SAS - Hospital Universitario San Cecilio

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Now showing 1 - 20 of 1261
  • 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
    A multi-criteria decision analysis on the value of nintedanib for interstitial lung diseases.
    (2022-08-01) Zozaya, Néboa; Arrizubieta Basterrechea, Maria Iciar; Bollo, Elena; Castellví, Iván; Espín, Jaime; Ortego, Norberto; Poveda-Andrés, José Luis; Rodríguez Portal, José Antonio; Rivero, Agustín; Marcos-Rodríguez, José Antonio; Verde, Luis
    Our aim was to assess the value of nintedanib for non-idiopathic progressive fibrosing interstitial lung disease (non-IPF PF-ILD) and systemic sclerosis-associated ILD (SSc-ILD) in the Spanish context, using a multi-criteria decision analysis (MCDA). Following an adaptation of the Evidence and Value: Impact on DEcision Making (EVIDEM) MCDA methodology, the estimated value of nintedanib was obtained by means of an additive linear model that combined individual weights (100-points distribution) of criteria with the individual scoring of nintedanib in each criterion for every indication, assigned by a multidisciplinary committee of twelve clinicians, patients, pharmacists, and decision-makers. To assess the reproducibility, an alternative weighting method was applied, as well as a re-test of weights and scores at a different moment of time. The experts committee recognized nintedanib as an intervention with a positive value contribution in comparison to placebo for the treatment of non-IPF PF-ILD (0.50 ± 0.16, on a scale from -1 to 1) and SSc-ILD (0.40 ± 0.12), diseases which were considered as very severe and with high unmet needs. The drug was perceived as a treatment that provides an added therapeutic benefit for patients (0.06-0.07), given its proven clinical efficacy (0.05-0.06), slight improvements in patient-reported outcomes (0.01-0.02), and similar safety profile than placebo (-0.04-0.00), which will likely be positioned as a recommended therapy in the next clinical practice guidelines updates. Under this increasingly used methodology, nintedanib has shown to provide a positive value estimate for non-IPF PF-ILD and SSc-ILD when compared to placebo in Spain.
  • Publication
    Relationship between the appearance of atopic dermatitis in childhood and the consumption of probiotics during the neonatal period in premature patients
    (Cambridge univ press, 2022-01-01) Campos Martinez, A. M.; Montilla, S. Jimenez; Cuesta, A. Garcia; Uberos, J.; [Campos Martinez, A. M.] San Cecilio Clin Hosp, Neonatal Intens Care Unit, Granada, Spain; [Cuesta, A. Garcia] San Cecilio Clin Hosp, Neonatal Intens Care Unit, Granada, Spain; [Uberos, J.] San Cecilio Clin Hosp, Neonatal Intens Care Unit, Granada, Spain; [Montilla, S. Jimenez] Infanta Margarita Hosp, Serv Pediat, Cabra, Spain; [Uberos, J.] Med Fac, Granada, Spain
  • Publication
    Arthrospira (Spirulina) platensis feeding reduces the early stage of chemically induced rat colon carcinogenesis.
    (2022-05-04) Amadeu, Simone Oliveira; Sarmiento-Machado, Luis Manuel; Bartolomeu, Ariane Rocha; Chaves, María Angel García; Romualdo, Guilherme Ribeiro; de Moura, Nelci Antunes; Barbisan, Luis Fernando
    Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1-G3) or vehicle (G4-G5) twice a week (weeks 3-4). During weeks 1-4, animals were fed a diet containing 1 % (G2) or 2 % (G3-G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2-G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2-G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.
  • Publication
    The association between restricted intra-uterine growth and inadequate postnatal nutrition in very-low-birth-weight infants and their neurodevelopmental outcomes: a 50-month follow-up study.
    (2021-04-19) Uberos, Jose; Jimenez-Montilla, Sara; Machado-Casas, Irene; Laynez-Rubio, Carolina; Fernández-Marin, Elizabeth; Campos-Martínez, Ana
    Inadequate nutrition during a critical period of development - as is the case during gestation and the first days of life, especially in very-low-birth-weight (VLBW) infants, can impact on neurodevelopment and favour co-morbidities. In this study, we evaluate how neurodevelopment may be affected by intra-uterine growth (IUGR) restriction and by an inadequate intake of nutritional energy during the early neonatal period. A longitudinal cohort study was conducted to analyse the nutritional contributions received during the first week of life, among a population of 396 VLBW infants. Motor, cognitive, sensory and behavioural development was assessed at 14, 25, 33 and 50 months. The association between IUGR, postnatal energy restriction and neurodevelopment was examined using multivariate logistic regression techniques. Mild cognitive delay was observed in 35·6 % of neonates with IUGR and in 24 % of those with appropriate birth weight. IUGR is associated with behavioural disorder (OR 2·60; 95 % CI 1·25, 5·40) and delayed cognitive development (OR 2·64; 95 % CI 1·34, 5·20). Energy restriction during the first week of life is associated with visual deficiency (OR 2·96; 95 % CI 1·26, 6·84) and cerebral palsy (OR 3·05; CI 95 % 1·00, 9·54). In VLBW infants, IUGR is associated with behavioural disorder, while postnatal energy restriction is significantly associated with motor disorder, infantile cerebral palsy and sensory disorder.
  • Publication
    Antimalarials exert a cardioprotective effect in lupus patients: Insights from the Spanish Society of Rheumatology Lupus Register (RELESSER) analysis of factors associated with heart failure.
    (2022-01-02) Rúa-Figueroa, Iñigo; Rúa-Figueroa, David; Pérez-Veiga, Natalia; Anzola, Ana M; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Fernández-Nebro, Antonio; Sangüesa, Clara; Menor-Almagro, Raúl; Tomero, Eva; Del Val, Natividad; Uriarte-Isazelaya, Esther; Blanco, Ricardo; Andreu, José L; Boteanu, Alina; Narváez, Javier; Cobo, Tatiana; Bohórquez, Cristina; Montilla, Carlos; Salas, Esteban; Toyos, Francisco J; Bernal, José A; Salgado, Eva; Freire, Mercedes; Mas, Antonio J; Expósito, Lorena; Hernández-Beriain, José A; Ibarguengoitia, Oihane; Velloso-Feijoo, María L; Lozano-Rivas, Nuria; Bonilla, Gemma; Moreno, Mireia; Jiménez, Inmaculada; Quevedo-Vila, Víctor; Pecondón, Angela; Aurrecoechea, Elena; Valls, Elia; Mouriño, Coral; Vázquez-Rodríguez, Tomás; Pego-Reigosa, José M
    Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01-15.48], p  Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect.
  • Publication
    Acute diverticulitis in the terminal ileum: A rare case to have in mind.
    (2021-07-31) García-Márquez, J; García-Verdejo, F J; Caballero-Mateos, A M
  • Publication
    miR-106b is a novel target to promote muscle regeneration and restore satellite stem cell function in injured Duchenne dystrophic muscle.
    (2022-08-20) Rodriguez-Outeiriño, Lara; Hernandez-Torres, Francisco; Ramirez de Acuña, Felicitas; Rastrojo, Alberto; Creus, Carlota; Carvajal, Alejandra; Salmeron, Luis; Montolio, Marisol; Soblechero-Martin, Patricia; Arechavala-Gomeza, Virginia; Franco, Diego; Aranega, Amelia Eva
    Satellite cells (SCs), muscle stem cells, display functional heterogeneity, and dramatic changes linked to their regenerative capabilities are associated with muscle-wasting diseases. SC behavior is related to endogenous expression of the myogenic transcription factor MYF5 and the propensity to enter into the cell cycle. Here, we report a role for miR-106b reinforcing MYF5 inhibition and blocking cell proliferation in a subset of highly quiescent SC population. miR-106b down-regulation occurs during SC activation and is required for proper muscle repair. In addition, miR-106b is increased in dystrophic mice, and intramuscular injection of antimiR in injured mdx mice enhances muscle regeneration promoting transcriptional changes involved in skeletal muscle differentiation. miR-106b inhibition promotes the engraftment of human muscle stem cells. Furthermore, miR-106b is also high in human dystrophic muscle stem cells and its inhibition improves intrinsic proliferative defects and increases their myogenic potential. This study demonstrates that miR-106b is an important modulator of SC quiescence, and that miR-106b may be a new target to develop therapeutic strategies to promote muscle regeneration improving the regenerative capabilities of injured dystrophic muscle.
  • Publication
    Relationship between nutritional treatment compliance and nutritional status improvements in patients with gastrointestinal impairment taking an oral peptide-based supplement.
    (2022-05-21) López-Medina, José A; López-Rodriguez, Cristóbal; Estornell-Gualde, María A; Rey-Fernández, Laura; Gómez-Senent, Silvia; Joaquín-Ortiz, Clara; Fernández-Soto, M Luisa; Hurtado-García, Roberto; Martín-Martín, Margarita; Barrera-Martín, Ana; Vitales-Farrero, M Teresa; Martínez-Ortega, Antonio J; Blanca-Martínez-Barbeito, María; Vázquez-Vizcaíno, Begoña; Tasende-Fernández, Clara; Penacho-Lázaro, M Ángeles; Jordá-Sorolla, Esther; Sánchez-Sánchez, Rebeca; Díaz-Gómez, Laura; Baos-Fernández, Sergio; Guzmán-Rolo, Germán; Ballesteros-Pomar, María D
    Compliance in outpatients with gastrointestinal (GI) malabsorption is key in nutritional treatment. The objective of this study was to assess compliance in patients with GI impairment and malnutrition taking a high-calorie, high-protein, peptide-based oral nutritional supplement (ONS-PBD). A prospective, multicenter, observational study was conducted in 19 medical sites in Spain where ONS-PBD were prescribed as standard of care. Patients consumed ONS-PBD daily for 12 wk. Compliance was calculated as the percentage consumed of the prescribed amount of ONS per day. A total of 90 adult patients were included in the study, of whom 64 completed the 12-wk regimine. Mean compliance was 78.8% ± 24.5%. Risk of malnutrition decreased in 56.3% of patients at 12 wk, as measured with the malnutrition universal screening tool. A reduction in abdominal pain was observed and stool consistency improved, with a mean of 54.7% and 27.5%, respectively. Improvements in quality of life and a decrease in percentage of patients with severe functional impairment were observed. These data show that ONS-PBD compliance in malnourished patients with GI symptoms is high, reducing GI symptoms and improving patients' nutritional status.
  • Publication
    Normative data for the Fototest from neurological patients with no cognitive impairment.
    (2020-02-07) Carnero Pardo, C; Carrera Muñoz, I; Triguero Cueva, L; López Alcalde, S; Vílchez Carrillo, R
    To contribute normative data for the Fototest from neurological patients with no cognitive impairment, including disaggregated data on each domain of the test (naming, free recall, total recall, and naming fluency). We performed a cross-sectional study in which neurological patients with no cognitive impairment were tested with the Fototest; we recorded total and domain scores. We performed a descriptive study of the total and domain scores, with data disaggregated by sex, age (over/under 65 years), and level of education (primary education completed/not completed; further study completed). We included a sample of 1055 patients, who were mainly women (57.1%), aged over 65 (60.6%), and had a low level of education (38.6% had not completed primary education). Sex, age, and level of education influence total Fototest score (34.6 ± 5.3; P10: 28; P5: 27) and free recall (8.5 ± 2.2; 6; 4), total recall (10.0 ± 1.5; 8; 7), and naming fluency scores (18.7 ± 4.9; 13; 12). For total score, the multivariate analysis revealed values of 1.5 ± 0.3 (ß ± SD) for sex (female), -2.4 ± 0.3 for age (>65), and -1.6 ± 0.4 and 3.3 ± 0.4 for incomplete primary education and completed post-primary education, respectively (completed primary study was used as a reference). We provide normative data for total and domain Fototest results for each of the groups defined according to sex, age, and level of education. We also provide a percentile distribution of scores. We hope that these normative data will translate into increases in efficiency in Fototest administration in the clinical setting.
  • Publication
    CKD: The burden of disease invisible to research funders.
    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.
  • Publication
    Story of two sisters with kidney disease: genetics command.
    (2020-12-19) Barral-Juez, Mikel; García-Rabaneda, Carmen; Poyatos-Andújar, Antonio Miguel; Martínez-Atienza, Margarita; Morales-García, Ana Isabel; Morales-Santana, Sonia; Bellido-Díaz, María Luz; Bravo-Soto, Juan Antonio; Esteban-de la Rosa, Rafael José
  • Publication
    Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults.
    (2021-12-12) Jurado-Fasoli, Lucas; Di, Xinyu; Kohler, Isabelle; Osuna-Prieto, Francisco J; Hankemeier, Thomas; Krekels, Elke; Harms, Amy C; Yang, Wei; Garcia-Lario, Jose V; Fernández-Veledo, Sonia; Ruiz, Jonatan R; Rensen, Patrick C N; Martinez-Tellez, Borja
    Omega-6 and omega-3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega-6 and omega-3 polyunsaturated fatty acid-derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed. Body composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women). Plasma levels of four omega-6 oxylipins (15-HeTrE, 5-HETE, 14,15-EpETrE, and the oxidative stress-derived 8,12-iso-iPF2α -VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega-3 oxylipins (14,15-DiHETE, 17,18-DiHETE, and 19,20-DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor-alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega-6 and lower plasma levels of omega-3 oxylipins than normal-weight individuals. Plasma levels of seven omega-6 and omega-3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.
  • Publication
    Long-term prognosis communication preferences in early-stage relapsing-remitting multiple sclerosis.
    (2022-06-14) Castillo-Triviño, Tamara; Gómez-Ballesteros, Rocío; Borges, Mónica; Martín-Martínez, Jesús; Sotoca, Javier; Alonso, Ana; Caminero, Ana B; Borrega, Laura; Sánchez-Menoyo, José L; Barrero-Hernández, Francisco J; Calles, Carmen; Brieva, Luis; Blasco-Quílez, María R; García-Soto, Julio Dotor; Del Campo-Amigo, María; Navarro-Cantó, Laura; Agüera, Eduardo; Garcés-Redondo, Moisés; Carmona, Olga; Gabaldón-Torres, Laura; Forero, Lucía; Hervás, Mariona; Mauriño, Jorge; Sainz de la Maza, Susana
    Multiple sclerosis is one of the most common causes of neurological disability in young adults with major consequences for their future lives. Improving communication strategies on prognosis may help patients deal with the disease and adjust their long-term life goals. However, there is limited information on patients' preferences of long-term prognosis (LTP) communication and associated factors. The aim of this study was to describe patients' preferences and assess the factors associated with LTP communication preferences in early-stage relapsing-remitting multiple sclerosis (RRMS) patients. A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration from first attack ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The Prognosis in MS questionnaire was used to assess how much patients want to know about their LTP. Different patient-reported measures were administered to gather information on symptom severity, pain, fatigue, mood/anxiety, quality of life, stigma, illness perception, feeling of hopelessness, self-efficacy, information avoidance and coping strategies. Cognition was assessed using the Symbol Digit Modalities Test (SDMT). A multivariate logistic regression analysis was performed to assess the association between LTP information preference and demographic and clinical characteristics, as well as patients' perspectives. A total of 189 patients were included (mean age: 36.1  ±  9.4 years, 71.4% female, mean disease duration: 1.2  ±  0.8 years). Median EDSS score was 1.0 (IQR = 0.0-2.0). A proportion of 68.5% (n  =  126) of patients had never discussed LTP with their neurologists, whereas 69.2% (n = 126) reported interest in knowing it (73.5% at diagnosis). Bivariate analyses suggested that patients were significantly more likely to have higher LTP information preferences if they were male and had a lower SDMT score. Male gender and a lower SDMT score were predictors of LTP information preferences. Patients with early-stage RRMS want to discuss their LTP shortly after diagnosis. Understanding the factors involved may be useful to design individualized communication strategies.
  • Publication
    Combined use of UV and MS data for ICH Stability-Indication Method: Quantification and isoforms identification of intact nivolumab
    (Elsevier, 2022-08-31) Torrente-Lopez, Anabel; Hermosilla, Jesus; Perez-Robles, Raquel; Salmeron-Garcia, Antonio; Cabeza, Jose; Navas, Natalia; [Torrente-Lopez, Anabel] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Hermosilla, Jesus] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Perez-Robles, Raquel] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Navas, Natalia] Univ Granada, Biomed Res Inst Ibs Granada, Sci Fac, Dept Analyt Chem, E-18071 Granada, Spain; [Perez-Robles, Raquel] Junta Andalucia, Fdn Invest Biosanitaria Andalucia Oriental Alejan, Granada, Spain; [Salmeron-Garcia, Antonio] San Cecilio Univ Hosp Granada, Biomed Res Inst Ibs Granada, UGC Hosp Pharm, E-18012 Granada, Spain; [Cabeza, Jose] San Cecilio Univ Hosp Granada, Biomed Res Inst Ibs Granada, UGC Hosp Pharm, E-18012 Granada, Spain; Ministry of Universities, Spain; Junta de Andalucia (Spain); European Regional Develop-ment Funds; Junta de Andalucia, Spain; I + D + i-Junta de Andalucia, Spain; Universidad de Granada, Proyectos I +D +i del Programa Operativo FEDER Andalucia 2020; European Regional Development Funds; CBUA/Universidad de Granada
    Nivolumab (Opdivo (R)) is a fully human immunoglobulin G4 isotype approved for the treatment of many cancers. It acts as an immune checkpoint inhibitor by blocking the interaction between PD-1 (Programmed Cell Death Protein 1) - an inhibitory receptor expressed on activated T cells- and its ligands, PD-L1 and PD-L2. The quantification of therapeutic proteins in their medicines and pharmaceutical preparations remains challenging because the protein content, a critical quality attribute, must be rigorously calculated using a validated stabilityindicating method, such as that indicated by the International Conference on Harmonization (ICH) quality guidelines, and this requires the analysis of the drug in the presence of its degraded products. In this work, we present an strategy based on the combined use of the UV and MS data to full file the requirement of the ICH-Q2 (R1) to develop and validated as stability indicated a (RP)UHPLC/UV-(HESI/OrbitrapTM)MS method for the quantification of nivolumab in medicinal products. A comparative study of all figures of merit of the method using UV or MS data are shown and discussed. The results show that linearity was similar for the two detectors and was established over a range of 4-45 mu g/mL and 1-45 mu g/mL for the UV and (HESI/OrbitrapTM)MS signals, respectively. The sensitivity of the method was higher when using the (HESI/OrbitrapTM)MS signal (0.2 mu g/mL) than with the UV(2.0 mu g/mL). However, the UV signal provided better accuracy and precision than the (HESI/ OrbitrapTM)MS signal, which did not meet the criteria for method robustness and system suitability. In spite of this, the MS signal plays a crucial role in this methodology by obtaining the molecular weight profile of the nivolumab isoforms, so enabling us to propose the glycans profile and detect structural modification due to degradation. The specificity of the method was evaluated by conducting forced degradation tests on samples of nivolumab in medicine form. The aim was to find out whether nivolumab suffers structural modifications when subject to stress. Structural modifications were detected by analysing the MS isoform profile, as changes of this kind promote new isoforms that are not chromatographically separated or detected by the UV signal. In this way, we demonstrated that the (RP)UHPLC/UV-(HESI/OrbitrapTM)MS method was capable of detecting nivolumab degradation, and was suitable for use in nivolumab stability studies. Thus, the protein content in the daily surplus of the Opdivo (R) medicine, stored either at room temperature (20 degrees C) or refrigerated at 4 degrees C, could be tracked for 15 days.
  • Publication
    Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.
    (2022) Estella, Á; Garcia Garmendia, J L; de la Fuente, C; Machado Casas, J F; Yuste, M E; Amaya Villar, R; Estecha, M A; Yaguez Mateos, L; Cantón Bulnes, M L; Loza, A; Mora, J; Fernández Ruiz, L; Díez Del Corral Fernández, B; Rojas Amezcua, M; Rodriguez Higueras, M I; Díaz Torres, I; Recuerda Núñez, M; Zaheri Beryanaki, M; Rivera Espinar, F; Matallana Zapata, D F; Moreno Cano, S G; Gimenez Beltrán, B; Muñoz, N; Sainz de Baranda Piñero, A; Bustelo Bueno, P; Moreno Barriga, E; Rios Toro, J J; Pérez Ruiz, M; Gómez González, C; Breval Flores, A; de San José Bermejo Gómez, A; Ruiz Cabello Jimenez, M A; Guerrero Marín, M; Ortega Ordiales, A; Tejero-Aranguren, J; Rodriguez Mejías, C; Gomez de Oña, J; de la Hoz, C; Ocaña Fernández, D; Ibañez Cuadros, S; Garnacho Montero, J; Work Group of Infectious Disease (GTEI) de la Sociedad Andaluza de Medicina Intensiva y Unidades coronarias SAMIUC
    The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. Prospective descriptive multicenter cohort study. 26 Intensive care units (ICU) from Andalusian region in Spain. Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. None. Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission 6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission 470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.
  • Publication
    Effect of tocilizumab versus standard of care in adults hospitalized with moderate-severe COVID-19 pneumonia.
    (2022-07-20) Aomar-Millán, Ismael F; Salvatierra, Juan; Raya Álvarez, Enrique
  • Publication
    Prevalence of fatigue during the SARS-CoV-2 pandemic in patients and workers of a hemodialysis unit.
    (2022-05-31) Hérnandez García, Elena; Ramírez Gómez, María; Álvarez Gómez, Carmen
  • Publication
    Clinical course of Covid-19 in a cohort of patients with Behçet disease.
    (2021-12-28) Correa-Rodríguez, María; Callejas-Rubio, José-Luis; Rueda-Medina, Blanca; Ríos-Fernández, Raquel; Hera-Fernández, Javier de la; Ortego-Centeno, Norberto
    The implications of Covid-19 in patients with Behçet's disease (BD) are unknown. Patients with BD usually take long-term therapy with therapeutic agents that have been tested in Covid-19 patients. We aimed to assess the prevalence of Covid-19 in a cohort of patients with BD and investigate whether those patients with a long-term treatment with colchicine, tumor necrosis factor inhibitors (TNFi) or glucocorticoids are at reduced or increased prevalence of Covid-19 related clinical outcomes. A retrospective study was conducted among 244 patients with BD (86.1% females; mean age 43.95±11.11 years). Each participant completed an online questionnaire regarding demographics, medical conditions, dispensed colchicine, TNFi or oral glucocorticoids, Covid-19 infection, clinical symptoms and recovery. The prevalence of Covid-19 infection was 14.75%. Regarding dose of colchicine, the presence of ageusia was lower in patients taking 0.5mg/day of colchicine compared to those taking 1.5mg/day (p=0.021). The prevalence of dyspnea was significantly higher in patients taking TNFi compared with those without therapy (p=0.032). With regards to oral glucocorticoids, no significant differences were found. The prevalence of Covid-19 among patients with BD seems to be higher than that among the general population in Spain. Continuous TNFi therapy might increase the prevalence of worse clinical outcomes such as dyspnea; oral glucocorticoids and colchicine apparently provided no protection against the Covid-19 related clinical outcomes of patients with BD.
  • Publication
    Autoimmune diseases and vaccines against COVID-19. Decision making in uncertain scenarios.
    (2021-11-13) Calvo Elías, Alberto E; Pérez Casado, Lucía; Callejas Rubio, José Luis