97 results on '"Moreno-Luna R"'
Search Results
2. Transcriptional analysis of nasal polyps fibroblasts reveals a new source of pro-inflammatory signaling in CRSwNP
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Porras-González, C, primary, Palacios-García, J M, additional, Sánchez-Gómez, S, additional, Maza-Solano, J M, additional, Alba, G, additional, Sánchez-Margalet, V, additional, Palomares, O, additional, Del Cuvillo, A, additional, Cordero-Varela, J A, additional, Moreno-Luna, R, additional, and Muñoz-Bravo, J L, additional
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- 2023
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3. Usefulness of bilateral mucoplasty plus reboot surgery in severe type-2 chronic rhinosinusitis with nasal polyps
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Moreno-Luna, R., primary, Martin-Jimenez, D.I., additional, Callejón-Leblic, M.A., additional, Gonzalez-Garcia, J., additional, Maza-Solano, J.M., additional, Porras-Gonzalez, C., additional, Del Cuvillo-Bernal, A., additional, and Sanchez-Gomez, S., additional
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- 2022
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4. Availability of Readable Online Spanish Rhinosinusitis Outcome Measures
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Thorp, B.D., Lee, S.E., Moreno-Luna, R., Ebert, C.S., Farzal, Z., Senior, B.A., and Kimple, A.J.
- Abstract
Background: Patient-reported outcome measures (PROMs) are useful instruments that give providers insight into patients’ experiences with disease by quantifying the symptoms that matter most to patients. Results of these questionnaires can help guide management in chronic rhinosinusitis. However, these tools are often developed for native English speakers, which disadvantages others, who already have a language barrier to care. The aim of this study is to evaluate accessibility and readability of Spanish PROMs used to evaluate rhinosinusitis. Methods: Three Spanish readability measures, Gilliam, Peña & Mountain; SOL; and Fernandez-Huerta were used to evaluate PROMs utilized for rhinosinusitis. PROMs with sixth-grade readability level or easier were considered to meet health literacy recommendations. Results: Four Spanish PROMs utilized in assessment of rhinosinusitis were identified and evaluated. Cuestionario Español de Calidad de Vida en Rinitis (ESPRINT-15) was the most readable PROM and met readability recommendations in two of three measures. Nasal Obstruction Symptom Evaluation met suggested levels in one measure. The remainder of readability scores were more difficult than recommended. Conclusion: PROMs are powerful clinical tools that help patients communicate their symptoms and self-advocate. For providers to gain accurate and useful information, these measures should be written at appropriate readability levels. Most Spanish PROMs used for assessment of rhinosinusitis were above recommended readability. Development of future PROMs should ensure appropriate readability levels to provide good patient-centered care for our primarily Spanish speaking patients.
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- 2022
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5. CAPN10 alleles modify laryngeal cancer risk in the Spanish population
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Esteban, F., Royo, J.L., González-Moles, M.A., Gonzalez-Perez, A., Redondo, M., Moreno-Luna, R., Rodríguez-Sola, M., Gonzalez, A., Real, L.M., Ruiz, A., and Ramírez-Lorca, R.
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- 2008
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6. Heterogeneity of the Endocannabinoid System Between Cerebral Cortex and Spinal Cord Oligodendrocytes
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Moreno-Luna, R., primary, Esteban, P. F., additional, Paniagua-Torija, B., additional, Arevalo-Martin, A., additional, Garcia-Ovejero, D., additional, and Molina-Holgado, E., additional
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- 2020
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7. Smell and Taste Dysfunction in COVID-19 Is Associated With Younger Age in Ambulatory Settings: A Multicenter Cross-Sectional Study
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Izquierdo-Domínguez, A, primary, Rojas-Lechuga, MJ, additional, Chiesa-Estomba, C, additional, Calvo-Henríquez, C, additional, Ninchritz-Becerra, E, additional, Soriano-Reixach, M, additional, Poletti-Serafini, D, additional, Villarreal, IM, additional, Maza-Solano, JM, additional, Moreno-Luna, R, additional, Villarroel, PP, additional, Mateos-Serrano, B, additional, Agudelo, D, additional, Valcarcel, F, additional, del Cuvillo, A, additional, Santamaría, A, additional, Mariño-Sánchez, F, additional, Aguilar, J, additional, Vergés, P, additional, Inciarte, A, additional, Soriano, A, additional, Mullol, J, additional, and Alobid, I, additional
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- 2020
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8. “ABCDEF Checklist" based on 3D radiological images for preoperative planning of endoscopic sinus surgery
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Maza-Solano, J.M., primary, Gonzalez-Garcia, J., additional, Moreno-Luna, R., additional, Ambrosiani-Fernandez, J., additional, Dominguez-Duran, E., additional, and Sanchez-Gomez, S., additional
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- 2018
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9. Evaluation of circulating cell-free DNA levels in patients with severe preeclampsia and HELLP syndrome
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Medrano, P., primary, Miranda, M.L., additional, Muñoz-Hernández, R., additional, Macher, H.C., additional, Vallejo-Vaz, A., additional, Moreno-Luna, R., additional, Villar, J., additional, Guerrero, J.M., additional, and Stiefel, P., additional
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- 2015
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10. Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after cpap
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Hernández, R. Muñoz, primary, Vallejo-Vaz, A.J., additional, Medrano-Campillo, P., additional, Armengol, A., additional, Moreno-Luna, R., additional, Macher, H.C., additional, Caballero-Eraso, C., additional, Merino, A.M., additional, Capote, F., additional, and Stiefel, P., additional
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- 2015
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11. PP.37.20
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Medrano, P., primary, Muñoz-Hernández, R., additional, Vallejo-Vaz, A.J., additional, Domínguez, M.J., additional, Moreno-Luna, R., additional, Caballero, C., additional, Sánchez-Armengol, M.A., additional, Villar, J., additional, Capote, F., additional, and Stiefel, P., additional
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- 2015
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12. Role of Circulating Cell-free DNA Levels in Patients With Severe Preeclampsia and HELLP Syndrome
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Miranda, M. L., primary, Macher, H. C., additional, Munoz-Hernandez, R., additional, Vallejo-Vaz, A., additional, Moreno-Luna, R., additional, Villar, J., additional, Guerrero, J. M., additional, and Stiefel, P., additional
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- 2013
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13. The Postprandial State and its Influence on the Development of Atherosclerosis
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Moreno-Luna, R., primary, Villar, J., additional, F. Costa-Martins, A., additional, Vallejo-Vaz, A., additional, and Stiefel, P., additional
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- 2011
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14. We-P14:459 Olive oil and walnut meals elicit the inflammatory response in mononuclear cells compared with butter meal during postprandial state in healthy men
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Jiménez-Gómez, Y., primary, López-Miranda, J., additional, Gómez Luna, P., additional, Marín Hinojosa, C., additional, Moreno Luna, R., additional, Romero García, I., additional, Galán, E., additional, Sánchez, E., additional, and Pérez-Jiménez, F., additional
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- 2006
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15. Which parameter is better to define endothelial dysfunction in a test of postocclusive hyperemia measured by Laser-Doppler flowmetry?
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Stiefel P, Moreno-Luna R, Vallejo-Vaz AJ, Beltrán LM, Costa A, Gómez L, Ordóñez A, and Villar J
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- 2012
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16. Utilidad de los colgajos e injertos endonasales en cirugía endoscópica nasosinusal y de base de cráneo. Documento de consenso
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Moreno-Luna, R., Mariño Sánchez, F., Kaen, A., Gras Cabrerizo, J.R., Mata Castro, N., González García, J., Villacampa Auba, J.M., Cárdenas Ruiz-Valdepeñas, E., Monjas Cánovas, I., del Cuvillo Bernal, A., García Piñero, A., Maza Solano, J.M., Fernández de Liesa, R., Sánchez Gómez, S., and Alobid, I.
- Abstract
de la cirugía endoscópica endonasal expandida. Existen multitud de injertos y colgajos de origen endonasal que han demostrado su utilidad en el control de complicaciones como las fístulas de LCR, entre otras. Se hace necesaria la revisión y el análisis de los recursos endonasales y su uso en cirugía endoscópica endonasal expandida (CEEE).
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- 2021
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17. 24-HOUR BLOOD PRESSURE MONITORING AND BIOCHEMICAL PARAMETERS IN PREGNANT WOMEN WITH PREECLAMPSIA AT DIAGNOSIS AND AFTER PUERPERIUM
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Vallejo Vaz, A. J., Luis M. Beltrán-Romero, Gomez Morales, L., Miranda Guisado, M. L., Pamies Andreu, E., Stiefel Garcia-Junco, P., Muniz Grijalvo, O., Lopez Chozas, J. M., Garcia Morillo, S., Nieto Martin, M. D., Alfaro Lara, V., Moreno Luna, R., and Villar Ortiz, J.
18. Unraveling the differential mechanisms of revascularization promoted by MSCs & ECFCs from adipose tissue or umbilical cord in a murine model of critical limb-threatening ischemia.
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Rojas-Torres M, Beltrán-Camacho L, Martínez-Val A, Sánchez-Gomar I, Eslava-Alcón S, Rosal-Vela A, Jiménez-Palomares M, Doiz-Artázcoz E, Martínez-Torija M, Moreno-Luna R, Olsen JV, and Duran-Ruiz MC
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- Animals, Mice, Umbilical Cord cytology, Male, Mesenchymal Stem Cell Transplantation methods, Neovascularization, Physiologic, Endothelial Cells, Humans, Adipose Tissue, Mice, Nude, Mice, Inbred BALB C, Disease Models, Animal, Mesenchymal Stem Cells, Ischemia therapy, Ischemia physiopathology
- Abstract
Background: Critical limb-threatening ischemia (CLTI) constitutes the most severe manifestation of peripheral artery disease, usually induced by atherosclerosis. CLTI patients suffer from high risk of amputation of the lower extremities and elevated mortality rates, while they have low options for surgical revascularization due to associated comorbidities. Alternatively, cell-based therapeutic strategies represent an effective and safe approach to promote revascularization. However, the variability seen in several factors such as cell combinations or doses applied, have limited their success in clinical trials, being necessary to reach a consensus regarding the optimal "cellular-cocktail" prior further application into the clinic. To achieve so, it is essential to understand the mechanisms by which these cells exert their regenerative properties. Herein, we have evaluated, for the first time, the regenerative and vasculogenic potential of a combination of endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs) isolated from adipose-tissue (AT), compared with ECFCs from umbilical cord blood (CB-ECFCs) and AT-MSCs, in a murine model of CLTI., Methods: Balb-c nude mice (n:32) were distributed in four different groups (n:8/group): control shams, and ischemic mice (after femoral ligation) that received 50 µl of physiological serum alone or a cellular combination of AT-MSCs with either CB-ECFCs or AT-ECFCs. Follow-up of blood flow reperfusion and ischemic symptoms was carried out for 21 days, when mice were sacrificed to evaluate vascular density formation. Moreover, the long-term molecular changes in response to CLTI and both cell combinations were analyzed in a proteomic quantitative approach., Results: AT-MSCs with either AT- or CB-ECFCs, promoted a significant recovery of blood flow in CLTI mice 21 days post-ischemia. Besides, they modulated the inflammatory and necrotic related processes, although the CB group presented the slowest ischemic progression along the assay. Moreover, many proteins involved in the repairing mechanisms promoted by cell treatments were identified., Conclusions: The combination of AT-MSCs with AT-ECFCs or with CB-ECFCs promoted similar revascularization in CLTI mice, by restoring blood flow levels, together with the modulation of the inflammatory and necrotic processes, and reduction of muscle damage. The protein changes identified are representative of the molecular mechanisms involved in ECFCs and MSCs-induced revascularization (immune response, vascular repair, muscle regeneration, etc.)., (© 2024. The Author(s).)
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- 2024
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19. Tissue-specific early and late activated lymphocytes immunophenotype in chronic rhinosinusitis with nasal polyps.
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López-Enríquez S, Porras-González C, Moreno-Luna R, Palomares F, Muñoz-Bravo JL, Alba G, Santa-María C, Maza-Solano J, Martín-Jiménez DI, Pérez-Pérez A, Moreno-Luna R, Sánchez-Margalet V, and Sánchez-Gómez S
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- Humans, Chronic Disease, Male, Adult, Middle Aged, Female, T-Lymphocytes, Cytotoxic immunology, Aged, Rhinosinusitis, Nasal Polyps immunology, Sinusitis immunology, Rhinitis immunology, Lymphocyte Activation immunology, Immunophenotyping
- Abstract
Key Points: T-cell activation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is enriched by late cytotoxic T cells. The proportion of early and intermediate activated cytotoxic T cells decreases in nasal polyps of patients with CRSwNP. Our results identify late activated cytotoxic T cells as potential biomarkers or therapeutic targets for patients with CRSwNP., (© 2024 ARS‐AAOA, LLC.)
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- 2024
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20. Improved quality of life in patients with chronic rhinosinusitis with nasal polyps associated with expanded types of endoscopic sinus surgery: A 2-year retrospective study.
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Martin-Jimenez DI, Moreno-Luna R, Callejon-Leblic A, Del Cuvillo Bernal A, Ebert CS Jr, Maza-Solano JM, Gonzalez-Garcia J, and Sanchez-Gomez S
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- Humans, Chronic Disease, Retrospective Studies, Female, Male, Middle Aged, Adult, Paranasal Sinuses surgery, Treatment Outcome, Aged, Rhinosinusitis, Nasal Polyps surgery, Sinusitis surgery, Rhinitis surgery, Quality of Life, Endoscopy
- Abstract
Key Points: Expanded types of functional endoscopic sinus surgery (FESS) significantly improve quality of life and reduce revision surgeries rates, supporting their early application for moderate-to-severe cases. Minimal clinically important difference may play as a crucial role in defining surgical treatment response (i.e., responder and super-responder conditions). Expanded FESS benefits patients with chronic rhinosinusitis with nasal polyps but more data are required to have a clearer understanding of its uses due to varied approaches and reported outcomes in the literature., (© 2024 ARS‐AAOA, LLC.)
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- 2024
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21. Role of Nasal Surgery in Adult Obstructive Sleep Apnea: A Systematic Review.
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Correa EJ, Conti DM, Moreno-Luna R, Sánchez-Gómez S, and O'Connor Reina C
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Objective To perform a systematic review to determine if isolated nasal surgery has any impact on subjective or objective parameters in adult obstructive sleep apnea (OSA) patients. Materials and Methods From December 2022 to March 2023, we conducted a search on the PubMed, Cochrane, Scopus, and Web of Science databases. Two independent investigators performed a study selection according to the established criteria, as well as data collection, including the study design, the subjective and objective parameters addressed, the type of intervention, and the outcomes, considering the methodological quality and risk of bias. Results In total, 25 studies met the selection criteria, and they showed that there is a significant improvement in sleep quality, sleepiness, nasal resistance, and snoring after isolated nasal surgery. Still, there is no relevant modification of other polysomnographic parameters. It also reduces the required titration pressures of continuous positive airway pressure (CPAP) and increases the duration of its use. Conclusion Isolated nasal surgery is not a primary treatment for OSA. Still, it improves the subjective parameters and can lead to CPAP therapy success by enhancing its effectiveness and long-term compliance., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)
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- 2024
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22. Effect of antihypertensive treatment on the quality of life of patients with chronic rhinosinusitis with nasal polyps.
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Maza-Solano J, Palma-Martínez C, Martín-Jiménez D, Sánchez-Gómez S, Moreno-Luna R, Calvo-Henriquez C, and Galera-Ruiz H
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- Adult, Aged, Female, Humans, Male, Middle Aged, Chronic Disease, Hypertension drug therapy, Hypertension complications, Retrospective Studies, Rhinosinusitis complications, Rhinosinusitis drug therapy, Antihypertensive Agents therapeutic use, Nasal Polyps complications, Nasal Polyps drug therapy, Nasal Polyps surgery, Quality of Life
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Aim: Nasal polyposis (CRSwNP) shares type 2 inflammation biomarkers with asthma, allergy or arterial hypertension (AH), including periostin, a predictive marker of severity and post-surgical recurrence of polyposis. Antihypertensives have been shown to decrease periostin expression. We set out to evaluate the effect of antihypertensives on the quality of life of patients with CRSwNP., Materials and Methods: Retrospective study of 43 patients with CRSwNP and ah with at least 1year of follow-up and antihypertensive treatment prescribed after the diagnosis of CRSwNP. Phenotypes were analyzed (F1: isolated CRSwNP; F2: CRSwNP with asthma and/or NERD) and aspects related to quality of life (SNOT-22), clinical severity (VAS), polypoid size (NPS), exacerbations and surgical needs after the initiation of antihypertensive treatment., Results: The predominant phenotype was F1 (62.8%). The number of exacerbations was 19.2% for F1, compared to 31.3% for F2. 34.8% underwent surgery after the start of antihypertensive treatment (F1=27.9% and F2=6.97%). A significant reduction in polypoid size, SNOT22 (16.4±19.6 points), and VAS scales (p<.05) was obtained., Conclusions: polypoid size, and reduce the risk of postoperative recurrence., (Copyright © 2023 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)
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- 2024
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23. Long-Term Clinical Outcomes in Patients with Chronic Rhinosinusitis with Nasal Polyps Associated with Expanded Types of Endoscopic Sinus Surgery.
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Martin-Jimenez D, Moreno-Luna R, Callejon-Leblic A, Del Cuvillo A, Ebert CS Jr, Maza-Solano J, Gonzalez-Garcia J, Infante-Cossio P, and Sanchez-Gomez S
- Abstract
(1) Background: Surgical criteria for chronic rhinosinusitis with nasal polyps (CRSwNP) remain unresolved. This study addresses these discrepancies by comparing the clinical outcomes of expanded-functional endoscopic sinus surgeries (E-FESS) with more-limited FESS (L-FESS). (2) Methods: A database was analyzed retrospectively to compare surgical outcomes in CRSwNP patients who underwent E-FESS versus those subjected to L-FESS. Quality of life, endoscopic and radiological outcomes were compared at the baseline and two years after surgery. The clinical status of the responder was defined when a minimal clinically important difference of 12 points in SNOT-22 change was achieved. (3) Results: A total of 274 patients met the inclusion criteria and were analyzed; 111 underwent E-FESS and 163 were subjected to L-FESS. Both groups exhibited significant clinical improvements, although a greater magnitude of change in SNOT-22 (14.8 ± 4.8, p = 0.002) was shown after E-FESS. Higher significant improvements for endoscopic and radiological scores and lower surgical revision rates were also noted in the E-FESS group. (4) Conclusions: E-FESS provides better clinical outcomes and reduced revision surgery rates when compared to L-FESS in CRSwNP patients two years after surgery, irrespective of any comorbidity. Further randomized prospective studies are needed to comprehensively contrast these results.
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- 2024
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24. Endoscopic Extended Sinus Surgery for Patients with Severe Chronic Rhinosinusitis with Nasal Polyps, the Choice of Mucoplasty: A Systematic Review.
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Martin-Jimenez D, Moreno-Luna R, Cuvillo A, Gonzalez-Garcia J, Maza-Solano J, and Sanchez-Gomez S
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- Humans, Quality of Life, Chronic Disease, Rhinitis complications, Rhinitis surgery, Nasal Polyps complications, Nasal Polyps surgery, Nasal Polyps drug therapy, Rhinosinusitis, Sinusitis complications, Sinusitis surgery, Sinusitis drug therapy
- Abstract
Purpose of Review: The advances in the knowledge of the molecular basis of the inflammatory response in chronic rhinosinusitis with nasal polyps (CRSwNP) have led the management of these patients towards personalized and precision medicine. Surgery has been positioned as a suitable alternative in patients who do not achieve control with appropriate medical treatment, but polypoid recurrences remain a constraint. The emergence of new surgical approaches based on patient phenotyping and the poor disease control associated with type 2 inflammatory phenotype makes it necessary to review the role of personalized and precision surgery in managing the disease., Recent Findings: Surgical approaches based on wide resection of bony sinus structures and the treatment of mucosa lining the sinonasal cavity have been analyzed and compared with other techniques and seem to offer more favorable surgical outcomes and improved quality of life (QoL), in addition to lower relapse rates. The innovations with new complementary surgical techniques, such as reboot surgery adding an extended autologous mucosal graft from the nasal floor (mucoplasty), may benefit endoscopic and QoL outcomes in the most severe CRSwNP patients with type 2 phenotype. Using bilateral endonasal mucoplasty as a complementary technique to reboot surgery is a suitable technical choice that has improved short- and medium-term QoL and endoscopic outcomes for patients with severe CRSwNP. These results are likely due to a combination of the extension of reboot and the inherent inflammatory and healing properties of mucoplasty. We propose this technique as a valuable surgical resource, although more robust clinical studies are needed to evaluate its long-term benefits comprehensively., (© 2023. The Author(s).)
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- 2023
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25. Omalizumab Treatment in Uncontrolled Asthma and CRSwNP Patients, with Previous Endoscopic Sinus Surgery, to Improve Quality of Life and Endoscopic Outcomes: a Two-Year Real-Life Study.
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Maza-Solano J, Callejon-Leblic A, Martin-Jimenez D, Moreno-Luna R, Gonzalez-Garcia J, Cuvillo A, and Sanchez-Gomez S
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- Humans, Chronic Disease, Quality of Life, Retrospective Studies, Asthma complications, Asthma drug therapy, Nasal Polyps complications, Nasal Polyps drug therapy, Nasal Polyps surgery, Omalizumab therapeutic use, Sinusitis complications, Sinusitis drug therapy, Sinusitis surgery
- Abstract
Purpose of Review: Despite molecular underlying advances, limited and divergent data on monoclonal antibodies (mAb) therapy in chronic rhinosinusitis with nasal polyps (CRSwNP) make further analysis necessary. The objective of this study is to evaluate the effect of omalizumab as an adjunct to endoscopic sinus surgery (ESS) on the treatment of CRSwNP under real-life conditions., Recent Findings: Since the introduction of omalizumab, as the first biologic agent for the treatment of diseases such as severe allergic asthma, different studies have demonstrated an effect of omalizumab on CRSwNP, with significant improvements in sinonasal symptoms and endoscopic scores. The high efficacy derived from mAb therapy and the need for ESS prior to mAb recommended by guidelines, has led to compare both therapeutic alternatives, finding discrepancies in their effect on quality of life (QoL) and complementary tests outcomes. Patients with moderate-to-severe asthma with clinical criteria for omalizumab indication, and coexistent CRSwNP disease, were selected for a non-randomized interventional retrospective study into four treatment subgroups. Measures were analyzed and compared between groups and over time at the baseline, 16 weeks and 1 and 2 years after treatment. Omalizumab treatment in patients with previous ESS exhibited an earlier and more pronounced improvement in QoL, symptoms scale and endoscopic findings (nasal polyp score and the bilateral modified Lund-Kennedy) as early from week 16, which improvement persisted for 2 years. A greater mean improvement of 33.4 ± 6.5 (95% CI: 20.3-46.4; p < 0.001) points in sinonasal outcome test 22 (SNOT-22) was associated with ESS at week 16, against omalizumab effect (17.8 ± 7.6 [95% CI: 2.6-33.0]; p = 0.023). At year 2, an improvement in SNOT-22 of 62.6 ± 8.9 (95% CI: 48.4-84.1; p < 0.001) points was exclusively associated with omalizumab. Clinical evidence of the effect of omalizumab added to ESS treatment is provided in this study in the short- and long-term., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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26. Role of Fibroblasts in Chronic Inflammatory Signalling in Chronic Rhinosinusitis with Nasal Polyps-A Systematic Review.
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Palacios-García J, Porras-González C, Moreno-Luna R, Maza-Solano J, Polo-Padillo J, Muñoz-Bravo JL, and Sánchez-Gómez S
- Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory disease of the nose and paranasal sinuses characterized by the presence of nasal polyps. The symptoms produced by the presence of nasal polyps such as nasal obstruction, nasal discharge, facial pain, headache, and loss of smell cause a worsening in the quality of life of patients. The source of the nasal polyps remains unclear, although it seems to be due to a chronic inflammation process in the sinonasal mucosa. Fibroblasts, the main cells in connective tissue, are intimately involved in the inflammation processes of various diseases; to this end, we carried out a systematic review to evaluate their inflammatory role in nasal polyps. Thus, we evaluated the main cytokines produced by nasal polyp-derived fibroblasts (NPDF) to assess their involvement in the production of nasal polyps and their involvement in different inflammatory pathways. The results of the review highlight the inflammatory role of NPDF through the secretion of various cytokines involved in the T1, T2, and T3 inflammatory pathways, as well as the ability of NPDF to be stimulated by a multitude of substances. With these findings, the fibroblast is positioned as a new potential therapeutic target in the treatment of CRSwNP.
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- 2023
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27. Tissue-specific Activated Regulatory Lymphocytes Immunophenotype in Chronic Rhinosinusitis with Nasal Polyps.
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López-Enríquez S, Porras-González C, Moreno-Luna R, Ebert CS Jr, Alba G, Santa-María C, Palacios-García JM, Maza-Solano J, Martín-Jiménez DI, Sánchez-Margalet V, and Sánchez-Gómez S
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- Humans, Lymphocytes pathology, Chronic Disease, Nasal Polyps complications, Nasal Polyps pathology, Sinusitis complications, Rhinitis complications
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- 2023
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28. Cardiovascular-related proteomic changes in ECFCs exposed to the serum of COVID-19 patients.
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Beltrán-Camacho L, Bhosale SD, Sánchez-Morillo D, Sánchez-Gomar I, Rojas-Torres M, Eslava-Alcón S, Martínez-Torija M, de Infante MAR, Nieto-Martín MD, Rodríguez-Iglesias MA, Moreno JA, Berrocoso E, Larsen MR, Moreno-Luna R, and Durán-Ruiz MC
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- Humans, Proteomics, SARS-CoV-2, Immunoglobulin G, Cells, Cultured, Membrane Proteins, Calpain, COVID-19, Cardiovascular System
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection significantly affects the cardiovascular system, causing vascular damage and thromboembolic events in critical patients. Endothelial dysfunction represents one of the first steps in response to COVID-19 that might lead to cardiovascular complications and long-term sequelae. However, despite the enormous efforts in the last two years, the molecular mechanisms involved in such processes remain poorly understood. Herein, we analyzed the protein changes taking place in endothelial colony forming cells (ECFCs) after the incubation with the serum from individuals infected with COVID-19, whether asymptomatic or critical patients, by application of a label free-quantitative proteomics approach. Specifically, ECFCs from healthy individuals were incubated ex-vivo with the serum of either COVID-19 negative donors (PCR-/IgG-, n:8), COVID-19 asymptomatic donors at different infective stages (PCR+/ IgG-, n:8and PCR-/IgG+, n:8), or hospitalized critical COVID-19 patients (n:8), followed by proteomics analysis. In total, 590 proteins were differentially expressed in ECFCs in response to all infected serums. Predictive analysis highlighted several proteins like CAPN5, SURF4, LAMP2 or MT-ND1, as highly discriminating features between the groups compared. Protein changes correlated with viral infection, RNA metabolism or autophagy, among others. Remarkably, the angiogenic potential of ECFCs in response to the infected serums was impaired, and many of the protein alterations in response to the serum of critical patients were associated with cardiovascular-related pathologies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
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- 2023
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29. Survival Analysis in Patients with Laryngeal Cancer: A Retrospective Cohort Study.
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Molina-Fernández E, Palacios-García JM, Moreno-Luna R, Herrero-Salado T, Ventura-Díaz J, Sánchez-Gómez S, and Vilches-Arenas Á
- Abstract
Introduction: The worldwide incidence rate of laryngeal cancer is declining. However, the 5-year survival for these patients has decreased in recent years from 66% to 63%. This may be due to changes in the treatment of the disease. The present study aimed to evaluate the survival rate of patients with LC according to the stage of the disease and the treatment applied. For this purpose, surgical versus organ preservation protocols (OPP) based on chemoradiotherapy were evaluated., Methods: A retrospective cohort study was conducted in a tertiary hospital. The study included adult patients with a clinical diagnosis of primary LC. Patients with LC and systemic metastases and those with synchronous tumors at diagnosis were excluded. Univariate and multivariate analyses were performed to determine the association between exposure to LC treatment and the time to event (death). Overall survival (OS), cause-specific survival (CSS), and disease-free survival (DFS) were calculated., Results: Patients with advanced tumors (stages III and IV) had almost three times the risk of LC death than those in the initial tumor stages (I and II) [HR CCS = 2.89 (95%CI 1.30-6.39)]; [HR OS = 2.01 (95%CI 1.35-2.98)]. Patients who underwent surgical treatment had a higher chance of survival than those who were treated according to OPP [HR = 0.62; 95%CI (0.38-1.02)] in CSS, 0.74 [95%CI (0.50-1.90)] in OS, and 0.61 [95%CI (0.40-0.91)] in DFS., Discussion: OPP changed the management of patients with advanced stages of LC, establishing CRT as an alternative to surgery. Our data did not reveal clinically relevant differences in OS between patients treated with OPP and those who underwent surgery; however, we reported differences in the DFS rate after five years of follow-up in favor of the surgery-treated group of patients., Conclusion: Surgical treatment improves CSS and DFS at five years in patients with initial LC with respect to radiation therapy alone. Furthermore, surgical treatment associated with complementary radiation therapy offers better CSS and DFS in patients with advanced LC.
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- 2023
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30. Endocannabinoid signaling in oligodendroglia.
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Molina-Holgado E, Esteban PF, Arevalo-Martin Á, Moreno-Luna R, Molina-Holgado F, and Garcia-Ovejero D
- Subjects
- Myelin Sheath metabolism, Axons metabolism, Central Nervous System metabolism, Cell Differentiation physiology, Endocannabinoids metabolism, Oligodendroglia metabolism
- Abstract
In the central nervous system, oligodendrocytes synthesize the myelin, a specialized membrane to wrap axons in a discontinuous way allowing a rapid saltatory nerve impulse conduction. Oligodendrocytes express a number of growth factors and neurotransmitters receptors that allow them to sense the environment and interact with neurons and other glial cells. Depending on the cell cycle stage, oligodendrocytes may respond to these signals by regulating their survival, proliferation, migration, and differentiation. Among these signals are the endocannabinoids, lipidic molecules synthesized from phospholipids in the plasma membrane in response to cell activation. Here, we discuss the evidence showing that oligodendrocytes express a full endocannabinoid signaling machinery involved in physiological oligodendrocyte functions that can be therapeutically exploited to promote remyelination in central nervous system pathologies., (© 2022 Wiley Periodicals LLC.)
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- 2023
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31. Availability of Readable Online Spanish Rhinosinusitis Outcome Measures.
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Lee SE, Farzal Z, Kimple AJ, Moreno-Luna R, Senior BA, Thorp BD, and Ebert CS
- Abstract
Background: Patient-reported outcome measures (PROMs) are useful instruments that give providers insight into patients' experiences with disease by quantifying the symptoms that matter most to patients. Results of these questionnaires can help guide management in chronic rhinosinusitis. However, these tools are often developed for native English speakers, which disadvantages others, who already have a language barrier to care. The aim of this study is to evaluate accessibility and readability of Spanish PROMs used to evaluate rhinosinusitis., Methods: Three Spanish readability measures, Gilliam, Peña & Mountain; SOL; and Fernandez-Huerta were used to evaluate PROMs utilized for rhinosinusitis. PROMs with sixth-grade readability level or easier were considered to meet health literacy recommendations., Results: Four Spanish PROMs utilized in assessment of rhinosinusitis were identified and evaluated. Cuestionario Español de Calidad de Vida en Rinitis (ESPRINT-15) was the most readable PROM and met readability recommendations in two of three measures. Nasal Obstruction Symptom Evaluation met suggested levels in one measure. The remainder of readability scores were more difficult than recommended., Conclusion: PROMs are powerful clinical tools that help patients communicate their symptoms and self-advocate. For providers to gain accurate and useful information, these measures should be written at appropriate readability levels. Most Spanish PROMs used for assessment of rhinosinusitis were above recommended readability. Development of future PROMs should ensure appropriate readability levels to provide good patient-centered care for our primarily Spanish speaking patients.
- Published
- 2022
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32. Nasal Symptoms in Asthmatic Patients under Treatment with Anti-IL-5 Monoclonal Antibodies. A Real-Life Cohort Study.
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Maza-Solano J, Calvo-Henríquez C, Alobid I, Álvarez-Cendrero M, Palomares Ó, Moreno-Luna R, Santos-Perez J, González-García J, and Sánchez-Gómez S
- Abstract
Currently, some monoclonal antibodies (mAbs) are being studied for chronic rhinosinusitis with nasal polyps (CRSwNP). Three anti-IL-5 mAb: mepolizumab, reslizumab and benralizumab, have been tested through randomized clinical trials. In this real-life study, we aimed to describe the nasal effects of a cohort of asthmatic adults treated with anti-IL-5 mAb. Methods: We carried out an observational study in adults (≥18 years) on anti-IL-5 mAb treatment. Variables included ACT and SNOT−22 questionnaires, nasal polyps score, blood total IgE levels and blood eosinophil count. Results: Overall, 38 participants were included in the study; 19 patients received mepolizumab, 17 were treated with benralizumab and 2 patients were given reslizumab. There was a statistically significant difference in the ACT and SNOT−22 scores before and after mAb treatment. ACT score increased from 11.05 to 21.5 after treatment (p < 0.001). SNOT−22 decreased from 57 to 37.3 after treatment (p = 0.004). No statistically significant differences between mAb groups were observed regarding the ACT or the SNOT−22 (p = 0.775) response (p = 0.775). In addition, 60.53% of patients obtained a minimal clinically important difference (MCID) in SNOT−22. Conclusions: A significant clinical response based on SNOT−22 score evolution after anti-IL-5 mAb treatment was observed. This study also demonstrated that blood eosinophil count, rather than serum total IgE levels, is the best predictor of asthma symptom improvement, which was assessed through the ACT and SNOT−22 questionnaires.
- Published
- 2022
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33. Serum microRNAs targeting ACE2 and RAB14 genes distinguish asymptomatic from critical COVID-19 patients.
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Calderon-Dominguez M, Trejo-Gutierrez E, González-Rovira A, Beltrán-Camacho L, Rojas-Torres M, Eslava-Alcón S, Sanchez-Morillo D, Calderon-Dominguez J, Martinez-Nicolás MP, Gonzalez-Beitia E, Nieto-Martín MD, Trujillo-Soto T, Rodríguez-Iglesias MA, Moreno JA, Moreno-Luna R, and Durán-Ruiz MC
- Abstract
Despite the extraordinary advances achieved to beat COVID-19 disease, many questions remain unsolved, including the mechanisms of action of SARS-CoV-2 and which factors determine why individuals respond so differently to the viral infection. Herein, we performed an in silico analysis to identify host microRNA targeting ACE2 , TMPRSS2 , and/or RAB14, all genes known to participate in viral entry and replication. Next, the levels of six microRNA candidates previously linked to viral and respiratory-related pathologies were measured in the serum of COVID-19-negative controls (n = 16), IgG-positive COVID-19 asymptomatic individuals (n = 16), and critical COVID-19 patients (n = 17). Four of the peripheral microRNAs analyzed (hsa-miR-32-5p, hsa-miR-98-3p, hsa-miR-423-3p, and hsa-miR-1246) were upregulated in COVID-19 critical patients compared with COVID-19-negative controls. Moreover, hsa-miR-32-5p and hsa-miR-1246 levels were also altered in critical versus asymptomatic individuals. Furthermore, these microRNA target genes were related to viral infection, inflammatory response, and coagulation-related processes. In conclusion, SARS-CoV-2 promotes the alteration of microRNAs targeting the expression of key proteins for viral entry and replication, and these changes are associated with disease severity. The microRNAs identified could be taken as potential biomarkers of COVID-19 progression as well as candidates for future therapeutic approaches against this disease., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)
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- 2022
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34. Usefulness of endonasal flaps and grafts in skull base surgery. Consensus document.
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Moreno-Luna R, Mariño Sánchez F, Kaen A, Gras Cabrerizo JR, Mata Castro N, González García J, Villacampa Aubá JM, Cárdenas Ruiz-Valdepeñas E, Monjas Cánovas I, Del Cuvillo Bernal A, García Piñero A, Maza Solano JM, Fernández de Liesa R, Sánchez-Gómez S, and Alobid I
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- Consensus, Humans, Retrospective Studies, Skull Base surgery, Surgical Flaps surgery, Plastic Surgery Procedures methods
- Abstract
Introduction: Skull base reconstruction is one of the greatest challenges extended endonasal endoscopic surgery. Many grafts and flaps from the endonasal fossa have been demonstrated to be useful in the control of complications such a cerebrospinal fluid leaks. Review and analysis of these resources are necessary in skull base recontruction to improve outcomes., Objectives: The target is to create a consensus document on the use of different endonasal flaps and grafts in the skull base surgery., Material and Methods: Literature review of the most relevant free grafts and vascularized flaps from the endonasal fossa. Analysis using the Delphi method on the use of the different endonasal resources for endoscopic repair of skull base defects., Results: We obtained two results: 1) A selection of the most representative flaps and grafts from the endonasal fossa, describing origin, surface and indications, based on a literature review. 2) A consensus document, using Delphi methodology, with general considerations (2), recommendations (10) and limitations (6) of the different endonasal flaps and grafts., Conclusions: We present the first consensus document in the field of extended endonasal endoscopic surgery using the Delphi method as a working tool. We highlight the usefulness of the nasoseptal flap together with other endonasal flaps and grafts for skull base reconstruction., (Copyright © 2021 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)
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- 2022
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35. Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients.
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Callejón-Leblic MA, Martín-Jiménez DI, Moreno-Luna R, Palacios-Garcia JM, Alvarez-Cendrero M, Vizcarra-Melgar JA, Fernandez-Velez C, Reyes-Tejero IM, Maza-Solano J, Gonzalez-Garcia J, Tena-García B, Acosta-Mosquera ME, Del Cuvillo A, and Sánchez-Gómez S
- Abstract
Background: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood., Methods: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT., Results: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS ( r = -0.36, p = 0.0027)., Conclusion: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.
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- 2022
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36. Supercritical Impregnation of Mango Leaf Extract into PLA 3D-Printed Devices and Evaluation of Their Biocompatibility with Endothelial Cell Cultures.
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Grosso P, Cejudo C, Sánchez-Gomar I, Durán-Ruiz MC, Moreno-Luna R, Casas L, Pereyra C, and Mantell C
- Abstract
The addition of natural substances with pharmacoactive properties to polymeric biomedical devices would provide beneficial regarding the assimilation of these endoprostheses when implanted into a patient's body. The added drug would facilitate endothelization by regulating the inflammatory processes that such interventions entail, preventing contamination hazards and favoring the angiogenesis or formation of blood vessels in the tissue. The present work used mango leaf extract (MLE) obtained through pressurized ethanol for this purpose. Polylactic acid (PLA) in the form of filaments or 3D-printed disks was impregnated by means of supercritical technology with MLE for the culture essays. The release kinetics has been studied and the polymer matrices have been examined by scanning electron microscopy (SEM). The impregnated devices were subjected to in vitro culture of colony-forming endothelial cells. The influence of the different impregnation conditions used for the production of the MLE impregnated polymeric devices on the development of the cell culture was determined by fluorescence microscopy. The best results were obtained from the calcein cultures on 35 °C MLE impregnated into 3D-printed polymer disks.
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- 2022
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37. Assessment of endothelial colony forming cells delivery routes in a murine model of critical limb threatening ischemia using an optimized cell tracking approach.
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Rojas-Torres M, Sánchez-Gomar I, Rosal-Vela A, Beltrán-Camacho L, Eslava-Alcón S, Alonso-Piñeiro JÁ, Martín-Ramírez J, Moreno-Luna R, and Durán-Ruiz MC
- Subjects
- Animals, Cells, Cultured, Disease Models, Animal, Humans, Ischemia therapy, Mice, Tissue Distribution, Cell Tracking, Neovascularization, Physiologic
- Abstract
Background: Endothelial colony forming cells (ECFCs), alone or in combination with mesenchymal stem cells, have been selected as potential therapeutic candidates for critical limb-threatening ischemia (CLTI), mainly for those patients considered as "no-option," due to their capability to enhance revascularization and perfusion recovery of ischemic tissues. Nevertheless, prior to translating cell therapy to the clinic, biodistribution assays are required by regulatory guidelines to ensure biosafety as well as to discard undesired systemic translocations. Different approaches, from imaging technologies to qPCR-based methods, are currently applied., Methods: In the current study, we have optimized a cell-tracking assay based on DiR fluorescent cell labeling and near-infrared detection for in vivo and ex vivo assays. Briefly, an improved protocol for DiR staining was set up, by incubation of ECFCs with 6.67 µM DiR and intensive washing steps prior cell administration. The minimal signal detected for the residual DiR, remaining after these washes, was considered as a baseline signal to estimate cell amounts correlated to the DiR intensity values registered in vivo. Besides, several assays were also performed to determine any potential effect of DiR over ECFCs functionality. Furthermore, the optimized protocol was applied in combination with qPCR amplification of specific human Alu sequences to assess the final distribution of ECFCs after intramuscular or intravenous administration to a murine model of CLTI., Results: The optimized DiR labeling protocol indicated that ECFCs administered intramuscularly remained mainly within the hind limb muscle while cells injected intravenously were found in the spleen, liver and lungs., Conclusion: Overall, the combination of DiR labeling and qPCR analysis in biodistribution assays constitutes a highly sensitive approach to systemically track cells in vivo. Thereby, human ECFCs administered intramuscularly to CLTI mice remained locally within the ischemic tissues, while intravenously injected cells were found in several organs. Our data corroborate the need to perform biodistribution assays in order to define specific parameters such as the optimal delivery route for ECFCs before their application into the clinic., (© 2022. The Author(s).)
- Published
- 2022
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38. Pro-Angiogenic Effects of Natural Antioxidants Extracted from Mango Leaf, Olive Leaf and Red Grape Pomace over Endothelial Colony-Forming Cells.
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Sánchez-Gomar I, Benítez-Camacho J, Cejudo-Bastante C, Casas L, Moreno-Luna R, Mantell C, and Durán-Ruiz MC
- Abstract
Cardiovascular diseases remain the leading cause of death worldwide, mainly triggered by the formation of atherosclerotic plaques that reduce blood flow. Angiogenic cell therapy based on endothelial colony forming cells (ECFCs) constitutes a promising alternative to promote vascular revascularization; however, under the oxidative environment that prevails in ischemic areas, these cells become impaired. Thus, it is necessary to investigate strategies to enhance their regenerative properties. Antioxidant substances, such as polyphenols, have been shown to be useful for this purpose. In the current study we evaluated the potential of mango leaves, olive leaves and red grape pomace extracts, rich in polyphenols, to promote ECFC reparative effects. For this, aqueous and ethanolic extracts of the aforementioned raw materials were obtained by pressurized liquid extraction (PLE). After evaluating the polyphenol content and the antioxidant activity, in vitro assays were carried out, and we found that ethanolic extracts at low concentrations improved angiogenic capacities of ECFCs and reduced proliferation, apoptosis, and the inflammatory response of these cells. Overall, mango leaves ethanolic extract provided the most promising results, but all three extracts ameliorated the functionality of ECFCs.
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- 2022
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39. Post-COVID Complications after Pressure Ulcer Surgery in Patients with Spinal Cord Injury Associate with Creatine Kinase Upregulation in Adipose Tissue.
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Martínez-Torija M, Esteban PF, Espino-Rodríguez FJ, Paniagua-Torija B, Molina-Holgado E, Ceruelo S, Barroso-Garcia G, Arandilla AG, Lopez-Almodovar LF, Arevalo-Martin A, Moreno JA, Garcia-Ovejero D, Durán-Ruiz MC, and Moreno-Luna R
- Subjects
- Adipose Tissue metabolism, COVID-19 Testing, Creatine Kinase metabolism, Creatine Kinase, Mitochondrial Form metabolism, Humans, Pandemics, Proteomics, SARS-CoV-2, Suppuration complications, Up-Regulation, COVID-19 complications, Pressure Ulcer epidemiology, Pressure Ulcer etiology, Pressure Ulcer surgery, Spinal Cord Injuries complications, Spinal Cord Injuries surgery
- Abstract
The risk of complications following surgical procedures is significantly increased in patients with SARS-CoV-2 infection. However, the mechanisms underlying these correlations are not fully known. Spinal cord injury (SCI) patients who underwent reconstructive surgery for pressure ulcers (PUs) before and during the COVID-19 pandemic were included in this study. The patient's postoperative progression was registered, and the subcutaneous white adipose tissue (s-WAT) surrounding the ulcers was analyzed by proteomic and immunohistochemical assays to identify the molecular/cellular signatures of impaired recovery. Patients with SCI and a COVID-19-positive diagnosis showed worse recovery and severe postoperative complications, requiring reintervention. Several proteins were upregulated in the adipose tissue of these patients. Among them, CKMT2 and CKM stood out, and CKM increased for up to 60 days after the COVID-19 diagnosis. Moreover, CKMT2 and CKM were largely found in MGCs within the s-WAT of COVID patients. Some of these proteins presented post-translational modifications and were targeted by autoantibodies in the serum of COVID patients. Overall, our results indicate that CKMT2, CKM, and the presence of MGCs in the adipose tissue surrounding PUs in post-COVID patients could be predictive biomarkers of postsurgical complications. These results suggest that the inflammatory response in adipose tissue may underlie the defective repair seen after surgery.
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- 2022
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40. The serum of COVID-19 asymptomatic patients up-regulates proteins related to endothelial dysfunction and viral response in circulating angiogenic cells ex-vivo.
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Beltrán-Camacho L, Eslava-Alcón S, Rojas-Torres M, Sánchez-Morillo D, Martinez-Nicolás MP, Martín-Bermejo V, de la Torre IG, Berrocoso E, Moreno JA, Moreno-Luna R, and Durán-Ruiz MC
- Subjects
- Humans, Immunoglobulin G, Nucleic Acid Amplification Techniques, SARS-CoV-2, COVID-19
- Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has already caused 6 million deaths worldwide. While asymptomatic individuals are responsible of many potential transmissions, the difficulty to identify and isolate them at the high peak of infection constitutes still a real challenge. Moreover, SARS-CoV-2 provokes severe vascular damage and thromboembolic events in critical COVID-19 patients, deriving in many related deaths and long-hauler symptoms. Understanding how these processes are triggered as well as the potential long-term sequelae, even in asymptomatic individuals, becomes essential., Methods: We have evaluated, by application of a proteomics-based quantitative approach, the effect of serum from COVID-19 asymptomatic individuals over circulating angiogenic cells (CACs). Healthy CACs were incubated ex-vivo with the serum of either COVID-19 negative (PCR -/IgG -, n:8) or COVID-19 positive asymptomatic donors, at different infective stages: PCR +/IgG - (n:8) and PCR -/IgG + (n:8). Also, a label free quantitative approach was applied to identify and quantify protein differences between these serums. Finally, machine learning algorithms were applied to validate the differential protein patterns in CACs., Results: Our results confirmed that SARS-CoV-2 promotes changes at the protein level in the serum of infected asymptomatic individuals, mainly correlated with altered coagulation and inflammatory processes (Fibrinogen, Von Willebrand Factor, Thrombospondin-1). At the cellular level, proteins like ICAM-1, TLR2 or Ezrin/Radixin were only up-regulated in CACs treated with the serum of asymptomatic patients at the highest peak of infection (PCR + /IgG -), but not with the serum of PCR -/IgG + individuals. Several proteins stood out as significantly discriminating markers in CACs in response to PCR or IgG + serums. Many of these proteins particiArticle title: Kindly check and confirm the edit made in the article title.pate in the initial endothelial response against the virus., Conclusions: The ex vivo incubation of CACs with the serum of asymptomatic COVID-19 donors at different stages of infection promoted protein changes representative of the endothelial dysfunction and inflammatory response after viral infection, together with activation of the coagulation process. The current approach constitutes an optimal model to study the response of vascular cells to SARS-CoV-2 infection, and an alternative platform to test potential inhibitors targeting either the virus entry pathway or the immune responses following SARS-CoV-2 infection., (© 2022. The Author(s).)
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- 2022
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41. Cannabinoid Receptor 1 associates to different molecular complexes during GABAergic neuron maturation.
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Molina-Holgado E, Paniagua-Torija B, Arevalo-Martin A, Moreno-Luna R, Esteban PF, Le MQU, Del Cerro MDM, and Garcia-Ovejero D
- Subjects
- Animals, Cells, Cultured, Female, Pregnancy, Rats, Rats, Wistar, Signal Transduction physiology, Cerebral Cortex embryology, Cerebral Cortex metabolism, GABAergic Neurons physiology, Receptor, Cannabinoid, CB1 genetics, Receptor, Cannabinoid, CB1 metabolism
- Abstract
CB
1 cannabinoid receptor is widely expressed in the central nervous system of animals from late prenatal development to adulthood. Appropriate activation and signaling of CB1 cannabinoid receptors in cortical interneurons are crucial during perinatal/postnatal ages and adolescence, when long-lasting changes in brain activity may elicit subsequent appearance of disorders in the adult brain. Here we used an optimized immunoprecipitation protocol based on specific antibodies followed by shot-gun proteomics to find CB1 interacting partners in postnatal rat GABAergic cortical neurons in vitro at two different stages of maturation. Besides describing new proteins associated with CB1 like dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (DLAT), fatty acid synthase (FASN), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), voltage-dependent anion channel 1 (VDAC1), myosin phosphatase Rho-interacting protein (MPRIP) or usher syndrome type-1C protein-binding protein 1 (USHBP1), we show that the signaling complex of CB1 is different between maturational stages. Interestingly, the CB1 signaling complex is enriched at the more immature stage in mitochondrial associated proteins and metabolic molecular functions, whereas at more mature stage, CB1 complex is increased in maturation and synaptic-associated proteins. We describe also interacting partners specifically immunoprecipitated with either N-terminal or C-terminal CB1 directed antibodies. Our results highlight new players that may be affected by altered cannabinoid signaling at this critical window of postnatal cortical development., (© 2021 International Society for Neurochemistry.)- Published
- 2021
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42. Usefulness of endonasal flaps and grafts in skull base surgery. Consensus document.
- Author
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Moreno-Luna R, Mariño Sánchez F, Kaen A, Gras Cabrerizo JR, Mata Castro N, González García J, Villacampa Aubá JM, Cárdenas Ruiz-Valdepeñas E, Monjas Cánovas I, Del Cuvillo Bernal A, García Piñero A, Maza Solano JM, Fernández de Liesa R, Sánchez-Gómez S, and Alobid I
- Abstract
Introduction: Skull base reconstruction is one of the greatest challenges extended endonasal endoscopic surgery. Many grafts and flaps from the endonasal fossa have been demonstrated to be useful in the control of complications such a cerebrospinal fluid leaks. Review and analysis of these resources are necessary in skull base recontruction to improve outcomes., Objectives: The target is to create a consensus document on the use of different endonasal flaps and grafts in the skull base surgery., Material and Methods: Literature review of the most relevant free grafts and vascularized flaps from the endonasal fossa. Analysis using the Delphi method on the use of the different endonasal resources for endoscopic repair of skull base defects., Results: We obtained two results: 1) A selection of the most representative flaps and grafts from the endonasal fossa, describing origin, surface and indications, based on a literature review. 2) A consensus document, using Delphi methodology, with general considerations (2), recommendations (10) and limitations (6) of the different endonasal flaps and grafts., Conclusions: We present the first consensus document in the field of extended endonasal endoscopic surgery using the Delphi method as a working tool. We highlight the usefulness of the nasoseptal flap together with other endonasal flaps and grafts for skull base reconstruction., (Copyright © 2021 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
43. Usefulness of endonasal mucoplasty in the surgical treatment of chronic rhinosinusitis with nasal polyps. Prospective study.
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Moreno-Luna R, González-García J, Palacios-García J, Maza-Solano JM, Del Cuvillo Bernal A, and Sánchez-Gómez S
- Subjects
- Case-Control Studies, Chronic Disease, Humans, Prospective Studies, Quality of Life, Nasal Polyps surgery, Sinusitis surgery
- Abstract
Chronic Rhinosinusitis with Nasal Polyps (CRScPN) is a disease with great impact on health. The surgical option using endoscopic nasosinus surgery is the therapeutic alternative when control of the disease is not achieved with medical treatment. Extensive endoscopic approaches are being postulated as a possible best surgical treatment option in certain phenotypes of CRScPN. Endonasal mucoplasty associated with these approaches has been shown to be a complementary technique that improves both healing and mucosal oedema in patients with CRScPN in the short term. The aim of our study was to analyse the results of endonasal mucoplasty associated with a complete ethmoid-sphenoidotomy plus grade III frontal sinusotomy in the treatment of CRScPN in the medium term. For this purpose, a prospective case-control study (10/10) was carried out on patients with CRScPN. In the case group, endonasal mucoplasty in the left nostril was associated with surgery, and the control group was not. The assessment of quality of life at one year after surgery, as measured by the mean difference in SNOT-22 (mean [SD]), in the case group was significantly better than in the control group, (45.9 [19.6]-26.6 [16.05], P = 0.027). The endoscopic improvement in healing and mucosal oedema, measured by the Modified Lund-Kennedy scale, showed relevant improvements, when comparing both pits, but without reaching significance (P = 0.29). Endonasal mucoplasty promotes short-term healing, improving the quality of life in the medium term (one year) of patients treated with extensive endoscopic breast resections., (Copyright © 2020 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Published by Elsevier España, S.L.U. All rights reserved.)
- Published
- 2021
- Full Text
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44. Loss of Smell and Taste Can Accurately Predict COVID-19 Infection: A Machine-Learning Approach.
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Callejon-Leblic MA, Moreno-Luna R, Del Cuvillo A, Reyes-Tejero IM, Garcia-Villaran MA, Santos-Peña M, Maza-Solano JM, Martín-Jimenez DI, Palacios-Garcia JM, Fernandez-Velez C, Gonzalez-Garcia J, Sanchez-Calvo JM, Solanellas-Soler J, and Sanchez-Gomez S
- Abstract
The COVID-19 outbreak has spread extensively around the world. Loss of smell and taste have emerged as main predictors for COVID-19. The objective of our study is to develop a comprehensive machine learning (ML) modelling framework to assess the predictive value of smell and taste disorders, along with other symptoms, in COVID-19 infection. A multicenter case-control study was performed, in which suspected cases for COVID-19, who were tested by real-time reverse-transcription polymerase chain reaction (RT-PCR), informed about the presence and severity of their symptoms using visual analog scales (VAS). ML algorithms were applied to the collected data to predict a COVID-19 diagnosis using a 50-fold cross-validation scheme by randomly splitting the patients in training (75%) and testing datasets (25%). A total of 777 patients were included. Loss of smell and taste were found to be the symptoms with higher odds ratios of 6.21 and 2.42 for COVID-19 positivity. The ML algorithms applied reached an average accuracy of 80%, a sensitivity of 82%, and a specificity of 78% when using VAS to predict a COVID-19 diagnosis. This study concludes that smell and taste disorders are accurate predictors, with ML algorithms constituting helpful tools for COVID-19 diagnostic prediction.
- Published
- 2021
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45. Acetazolamide conceals a pituitary macroadenoma in a patient with criteria of vestibular migraine.
- Author
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Prieto-Sánchez-de-Puerta L, Domínguez-Durán E, Moreno-Luna R, and Sánchez-Gómez S
- Published
- 2021
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46. Radioanatomical study of the extended free nasal floor mucosal graft and its clinical applications.
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González-García J, Moreno-Luna R, Palacios-García J, Del Cuvillo Bernal A, Maza-Solano JM, Santos Pérez J, Pinheiro-Neto CD, Sánchez-Gómez S, and Ambrosiani Fernández J
- Abstract
Objectives: To perform a radio-anatomical evaluation of the nasal cavity floor free mucosal graft (endonasal extended mucoplasty, EEM) to repair mucosal defects after an extended ethmoid-sphenoidotomy., Methods: A human cadaveric study (radiological and anatomical dissection) and an in vivo study in surgical patients with CRSwNP were performed. The EEM areas were compared between 3D reconstruction from CT scans and anatomical/surgical dissections, both in cadaver specimens and in patients. Feasibility was assessed by correlation between the EEM area on CT scans and when harvested in cadavers and when grafted in patients. Usefulness was assessed by the degree of coverage of the EEM in the surface exposed after an extended ethmoid-sphenoidotomy. Both feasibility and usefulness were assessed in cadaveric specimens (n = 15) and patients (n = 4)., Results: Fifteen cadaveric specimens and 4 patients with bilateral CRSwNP were included. The mean (SD) areas obtained in the cadaveric radiological and anatomical studies were 9.44 (2.07) cm
2 and 8.03 (1.36) cm2 , respectively (intraclass correlation coefficient 0.59, moderate correlation), and in 3D reconstruction for operated patients were 10.32 (0.98) cm2 and 11.27 (2.44) cm2 , respectively. The coverage of the ethmoidal roof in the cadaveric dissection study was 100%, from the anterior ethmoidal artery to the posterior ethmoidal artery, covering the planun sphenoidale up to 75% in the case series. In 87.5% of the cases, up to 50% of the papiracea lamina was covered., Conclusion: The EEM have shown to be a feasible and useful grafting technique to repair skull base defects after performing an extended ethmoid-sphenoidotomy during surgery for CRSwNP., Level of Evidence: NA., Competing Interests: The authors declare no potential conflict of interest., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)- Published
- 2020
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47. Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis.
- Author
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Martin-Rojas T, Sastre-Oliva T, Esclarín-Ruz A, Gil-Dones F, Mourino-Alvarez L, Corbacho-Alonso N, Moreno-Luna R, Hernandez-Fernandez G, Lopez JA, Oliviero A, and Barderas MG
- Abstract
Despite promising advances in the medical management of spinal cord injury (SCI), there is still no available effective therapy to repair the neurological damage in patients who experience this life-transforming condition. Recently, we performed a phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone (GH) treatment in incomplete chronic traumatic spinal cord injury. The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo slightly improves the SCI individual motor score. Moreover, we found that an intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals. To understand the possible mechanisms of the improvement due to GH treatment (motor score) and due to rehabilitation (functional outcome), we used a proteomic approach. Here, we used a multiple proteomic strategy to search for recovery biomarkers in blood plasma with the potential to predict response to somatropin treatment and to delayed intensive rehabilitation. Forty-six patients were recruited and followed for a minimum period of 1 year. Patients were classified into two groups based on their treatment: recombinant somatropin (0.4 mg) or placebo. Both groups received rehabilitation treatment. Our strategy allowed us to perform one of the deepest plasma proteomic analyses thus far, which revealed two proteomic signatures with predictive value: (i) response to recombinant somatropin treatment and (ii) response to rehabilitation. The proteins implicated in these signatures are related to homeostasis, inflammation, and coagulation functions. These findings open novel possibilities to assess and therapeutically manage patients with SCI, which could have a positive impact on their clinical response.
- Published
- 2020
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48. Atherosclerotic Pre-Conditioning Affects the Paracrine Role of Circulating Angiogenic Cells Ex-Vivo.
- Author
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Eslava-Alcon S, Extremera-García MJ, Sanchez-Gomar I, Beltrán-Camacho L, Rosal-Vela A, Muñoz J, Ibarz N, Alonso-Piñero JA, Rojas-Torres M, Jiménez-Palomares M, González-Rovira A, Conejero R, Doiz E, Rodriguez-Piñero M, Moreno-Luna R, and Durán-Ruiz MC
- Subjects
- Atherosclerosis pathology, Endothelial Progenitor Cells pathology, Humans, Atherosclerosis metabolism, Cell Movement, Cell Proliferation, Endothelial Progenitor Cells metabolism, Neovascularization, Physiologic, Paracrine Communication, Signal Transduction
- Abstract
In atherosclerosis, circulating angiogenic cells (CAC), also known as early endothelial progenitor cells (eEPC), are thought to participate mainly in a paracrine fashion by promoting the recruitment of other cell populations such as late EPC, or endothelial colony-forming cells (ECFC), to the injured areas. There, ECFC replace the damaged endothelium, promoting neovascularization. However, despite their regenerative role, the number and function of EPC are severely affected under pathological conditions, being essential to further understand how these cells react to such environments in order to implement their use in regenerative cell therapies. Herein, we evaluated the effect of direct incubation ex vivo of healthy CAC with the secretome of atherosclerotic arteries. By using a quantitative proteomics approach, 194 altered proteins were identified in the secretome of pre-conditioned CAC, many of them related to inhibition of angiogenesis (e.g., endostatin, thrombospondin-1, fibulins) and cell migration. Functional assays corroborated that healthy CAC released factors enhanced ECFC angiogenesis, but, after atherosclerotic pre-conditioning, the secretome of pre-stimulated CAC negatively affected ECFC migration, as well as their ability to form tubules on a basement membrane matrix assay. Overall, we have shown here, for the first time, the effect of atherosclerotic factors over the paracrine role of CAC ex vivo. The increased release of angiogenic inhibitors by CAC in response to atherosclerotic factors induced an angiogenic switch, by blocking ECFC ability to form tubules in response to pre-conditioned CAC. Thus, we confirmed here that the angiogenic role of CAC is highly affected by the atherosclerotic environment.
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- 2020
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49. Revisiting CB 1 cannabinoid receptor detection and the exploration of its interacting partners.
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Esteban PF, Garcia-Ovejero D, Paniagua-Torija B, Moreno-Luna R, Arredondo LF, Zimmer A, Arevalo-Martin A, and Molina-Holgado E
- Subjects
- Animals, Blotting, Western, Mice, Mice, Knockout, Receptor, Cannabinoid, CB1 genetics, Receptor, Cannabinoid, CB2, Receptors, Cannabinoid genetics, Brain, Eating
- Abstract
Background: Cannabinoid receptor 1 (CB
1 ) identification by western blot (WB) has generated a great deal of controversial data making the interpretation of the results difficult. Our purpose is to find the most adequate experimental conditions to detect CB1 by WB and immunoprecipitation (IP) as a first step towards the study of CB1 interactome., New Method: We use CB1 knockout mice tissue as negative controls and describe appropriate sample handling conditions for CB1 detection by WB and IP from brain and cortical neuron cultures., Results: Sample heating above 65 °C greatly impaired CB1 detection by WB, since it favored the formation of high molecular weight aggregates. We also show the convenience of using n-dodecyl-β-d-maltoside (DDM) as a detergent for the detection of CB1 by WB and, mostly, for IP., Comparison With Existing Method(s): We obtain consistent and specific CB1 detection by WB and IP using four different commercial antibodies and KO tissue for an accurate CB1 identification. We clarify the identification of the receptor in complex samples compared with the diverse and unclear results obtained using standard WB methods., Conclusions: We establish experimental guidelines for the detection of CB1 by WB and the study of CB1 interacting proteins by IP. We propose a new interpretation of CB1 WB and IP data based on the folding and packing state of the protein and the detergent used. The standardization of the most advantageous conditions for coimmunoprecipitation (CoIP) would be a useful tool for the future study of the interactome of CB1 ., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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50. Identification of the initial molecular changes in response to circulating angiogenic cells-mediated therapy in critical limb ischemia.
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Beltran-Camacho L, Jimenez-Palomares M, Rojas-Torres M, Sanchez-Gomar I, Rosal-Vela A, Eslava-Alcon S, Perez-Segura MC, Serrano A, Antequera-González B, Alonso-Piñero JA, González-Rovira A, Extremera-García MJ, Rodriguez-Piñero M, Moreno-Luna R, Larsen MR, and Durán-Ruiz MC
- Subjects
- Animals, Cell- and Tissue-Based Therapy, Humans, Ischemia therapy, Mice, Mice, Nude, Neovascularization, Physiologic, Peripheral Arterial Disease therapy
- Abstract
Background: Critical limb ischemia (CLI) constitutes the most aggressive form of peripheral arterial occlusive disease, characterized by the blockade of arteries supplying blood to the lower extremities, significantly diminishing oxygen and nutrient supply. CLI patients usually undergo amputation of fingers, feet, or extremities, with a high risk of mortality due to associated comorbidities. Circulating angiogenic cells (CACs), also known as early endothelial progenitor cells, constitute promising candidates for cell therapy in CLI due to their assigned vascular regenerative properties. Preclinical and clinical assays with CACs have shown promising results. A better understanding of how these cells participate in vascular regeneration would significantly help to potentiate their role in revascularization. Herein, we analyzed the initial molecular mechanisms triggered by human CACs after being administered to a murine model of CLI, in order to understand how these cells promote angiogenesis within the ischemic tissues., Methods: Balb-c nude mice (n:24) were distributed in four different groups: healthy controls (C, n:4), shams (SH, n:4), and ischemic mice (after femoral ligation) that received either 50 μl physiological serum (SC, n:8) or 5 × 10
5 human CACs (SE, n:8). Ischemic mice were sacrificed on days 2 and 4 (n:4/group/day), and immunohistochemistry assays and qPCR amplification of Alu-human-specific sequences were carried out for cell detection and vascular density measurements. Additionally, a label-free MS-based quantitative approach was performed to identify protein changes related., Results: Administration of CACs induced in the ischemic tissues an increase in the number of blood vessels as well as the diameter size compared to ischemic, non-treated mice, although the number of CACs decreased within time. The initial protein changes taking place in response to ischemia and more importantly, right after administration of CACs to CLI mice, are shown., Conclusions: Our results indicate that CACs migrate to the injured area; moreover, they trigger protein changes correlated with cell migration, cell death, angiogenesis, and arteriogenesis in the host. These changes indicate that CACs promote from the beginning an increase in the number of vessels as well as the development of an appropriate vascular network.- Published
- 2020
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