SAS - Hospital Universitario Virgen de la Victoria

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  • Publication
    The emergent role of mitochondrial RNA modifications in metabolic alterations.
    (2022-07-25) Boughanem, Hatim; Böttcher, Yvonne; Tomé-Carneiro, João; López de Las Hazas, María-Carmen; Dávalos, Alberto; Cayir, Akin; Macias-González, Manuel
    Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases. In the light of current knowledge about the involvement, the association between mitochondrial RNA modifications and diseases arises from studies focusing on mutations in both mitochondrial and nuclear DNA genes encoding enzymes involved in such modifications. Here, we review the current evidence available for mitochondrial RNA modifications and their role in metabolic disorders, and we also explore the possibility of using them as promising targets for prevention and early detection. Finally, we discuss future directions of mitochondrial epitranscriptomics in these metabolic alterations, and how these RNA modifications may offer a new diagnostic and theragnostic avenue for preventive purposes. This article is categorized under: RNA Processing > RNA Editing and Modification.
  • Publication
    Dietary diversity and depression: cross-sectional and longitudinal analyses in Spanish adult population with metabolic syndrome. Findings from PREDIMED-Plus trial.
    (2022-07-19) Cano-Ibáñez, Naomi; Serra-Majem, Lluis; Martín-Peláez, Sandra; Martínez-González, Miguel Ángel; Salas-Salvadó, Jordi; Corella, Dolores; Lassale, Camille; Martínez, Jose Alfredo; Alonso-Gómez, Ángel M; Wärnberg, Julia; Vioque, Jesús; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Gómez-Pérez, Ana María; Lapetra, José; Fernández-Aranda, Fernando; Bueno-Cavanillas, Aurora; Tur, Josep A; Cubelos, Naiara; Pintó, Xavier; Gaforio, José Juan; Matía-Martín, Pilar; Vidal, Josep; Calderón, Cristina; Daimiel, Lidia; Ros, Emilio; Gea, Alfredo; Babio, Nancy; Gimenez-Alba, Ignacio Manuel; Zomeño-Fajardo, María Dolores; Abete, Itziar; Tojal Sierra, Lucas; Romero-Galisteo, Rita P; García de la Hera, Manoli; Martín-Padillo, Marian; García-Ríos, Antonio; Casas, Rosa M; Fernández-García, J C; Santos-Lozano, José Manuel; Toledo, Estefanía; Becerra-Tomas, Nerea; Sorli, Jose V; Schröder, Helmut; Zulet, María A; Sorto-Sánchez, Carolina; Diez-Espino, Javier; Gómez-Martínez, Carlos; Fitó, Montse; Sánchez-Villegas, Almudena
    To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms. An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used. Spanish older adults with metabolic syndrome (MetS). A total of 6625 adults aged 55-75 years from the PREDIMED-Plus study with overweight or obesity and MetS. Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)). According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.
  • Publication
    The Mediterranean diet and physical activity: better together than apart for the prevention of premature mortality.
    (2021-08-31) Hershey, Maria Soledad; Martínez-González, Miguel Ángel; Álvarez-Álvarez, Ismael; Martínez Hernández, José Alfredo; Ruiz-Canela, Miguel
    Diet and physical activity (PA) have been studied extensively in epidemiology as single or combined lifestyle factors; however, their interaction has not been studied thoroughly. Studying potential synergisms between lifestyle components with a comprehensive interaction analysis, including additive measures of interaction, provides key insights into the nature of their joint effect and helps target interventions more effectively. First, a comprehensive review was conducted to assess the potential research gap regarding reported interaction analyses conducted in studies assessing the Mediterranean diet (MedDiet) in combination with PA on all-cause mortality. Thereafter, we prospectively assessed the joint association of the MedDiet with PA on all-cause mortality in the Seguimiento Universidad de Navarra (SUN) cohort, followed by both multiplicative and additive interaction analyses. The conjoint effect of low adherence to the MedDiet and low PA observed an increased risk greater than the individual risk factors, suggesting a potential additive interaction or synergism between both exposures, with relative risk due to interaction (RERI) and (95 % confidence interval (95 % CI)) = 0·46 (–0·83 to 1·75) and attributable proportion (95 % CI) due to interaction of 36 % (–0·62, 1·34). No multiplicative interaction was detected. Studying interactions between lifestyle factors, such as the MedDiet and PA, is particularly relevant given the current research gaps in studying the complexities of combined aspects of lifestyle in comparison with isolated behaviours. Our findings underline the important public health message of adhering to both the MedDiet and PA for the prevention of premature mortality.
  • 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
    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
    Analysis and evaluation of the operational characteristics of a new photodynamic therapy device.
    (2022-01-10) Gálvez, Enrique Navarrete-de; Aguilera, José; Fonda-Pascual, Pablo; de Gálvez, María Victoria; de Andrés-Díaz, José Ramón; Vidal-Asensi, Santiago; Herrera-Acosta, Enrique; Gago-Calderon, Alfonso
    One of the key aspects of photodynamic therapy is the light source that is used to irradiate the lesion to be treated. The devices used must ensure that their emission spectrum matches the absorption spectrum of the photosensitizer, so that treatment radiation is delivered only on the target area, without irradiating healthy tissue at superficial or deep levels. Irradiance values must be adequate in order to avoid thermal damage, exceed the oxygen replenishment rate and avoid long treatment times. Furthermore, the device should be user-friendly, inexpensive, and able to be adapted to different photosensitizers. We have developed an easy-to-use and highly customizable device based on LED technology. Its innovative geometric design allows radiation to be delivered to a small treatment surface, since the LEDs are arranged in three arms, the configuration of which directs their radiation on the treatment point. Different high-power color LEDs are disposed on the arms, and can be independently selected based on the most effective wavelengths for exciting the different photodynamic therapy photosensitizers. We have tested the prototype in 5 different patients (1 actinic keratose, 1 actinic cheilitis, 1 superficial basal cell carcinoma and 2 Bowen's disease) and after 1-2 sessions of total cumulative dose of 25-50 J / cm2, 100% clearance of lesions were obtained. Our device can be used by any professional in the field, whether for medical or research purposes. It facilitates the development of treatment protocols and trials with different photosensitizers.
  • Publication
    Door-to-needle times in patients treated by on-site and off-site on-call neurologists. PRISA study.
    (2021-09-17) Gallardo-Tur, A; Carazo-Barrios, L; de la Cruz-Cosme, C
    Hospital on-call neurology shifts are frequently on-site, but some on-call services may be off-site or mixed. Intravenous tissue plasminogen activator (tPA) is one of the main reperfusion treatments for acute ischaemic stroke (AIS). This study assesses door-to-needle times (DNT) when the neurologist is on-site or off-site. We performed a prospective, observational study from 2012 to 2017, including patients with AIS and treated with tPA. Data were collected on sex, age, door-to-scan time, scan-to-needle time, and DNT. The on-duty neurologist was on-site from 08:00 to 20:00, and on call but off-site from 20:00 to 8:00. Three groups were formed: on-site, off-site, and off-site with resident present. Our sample included 138 patients. The mean age was 69.7 years, and 45.7% of patients were women. Ninety-six patients were admitted during the on-site shift, 25 during the off-site shift, and 17 during the off-site-resident present shift. Patients admitted during the on-site and off-site shifts presented DNTs of 59 and 72 minutes, respectively (P =  .003). DNTs were 59, 74, and 68 minutes (P =  .001), respectively, for the on-site, off-site, and off-site-resident present shifts; the difference between DNTs for on-site and off-site shifts was statistically significant. No differences were observed between DNTs according to time of day (morning, afternoon, or night), or between weekdays and weekends. DNT is influenced by whether the on-duty neurologist is on- or off-site at the time of code stroke activation. The presence of a neurology resident can reduce DNT.
  • Publication
    Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial.
    (2022-08-18) Fernández-García, José Carlos; Barrios-Rodríguez, Rocío; Asenjo-Plaza, Maite; Ramos-Molina, Bruno; Molina-Vega, María; Guzmán-Guzmán, Antonio; Moreno-León, Luis; Yubero-Serrano, Elena M; Rius-Díaz, Francisca; Valdés, Sergio; Martínez-González, Miguel Ángel; Jiménez-Moleón, José Juan; Tinahones, Francisco J
    Men with obesity tend to be insulin resistant and often have low-normal testosterone concentrations. We conducted a clinical trial aimed to evaluate potential therapeutic strategies for low testosterone in men with obesity. We did a 1-year, parallel, randomized, double-blind, placebo-controlled trial, where we evaluated the independent and combined effects of metformin and testosterone in 106 men with obesity, aged 18-50 years, who had low levels of testosterone and no diabetes mellitus. The primary outcome was change in insulin resistance, measured as Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index. Secondary outcomes included changes in total and free serum testosterone, body composition, metabolic variables, erectile function, and health-related quality of life (HRQoL). In the intention-to-treat analysis, the HOMA-IR index decreased significantly in all active groups compared to placebo (metformin -2.4, 95 % CI -4.1 to -0.8, p = 0.004; testosterone -2.7, 95 % CI -4.3 to -1.1, p = 0.001; combination -3.4, 95 % CI -5.0 to -1.8, p  Among men with obesity and low testosterone concentrations, the combination of metformin plus testosterone, metformin only, and testosterone only, compared to placebo, reduced insulin resistance with no evidence of additive benefit.
  • 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
    Cryoglobulinemic purpura and COVID-19 infection.
    (2022-08-02) Martín Moyano, Javier
  • Publication
    Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC: Results of the ETOP ALERT-lung trial.
    (2022-08-12) Felip, Enriqueta; Smit, Egbert F; Molina-Vila, Miguel A; Dafni, Urania; Massuti, Bartomeu; Berghmans, Thierry; de Marinis, Filippo; Passiglia, Francesco; Dingemans, Anne-Marie C; Cobo, Manuel; Viteri, Santiago; Britschgi, Christian; Cuffe, Sinead; Provencio, Mariano; Merkelbach-Bruse, Sabine; Andriakopoulou, Charitini; Kammler, Roswitha; Ruepp, Barbara; Roschitzki-Voser, Heidi; Peters, Solange; Wolf, Jürgen; Stahel, Rolf; ETOP 12-17 ALERT-lung Collaborators
    Alectinib, a highly selective next generation ALK-inhibitor, has exhibited potent anti-tumour activity in RET-rearranged NSCLC in the preclinical stage. ALERT-lung is a single-arm, phase II trial evaluating the activity of alectinib for the treatment of pretreated RET-rearranged advanced NSCLC. Alectinib was administered orally, 600 mg, twice per day until progression, refusal or unacceptable toxicity (treatment could continue beyond progression, if patient was deriving clinical benefit). Patient recruitment closed prematurely due to discouraging results for alectinib in a phase I/II study in the same indication. All 14 patients who enrolled until the premature accrual closure, received at lease one dose of alectinib. Among them, median age was 61 years, majority (71 %) was female, never smokers, of ECOG PS 1. No objective response (complete or partial response) was recorded. Of the 13 evaluable patients, three (23 %) achieved and maintained disease stabilisation for 24 weeks. Up to 31 March 2021 (median follow-up 15.9 months), 12 PFS-events (92 %) were observed, with median PFS of 3.7 months (95 % C.I.: 1.8 - 7.3 months). Overall, three deaths (23 %) were reported. Seven patients (50 %) experienced grade ≥ 3 adverse events, while three discontinued treatment due to erythema multiforme of grade 3, related to alectinib. No treatment-related serious adverse event was reported. Accrual into our trial was terminated early in response to other reports of limited activity of alectinib in patients with RET-fusion NSCLC and the emergence of more potent selective RET-inhibitors. Also in our trial, alectinib did not show the expected potential for anti-tumour activity in NSCLC.
  • Publication
    Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations who progressed after platinum-based chemotherapy.
    (2022-03-08) Minchom, Anna; Viteri, Santiago; Bazhenova, Lyudmila; Gadgeel, Shirish M; Ou, Sai-Hong Ignatius; Trigo, José; Bauml, Joshua M; Backenroth, Daniel; Bhattacharya, Archan; Li, Tracy; Mahadevia, Parthiv; Girard, Nicolas
    In the single-arm CHRYSALIS study, amivantamab showed durable responses and manageable safety in patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) who progressed on prior platinum-based chemotherapy. External controls can provide context for interpreting amivantamab efficacy. External controls were selected from three US-based databases (ConcertAI, COTA, and Flatiron). Key inclusion criteria were diagnosis of EGFR ex20ins advanced NSCLC, prior platinum-based chemotherapy, and performance status score ≤ 1. Duplicate external controls were identified using a tokenization procedure and removed, and adjustment for differences in baseline characteristics between amivantamab-treated and external control cohorts was achieved using propensity score weighting. Amivantamab-treated and pooled external control cohorts included 81 and 125 patients, respectively. Baseline characteristics were generally similar across cohorts, except more amivantamab-treated patients were Asian (56% vs 13%). Most common therapies received by external controls were non-platinum-based chemotherapy (25.1%), immuno-oncology therapies (24.2%), EGFR tyrosine kinase inhibitors (16.3%), and platinum-based chemotherapy (16.3%). Overall response rate was 40% among amivantamab-treated patients and 16% among external controls. Amivantamab-treated patients had longer progression-free survival (median 8.3 vs 2.9 months; hazard ratio [HR; 95% CI]: 0.47 [0.34-0.65]), time to next therapy (median 14.8 vs 4.8 months; HR [95% CI]: 0.40 [0.28-0.57]), and overall survival (median 22.8 vs 12.8 months; HR [95% CI]: 0.49 [0.31-0.77]) than external controls. Results were consistent in sensitivity analyses comparing each external control dataset against the amivantamab-treated group separately. Among post-platinum patients with EGFR ex20ins advanced NSCLC, those treated with amivantamab had improved outcomes, including 10-month longer overall survival, versus external controls.
  • Publication
    Heterologous COVID-19 Vaccination in Spain: A Case Study of Individual Autonomy in the Real World.
    (2022-02-05) Dal-Ré, Rafael; Farré, Magí; Lucena, M Isabel
    In Spain, 1.5 million essential
  • Publication
    The potential role of UV and blue light from the sun, artificial lighting, and electronic devices in melanogenesis and oxidative stress.
    (2022-02-04) de Gálvez, Enrique Navarrete; Aguilera, José; Solis, Alba; de Gálvez, María Victoria; de Andrés, José Ramón; Herrera-Ceballos, Enrique; Gago-Calderon, Alfonso
    Our exposure to blue light from artificial sources such as indoor lights (mainly light-emitting diodes [LEDs]) and electronic devices (e.g., smartphones, computer monitors, and television screens), has increased in recent years, particularly during the recent coronavirus disease 2019 lockdown. This radiation has been associated to skin damage across its potential in generating reactive oxygen species in both the epidermis and the dermis, skin water imbalances and of potential activating melanin production. These circumstances make it important to determine whether current blue light exposure levels under artificial illumination and electronic devices exposure can cause the previously indicated disorders as compared to solar UV and visible radiation in a typical summer day. Blue light accounted for 25% of the sun's rays, approximately 30% of radiation emitted by electronic devices, and approximately from 6% to 40% of that emitted by indoor lights. The reference equations showed that the sun was the main source of effective irradiance for immediate and persistent pigmentation as well as for potential oxidative stress in our skin. Effective blue light exposure to artificial devices is significantly lower than the solar contribution. However, its contribution must be considered as accumulative dose effect, and especially in people with hypersensitivity promoting skin hyperpigmentation.
  • Publication
    Dairy Product Consumption and Changes in Cognitive Performance: Two-Year Analysis of the PREDIMED-Plus Cohort.
    (2022-06-01) Ni, Jiaqi; Nishi, Stephanie K; Babio, Nancy; Martínez-González, Miguel A; Corella, Dolores; Castañer, Olga; Martínez, J Alfredo; Alonso-Gómez, Ángel M; Gómez-Gracia, Enrique; Vioque, Jesús; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Lapetra, José; Serra-Majem, J Luís; Bueno-Cavanillas, Aurora; Tur, Josep A; Martín-Sánchez, Vicente; Pintó, Xavier; Gaforio, José J; Barabash Bustelo, Ana; Vidal, Josep; Vázquez, Clotilde; Daimiel, Lidia; Ros, Emili; Toledo, Estefanía; Coltell, Oscar; Gómez-Martínez, Carlos; Zomeño, María Dolores; Donat-Vargas, Carolina; Goicolea-Güemez, Leire; Bouzas, Cristina; Garcia-de-la-Hera, Manoli; Chaplin, Alice; Garcia-Rios, Antonio; Casas, Rosa; Cornejo-Pareja, Isabel; Santos-Lozano, José Manuel; Rognoni, Teresa; Saiz, Carmen; Paz-Graniel, Indira; Malcampo, Mireia; Sánchez-Villegas, Almudena; Salaverria-Lete, Itziar; García-Arellano, Ana; Schröder, Helmut; Salas-Salvadó, Jordi; PREDIMED-Plus investigators.
    Dairy consumption has been suggested to impact cognition; however, evidence is limited and inconsistent. This study aims to longitudinally assess the association between dairy consumption with cognitive changes in an older Spanish population at high cardiovascular disease risk. Four thousand six hundred sixty eight participants aged 55-75 years, completed a validated food frequency questionnaire at baseline and a neuropsychological battery of tests at baseline and 2-year follow-up. Multivariable linear regression models are used, scaled by 100 (i.e., the units of β correspond to 1 SD/100), to assess associations between baseline tertile daily consumption and 2-year changes in cognitive performance. Participants in the highest tertile of total milk and whole-fat milk consumption have a greater decline in global cognitive function (β: -4.71, 95% CI: -8.74 to -0.69, p-trend = 0.020 and β: -6.64, 95% CI: -10.81 to -2.47, p-trend = 0.002, respectively) compared to those in the lowest tertile. No associations are observed between low fat milk, yogurt, cheese or fermented dairy consumption, and changes in cognitive performance. Results suggest there are no clear prospective associations between consumption of most commonly consumed dairy products and cognition, although there may be an association with a greater rate of cognitive decline over a 2-year period in older adults at high cardiovascular disease risk for whole-fat milk.
  • Publication
    Long-term sequelae of drug-induced liver injury.
    (2021-10-22) Björnsson, Einar S; Andrade, Raul J
    Drug-induced liver injury (DILI) has a very variable clinical and biochemical phenotype and differs widely in severity, from mild injury to life-threatening liver failure. Chronic injury has also been reported to occur at a variable frequency, ranging from 3.4% to 39%, 6-12 months after discontinuing the implicated agent. This wide range is probably related to various definitions of chronic liver injury and variable selection of patients. The long-term sequalae of this chronic injury in terms of morbidity and mortality are unclear, although rare vanishing bile duct syndrome is associated with an unfavourable prognosis, with increased risk of chronic liver failure and need for liver transplantation. Other forms of long-term sequalae associated with DILI are progressive fibrosis, autoimmune-like hepatitis, secondary sclerosing cholangitis, sinusoidal obstruction syndrome and, as a common final stage, the development of cirrhosis, portal hypertension and its complications. Immune checkpoint inhibitors, which can cause an autoimmune-like phenotype have also recently been shown to cause sclerosing cholangitis with cytotoxic T CD8+ cell infiltration in biliary tracts. DILI has been shown to have a significant impact on health-related quality of life but very little is known about its psychological consequences in the long-term. Further investigations with structured long-term follow-up and periodic quality of life surveys are needed to assess the impact of DILI on psychological outcomes, particularly in those with chronic sequelae.
  • Publication
    Natural History of MYH7-Related Dilated Cardiomyopathy.
    (2022-08-22) de Frutos, Fernando; Ochoa, Juan Pablo; Navarro-Peñalver, Marina; Baas, Annette; Bjerre, Jesper Vandborg; Zorio, Esther; Méndez, Irene; Lorca, Rebeca; Verdonschot, Job A J; García-Granja, Pablo Elpidio; Bilinska, Zofia; Fatkin, Diane; Fuentes-Cañamero, M Eugenia; García-Pinilla, José M; García-Álvarez, María I; Girolami, Francesca; Barriales-Villa, Roberto; Díez-López, Carles; Lopes, Luis R; Wahbi, Karim; García-Álvarez, Ana; Rodríguez-Sánchez, Ibon; Rekondo-Olaetxea, Javier; Rodríguez-Palomares, José F; Gallego-Delgado, María; Meder, Benjamin; Kubanek, Milos; Hansen, Frederikke G; Restrepo-Córdoba, María Alejandra; Palomino-Doza, Julián; Ruiz-Guerrero, Luis; Sarquella-Brugada, Georgia; Perez-Perez, Alberto José; Bermúdez-Jiménez, Francisco José; Ripoll-Vera, Tomas; Rasmussen, Torsten Bloch; Jansen, Mark; Sabater-Molina, Maria; Elliot, Perry M; Garcia-Pavia, Pablo; European Genetic Cardiomyopathies Initiative Investigators
    Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at  MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.
  • Publication
    Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy.
    (2022) Escobar-Lopez, Luis; Ochoa, Juan Pablo; Royuela, Ana; Verdonschot, Job A J; Dal Ferro, Matteo; Espinosa, Maria Angeles; Sabater-Molina, Maria; Gallego-Delgado, Maria; Larrañaga-Moreira, Jose M; Garcia-Pinilla, Jose M; Basurte-Elorz, Maria Teresa; Rodríguez-Palomares, José F; Climent, Vicente; Bermudez-Jimenez, Francisco J; Mogollón-Jiménez, María Victoria; Lopez, Javier; Peña-Peña, Maria Luisa; Garcia-Alvarez, Ana; López-Abel, Bernardo; Ripoll-Vera, Tomas; Palomino-Doza, Julian; Bayes-Genis, Antoni; Brugada, Ramon; Idiazabal, Uxua; Mirelis, Jesus G; Dominguez, Fernando; Henkens, Michiel T H M; Krapels, Ingrid P C; Brunner, Han G; Paldino, Alessia; Zaffalon, Denise; Mestroni, Luisa; Sinagra, Gianfranco; Heymans, Stephane R B; Merlo, Marco; Garcia-Pavia, Pablo
    Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P  The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.
  • Publication
    Secukinumab is effective in the treatment of recalcitrant palmoplantar psoriasis and palmoplantar pustular psoriasis in a daily practice setting.
    (2022-05-28) Reolid, Alejandra; Armesto, Susana; Sahuquillo-Torralba, Antonio; Torres, Tiago; Feltes, Rosa; Vilarrasa, Eva; Belinchón, Isabel; Cueva, Pablo de la; Rodríguez, Lourdes; Romero-Maté, Alberto; Vidal, David; Coto-Segura, Pablo; Herrera-Acosta, Enrique; Riera-Monroig, Josep; Salgado, Laura; Llamas-Velasco, Mar; Daudén, Esteban