Ramírez, Pablo (Ramírez Romero)

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Ramírez, Pablo (Ramírez Romero)

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Ramírez, Pablo (Ramírez Romero)

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Universidad de Murcia. Departamento de Cirugía, Pediatría, Obstetriciay Ginecología

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Student nurses at Spanish universities and their attitude toward xenotransplantation
(Wiley, 2019-05) Martinez Alarcon, Laura; Santainés-Borreda, Elena; Parrilla, Pascual; Ramírez, Pablo (Ramírez Romero); Rios Zambudio, Antonio; Cirugía, Pediatría y Obstetricia y Ginecología
Abstract Introduction: Recent immunological and transgenic advances are a promising alternative using limited materials of human origin for transplantation. However, it is essential to achieve social acceptance of this therapy. Objective: To analyze the attitude of nursing students from Spanish universities toward organ xenotransplantation (XTx) and to determine the factors affecting their attitude. Materials and methods: Type of study: A sociological, multicentre, and observational study. Study population: Nursing students enrolled in Spain (n = 28,000). Sample size: A sample of 10 566 students estimating a proportion of 76% (99% confidence and precision of ±1%), stratified by geographical area and year of study. Instrument of measurement: A validated questionnaire (PCID‐XenoTx‐RIOS) was handed out to every student in a compulsory session. This survey was self‐administered and selfcompleted voluntarily and anonymously by each student in a period of 5‐10 min. Statistical analysis: descriptive analysis, Student's t test, the chi‐square test, and a logistic regression analysis. Results: A completion rate: 84% (n = 8913) was obtained. If the results of XTx were as good as in human donation, 74% (n = 6564) would be in favor and 22% (n = 1946) would have doubts. The following variables affected this attitude: age (P < 0.001); sex (P < 0.001); geographical location (P < 0.001); academic year of study (P < 0.001); attitude toward organ donation (P < 0.001); belief in the possibility of needing a transplant (P < 0.001); discussion of transplantation with one's family (P < 0.001) and friends (P < 0.001); and the opinion of one's partner (P < 0.001). The following variables persisted in the multivariate analysis: being a male (OR = 1.436; P < 0.001); geographical location (OR = 1.937; P < 0.001); an attitude in favor of donation (OR = 1.519; P < 0.001); belief in the possibility of needing a transplant (OR = 1.497; P = 0.036); and having spoken about the issue with family (OR = 1.351; P < 0.001) or friends (OR = 1.240; P = 0.001). Conclusions: The attitude of nursing students toward organ XTx is favorable and is associated with factors of general knowledge about organ donation and transplantation and social interaction.
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Tolerance biomarkers in liver transplantation: independent external validation of the predictive strength of SENP6 and FEM1C gene expression
(Lippincott, Williams & Wilkins, 2019-09) Perez-Sanz, Fernando; Revilla-Nuin, Beatriz; Martinez-Alarcon, Laura; Herrero, José I.; Pons Miñano, José Antonio; Baroja-Mazo, Alberto; Ramírez, Pablo (Ramírez Romero); Medicina
Background. Numerous studies have emphasized the genetic and phenotypic profiles of tolerant transplant patients.Moreover, different groups have defined several biomarkers, trying to distinguish patients who are going to be tolerant from those who are going to reject. However, most of these biomarkers have not been validated by other groups or even established for clinical practice. Methods. We reanalyzed and stratified the predictive capacity of 20 previously described biomarkers for liver transplantation tolerance in a cohort of 17 liver transplant patients subjected to an independent, nonrandomized, prospective study of immunosuppression drug withdrawal. Results. Only 4 of the 20 studied biomarkers (expression of SENP6, FEM1C, miR31, and miR95) showed a strong predictive capacity in the present study. miR31 and FEM1C presented an area under the ROC curve of 96.7%, followed by SENP1 with 93.3%. Finally, miR95 had an area under the ROC curve value <86.7%. Conclusions. Even though this independent analysis seems to confirm the predictive strength of SENP6 and FEM1C in liver transplantation tolerance, there are also risks in establishing biomarkers for clinical phenotypes without an understanding of how they are biologically relevant. Future collaborations between groups should be promoted so that the most promising biomarkers can be validated and implemented in daily clinical practice.
Open Access
Endothelial cell activation mediated by cold ischemia-released mitochondria is partially inhibited by defibrotide and impacts on early allograft function following liver transplantation
(Elsevier, 2023-09-18) Villalba-Lopez, Francisco; Mateo, Sandra V.; Vidal-Correoso, Daniel; Jover-Aguilar, Marta; Martínez-Alarcón, Laura; López-López, Víctor; Pons Miñano, José Antonio; Baroja-Mazo, Alberto; García Bernal, David; Pelegrín Vivancos, Pablo; Alconchel Gago, Felipe; Cascales Campos, Pedro Antonio; Ramírez, Pablo (Ramírez Romero); Rios Zambudio, Antonio; Medicina
DAMPs (danger-associated molecular patterns) are self-molecules of the organism that appear after damage. The endothelium plays several roles in organ rejection, such as presenting alloantigens to T cells and contributing to the development of inflammation and thrombosis. This study aimed to assess whether DAMPs present in the organ preservation solution (OPS) after cold ischemic storage (CIS) contribute to exacerbating the endothelial response to an inflammatory challenge and whether defibrotide treatment could counteract this effect. The activation of cultured human umbilical vein endothelial cells (HUVECs) was analyzed after challenging with endischemic OPS (eiOPS) obtained after CIS. Additionally, transwell assays were performed to study the ability of eiOPS to attract lymphocytes across the endothelium. The study revealed that eiOPS upregulated the expression of MCP-1 and IL-6 in HUVECs. Moreover, eiOPS increased the membrane expression of ICAM-1and HLA-DR, which facilitated leukocyte migration toward a chemokine gradient. Furthermore, eiOPS demonstrated its chemoattractant ability. This activation was mediated by free mitochondria. Defibrotide was found to partially inhibit the eiOPS-mediated activation. Moreover, the eiOPS-mediated activation of endothelial cells (ECs) correlated with early allograft dysfunction in liver transplant patients. Our finding provide support for the hypothesis that mitochondria released during cold ischemia could trigger EC activation, leading to complications in graft outcomes. Therefore, the analysis and quantification of free mitochondria in the eiOPS samples obtained after CIS could provide a predictive value for monitoring the progression of transplantation. Moreover, defibrotide emerges as a promising therapeutic agent to mitigate the damage induced by ischemia in donated organs.
Open Access
Danger signals released during cold ischemia storage activate NLRP3 inflammasome in myeloid cells and influence early allograft function in liver transplantation
(Elsevier, 2022-12-19) Lucas-Ruiz, Fernando; Mateo, Sandra V.; Jover-Aguilar, Marta; Martínez-Alarcón, Laura; Torre-Minguela, Carlos de; Vidal-Correoso, Daniel; Villalva-López, Francisco; López-López, Víctor; Pons Miñano, José Antonio; Baroja-Mazo, Alberto; Pelegrín Vivancos, Pablo; Alconchel Gago, Felipe; Ramírez, Pablo (Ramírez Romero); Rios Zambudio, Antonio; Medicina
Background Innate immunity plays a fundamental role in solid organ transplantation. Myeloid cells can sense danger signals or DAMPs released after tissue or cell damage, such as during ischemia processes. This study aimed to identify DAMPs released during cold ischemia storage of human liver and analyze their ability to activate the inflammasome in myeloid cells and the possible implications in terms of short-term outcomes of liver transplantation. Methods 79 samples of organ preservation solution (OPS) from 79 deceased donors were collected after cold static storage. We used different analytical methods to measure DAMPs in these end-ischemic OPS (eiOPS) samples. We also used eiOPS in the human macrophage THP-1 cell line and primary monocyte cultures to study inflammasome activation. Findings Different DAMPs were identified in eiOPS, several of which induced both priming and activation of the NLRP3 inflammasome in human myeloid cells. Cold ischemia time and donation after circulatory death negatively influenced the DAMP signature. Moreover, the presence of oligomeric inflammasomes and interleukin-18 in eiOPS correlated with early allograft dysfunction in liver transplant patients. Interpretation DAMPs released during cold ischemia storage prime and activate the NLRP3 inflammasome in liver macrophages after transplantation, inducing a pro-inflammatory environment that will complicate the outcome of the graft. The use of pharmacological blockers targeting DAMPs or the NLRP3 inflammasome in liver ischemia during static cold storage or through extracorporeal organ support could be a suitable strategy to increase the success of liver transplantation.
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Cell-specific extracellular vesicles and their miRNA cargo released Into the organ preservations solution during cold ischemia storage as biomarkers for liver transplant outcomes
(Lippincott, Williams & Wilkins, 2024-10) Vidal-Correoso, Daniel; Mateo, Sandra V.; Muñoz-Morales, Ana M.; Lucas-Ruiz, Fernando; Jover-Aguilar, Marta; Martinez-Alarcon, Laura; Sanchez-Redondo, Sara; Santos, Vanesa; Lopez-Lopez, Victor; Pons Miñano, José Antonio; Peinado, Hector; Baroja-Mazo, Alberto; Pelegrín Vivancos, Pablo; Alconchel Gago, Felipe; Cascales Campos, Pedro Antonio; Ramírez, Pablo (Ramírez Romero); Rios Zambudio, Antonio; Medicina
Background. Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools. Methods. EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform. Results. Differentsized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p, miR-28-5p, miR-200a-3p, miR- 200b-3p, miR-200c-3p, and miR-429, were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT. Conclusions. These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT.
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Learning Curve for Laparoscopic Sleeve Gastrectomy: a Cumulative Summation (CUSUM) Analysis
(Springer, 2022-08-01) Gil, Pedro J; Ruíz‑Manzanera, Juan José; Ruíz de Antgulo, David; Ferreras, David; López, Victor; Conesa, ANA; Ortiz, Angeles; Martínez de Haro, Luisa Fernanda; Munitiz Ruiz, Vicente; Ramírez, Pablo (Ramírez Romero); Cirugía, Pediatría y Obstetricia y Ginecología
Abstract Purpose Bariatric surgery is currently considered the most effective and durable treatment option for morbid obesity. Laparoscopic sleeve gastrectomy (LSG) has become a popular technique and may currently be the most frequently practiced surgical operation to treat obesity. However, no objective analyses of its learning curve have been reported. Objective: to analyze the learning curve for LSG. Materials and Methods We included all LSGs performed in our hospital (University Hospital, Spain; Public Practice) from April 2013 to February 2016. The learning curve for LSG was evaluated using cumulative sum (CUSUM) analysis. All variables among the learning curve phases were compared. Results According to the CUSUM analysis, the learning curve was divided into three unique phases: early learning (the initial 26 patients), acquisition of skills (the middle 30 patients), and mastery of technique (the final 56 patients). The operative time and gastric stenosis significantly decreased with progression of the learning curve without differences in the 30-day postoperative complication rate, postoperative stay, or weight loss. Conclusion According to this study, the learning curve for LSG can be divided into 3 distinct phases, and about 25 patients are needed to demonstrate an improvement in surgical skill.
Open Access
Transcriptional regulation by poly(ADP-ribose) polymerase-1 during T cell activation
(BMC, 2008-04-16) Saenz, Luis; Lozano, Juan J; Baroja Mazo, , Alberto; Parrilla, Pascual; Aparicio, Pedro; Sumoy, Lauro; Yélamos, José; Valdor Alonso, Rut; Ramírez, Pablo (Ramírez Romero); Bioquímica y Biología Molecular B e Inmunología
Background: Accumulating evidence suggests an important role for the enzyme poly(ADPribose) polymerase-1 (PARP-1) as an integral part of the gene expression regulatory machinery during development and in response to specific cellular signals. PARP-1 might modulate gene expression through its catalytic activity leading to poly(ADP-ribosyl)ation of nuclear proteins or by its physical association with relevant proteins. Recently, we have shown that PARP-1 is activated during T cell activation. However, the proposed role of PARP-1 in reprogramming T cell gene expression upon activation remains largely unexplored. Results: In the present study we use oligonucleotide microarray analysis to gain more insight into the role played by PARP-1 during the gene expression reprogramming that takes place in T cells upon activation with anti-CD3 stimulation alone, or in combination with anti-CD28 co-stimulation. We have identified several groups of genes with expression modulated by PARP-1. The expression of 129 early-response genes to anti-CD3 seems to be regulated by PARP-1 either in a positive (45 genes) or in a negative manner (84 genes). Likewise, in the presence of co-stimulation (anti-CD3 + anti-CD28 stimulation), the expression of 203 genes is also regulated by PARP-1 either up (173 genes) or down (30 genes). Interestingly, PARP-1 deficiency significantly alters expression of genes associated with the immune response such as chemokines and genes involved in the Th1/Th2 balance. Conclusion: This study provides new insights into changes in gene expression mediated by PARP1 upon T cell activation. Pathway analysis of PARP-1 as a nuclear signalling molecule in T cells would be of relevance for the future development of new therapeutic approaches targeting PARP-1 in the acquired immune response.
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Alteraciones de la motilidad del intestino delgado en situaciones de estrés físico agudo ; Estudio experimental en perros / Pablo Ramírez Romero; dirigido por Pascual Paricio, José Luis Ponce Marco
(Murcia : Universidad, Facultad de Medicina,, 1985) Ramírez, Pablo (Ramírez Romero)
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Hematic antegrade repriming: a reproducible method to decrease the cardiopulmonary bypass Insult
(EDPSciences, 2021-03-15) Blanco Morillo, Juan; Farina, Piero; Fernández González, Angel Luis; Sornichero Caballero, Ángel; Chen, Tyler N.; Cánovas López, Sergio; Salmerón Martínez, Diego; Arribas Leal, José María; Ramírez, Pablo (Ramírez Romero); Cirugía, Pediatría y Obstetricia y Ginecología
The current practice of cardiopulmonary bypass (CPB) requires a preoperative priming of the circuit that is frequently performed with crystalloid solutions. Crystalloid priming avoids massive embolism but is unable to eliminate all microbubbles contained in the circuit. In addition, it causes a sudden hemodilution which is correlated with transfusion requirements and an increased risk of cognitive impairment. Several repriming techniques using autologous blood, collectively termed retrograde autologous priming (RAP), have been demonstrated to reduce the hemodilutional impact of CPB. However, the current heterogeneity in the practice of RAP limits its evidence and benefits. Here, we describe hematic antegrade repriming as an easy and reliable method that could be applied with any circuit in the market to decrease transfusion requirements, emboli, and inflammatory responses, reducing costs and the impact of CPB on postoperative recovery.
Open Access
Confirmation of SARS-CoV-2 airborne dissemination indoors using “COVID-19 traps”
(Elsevier, 2021-12-15) Navas-Carrillo, Diana; Moreno-Docón, Antonio; García-Vázquez, Elisa; Orenes-Piñero, Esteban; Torres Cantero, Alberto Manuel; Ortega García, Juan Antonio; Ramírez, Pablo (Ramírez Romero); Medicina