhering to Mediterranean diet or little physical activity) participated. Centers were randomly assigned. The sample size was estimated to be 420 people for the main outcome variable. Educational intervention was done to improve adherence to Mediterranean diet, physical activity and smoking cessation by individual, group and community interventions for 12 months. Controls received the usual health care. The outcome variables were: HbA1c (main), the Mediterranean diet adherence score (MEDAS), the international diet quality index (DQI-I), the international physical activity questionnaire (IPAQ), sedentary lifestyle, smoking >= 1 cigarette/day and the EuroQuol questionnaire (EVA-EuroQol5D5L). Results: In total, 13 control centers (n = 356) and 12 intervention centers (n = 338) were included with similar baseline conditions. An analysis for intention-to-treat was done by applying multilevel mixed models fitted by basal values and the health center: the HbA1c adjusted mean difference = -0.09 (95% CI: -0.29-0.10), the DQI-I adjusted mean difference = 0.25 (95% CI: -0.32-0.82), the MEDAS adjusted mean difference = 0.45 (95% CI: 0.01-0.89), moderate/high physical activity OR = 1.09 (95% CI: 0.64-1.86), not living a sedentary lifestyle OR = 0.97 (95% CI: 0.55-1.73), no smoking OR = 0.61 (95% CI: 0.54-1.06), EVA adjusted mean difference = -1.26 (95% CI: -4.98-2.45). Conclusions: No statistically significant changes were found for either glycemic control or physical activity, sedentary lifestyle, smoking and quality of life. The multicomponent individual, group and community interventions only showed a statistically significant improvement in adhering to Mediterranean diet. Such innovative interventions need further research to demonstrate their effectiveness in patients with poor glycemic control.
HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer
(Nature Publishing Group, 2023) Olivera-Salguero, Rubén; Seguí, Elia; Cejalvo, Juan Miguel; Oliveira, Mafalda; Tolosa, Pablo; Vidal, Maria; Malumbres Martinez, Marcos; Gavilá, Joaquín; Saura, Cristina; Pernas, Sonia; López, Rafael; Margelí, Mireia; Balmaña, Judith; Muñoz, Montserrat; Blancas, Isabel; Boni, Valentina; Ciruelos, Eva; Galve, Elena; Perelló, Antonia; Sánchez-Bayona, Rodrigo; de la Cruz, Susana; de la Hoya, Miguel; Galván, Patricia; Sanfeliu, Esther; Gonzalez-Farre, Blanca; Sirenko, Valeria; Blanch-Torras, Aura; Canes, Jordi; Masanas, Helena; Olmos, Rosa; Forns, Margarita; Prat, Aleix; Casas, Ana; Pascual, Tomás; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos III
BACKGROUND: Metastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients' outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems. TRIAL DESIGN: After self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient's medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment. CLINICAL TRIAL REGISTRATION: www.soltihope.com, identifier NCT04497285.
GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
(Nature Publishing Group, 2023-05) Pairo-Castineira, Erola; Rawlik, Konrad; Bretherick, Andrew D; Qi, Ting; Wu, Yang; Nassiri, Isar; McConkey, Glenn A; Zechner, Marie; Klaric, Lucija; Griffiths, Fiona; Oosthuyzen, Wilna; Kousathanas, Athanasios; Richmond, Anne; Millar, Jonathan; Russell, Clark D; Malinauskas, Tomas; Thwaites, Ryan; Morrice, Kirstie; Keating, Sean; Maslove, David; Nichol, Alistair; Semple, Malcolm G; Knight, Julian; Shankar-Hari, Manu; Summers, Charlotte; Hinds, Charles; Horby, Peter; Ling, Lowell; McAuley, Danny; Montgomery, Hugh; Openshaw, Peter J M; Begg, Colin; Walsh, Timothy; Tenesa, Albert; Flores, Carlos; Riancho, José A; Rojas-Martinez, Augusto; Lapunzina, Pablo; Yang, Jian; Ponting, Chris P; Wilson, James F; Vitart, Veronique; Abedalthagafi, Malak; Luchessi, Andre D; Parra, Esteban J; Cruz, Raquel; Carracedo, Angel; Fawkes, Angie; Murphy, Lee; Rowan, Kathy; Pereira, Alexandre C; Law, Andy; Fairfax, Benjamin; Hendry, Sara Clohisey; Baillie, J Kenneth; Sepsis Research (the Fiona Elizabeth Agnew Trust); Intensive Care Society; Wellcome Trust; UK Research and Innovation; Department of Health and Social Care (DHSC); BBSRC Institute Program Support Grant; Edinburgh Clinical Academic Track (ECAT) programm; Health Data Research UK; RCUK Innovation Fellowship from the National Productivity Investment Fund; Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Fundacion Amancio Ortega; Fundación Canaria Instituto de Investigación Sanitaria de Canarias; Centro National de Genotipado (CEGEN); Centro de Supercomputacion de Galicia (CESGA); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ)
Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).
Genome-wide Association Study of Bladder Cancer Reveals New Biological and Translational Insights
(Elsevier, 2023-07) Koutros, Stella; Kiemeney, Lambertus A; Pal Choudhury, Parichoy; Milne, Roger L; Lopez de Maturana, Evangelina; Ye, Yuanqing; Joseph, Vijai; Florez-Vargas, Oscar; Dyrskjøt, Lars; Figueroa, Jonine; Dutta, Diptavo; Giles, Graham G; Hildebrandt, Michelle A T; Offit, Kenneth; Kogevinas, Manolis; Weiderpass, Elisabete; McCullough, Marjorie L; Freedman, Neal D; Albanes, Demetrius; Kooperberg, Charles; Cortessis, Victoria K; Karagas, Margaret R; Johnson, Alison; Schwenn, Molly R; Baris, Dalsu; Furberg, Helena; Bajorin, Dean F; Cussenot, Olivier; Cancel-Tassin, Geraldine; Benhamou, Simone; Kraft, Peter; Porru, Stefano; Carta, Angela; Bishop, Timothy; Southey, Melissa C; Matullo, Giuseppe; Fletcher, Tony; Kumar, Rajiv; Taylor, Jack A; Lamy, Philippe; Prip, Frederik; Kalisz, Mark; Weinstein, Stephanie J; Hengstler, Jan G; Selinski, Silvia; Harland, Mark; Teo, Mark; Kiltie, Anne E; Tardón, Adonina; Serra, Consol; Carrato, Alfredo; García-Closas, Reina; Lloreta, Josep; Schned, Alan; Lenz, Petra; Riboli, Elio; Brennan, Paul; Tjønneland, Anne; Otto, Thomas; Ovsiannikov, Daniel; Volkert, Frank; Vermeulen, Sita H; Aben, Katja K; Galesloot, Tessel E; Turman, Constance; De Vivo, Immaculata; Giovannucci, Edward; Hunter, David J; Hohensee, Chancellor; Hunt, Rebecca; Patel, Alpa V; Huang, Wen-Yi; Thorleifsson, Gudmar; Gago-Dominguez, Manuela; Amiano, Pilar; Golka, Klaus; Stern, Mariana C; Yan, Wusheng; Liu, Jia; Li, Shengchao Alfred; Katta, Shilpa; Hutchinson, Amy; Hicks, Belynda; Wheeler, William A; Purdue, Mark P; McGlynn, Katherine A; Kitahara, Cari M; Haiman, Christopher A; Greene, Mark H; Rafnar, Thorunn; Chatterjee, Nilanjan; Chanock, Stephen J; Wu, Xifeng; Real, Francisco X; Silverman, Debra T; Garcia-Closas, Montserrat; Stefansson, Kari; Prokunina-Olsson, Ludmila; Malats, Nuria; Rothman, Nathaniel; NIH - National Cancer Institute (NCI) (Estados Unidos); Radboud University Medical Center; Asociación Española Contra el Cáncer; Instituto de Salud Carlos III; Canadian Institutes of Health Research (CIHR) Cancer Council Victoria; National Health and Medical Research Council (Australia)
Background: Genomic regions identified by genome-wide association studies (GWAS) for bladder cancer risk provide new insights into etiology. Objective: To identify new susceptibility variants for bladder cancer in a meta-analysis of new and existing genome-wide genotype data. Design, setting, and participants: Data from 32 studies that includes 13,790 bladder cancer cases and 343,502 controls of European ancestry were used for meta-analysis. Outcome measurements and statistical analyses: Log-additive associations of genetic variants were assessed using logistic regression models. A fixed-effects model was used for meta-analysis of the results. Stratified analyses were conducted to evaluate effect modification by sex and smoking status. A polygenic risk score (PRS) was generated on the basis of known and novel susceptibility variants and tested for interaction with smoking. Results and limitations: Multiple novel bladder cancer susceptibility loci (6p.22.3, 7q36.3, 8q21.13, 9p21.3, 10q22.1, 19q13.33) as well as improved signals in three known regions (4p16.3, 5p15.33, 11p15.5) were identified, bringing the number of independent markers at genome-wide significance (p < 5 × 10-8) to 24. The 4p16.3 (FGFR3/TACC3) locus was associated with a stronger risk for women than for men (p-interaction = 0.002). Bladder cancer risk was increased by interactions between smoking status and genetic variants at 8p22 (NAT2; multiplicative p value for interaction [pM-I] = 0.004), 8q21.13 (PAG1; pM-I = 0.01), and 9p21.3 (LOC107987026/MTAP/CDKN2A; pM-I = 0.02). The PRS based on the 24 independent GWAS markers (odds ratio per standard deviation increase 1.49, 95% confidence interval 1.44-1.53), which also showed comparable results in two prospective cohorts (UK Biobank, PLCO trial), revealed an approximately fourfold difference in the lifetime risk of bladder cancer according to the PRS (e.g., 1st vs 10th decile) for both smokers and nonsmokers. Conclusions: We report novel loci associated with risk of bladder cancer that provide clues to its biological underpinnings. Using 24 independent markers, we constructed a PRS to stratify lifetime risk. The PRS combined with smoking history, and other established risk factors, has the potential to inform future screening efforts for bladder cancer. Patient summary: We identified new genetic markers that provide biological insights into the genetic causes of bladder cancer. These genetic risk factors combined with lifestyle risk factors, such as smoking, may inform future preventive and screening strategies for bladder cancer.
Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain
(Nature Publishing Group, 2020-02-18) Cullell, Natalia; Carrera, Caty; Muino, Elena; Torres-Aguila, Nuria-Paz; Carcel-Marquez, Jara; Gonzalez-Sanchez, Jonathan; Gallego-Fabrega, Cristina; Molina, Jessica; Besora, Sarah; Sotoca, Javier; Buongiorno, Maria-Teresa; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; de Torres-Chacon, Reyes; Montaner, Joan; Mancha, Fernando; Cabezas, Juan A; Marti-Fabregas, Joan; Prats-Sanchez, Luis; Camps-Renom, Pol; Purroy, Francisco; Cambray, Serafi; Freijo Guerrero, Maria del Mar; Vives-Bauza, Cristofol; Tur Campos, Silvia; Font, Maria-Angels; Lopez-Cancio, Elena; Hernandez-Perez, Maria; Obach, Victor; Calleja, Ana; Arenillas, Juan Francisco; Rodriguez-Yanez, Manuel; Castillo, Jose; Sobrino, Tomas; Fernandez-Cadenas, Israel; Krupinski, Jerzy
Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p<0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p<0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.
Detection of MET Alterations Using Cell Free DNA and Circulating Tumor Cells from Cancer Patients
(Multidisciplinary Digital Publishing Institute (MDPI), 2020-02) Mondelo-Macia, Patricia; Rodriguez-Lopez, Carmela; Valina, Laura; Aguin, Santiago; Leon-Mateos, Luis; Garcia-Gonzalez, Jorge; Abalo, Alicia; Rapado-Gonzalez, Oscar; Suarez-Cunqueiro, Mercedes; Diaz-Lagares, Angel; Curiel, Teresa; Calabuig-Farinas, Silvia; Azkárate, Aitor; Obrador-Hevia, Antonia; Abdulkader, Ihab; Muinelo-Romay, Laura; Diaz-Pena, Roberto; Lopez-Lopez, Rafael
MET alterations may provide a potential biomarker to evaluate patients who will benefit from treatment with MET inhibitors. Therefore, the purpose of the present study is to investigate the utility of a liquid biopsy-based strategy to assess MET alterations in cancer patients. We analyzed MET amplification in circulating free DNA (cfDNA) from 174 patients with cancer and 49 healthy controls and demonstrated the accuracy of the analysis to detect its alteration in patients. Importantly, a significant correlation between cfDNA concentration and MET copy number (CN) in cancer patients (r = 0.57, p <10(-10)) was determined. Furthermore, we evaluated two approaches to detect the presence of MET on circulating tumor cells (CTCs), using the CellSearch((R)) and Parsortix systems and monitored patients under anti-EGFR treatment (n = 30) combining both cfDNA and CTCs analyses. This follow-up provides evidence for the potential of MET CN assessment when patients develop resistance to anti-EGFR therapy and a significant association between the presence of CTCs MET+ and the Overall Survival (OS) in head and neck cancer patients (P = 0.05; HR = 6.66). In conclusion, we develop specific and noninvasive assays to monitor MET status in cfDNA/CTCs and demonstrate the utility of plasma MET CN determination as a biomarker for monitoring the appearance of resistance to anti-EGFR therapy.
Surveillance of invasive pneumococcal disease in Spain exploring the impact of the COVID-19 pandemic (2019-2023)
(Elsevier, 2024-06-19) Perez-Garcia, Covadonga; Sempere, Julio; Miguel, Sara de; Hita, Samantha; Úbeda, Aída; Vidal-Alcántara, Erick Joan; Llorente, Joaquín; Limia, Aurora; Gil-de-Miguel, Ángel; Sanz, Juan Carlos; Martinón-Torres, Federico; Ardanuy, Carmen; Domenech Lucas, Mirian; Yuste, Jose Enrique; Ministerio de Ciencia e Innovación (España); Instituto de Salud Carlos III; Merck, Sharp & Dohme
Objectives: Dynamic trends of invasive pneumococcal disease (IPD) including the evolution of prevalent serotypes are very useful to evaluate the impact of current and future pneumococcal conjugate vaccines (PCVs) and the rise of non-vaccine serotypes. In this study, we include epidemiological patterns of S. pneumoniae before and after COVID-19 pandemic. Methods: We characterized all national IPD isolates from children and adults received at the Spanish Pneumococcal Reference Laboratory during 2019-2023. Results: In the first pandemic year 2020, we found a general reduction in IPD cases across all age groups, followed by a partial resurgence in children in 2021 but not in adults. By 2022, IPD cases in children had returned to pre-pandemic levels, and partially in adults. In 2023, IPD rates surpassed those of the last pre-pandemic year. Notably, the emergence of serotype 3 is of significant concern, becoming the leading cause of IPD in both pediatric and adult populations over the last two years (2022-2023). Increase of serotype 4 in young adults occurred in the last epidemiological years. Conclusions: The COVID-19 pandemic led to a temporary decline in all IPD cases during 2020 attributable to non-pharmaceutical interventions followed by a subsequent rise. Employing PCVs with broader coverage and/or enhanced immunogenicity may be critical to mitigate the marked increase of IPD.
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
(Nature Publishing Group, 2024-02-19) Pérez-Jurado, Luis A; Cáceres, Alejandro; Balagué-Dobón, Laura; Esko, Tonu; López de Heredia, Miguel; Quintela, Inés; Cruz, Raquel; Lapunzina, Pablo; Carracedo, Ángel; SCOURGE Cohort Group; González, Juan R; Meijome, Xose M.; Brochado-Kith, Oscar; Ceballos, Francisco C; Fernandez-Rodriguez, Amanda; Jimenez-Sousa, Maria Angeles; Martin-Vicente, Maria; Resino, Salvador; Virseda-Berdices, Ana; Government of Catalonia (España); Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España); Ministerio de Ciencia e Innovación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Estonian Research Council; Instituto de Salud Carlos III; Amancio Ortega Foundation; Banco Santander
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people.
Respiratory Syncytial Virus Vaccination Recommendations for Adults Aged 60 Years and Older: The NeumoExperts Prevention Group Position Paper
(Elsevier, 2024-03) Redondo, Esther; Rivero-Calle, Irene; Mascarós, Enrique; Ocaña, Daniel; Jimeno, Isabel; Gil, Ángel; Linares, Manuel; Onieva-García, María Ángeles; González-Romo, Fernando; Yuste, Jose Enrique; Martinón-Torres, Federico; Centro de Investigación Biomédica en Red - CIBERES (Enfermedades Respiratorias); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Xunta de Galicia (España)
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in adults, particularly older adults and those with underlying medical conditions. Vaccination has emerged as a potential key strategy to prevent RSV-related morbidity and mortality. This Neumoexperts Prevention (NEP) Group scientific paper aims to provide an evidence-based positioning and RSV vaccination recommendations for adult patients. We review the current literature on RSV burden and vaccine development and availability, emphasising the importance of vaccination in the adult population. According to our interpretation of the data, RSV vaccines should be part of the adult immunisation programme, and an age-based strategy should be preferred over targeting high-risk groups. The effectiveness and efficiency of this practice will depend on the duration of protection and the need for annual or more spaced doses. Our recommendations should help healthcare professionals formulate guidelines and implement effective vaccination programmes for adult patients at risk of RSV infection now that specific vaccines are available.
A second update on mapping the human genetic architecture of COVID-19
(Nature Publishing Group, 2023-09) COVID-19 Host Genetics Initiative; Fernandez-Rodriguez, Amanda; Jimenez-Sousa, Maria Angeles; Ceballos, Francisco C; Resino, Salvador
Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis
(BioMed Central (BMC), 2014-03-11) M�rquez, Ana; Ferreiro-Iglesias, Aida; D�vila-Fajardo, Cristina L; Montes, Ariana; Pascual-Salcedo, Dora; Perez-Pampin, Eva; Moreno-Ramos, Manuel J; Garc�a-Portales, Rosa; Navarro, Federico; Moreira, Virginia; Magro, C�sar; Caliz, Rafael; Ferrer, Miguel Angel; Alegre-Sancho, Juan Jos�; Joven, Beatriz; Carreira, Patricia; Balsa, Alejandro; Vasilopoulos, Yiannis; Sarafidou, Theologia; Cabeza-Barrera, Jos�; Narvaez, Javier; Raya, Enrique; Ca�ete, Juan D; Fern�ndez-Nebro, Antonio; Ord��ez, Mar�a del Carmen; de la Serna, Arturo R; Magallares, Berta; Gomez-Reino, Juan J; Gonz�lez, Antonio; Mart�n, Javier; [M�rquez,A; D�vila-Fajardo,CL; Mart�n,J] Instituto de Parasitolog�a y Biomedicina L�pez-Neyra, Consejo Superior de Investigaciones Cient�ficas (CSIC), Armilla, Granada, Spain. [Ferreiro-Iglesias,A; Montes,A; Perez-Pampin,E; Gomez-Reino,JJ; Gonz�lez,A] Laboratorio Investigaci�n 10 and Rheumatology Unit, Instituto de Investigaci�n Sanitaria-Hospital Cl�nico Universitario de Santiago, Santiago de Compostela, Spain. [D�vila-Fajardo,CL; Cabeza-Barrera,J] Department of Clinical Pharmacy, Hospital Universitario San Cecilio, Instituto de Investigaci�n Biosanitaria de Granada (IBIG), Granada, Spain. [Pascual-Salcedo,D] Department of Immunology, Instituto de Investigaci�n Sanitaria del Hospital Universitario La Paz (IdiPAZ),Research Network in Inflammation and Rheumatic Diseases (RIER), Hospital La Paz, Madrid, Spain. [Moreno-Ramos,MJ] Department of Rheumatology, Hospital Virgen de la Arrixaca,El Palmar Murcia, Spain. [Garc�a-Portales,R] Department of Rheumatology, Hospital Virgen de la Victoria, Campus de Teatinos M�laga, Spain. [Navarro,F; Moreira,V] Rheumatology Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Magro,C] Department of Rheumatology, Hospital Cl�nico San Cecilio, Granada, Spain. [Caliz,R; Ferrer,MA] Rheumatology Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Alegre-Sancho,JJ] Department of Rheumatology, Hospital Doctor Peset, Valencia, Spain. [Joven,B; Carreira,P] Department of Rheumatology, Instituto de Investigaci�n I+12, Research Network in Inflammation and Rheumatic Diseases (RIER), Hospital Universitario 12 de Octubre, Madrid, Spain. [Balsa,A] Department of Rheumatology, Instituto de Investigaci�n Sanitaria del Hospital Universitario La Paz (IdiPAZ), Research Network in Inflammation and Rheumatic Diseases (RIER), Madrid, Spain. [Vasilopoulos,Y; Sarafidou,T] Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece. [Narvaez,J] Rheumatology Department, Hospital Universitario de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. [Ca�ete,JD] Rheumatology Department, Hospital Clinic and Institut d�Investigacions Biom�diques August Pi I Sunyer (IDIBAPS), Barcelona, Spain. [Fern�ndez-Nebro,A; Ord��ez,MC] Unidad de Gesti�n Cl�nica (UGC) Rheumatology, Hospital Regional Universitario de M�laga, Instituto de Investigaci�n Biom�dica de M�laga (IBIMA), M�laga, Spain. [de la Serna,AR; Magallares,B] Rheumatology Unit, Hospital Santa Creu e San Pau, Barcelona, Spain. [Gomez-Reino,JJ] Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain.
Introduction: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. Methods: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. Results: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. Conclusion: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.
Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study
(2020-08-12) Pablos, Jose L; Galindo, María; Carmona, Loreto; Lledó, Ana; Retuerto, Miriam; Blanco, Ricardo; Gonzalez-Gay, Miguel A; Martinez-Lopez, David; Castrejon, Isabel; Álvaro-Gracia, José M; Fernández Fernández, David; Mera-Varela, Antonio; Manrique-Arija, Sara; Mena-Vázquez, Natalia; Fernandez-Nebro, Antonio; RIER Investigators Group
Objectives: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. Methods: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. Results: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). Conclusion: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.
Identification of Clinical Variants beyond the Exome in Inborn Errors of Metabolism.
(2022-10-25) Soriano-Sexto, Alejandro; Gallego, Diana; Leal, Fátima; Castejón-Fernández, Natalia; Navarrete, Rosa; Alcaide, Patricia; Couce, María L; Martín-Hernández, Elena; Quijada-Fraile, Pilar; Peña-Quintana, Luis; Yahyaoui, Raquel; Correcher, Patricia; Ugarte, Magdalena; Rodríguez-Pombo, Pilar; Pérez, Belén
Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency. Eight novel variants in six genes were identified: six (four of them deep intronic) located in GALE, IDUA, PTS, ASS1 and OTC, all affecting the splicing process, and two located in the promoters of IDUA and PTS, thus affecting these genes' expression. All the new variants were subjected to functional analysis to verify their pathogenic effects. This work underscores how the combination of different omics technologies and functional analysis can solve elusive cases in clinical practice.
Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain.
(2022-08-28) Martín-Hernández, Elena; Quijada-Fraile, Pilar; Correcher, Patricia; Meavilla, Silvia; Sánchez-Pintos, Paula; de Las Heras Montero, Javier; Blasco-Alonso, Javier; Dougherty, Lucy; Marquez, Ana; Peña-Quintana, Luis; Cañedo, Elvira; García-Jimenez, María Concepción; Moreno Lozano, Pedro Juan; Murray Hurtado, Mercedes; Camprodon Gómez, María; Barrio-Carreras, Delia; de Los Santos, Mariela; Del Toro, Mireia; Couce, María L; Vitoria Miñana, Isidro; Morales Conejo, Montserrat; Bellusci, Marcello
Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 ± 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 ± 102.1 mg/kg/day dose, compared to 262.6 ± 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 ± 59 days), a statistically significant reduction in ammonia (from 40.2 ± 17.3 to 32.6 ± 13.9 μmol/L, p
Thirty-second sit-to-stand test as an alternative for estimating peak oxygen uptake and 6-min walking distance in women with breast cancer: a cross-sectional study.
(2022-07-11) Díaz-Balboa, Estíbaliz; González-Salvado, Violeta; Rodríguez-Romero, Beatriz; Martínez-Monzonís, Amparo; Pedreira-Pérez, Milagros; Cuesta-Vargas, Antonio I; López-López, Rafael; González-Juanatey, José R; Pena-Gil, Carlos
To determine whether the 30-s sit-to-stand (30STS) test can be a valid tool for estimating and stratifying peak oxygen uptake (VO2peak) and 6-min walking distance (6MWD) in women with breast cancer. This cross-sectional study uses data from the ONCORE randomized controlled trial, including 120 women aged 18-70 years with early-stage breast cancer under treatment with anthracycline and/or anti-HER2 antibodies. Participant characteristics were collected at baseline and pooled data from functional assessment (30STS test, relative and absolute VO2peak, and 6MWD) were collected at baseline and post-intervention (comprehensive cardio-oncology rehabilitation program vs. usual care). Bivariate correlations and multivariate linear regression analyses were performed to study the relationship between functional test variables. The number of repetitions in the 30STS test showed (i) a moderate correlation with relative VO2peak (ml/kg/min) (r = 0.419; p The 30STS test was found to be a useful tool to estimate VO2peak and/or 6MWD in women with early-stage breast cancer. Its use may facilitate the assessment and stratification of functional capacity in this population for the implementation of therapeutic exercise programs if cardiopulmonary exercise testing (CPET) or 6MWT are not available. ClinicalTrials.gov Identifier: NCT03964142. Registered on 28 May 2019. Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT03964142.
Striatal synaptic bioenergetic and autophagic decline in premotor experimental parkinsonism.
(2022) Merino-Galán, Leyre; Jimenez-Urbieta, Haritz; Zamarbide, Marta; Rodríguez-Chinchilla, Tatiana; Belloso-Iguerategui, Arantzazu; Santamaria, Enrique; Fernández-Irigoyen, Joaquín; Aiastui, Ana; Doudnikoff, Evelyne; Bézard, Erwan; Ouro, Alberto; Knafo, Shira; Gago, Belén; Quiroga-Varela, Ana; Rodríguez-Oroz, María Cruz
Synaptic impairment might precede neuronal degeneration in Parkinson's disease. However, the intimate mechanisms altering synaptic function by the accumulation of presynaptic α-synuclein in striatal dopaminergic terminals before dopaminergic death occurs, have not been elucidated. Our aim is to unravel the sequence of synaptic functional and structural changes preceding symptomatic dopaminergic cell death. As such, we evaluated the temporal sequence of functional and structural changes at striatal synapses before parkinsonian motor features appear in a rat model of progressive dopaminergic death induced by overexpression of the human mutated A53T α-synuclein in the substantia nigra pars compacta, a protein transported to these synapses. Sequential window acquisition of all theoretical mass spectra proteomics identified deregulated proteins involved first in energy metabolism and later, in vesicle cycling and autophagy. After protein deregulation and when α-synuclein accumulated at striatal synapses, alterations to mitochondrial bioenergetics were observed using a Seahorse XF96 analyser. Sustained dysfunctional mitochondrial bioenergetics was followed by a decrease in the number of dopaminergic terminals, morphological and ultrastructural alterations, and an abnormal accumulation of autophagic/endocytic vesicles inside the remaining dopaminergic fibres was evident by electron microscopy. The total mitochondrial population remained unchanged whereas the number of ultrastructurally damaged mitochondria increases as the pathological process evolved. We also observed ultrastructural signs of plasticity within glutamatergic synapses before the expression of motor abnormalities, such as a reduction in axospinous synapses and an increase in perforated postsynaptic densities. Overall, we found that a synaptic energetic failure and accumulation of dysfunctional organelles occur sequentially at the dopaminergic terminals as the earliest events preceding structural changes and cell death. We also identify key proteins involved in these earliest functional abnormalities that may be modulated and serve as therapeutic targets to counterbalance the degeneration of dopaminergic cells to delay or prevent the development of Parkinson's disease.
CKD: The burden of disease invisible to research funders.
(2021-11-17) AIRG-E, EKPF, ALCER, FRIAT, REDINREN, RICORS2040, SENEFRO; SET, ONT
The uptake of the current concept of chronic kidney disease (CKD) by the public, physicians and health authorities is low. Physicians still mix up CKD with chronic kidney insufficiency or failure. In a recent manuscript, only 23% of participants in a cohort of persons with CKD had been diagnosed by their physicians as having CKD while 29% has a diagnosis of cancer and 82% had a diagnosis of hypertension. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. A prevalent view is that for those in whom kidneys fail, the problem is "solved" by dialysis or kidney transplantation. However, the main burden of CKD is accelerated aging and all-cause and cardiovascular premature death. CKD is the most prevalent risk factor for lethal COVID-19 and the factor that most increases the risk of death in COVID-19, after old age. Moreover, men and women undergoing KRT still have an annual mortality which is 10-100-fold higher than similar age peers, and life expectancy is shortened by around 40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth global cause of death by 2040 and the second cause of death in Spain before the end of the century, a time when 1 in 4 Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded CIBER network research structure in Spain. Leading Spanish kidney researchers grouped in the kidney collaborative research network REDINREN have now applied for the RICORS call of collaborative research in Spain with the support of the Spanish Society of Nephrology, ALCER and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true. However, only the highest level of research funding through the CIBER will allow to adequately address the issue before it is too late.
Early Clinical Experience with Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: The ROS Study
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-09-08) García-Alfonso, Pilar; Muñoz, Andrés; Jiménez-Castro, Jerónimo; Jiménez-Fonseca, Paula; Pericay, Carles; Longo-Muñoz, Federico; Reyna-Fortes, Carmen; Argilés-Martínez, Guillem; González-Astorga, Beatriz; Gómez-Reina, María José; Ruiz-Casado, Ana; Rodríguez-Salas, Nuria; López-López, Rafael; Carmona-Bayonas, Alberto; Conde-Herrero, Verónica; Aranda, Enrique; [García-Alfonso,P; Muñoz,A] Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. [Jiménez-Castro,J] Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Seville, Spain. [Jiménez-Fonseca,P] Department of Medical Oncology, Hospital Universitario Central de Asturias, ISPA, Oviedo, Spain. [Pericay,C] Department of Medical Oncology, Hospital Universitari Parc Taulí, Sabadell, Spain. [Longo-Muñoz,F] Department of Medical Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain. [Reyna-Fortes,C] Department of Medical Oncology, UGC Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain. [Argilés-Martínez,G] Department of Medical Oncology, Hospital Universitari Vall d’Hebrón, Barcelona, Spain. [González-Astorga,B] Department of Medical Oncology, Hospital Universitario Clínico San Cecilio, Granada, Spain. [Gómez-Reina,MJ] Department of Medical Oncology, Hospital Universitario Puerta del Mar, Cádiz, Spain. [Ruiz-Casado,A] Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain. [Rodríguez-Salas,N] Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC, Madrid, Spain. [López-López,R] Translational Medical Oncology Group, Department of Medical Oncology, Hospital Clínico Universitario e Instituto de Investigación Sanitaria (IDIS), CIBERONC, Facultad de Medicina de la Universidad de Santiago de Compostela, Santiago de Compostela, Spain. [Carmona-Bayonas,A] Department of Medical Oncology, Hospital General Universitario Morales Meseguer, Murcia, Spain. [Conde-Herrero,V] Department of Medical Oncology, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Aranda,E] Department of Medical Oncology, Hospital Universitario Reina Sofía, IMIBIC, Universidad de Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain.
Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.

Browse

Recent Submissions