SAS - Hospital Universitario Regional de Málaga

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  • Publication
    Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study.
    (2022-05-25) White, Helen E; Salmon, Matthew; Albano, Francesco; Andersen, Christina Søs Auður; Balabanov, Stefan; Balatzenko, Gueorgui; Barbany, Gisela; Cayuela, Jean-Michel; Cerveira, Nuno; Cochaux, Pascale; Colomer, Dolors; Coriu, Daniel; Diamond, Joana; Dietz, Christian; Dulucq, Stéphanie; Engvall, Marie; Franke, Georg N; Gineikiene-Valentine, Egle; Gniot, Michal; Gómez-Casares, María Teresa; Gottardi, Enrico; Hayden, Chloe; Hayette, Sandrine; Hedblom, Andreas; Ilea, Anca; Izzo, Barbara; Jiménez-Velasco, Antonio; Jurcek, Tomas; Kairisto, Veli; Langabeer, Stephen E; Lion, Thomas; Meggyesi, Nora; Mešanović, Semir; Mihok, Luboslav; Mitterbauer-Hohendanner, Gerlinde; Moeckel, Sylvia; Naumann, Nicole; Nibourel, Olivier; Oppliger Leibundgut, Elisabeth; Panayiotidis, Panayiotis; Podgornik, Helena; Pott, Christiane; Rapado, Inmaculada; Rose, Susan J; Schäfer, Vivien; Touloumenidou, Tasoula; Veigaard, Christopher; Venniker-Punt, Bianca; Venturi, Claudia; Vigneri, Paolo; Vorkinn, Ingvild; Wilkinson, Elizabeth; Zadro, Renata; Zawada, Magdalena; Zizkova, Hana; Müller, Martin C; Saussele, Susanne; Ernst, Thomas; Machova Polakova, Katerina; Hochhaus, Andreas; Cross, Nicholas C P
    Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1IS and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.
  • Publication
    Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort Di@bet.es study.
    (2022-08-20) Lago-Sampedro, Ana; Lhamyani, Said; Valdés, Sergio; Colomo, Natalia; Maldonado-Araque, Cristina; González-Molero, Inmaculada; Doulatram-Gamgaram, Viyey; Delgado, Elias; Chaves, Felipe J; Castaño, Luis; Calle-Pascual, Alfonso; Franch-Nadal, Josep; Rojo-Martínez, Gemma; García-Serrano, Sara; García-Escobar, Eva
    Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria. A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category. Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables.
  • Publication
    Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for "Diabesity".
    (2022-03-29) Decara, Juan M; Vázquez-Villa, Henar; Brea, José; Alonso, Mónica; Srivastava, Raj Kamal; Orio, Laura; Alén, Francisco; Suárez, Juan; Baixeras, Elena; García-Cárceles, Javier; Escobar-Peña, Andrea; Lutz, Beat; Rodríguez, Ramón; Codesido, Eva; Garcia-Ladona, F Javier; Bennett, Teresa A; Ballesteros, Juan A; Cruces, Jacobo; Loza, María I; Benhamú, Bellinda; Rodríguez de Fonseca, Fernando; López-Rodríguez, María L
    Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small molecules acting as positive allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4-{[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-molecule PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.
  • Publication
    Shared Clavulanate and Tazobactam Antigenic Determinants Activate T-Cells from Hypersensitive Patients.
    (2022-09-22) Ariza, Adriana; Jaruthamsophon, Kanoot; Meng, Xiaoli; Labella, Marina; Adair, Kareena; Tailor, Arun; Sukasem, Chonlaphat; Whitaker, Paul; Peckham, Daniel; Pirmohamed, Munir; Torres, María José; Naisbitt, Dean John
    β-Lactamase inhibitors such as clavulanic acid and tazobactam were developed to overcome β-lactam antibiotic resistance. Hypersensitivity reactions to these drugs have not been studied in detail, and the antigenic determinants that activate T-cells have not been defined. The objectives of this study were to (i) characterize clavulanate- and tazobactam-responsive T-cells from hypersensitive patients, (ii) explore clavulanate and tazobactam T-cell crossreactivity, and (iii) define the antigenic determinants that contribute to T-cell reactivity. Antigen specificity, pathways of T-cell activation, and crossreactivity with clavulanate- and tazobactam-specific T-cell clones were assessed by proliferation and cytokine release assays. Antigenic determinants were analyzed by mass spectrometry-based proteomics methods. Clavulanate- and tazobactam-responsive CD4+ T-cell clones were stimulated to proliferate and secrete IFN-γ in an MHC class II-restricted and dose-dependent manner. T-cell activation with clavulanate- and tazobactam was dependent on antigen presenting cells because their fixation prevented the T-cell response. Strong crossreactivity was observed between clavulanate- and tazobactam-T-cells; however, neither drug activated β-lactam antibiotic-responsive T-cells. Mass spectrometric analysis revealed that both compounds form multiple antigenic determinants with lysine residues on proteins, including an overlapping aldehyde and hydrated aldehyde adduct with mass additions of 70 and 88 Da, respectively. Collectively, these data show that although clavulanate and tazobactam are structurally distinct, the antigenic determinants formed by both drugs overlap, which explains the observed T-cell cross-reactivity.
  • Publication
    Molecular epidemiology of paediatric invasive pneumococcal disease in Andalusia, Spain.
    (2022-08-22) de Felipe, Beatriz; Obando Pacheco, Pablo; Carazo Gallego, Begoña; López Martín, David; Santos Pérez, Juan Luis; González Jiménez, Yolanda; Muñoz Vilches, María José; Cardelo Autero, Nerea; González Galán, Verónica; Morón, Francisco José; Cordero Varela, Juan Antonio; Torres Sánchez, María José; Medina Claros, Antonio; Moreno Pérez, David; Obando, Ignacio
    This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged
  • Publication
    EEG abnormalities and clinical phenotypes in pre-school children with autism spectrum disorder.
    (2022-03-15) Romero-González, Marina; Navas-Sánchez, Patricia; Marín-Gámez, Ester; Barbancho-Fernández, Miguel Angel; Fernández-Sánchez, Victoria Eugenia; Lara-Muñoz, José Pablo; Guzmán-Parra, José
    Abnormalities on electroencephalography (EEG) results have been reported in a high percentage of children with Autism Spectrum Disorder (ASD). The purpose of this study was to explore the prevalence of EEG abnormalities in a clinical population of pre-school children with Autism Spectrum Disorder and the differences in terms of the following phenotypic characteristics: adaptive behavior, executive functioning, severity of Autism Spectrum Disorder core symptoms, and comorbidity symptoms. A cross-sectional analysis of 69 children who attended the Autism Spectrum Disorder early diagnosis program with electroencephalography and clinical diagnosis was performed. A battery of questionnaires was also made to parents to evaluate emotions, behavior, and functional skills for daily living. Out of 69 pre-school children with Autism Spectrum Disorder, twenty nine (42%) had abnormalities in electroencephalography results. The group with abnormal epileptiform electroencephalography exhibited more impairment in executive functioning and social-relationship coexisting symptoms. The presence of an abnormal epileptiform electroencephalography in pre-school children with ASD already suggests a worse development in clinical features.
  • Publication
    Standards for practical intravenous rapid drug desensitization & delabeling: A WAO committee statement
    (Elsevier, 2022-05-31) Madrigal-Burgaleta, Ricardo; [Madrigal-Burgaleta, Ricardo] Ramon & Cajal Univ Hosp, Madrid, Spain; [Madrigal-Burgaleta, Ricardo] St Bartholomews Hosp, Resp Dept, Allergy & Severe Asthma Serv, Barts Hlth NHS Trust, 4th Floor,King George 5 Bldg, London EC1A 7BE, England
    Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe , might leave pa-tients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics , antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first -choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).
  • Publication
    Incidence of Lymphoproliferative Disorders After Renal Transplantation is Down, but the Poor Prognosis Remains. Multicenter 32-Year Cohort Study.
    (2022-11-12) Franco, Antonio; Hernández, Domingo; Más-Serrano, Patricio; Zarraga, Sofia; Sanchez, Ana; Crespo, Marta; Mazuecos, Auxiliadora; Diaz-Corte, Carmen; Rodriguez-Benot, Alberto; Jimenez, Carlos; Gonzalez, Yussel
    Post-transplant lymphoproliferative disorders represent rare but serious complications of kidney transplantation. We assessed incidence, risk factors, and outcomes in 21,546 patients receiving grafts between 1990 and 2009. Data were compared by decade of transplant (1990-1999 vs 2000-2009). Patients were followed for at least 12 years over a 32-year study period. In total, 331 patients (1.5%) developed PTLD: 189 of 9740 transplanted in the first decade, and 142 of 11,806 in the second. Incidence decreased significantly (19.40 vs12.02 cases/1000 patients; P Post-transplant lymphoproliferative disorders have a low and decreasing incidence, but the poor prognosis has not changed.
  • Publication
    Humoral Response After SARS-CoV-2 Vaccination in Kidney Transplant Recipients: Role of Immunosuppression Therapy.
    (2022-10-03) López, Verónica; Polo, Carolina; Schuldt, Ruben; Vázquez, Teresa; Gutiérrez-Vílchez, Elena; Moliz, Candela; Hernández, Domingo
    Messenger RNA vaccination against COVID-19 has been shown to produce an immune response with sufficient efficacy to prevent natural infection in immunocompetent recipients. However, the response in kidney transplant recipients is low. We aimed to evaluate the specific humoral response to SARS-CoV-2 after vaccination in a population of kidney transplant recipients and assess the main factors associated with a lack of response. We undertook a prospective study of 105 kidney transplant recipients and 11 recipients of a combined kidney-pancreas transplant. We analyzed immunoglobulin G and immunoglobulin M antibodies after the patients received their second and third doses of the messenger RNA 1273 (Moderna) or BNT162b1 (BionTECH-Pfizer) vaccinations between February and November 2021. Mean (SD) age of the 116 patients was 50 (16) years, and 65% were men. They had their transplants for 40 months (IQR, 15-123 months), with 14% undergoing retransplant and 11% sensitized. The maintenance immunosuppression regimen was steroids + tacrolimus + mycophenolate (MMF) in 68% of the patients and any combination with mammalian target of rapamycin inhibitor (mTORi) in 28%. A humoral response developed in 40% of the patients 6 weeks (IQR, 4-10 weeks) after receiving the second dose of the vaccine. Of the 67 patients with no response to the second dose, 51 had an analysis of the humoral response after the third dose, which was positive in 16 (31%). A total of 80% received the Moderna vaccine and 20% the BionTECH-Pfizer. No patient experienced major adverse effects after the vaccination. Factors associated with a lack of humoral response to the vaccine were recipient age (odds ratio [OR], 1.02; 95% CI, 1.001-1.05; P = .04), diabetes (OR, 2.8; 95% CI, 1.2-6.9; P = .02), and treatment with MMF (OR, 2.6; 95% CI, 1.08-6.8; P = .03). Treatment with mTORi was associated with a better response to vaccination (OR, 0.3; 95% CI, 0.1-0.9; P = .04). The humoral response to the COVID-19 vaccine in kidney transplant recipients is poor. Factors related with this lack of immunity are recipient age and diabetes, plus MMF therapy, whereas mTORi therapy was associated with a better response to vaccination.
  • Publication
    Enoxaparin versus dalteparin or tinzaparin in patients with cancer and venous thromboembolism: The RIETECAT study.
    (2022-06-03) Trujillo-Santos, Javier; Farge-Bancel, Dominique; Pedrajas, José María; Gómez-Cuervo, Covadonga; Ballaz, Aitor; Braester, Andrei; Mahé, Isabelle; Villalobos, Aurora; Porras, José Antonio; Monreal, Manuel; RIETE Investigators
    Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death. The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer. We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point. From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups. In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.
  • Publication
    Emerging noninvasive methylation biomarkers of cancer prognosis and drug response prediction.
    (2021-03-20) Oliver, Javier; Garcia-Aranda, Marilina; Chaves, Patricia; Alba, Emilio; Cobo-Dols, Manuel; Onieva, Juan Luis; Barragan, Isabel
    Cancer is the second leading cause of death worldwide being responsible for 9.6 million deaths in 2018. Epigenetic alterations are key in directing the aberrant expression of tumor-associated genes that drive cellular malignant transformation and cancer progression. Among epigenetic alterations, DNA methylation is the most deeply studied one in relation to environmental exposure. Tissue biopsies have traditionally been the main procedure by which a small sample of body tissue is excised to confirm cancer diagnosis or to indicate the primary site when cancer has spread. In contrast, the analysis of circulating tumor-derived material, or tumor circulome, by means of liquid biopsy of peripheral blood, urine, saliva or sputum is a noninvasive, fast and reproducible alternative to tissue biopsy. Recently, the assessment of epigenetic alterations such as DNA methylation and hydroxymethylation in circulating free DNA has been proved possible. These marks can be associated to prognosis and response to a variety of treatments including chemotherapy, hormonotherapy or immunotherapy. Epigenetic biomarkers may offer some advantages over RNA or genetic biomarkers given their stability in bodily fluids and their high tissue-specificity. While many challenges are still ahead, the unique advantages of these types of biomarkers is urging the scientific community to persevere in their clinical validation and integration into reliable prediction models. This review aims at recapitulating the emerging noninvasive DNA methylated biomarkers of importance for prediction of prognosis and drug response in cancer.
  • Publication
    Executive summary on the treatment of type 2 diabetes mellitus in elderly or frail individuals. 2022 update of the 2018 consensus document "Treatment of type 2 diabetes mellitus in the elderly".
    (2022-06-24) Gómez-Peralta, F; Carrasco-Sánchez, F J; Pérez, A; Escalada, J; Álvarez-Guisasola, F; Miranda-Fernández-Santos, C; Mediavilla-Bravo, J J; Gómez-Huelgas, R
    The population with type 2 DM (DM2) is highly heterogeneous, representing an important challenge for healthcare professionals. The therapeutic choice should be individualized, considering the functional status, frailty, the occurrence of comorbidities, and the preferences of patients and their caregivers. New evidence on the cardiovascular and renal protection of specific therapeutic groups and on the usefulness of new technologies for DM2 management, among other aspects, warrant an update of the consensus document on the DM2 in the elderly that was published in 2018.
  • Publication
    [Persistent COVID-19 syndrome. A narrative review].
    (2021-11-15) López-Sampalo, A; Bernal-López, M R; Gómez-Huelgas, R
    As the coronavirus-2019 disease (COVID-19) pandemic, caused by the infection with severe acute respiratory syndrome (SARS-CoV-2) coronavirus type 2, has progressed, persistent COVID-19 syndrome is an increasingly recognized problem on which a significant volume of medical literature is developing. Symptoms may be persistent or appear, after an asymptomatic period, weeks or months after the initial infection. The clinical picture is as markedly heterogeneous and multisystemic as in the acute phase, so multidisciplinary management is required. In addition, their appearance is not related to the severity of the initial infection, so they can affect both mild patients, even asymptomatic, and seriously ill patients who have required hospitalization. Although it can affect people of any age, it is more common in middle-aged women. The sequelae can generate a high impact on the quality of life, and in the work and social environment. The objective of this paper is to review persistent COVID-19 syndrome, to know its clinical manifestations and the strategies for the management and follow-up of these patients.
  • Publication
    [Derivation and validation of a risk score for admission to the Intensive Care Unit in patients with COVID-19].
    (2021-06-23) Ena, J; Segura-Heras, J V; Fonseca-Aizpuru, E M; López-Reboiro, M L; Gracia-Gutiérrez, A; Martín-Oterino, J A; Martín-Urda Diez-Canseco, A; Pérez-García, C; Ramos-Rincón, J M; Gómez-Huelgas, R; en nombre del grupo de trabajo SEMI-COVID-19
    This work aims to identify and validate a risk scale for admission to intensive care units (ICU) in hospitalized patients with coronavirus disease 2019 (COVID-19). We created a derivation rule and a validation rule for ICU admission using data from a national registry of a cohort of patients with confirmed SARS-CoV-2 infection who were admitted between March and August 2020 (n = 16,298). We analyzed the available demographic, clinical, radiological, and laboratory variables recorded at hospital admission. We evaluated the performance of the risk score by estimating the area under the receiver operating characteristic curve (AUROC). Using the β coefficients of the regression model, we developed a score (0 to 100 points) associated with ICU admission. The mean age of the patients was 67 years; 57% were men. A total of 1,420 (8.7%) patients were admitted to the ICU. The variables independently associated with ICU admission were age, dyspnea, Charlson Comorbidity Index score, neutrophil-to-lymphocyte ratio, lactate dehydrogenase levels, and presence of diffuse infiltrates on a chest X-ray. The model showed an AUROC of 0.780 (CI: 0.763-0.797) in the derivation cohort and an AUROC of 0.734 (CI: 0.708-0.761) in the validation cohort. A score of greater than 75 points was associated with a more than 30% probability of ICU admission while a score of less than 50 points reduced the likelihood of ICU admission to 15%. A simple prediction score was a useful tool for forecasting the probability of ICU admission with a high degree of precision.
  • Publication
    The Benefits of a Therapeutic Exercise and Educational Intervention Program on Central Sensitization Symptoms and Pain-Related Fear Avoidance in Breast Cancer Survivors.
    (2022-03-09) Gutiérrez-Sánchez, Daniel; Pajares-Hachero, Bella I; Trinidad-Fernández, Manuel; Escriche-Escuder, Adrian; Iglesias-Campos, Marcos; Bermejo-Pérez, María José; Alba-Conejo, Emilio; Roldán-Jiménez, Cristina; Cuesta-Vargas, Antonio
    Central sensitization symptoms and pain-related fear avoidance are two common problems in breast cancer survivors. Non-pharmacologic interventions such as therapeutic exercise and patient education can be effective in this population. This study aimed to: (1) analyze the benefits of a therapeutic exercise and educational program on central sensitization symptoms and pain-related fear avoidance in breast cancer survivors, and (2) explore the association between pain-related fear avoidance and central sensitization symptoms. A single group pre-post intervention study was conducted. Patients were recruited from the service of Medical Oncology of the University Clinical Hospital Virgen de la Victoria, in Málaga (Spain). The intervention consisted of a therapeutic exercise and educational program that lasted 12 weeks, twice a week, for 1 hour. Two instruments were used: the Spanish version of the Central Sensitization Inventory and the Spanish Fear Avoidance Components Scale. A total of 82 breast cancer survivors participated in the study. Pre-post change on Central Sensitization Inventory was statistically significant (p = .007). There was a trend towards a significant difference for the Spanish Fear Avoidance Components Scale (p = .062). There was a statistically significant correlation between pain-related fear avoidance and central sensitization symptoms (r = 0.536, p The current study has provided preliminary evidence on the benefits of this intervention in pain-related fear avoidance and central sensitization symptoms in breast cancer survivors. The Spanish version of the Central Sensitization Inventory and the Spanish Fear Avoidance Components Scale demonstrated responsiveness to change.
  • Publication
    Microbiota diversity in nonalcoholic fatty liver disease and in drug-induced liver injury.
    (2022-07-08) Rodriguez-Diaz, Cristina; Taminiau, Bernard; García-García, Alberto; Cueto, Alejandro; Robles-Díaz, Mercedes; Ortega-Alonso, Aida; Martín-Reyes, Flores; Daube, Georges; Sanabria-Cabrera, Judith; Jimenez-Perez, Miguel; Isabel Lucena, M; Andrade, Raúl J; García-Fuentes, Eduardo; García-Cortes, Miren
    The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liver fibrosis, and in DILI, and we identified the main associated bacterial metabolic pathways. In the NAFLD group, we found a decrease in Alistipes, Barnesiella, Eisenbergiella, Flavonifractor, Fusicatenibacter, Gemminger, Intestinimonas, Oscillibacter, Parasutterella, Saccharoferementans and Subdoligranulum abundances compared with those in both the DILI and control groups. Additionally, we detected an increase in Enterobacter, Klebsiella, Sarcina and Turicibacter abundances in NAFLD, with significant liver fibrosis, compared with those in NAFLD with no/mild liver fibrosis. The DILI group exhibited a lower microbial bacterial richness than the control group, and lower abundances of Acetobacteroides, Blautia, Caloramator, Coprococcus, Flavobacterium, Lachnospira, Natronincola, Oscillospira, Pseudobutyrivibrio, Shuttleworthia, Themicanus and Turicibacter compared with those in the NAFLD and control groups. We found seven bacterial metabolic pathways that were impaired only in DILI, most of which were associated with metabolic biosynthesis. In the NAFLD group, most of the differences in the bacterial metabolic pathways found in relation to those in the DILI and control groups were related to fatty acid and lipid biosynthesis. In conclusion, we identified a distinct bacterial profile with specific bacterial metabolic pathways for each type of liver disorder studied. These differences can provide further insight into the physiopathology and development of NAFLD and DILI.
  • Publication
    Genetic landscape of Segawa disease in Spain. Long-term treatment outcomes.
    (2021-11-25) Fernández-Ramos, Joaquín A; De la Torre-Aguilar, María José; Quintáns, Beatriz; Pérez-Navero, Juan Luis; Beyer, Katrin; López-Laso, Eduardo; Spanish Segawa Disease Research group
    In 2009, we described a possible founder effect of autosomal dominant Segawa disease in Córdoba (Spain) due to mutation c.265C>T (p. Q89*) in the GCH1 gene. We present a retrospective multicentre study aimed at improving our knowledge of Segawa disease in Spain and providing a detailed phenotypic-genotypic description of patients. Clinical-genetic information were obtained from standardized questionnaires that were completed by the neurologists attending children and/or adults from 16 Spanish hospitals. Eighty subjects belonging to 24 pedigrees had heterozygous mutations in GCH1. Seven genetic variants have been described only in our cohort of patients, 5 of which are novel mutations. Five families not previously described with p. Q89* were detected in Andalusia due to a possible founder effect. The median latency to diagnosis was 5 years (IQR 0-16). The most frequent signs and/or symptoms were lower limb dystonia (38/56, 67.8%, p = 0.008) and diurnal fluctuations (38/56, 67.8%, p = 0.008). Diurnal fluctuations were not present in the phenotypes other than dystonia. Fifty-three of 56 symptomatic patients were treated with a levodopa/decarboxylase inhibitor for (mean ± SD) 12.4 ± 8.12 years, with 81% at doses lower than 350 mg/day (≤5 mg/kg/d in children). Eleven of 53 (20%) patients had nonresponsive symptoms that affected daily life activities. Dyskinesias (4 subjects) were the most prominent adverse effects. This study identifies 5 novel mutations and supports the hypothesis of a founder effect of p. Q89* in Andalusia. New insights are provided for the phenotypes and long-term treatment responses, which may improve early recognition and therapeutic management.
  • Publication
    Delphi consensus on recommendations for the treatment of spinal muscular atrophy in Spain (RET-AME consensus).
    (2022-02-28) Pitarch Castellano, I; Cabrera-Serrano, M; Calvo Medina, R; Cattinari, M G; Espinosa García, S; Fernández-Ramos, J A; García Campos, O; Gómez-Andrés, D; Grimalt Calatayud, M A; Gutiérrez Martínez, A J; Ibáñez Albert, E; Kapetanovic García, S; Madruga-Garrido, M; Martínez-Moreno, M; Medina Cantillo, J; Melián Suárez, A I; Moreno Escribano, A; Munell, F; Nascimento Osorio, A; Pascual-Pascual, S I; Povedano, M; Santana Casiano, I M; Vázquez-Costa, J F
    Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by a biallelic mutation of the SMN1 gene, located on the long arm of chromosome 5, and predominantly affects the motor neurons of the anterior horn of the spinal cord, causing progressive muscle weakness and atrophy. The development of disease-modifying treatments is significantly changing the natural history of SMA, but uncertainty remains about which patients can benefit from these treatments and how that benefit should be measured. A group of experts specialised in neurology, neuropediatrics, and rehabilitation and representatives of the Spanish association of patients with SMA followed the Delphi method to reach a consensus on 5 issues related to the use of these new treatments: general aspects, treatment objectives, outcome assessment tools, requirements of the treating centres, and regulation of their use. Consensus was considered to be achieved when a response received at least 80% of votes. Treatment protocols are useful for regulating the use of high-impact medications and should guide treatment, but should be updated regularly to take into account the most recent evidence available, and their implementation should be assessed on an individual basis. Age, baseline functional status, and, in the case of children, the type of SMA and the number of copies of SMN2 are characteristics that should be considered when establishing therapeutic objectives, assessment tools, and the use of such treatments. The cost-effectiveness of these treatments in paediatric patients is mainly influenced by early treatment onset; therefore, the implementation of neonatal screening is recommended. The RET-AME consensus recommendations provide a frame of reference for the appropriate use of disease-modifying treatments in patients with SMA.
  • Publication
    FLAIR-hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) in a patient with Crohn's disease on anti-TNF treatment.
    (2021-07-19) Cabezudo-García, P; Vidal Denis, M; Ciano-Petersen, N L; Irigoyen-Oyarzábal, M V; Serrano-Castro, P J
  • Publication
    Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.
    (2020-01-25) Meca-Lallana, J E; Fernández-Prada, M; García Vázquez, E; Moreno Guillén, S; Otero Romero, S; Rus Hidalgo, M; Villar Guimerans, L M; Eichau Madueño, S; Fernández Fernández, Ó; Izquierdo Ayuso, G; Álvarez Cermeño, J C; Arnal García, C; Arroyo González, R; Brieva Ruiz, L; Calles Hernández, C; García Merino, A; González Platas, M; Hernández Pérez, M Á; Moral Torres, E; Olascoaga Urtaza, J; Oliva-Nacarino, P; Oreja-Guevara, C; Ortiz Castillo, R; Oterino, A; Prieto González, J M; Ramió-Torrentá, L; Rodríguez-Antigüedad, A; Saiz, A; Tintoré, M; Montalbán Gairin, X
    Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.