26 results on '"Bravo, Miguel A."'
Search Results
2. Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).
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Serradilla-Martín M, Villodre C, Falgueras-Verdaguer L, Zambudio-Carroll N, Castell-Gómez JT, Blas-Laina JL, Borrego-Estella V, Domingo-Del-Pozo C, García-Plaza G, González-Rodríguez FJ, Montalvá-Orón EM, Moya-Herraiz Á, Paterna-López S, Suárez-Muñoz MA, Alkorta-Zuloaga M, Blanco-Fernández G, Dabán-Collado E, Gómez-Bravo MA, Miota-de-Llamas JI, Rotellar F, Sánchez-Pérez B, Sánchez-Cabús S, Pacheco-Sánchez D, Rodríguez-Sanjuan JC, Varona-Bosque MA, Carrión-Álvarez L, de la Serna-Esteban S, Dopazo C, Martín-Pérez E, Martínez-Cecilia D, Castro-Santiago MJ, Dorcaratto D, Gutiérrez-Díaz ML, Asencio-Pascual JM, Burdío-Pinilla F, Carracedo-Iglesias R, Escartín-Arias A, Ielpo B, Rodríguez-Laiz G, Valdivieso-López A, De-Vicente-López E, Alonso-Orduña V, and Ramia JM
- Abstract
(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.
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- 2024
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3. Development of a liver graft assessment expert machine-learning system: when the artificial intelligence helps liver transplant surgeons.
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Pontes Balanza B, Castillo Tuñón JM, Mateos García D, Padillo Ruiz J, Riquelme Santos JC, Álamo Martinez JM, Bernal Bellido C, Suarez Artacho G, Cepeda Franco C, Gómez Bravo MA, and Marín Gómez LM
- Abstract
Background: The complex process of liver graft assessment is one point for improvement in liver transplantation. The main objective of this study is to develop a tool that supports the surgeon who is responsible for liver donation in the decision-making process whether to accept a graft or not using the initial variables available to it., Material and Method: Liver graft samples candidate for liver transplantation after donor brain death were studied. All of them were evaluated " in situ " for transplantation, and those discarded after the " in situ " evaluation were considered as no transplantable liver grafts, while those grafts transplanted after " in situ " evaluation were considered as transplantable liver grafts. First, a single-center, retrospective and cohort study identifying the risk factors associated with the no transplantable group was performed. Then, a prediction model decision support system based on machine learning, and using a tree ensemble boosting classifier that is capable of helping to decide whether to accept or decline a donor liver graft, was developed., Results: A total of 350 liver grafts that were evaluated for liver transplantation were studied. Steatosis was the most frequent reason for classifying grafts as no transplantable, and the main risk factors identified in the univariant study were age, dyslipidemia, personal medical history, personal surgical history, bilirubinemia, and the result of previous liver ultrasound ( p < 0.05). When studying the developed model, we observe that the best performance reordering in terms of accuracy corresponds to 76.29% with an area under the curve of 0.79. Furthermore, the model provides a classification together with a confidence index of reliability, for most cases in our data, with the probability of success in the prediction being above 0.85., Conclusion: The tool presented in this study obtains a high accuracy in predicting whether a liver graft will be transplanted or deemed non-transplantable based on the initial variables assigned to it. The inherent capacity for improvement in the system causes the rate of correct predictions to increase as new data are entered. Therefore, we believe it is a tool that can help optimize the graft pool for liver transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pontes Balanza, Castillo Tuñón, Mateos García, Padillo Ruiz, Riquelme Santos, Álamo Martinez, Bernal-Bellido, Suarez Artacho, Cepeda Franco, Gomez Bravo and Marin Gome.)
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- 2023
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4. Humanization of care in acute psychiatric hospitalization units: A scoping review.
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Sanz-Osorio MT, Sastre-Rus M, Monistrol O, Pérez Criado M, Vallès V, and Escobar-Bravo MA
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- Humans, Mental Health, Hospitalization, Psychotic Disorders
- Abstract
WHAT IS KNOWN ON THE SUBJECT?: Humanizing the world of health is a complex process that includes all the dimensions of the person. When a person has from a mental illness, the humanization of care becomes more important, as the disorder itself prevents the person to participate in their health process, even when showing self-harm or aggressive behaviours. These situations jointly with other factors related with professionals (insufficient ratio, inadequate treatment or lack of training) may cause the patient admitted to the acute psychiatric hospitalization unit to require the use of restrictive measures (involuntary admissions, mechanical restraints or forced administration of medication). WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: We identify the relevance of the perception the patient and family have regarding the care received, as well as the relevance of factors related to the professionals, among which the attitude, the staff ratio, the nursing time of direct dedication, and the therapeutic environment and safety of the patient and the professionals. All patients must be treated with dignity, respect, regardless of the aggressive manifestations caused by their pathology. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A greater understanding of the care offered to admitted people affected by a mental disorder, their families and professionals who care for them in acute mental health units, giving greater importance to "caring" and not exclusively to "curing.", Abstract: INTRODUCTION: Humanization in Mental Health refers to give the same relevance to the clinical needs and to the social, emotional and psychological needs., Aim: To identify the published knowledge on current care models related to the humanization of care in acute psychiatric units., Method: Scoping review based on the methodological model of Arksey and O'Malley, and PRISMA methodology. Database searches (Pubmed, Cinahl, Virtual Library, Cuiden, Academic Google and PsycInfo) with the terms: "Humanization," "Hospitals Psychiatric," "Emergency Psychiatric," "Psychiatric Service" and "Psychiatric intensive care units.", Results: Twenty-two articles met the inclusion criteria. Four thematic units were identified: aspects related to (i) patient perceptions; (ii) Government policies and hospitality organizational culture; (iii) external factors such as the environment, family or associations; and (iv) safety and security., Discussion: Only one of the articles mentions the concept analysed, although all of them contribute with key aspects of healthcare humanization, such as the empowerment of the patient, the care model, the staff ratio, the therapeutic relationship, the nursing time of direct dedication to the patient, the therapeutic environment, safety and patient and staff perception of feeling safe., Implications for Practice: The present study can help to improve the care offered in acute mental health units., (© 2022 John Wiley & Sons Ltd.)
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- 2023
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5. Clinical decisions in pancreatic cancer surgery: a national survey and case-vignette study.
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Ramia JM, Cugat E, De la Plaza R, Gomez-Bravo MA, Martín E, Muñoz-Bellvis L, Padillo FJ, Sabater L, and Serradilla-Martín M
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- Humans, Prospective Studies, Pancreas, Hospitals, High-Volume, Pancreatic Neoplasms, Pancreatic Neoplasms surgery
- Abstract
Very few surveys have been carried out of oncosurgical decisions made in patients with pancreatic cancer (PC), or of the possible differences in therapeutic approaches between low/medium and high-volume centers. A survey was sent out to centers affiliated to the Spanish Group of Pancreatic Surgery (GECP) asking about their usual pre-, intra- and post-operative management of PC patients and describing five imaginary cases of PC corresponding to common scenarios that surgeons regularly assess in oncosurgical meetings. A consensus was considered to have been reached when 80% of the answers coincided. We received 69 responses from the 72 GECP centers (response rate 96%). Pre-operative management: consensus was obtained on 7/16 questions (43.75%) with no significant differences between low- vs high-volume centers. Intra-operative: consensus was obtained on 11/28 questions (39.3%). D2 lymphadenectomy, biliary culture, intra-operative biliary margin study, pancreatojejunostomy, and two loops were significantly more frequent in high-volume hospitals (p < 0.05). Post-operative: consensus was obtained on 2/8 questions (25%). No significant differences were found between low-/medium- vs high-volume hospitals. Of the 41 questions asked regarding the cases, consensus was reached on 22 (53.7%). No differences in the responses were found according to the type of hospital. Management and cases: consensus was reached in 42/93 questions (45.2%). At GECP centers, consensus was obtained on 45% of the questions. Only 5% of the answers differed between low/medium and high-volume centers (all intra-operative). A more specific assessment of why high-volume centers obtain the best results would require the design of complex prospective studies able to measure the therapeutic decisions made and the effectiveness of their execution. Clinicaltrials.gov identifier: NCT04755036., (© 2022. Italian Society of Surgery (SIC).)
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- 2023
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6. miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma.
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de la Cruz-Ojeda P, Schmid T, Boix L, Moreno M, Sapena V, Praena-Fernández JM, Castell FJ, Falcón-Pérez JM, Reig M, Brüne B, Gómez-Bravo MA, Giráldez Á, Bruix J, Ferrer MT, and Muntané J
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- Biomarkers, Humans, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Liver Neoplasms metabolism, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, MicroRNAs genetics, MicroRNAs metabolism, Sorafenib pharmacology, Sorafenib therapeutic use
- Abstract
Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response., Methods: miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients., Results: Sorafenib altered the expression of 11 miRNAs in HepG2 cells. miR-200c-3p and miR-27a-3p exerted an anti-tumoral activity by decreasing cell migration and invasion, whereas miR-122-5p, miR-148b-3p, miR-194-5p, miR-222-5p, and miR-512-3p exerted pro-tumoral properties by increasing cell proliferation, migration, or invasion, or decreasing apoptosis. Sorafenib induced a change in EVs population with an increased number of larger EVs, and promoted an accumulation of miR-27a-3p, miR-122-5p, miR-148b-3p, miR-193b-3p, miR-194-5p, miR-200c-3p, and miR-375 into exosomes. In HCC patients, circulating miR-200c-3p baseline levels were associated with increased survival, whereas high levels of miR-222-5p and miR-512-3p after 1 month of sorafenib treatment were related to poor prognosis. The RNA sequencing revealed that miR-200c-3p was related to the regulation of cell growth and death, whereas miR-222-5p and miR-512-3p were related to metabolic control., Conclusions: The study showed that Sorafenib regulates a specific miRNA signature in which miR-200c-3p, miR-222-5p, and miR-512-3p bear prognostic value and contribute to treatment response.
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- 2022
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7. Differential effectiveness of tyrosine kinase inhibitors in 2D/3D culture according to cell differentiation, p53 status and mitochondrial respiration in liver cancer cells.
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Rodríguez-Hernández MA, Chapresto-Garzón R, Cadenas M, Navarro-Villarán E, Negrete M, Gómez-Bravo MA, Victor VM, Padillo FJ, and Muntané J
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- Adult, Anilides pharmacology, Apoptosis drug effects, Cell Proliferation drug effects, Cell Respiration drug effects, Female, Hep G2 Cells, Hepatocytes drug effects, Hepatocytes metabolism, Hepatocytes pathology, Humans, Male, Mitochondria drug effects, Oxygen Consumption drug effects, Phenylurea Compounds pharmacology, Pyridines pharmacology, Quinolines pharmacology, Sorafenib pharmacology, Spheroids, Cellular drug effects, Spheroids, Cellular metabolism, Spheroids, Cellular pathology, Cell Culture Techniques, Cell Differentiation drug effects, Liver Neoplasms pathology, Mitochondria metabolism, Protein Kinase Inhibitors pharmacology, Tumor Suppressor Protein p53 metabolism
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Sorafenib and Regorafenib are the recommended first- and second-line therapies in patients with advanced hepatocellular carcinoma (HCC). Lenvatinib and Cabozantinib have shown non-inferior antitumoral activities compared with the corresponding recommended therapies. The clinical trials have established recommended doses for each treatment that lead different blood concentrations in patients for Sorafenib (10 µM), Regorafenib (1 µM), Lenvatinib (0.1 µM), and Cabozantinib (1 µM). However, very low response rates are observed in patients attributed to intrinsic resistances or upregulation of survival signaling. The aim of the study was the comparative dose-response analysis of the drugs (0-100 µM) in well-differentiated (HepG2, Hep3B, and Huh7), moderately (SNU423), and poorly (SNU449) differentiated liver cancer cells in 2D/3D cultures. Cells harbors wild-type p53 (HepG2), non-sense p53 mutation (Hep3B), inframe p53 gene deletion (SNU423), and p53 point mutation (Huh7 and SNU449). The administration of regular used in vitro dose (10 µM) in 3D and 2D cultures, as well as the dose-response analysis in 2D cultures showed Sorafenib and Regorafenib were increasingly effective in reducing cell proliferation, and inducing apoptosis in well-differentiated and expressing wild-type p53 in HCC cells. Lenvatinib and Cabozantinib were particularly effective in moderately to poorly differentiated cells with mutated or lacking p53 that have lower basal oxygen consumption rate (OCR), ATP, and maximal respiration capacity than observed in differentiated HCC cells. Sorafenib and Regorafenib downregulated, and Lenvatinib and Cabozantinib upregulated epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor receptor (c-Met) in HepG2 cells. Conclusions: Sorafenib and Regorafenib were especially active in well-differentiated cells, with wild-type p53 and increased mitochondrial respiration. By contrast, Lenvatinib and Cabozantinib appeared more effective in moderately to poorly differentiated cells with mutated p53 and low mitochondrial respiration. The development of strategies that allow us to deliver increased doses in tumors might potentially enhance the effectiveness of the treatments.
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- 2020
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8. Molecular Pathways Leading to Induction of Cell Death and Anti-Proliferative Properties by Tacrolimus and mTOR Inhibitors in Liver Cancer Cells.
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Navarro-Villarán E, de la Cruz-Ojeda P, Contreras L, González R, Negrete M, Rodríguez-Hernández MA, Marín-Gómez LM, Álamo-Martínez JM, Calvo A, Gómez-Bravo MA, de la Cruz J, Padillo J, and Muntané J
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- Autophagy drug effects, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Cell Proliferation drug effects, Cyclin-Dependent Kinase Inhibitor p21 metabolism, Endoplasmic Reticulum Stress drug effects, Everolimus pharmacology, Gene Expression Regulation, Neoplastic drug effects, Hep G2 Cells, Hepatocytes drug effects, Humans, Liver Neoplasms genetics, Liver Neoplasms pathology, MicroRNAs genetics, MicroRNAs metabolism, RNA, Small Interfering, Sirolimus pharmacology, TOR Serine-Threonine Kinases antagonists & inhibitors, TOR Serine-Threonine Kinases genetics, Tacrolimus Binding Protein 1A metabolism, Tumor Suppressor Protein p53 metabolism, eIF-2 Kinase metabolism, Apoptosis drug effects, Carcinoma, Hepatocellular metabolism, Immunosuppressive Agents pharmacology, Liver Neoplasms metabolism, TOR Serine-Threonine Kinases metabolism, Tacrolimus pharmacology, Tacrolimus Binding Proteins metabolism
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Background/aims: Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with portal hypertension and/or increased bilirubinemia, but without vascular-associated diseases. Tumor recurrence, which is the main drawback for the survival of patients submitted to OLT for HCC, has been related to tumor-related variables and the immunosuppressive therapies. We have previously shown that Tacrolimus (FK506) exerts a more potent pro-apoptotic and anti-proliferative effects than the mammalian target of rapamycin (mTOR) inhibitors (Sirolimus and Everolimus) in liver cancer cells. This study identified the role of the immunosuppressant partners such as FK506-binding proteins (FKBPs) in the induction of cell death and arrest of cell proliferation by immunosuppressants in two representative liver cancer cells., Methods: The regulation of endoplasmic reticulum (ER) stress, apoptosis/autophagy, cell proliferation, and FKBPs expression was determined in Tacrolimus-, Sirolimus- and Everolimus-treated primary human hepatocytes, and hepatoma HepG2 and Huh7 cell lines. The functional repercussion of FKBPs on cell death and proliferation was also addressed using the siRNA technology. The assessed antitumoral properties of the immunosuppressants were associated to microRNAs (miRNAs) pattern., Results: The enhanced pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with increased protein kinase RNA-like endoplasmic reticulum kinase (PERK)-related ER stress,
Ser15 P-p53/p53 ratio and p21 protein expression that may counterbalance the risk of proliferative upregulation caused by enhancedThr172 P-Cdk4/Cdk4 activation in liver cancer cells. The inhibition of the mTOR pathway by Sirolimus and Everolimus was related to an induction of autophagy; and at a high dose, these drugs impaired translation likely at a very early step of the elongation phase. Tacrolimus and mTOR inhibitors increased the protein expression of FKBP12 and FKBP51 that appeared to play pro-survival role. Interestingly, the administration of immunosuppressants yields a specific pattern of miRNAs. Tacrolimus and mTOR inhibitors decreased miR-92a-1-5p, miR-197-3p, miR-483-3p and miR-720, and increased miR-22-3p, miR-376a-3p, miR-663b, miR-886-5p, miR-1300 and miR-1303 expressions in HepG2 cells., Conclusion: The more potent pro-apoptotic and anti-proliferative properties of Tacrolimus versus mTOR inhibitors were associated with an increased activation of PERK and p53 signaling, and p21 protein expression. FKBP12 and FKBP51 appeared to be the most relevant partners of Tacrolimus and mTOR inhibitors exerting a pro-survival effect in HepG2 cells. The observed effects of immunosuppressants were related to a specific miRNA signature in liver cancer cells., Competing Interests: The authors have no conflicts of interest to declare., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)- Published
- 2020
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9. Health Care-Associated Infection in Solid Organ Transplant Recipients.
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Abdo-Cuza AA, Gómez-Bravo MA, Pérez-Bernal JB, Suárez-López J, Gómez-Peire F, Leiva-Torres JL, Bejerano-Gil N, Leal-Alpizar G, Espinosa-Nodarse N, and Castellanos-Gutiérrez R
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- Adult, Bacteremia epidemiology, Female, Humans, Incidence, Intensive Care Units, Male, Middle Aged, Risk Factors, Surgical Wound Infection epidemiology, Urinary Tract Infections epidemiology, Cross Infection epidemiology, Kidney Transplantation adverse effects, Liver Transplantation adverse effects, Postoperative Complications epidemiology
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Background: Health care-associated infection (HAI) represent a global health problem with an increase in hospital stays, deaths, and monetary costs. Recipients of solid organ transplants are a population at risk. The objectives of the study were to characterize the incidence of HAI in renal and hepatic transplant recipients as well as to compare them with the population without transplants in intensive care units (ICU)., Methods: The data on the incidence of HAI, localization, microorganisms, and demographics were taken from the patients admitted between the years 2013 to 2018 (n = 4307) from the registration of the Project for the Reduction of Nosocomial Infection in Intensive Care Units. The variables were compared with those of renal transplant (n = 96) and liver transplants (n = 68) recipients., Results: Renal transplant recipients showed 26% incidence of HAI. The most frequent were surgical site infection (SSI), urinary tract infection, and primary bacteremia; the most frequent microorganism was Staphylococcus spp, mortality 3.8%. Liver transplant recipients showed 41% incidence of HAI. The most frequent were tracheobronchitis associated with mechanical ventilation, SSI, and primary bacteremia; the most frequent microorganism was Staphylococcus spp, mortality 37%. The population without transplants in the ICU showed 17% incidence of HAI. The most frequent were respiratory infections associated with mechanical ventilation, primary bacteremia, and SSI; the most frequent microorganism was Acinetobacter spp, mortality 21%., Conclusions: HAI in recipients of solid organ transplants (renal and hepatic) have a higher incidence than in a population without transplants. The location and causal microorganisms have particularities that must be taken into account for the development of prevention protocols., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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10. Successful domino liver transplantation using a graft from a controlled donation after circulatory death (Maastricht III).
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Marín-Gómez LM, Suárez-Artacho G, Padillo-Ruiz J, and Gómez-Bravo MA
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- Aged, Female, Humans, Male, Middle Aged, Registries, Tissue Donors, Allografts transplantation, Liver Transplantation methods, Tissue and Organ Procurement methods
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- 2019
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11. Point-of-care haemostasis monitoring during liver transplantation is cost effective.
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Leon-Justel A, Alvarez-Rios AI, Noval-Padillo JA, Gomez-Bravo MA, Porras M, Gomez-Sosa L, Lopez-Romero JL, and Guerrero JM
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- Blood Coagulation Tests, Erythrocyte Transfusion, Humans, Length of Stay, Cost-Benefit Analysis, End Stage Liver Disease therapy, Liver Transplantation, Point-of-Care Systems economics
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Background Optimal haemostasis management in orthotropic liver transplant (OLT) could reduce blood loss and transfusion volume, improve patient outcomes and reduce cost. Methods We performed a study including 336 OLTs to evaluate the clinical and cost effectiveness of a new point-of-care (POC)-based haemostatic management approach in OLT patients. Results In terms of health benefit we found that the new approach showed a significant reduction in transfusion requirements (red blood cell transfusion units were reduced from 5.3±4.6 to 2.8±2.9 [p<0.001], free frozen plasma from 3.1±3.3 to 0.4±1.0 [p<0.001] and platelets from 2.9±3.9 to 0.4±0.9 [p<0.001], transfusion avoidance, 9.7% vs. 29.1% [p<0.001] and massive transfusion, 14.5% vs. 3.8% [p=0.001]); we also found a significant improvement in patient outcomes, such, reoperation for bleeding or acute-kidney-failure (8.3% vs. 2.4%, p=0.015; 33.6% vs. 5.4%, p<0.001), with a significant reduction in the length of the hospital total stay (40.6±13.8 days vs. 38.2±14.4 days, p=0.001). The lowest cost incurred was observed with the new approach (€73,038.80 vs. €158,912.90) with significant patient saving associated to transfusion avoidance (€1278.36), ICU-stay (€3037.26), total-stay (€3800.76) and reoperation for bleeding (€80,899.64). Conclusions POC haemostatic monitoring during OLT is cost effective.
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- 2019
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12. Impact of Early Initiated Everolimus on the Recurrence of Hepatocellular Carcinoma After Liver Transplantation.
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Rodríguez-Perálvarez M, Guerrero M, Barrera L, Ferrín G, Álamo JM, Ayllón MD, Artacho GS, Montero JL, Briceño J, Bernal C, Padillo J, Marín-Gómez LM, Pascasio JM, Poyato A, Gómez-Bravo MA, and De la Mata M
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- Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Case-Control Studies, Drug Administration Schedule, Everolimus adverse effects, Female, Humans, Immunosuppressive Agents adverse effects, Liver Neoplasms mortality, Liver Neoplasms pathology, Liver Transplantation mortality, Male, Middle Aged, Progression-Free Survival, Prospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Carcinoma, Hepatocellular surgery, Everolimus administration & dosage, Immunosuppressive Agents administration & dosage, Liver Neoplasms surgery, Liver Transplantation adverse effects, Neoplasm Recurrence, Local
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Background: Many centers implement everolimus-based immunosuppression in liver transplant patients with hepatocellular carcinoma. We aimed to explore the potential impact of early initiated everolimus on tumor recurrence after liver transplantation., Methods: This study included 192 patients with hepatocellular carcinoma undergoing liver transplantation among who 64 individuals were prospectively enrolled (2012-2015) and received early initiated everolimus (ie, started between postoperative day 15 to 21), whereas the remaining 128 patients acted as historical controls without everolimus. Propensity score matching was performed to ensure comparability. Multivariate Cox regression and competing risks analysis were used to control for potential confounders., Results: Patients with and without everolimus were comparable in terms of number of nodules (P = 0.37), total tumor diameter (P = 0.44), Milan criteria fulfillment (P = 0.56), and histological differentiation (P = 0.61), but there were increased microvascular invasion rates in the everolimus group (26.5% vs 13.3%; P = 0.026). Tumor recurrence rates were similar with and without everolimus (10.9% vs 9.9% at 36 months respectively; P = 0.18). After controlling for microvascular invasion among other potential confounders, everolimus had no significant impact on tumor recurrence, neither in the multivariate Cox regression (relative risk = 3.23; P = 0.09), nor in the competing risks analysis for tumor recurrence-death (relative risk = 1.02; P = 0.94). Patients receiving everolimus had reduced tacrolimus trough concentrations and lower serum creatinine within the first 18 months postliver transplantation., Conclusion: Everolimus may not be universally prescribed to prevent tumor recurrence in liver transplant patients with hepatocellular carcinoma. Future randomized trials should be focused on patients with histological features of increased tumor aggressiveness, in whom the potential benefit would be higher.
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- 2018
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13. Vascular invasion and survival after liver transplantation for hepatocellular carcinoma: a study from the European Liver Transplant Registry.
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Pommergaard HC, Rostved AA, Adam R, Thygesen LC, Salizzoni M, Gómez Bravo MA, Cherqui D, Filipponi F, Boudjema K, Mazzaferro V, Soubrane O, García-Valdecasas JC, Prous JF, Pinna AD, O'Grady J, Karam V, Duvoux C, and Rasmussen A
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- Aged, Biopsy, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Clinical Decision-Making, Databases, Factual, Europe, Female, Humans, Liver Neoplasms mortality, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Invasiveness, Patient Selection, Registries, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Carcinoma, Hepatocellular surgery, Liver Neoplasms surgery, Liver Transplantation adverse effects, Liver Transplantation mortality
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Background: Studies suggest that vascular invasion may be a superior prognostic marker compared with traditional selection criteria, e.g. Milan criteria. This study aimed to investigate the prognostic value of micro and macrovascular invasion in a large database material., Methods: Patients liver transplanted for HCC and cirrhosis registered in the European Liver Transplant Registry (ELTR) database were included. The association between the Milan criteria, Up-to-seven criteria and vascular invasion with overall survival and HCC specific survival was investigated with univariate and multivariate Cox regression analyses., Results: Of 23,124 patients transplanted for HCC, 9324 had cirrhosis and data on explant pathology. Patients without microvascular invasion, regardless of number and size of HCC nodules, had a five-year overall survival of 73.2%, which was comparable with patients inside both Milan and Up-to-seven criteria. Patients without macrovascular invasion had an only marginally reduced survival of 70.7% after five years. Patients outside both Milan and Up-to-seven criteria without micro or macrovascular invasion still had a five-year overall survival of 65.8%., Conclusion: Vascular invasion as a prognostic indicator remains superior to criteria based on size and number of nodules. With continuously improving imaging studies, microvascular invasion may be used for selecting patients for transplantation in the future., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
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- 2018
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14. Corrigendum to 'Risk factors associated with dehydration in older people living in nursing homes: Scoping review' [ International Journal of Nursing Studies, Volume 82 (2018) Pages 90-98].
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Masot O, Lavedán A, Nuin C, Escobar-Bravo MA, Miranda J, and Botigué T
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- 2018
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15. Risk factors associated with dehydration in older people living in nursing homes: Scoping review.
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Masot O, Lavedán A, Nuin C, Escobar-Bravo MA, Miranda J, and Botigué T
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- Aged, Humans, Ontario, Risk Factors, Dehydration epidemiology, Nursing Homes
- Abstract
Background: Dehydration in the older people is a prevalent problem that is often associated with physiological changes, physical limitations and environmental conditions., Objectives: The scoping review was carried out to identify risk factors associated with dehydration in older people living in nursing homes., Design: The revised scoping methodology framework of Arksey and O'Malley (2005) was applied. Study selection was carried out in accordance with Davis et al. (2009) and focused on the inclusion criteria (people over 65 years old and living in nursing homes). Risk factors were classified using the geriatric assessment., Data Sources: An electronic database search was performed in PubMed, Scopus and CINAHL. The literature search was carried out between October 2016 and January 2017., Review Methods: Thematic reporting was performed and study findings were validated through interdisciplinary meetings of experts. The quality of the papers consulted was also evaluated using the Newcastle-Ottawa Scale adapted for cross-sectional, cohort and case-control studies., Results: In all, 16 papers were analysed, all of which were observational studies. The risk of bias ranged from very low (n = 1), to medium (n = 13) and high (n = 2). The risk factors were classified in line with the different components of the geriatric assessment. In the socio-demographic characteristics age and gender were identified. In the clinical component, infections, renal and cardiovascular diseases and end-of-life situations were the most common factors highlighted in the papers analysed. With reference to the functional component, its limitation was associated with dehydration, while for factors of mental origin, it was related to dementia and behavioural disorders. Finally, the factors relating to the social component were institutionalisation, requiring a skilled level of care and it being winter., Conclusions: The most commonly repeated factors highlighted in the review were age, gender, infections, end of life and dementia, with it being important to highlight the large number of factors in the clinical component. Even so, the great majority of the factors were unmodifiable conditions associated typically associated with the physiology of ageing., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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16. Influence of donor liver CYP3A4*20 loss-of-function genotype on tacrolimus pharmacokinetics in transplanted patients.
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Gómez-Bravo MA, Apellaniz-Ruiz M, Salcedo M, Fondevila C, Suarez F, Castellote J, Rufian S, Pons JA, Bilbao I, Alamo JM, Millán O, Brunet M, and Rodríguez-Antona C
- Subjects
- Adult, Aged, Alleles, Dose-Response Relationship, Drug, Female, Genotype, Graft Rejection genetics, Graft Rejection pathology, Humans, Immunosuppressive Agents pharmacokinetics, Liver Transplantation adverse effects, Male, Middle Aged, Polymorphism, Single Nucleotide, Tacrolimus pharmacokinetics, Tissue Donors, Cytochrome P-450 CYP3A genetics, Graft Rejection drug therapy, Immunosuppressive Agents administration & dosage, Tacrolimus administration & dosage
- Abstract
Objective: Cytochrome P450 3A4 (CYP3A4) metabolizes about half of all drugs on the market; however, the impact of CYP3A4 loss-of-function variants on drug exposures remains poorly characterized. Here, we report the effect of the CYP3A4*20 frameshift allele in two Spanish liver transplant patients treated with tacrolimus., Patients and Methods: A series of 90 transplanted patients (with DNA available for 89 of the recipients and 76 of the liver donors) treated with tacrolimus were included in the study. The genotypes of liver donors and of the recipients for CYP3A4*20 (rs67666821), CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) were compared with weight-adjusted tacrolimus dose (D), tacrolimus trough concentration (C0), and dose-adjusted tacrolimus trough concentrations (C0/D) using the Mann-Whitney U-nonparametric test., Results: The CYP3A4*20 allele was detected in two of the liver donors. This genotype yielded at all times higher C0/D (2.6-fold, average) than intermediate CYP3A metabolizers (CYP3A4*1/*1 and CYP3A5*3/*3) (P=0.045, 90 days after transplantation). CYP3A4*22 carriers showed a 1.9-fold average increase in C0/D (P=0.047, 0.025, and 0.053; at days 7, 14, and 30 after transplantation, respectively) compared with intermediate metabolizers. In terms of recipients' genotype, CYP3A5*1 had reduced (P=0.025) and CYP3A4*22 increased C0/D (P=0.056) 7 days after transplantation. The incidence of biopsy-proven acute rejection was 0, 12, and 20% for livers with poor, intermediate, and extensive CYP3A-metabolizing capacity, respectively (P=0.0995)., Conclusion: This first description of CYP3A4*20 null genotype in liver-transplanted patients, supports the relevance of CYP3A genotyping in tacrolimus therapy.
- Published
- 2018
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17. Role of p63 and p73 isoforms on the cell death in patients with hepatocellular carcinoma submitted to orthotopic liver transplantation.
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González R, De la Rosa ÁJ, Rufini A, Rodríguez-Hernández MA, Navarro-Villarán E, Marchal T, Pereira S, De la Mata M, Müller-Schilling M, Pascasio-Acevedo JM, Ferrer-Ríos MT, Gómez-Bravo MA, Padillo FJ, and Muntané J
- Subjects
- Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular virology, Cell Death, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Hepatitis B complications, Hepatitis B virus isolation & purification, Humans, Liver metabolism, Liver virology, Liver Neoplasms genetics, Liver Neoplasms pathology, Liver Neoplasms virology, Male, Protein Isoforms genetics, Receptors, Death Domain genetics, Carcinoma, Hepatocellular therapy, Liver pathology, Liver Neoplasms therapy, Liver Transplantation methods, Transcription Factors genetics, Tumor Protein p73 genetics, Tumor Suppressor Proteins genetics
- Abstract
Background & Aims: Patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT) have a variable 5-year survival rate limited mostly by tumor recurrence. The etiology, age, sex, alcohol, Child-Pugh, and the immunesuppressor have been associated with tumour recurrence. The expression of ΔNp73 is related to the reduced survival of patients with HCC. The study evaluated the expression of p63 and p73 isoforms and cell death receptors, and their relation to tumour recurrence and survival. The results were in vitro validated in HCC cell lines., Methods: HCC sections from patients submitted to OLT were used. The in vitro study was done in differentiated hepatitis B virus (HBV)-expressing Hep3B and control HepG2 cells. The expression of cell death receptors and cFLIPS/L, caspase-8 and -3 activities, and cell proliferation were determined in control and p63 and p73 overexpressing HCC cells., Results: The reduced tumor expression of cell death receptors and TAp63 and TAp73, and increased ΔNp63 and ΔNp73 expression were associated with tumor recurrence and reduced survival. The in vitro study demonstrated that HBV-expressing Hep3B vs HepG2 cells showed reduced expression of p63 and p73, cell death receptors and caspase activation, and increased cFLIPL/cFLIPS ratio. The overexpression of TAp63 and TAp73 exerted a more potent pro-apoptotic and anti-proliferative effects in Hep3B than HepG2-transfected cells which was related to cFLIPL upregulation., Conclusions: The reduction of TAp63 and TAp73 isoforms, rather than alteration of ΔN isoform expression, exerted a significant functional repercussion on cell death and proliferation in HBV-expressing HepB cells.
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- 2017
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18. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry.
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Krawczyk M, Grąt M, Adam R, Polak WG, Klempnauer J, Pinna A, Di Benedetto F, Filipponi F, Senninger N, Foss A, Rufián-Peña S, Bennet W, Pratschke J, Paul A, Settmacher U, Rossi G, Salizzoni M, Fernandez-Selles C, Martínez de Rituerto ST, Gómez-Bravo MA, Pirenne J, Detry O, Majno PE, Nemec P, Bechstein WO, Bartels M, Nadalin S, Pruvot FR, Mirza DF, Lupo L, Colledan M, Tisone G, Ringers J, Daniel J, Charco Torra R, Moreno González E, Bañares Cañizares R, Cuervas-Mons Martinez V, San Juan Rodríguez F, Yilmaz S, and Remiszewski P
- Subjects
- Female, Graft Rejection etiology, Humans, Injury Severity Score, Male, Registries, Retrospective Studies, Liver injuries, Liver Transplantation adverse effects, Liver Transplantation mortality
- Abstract
Background: Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma., Methods: This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively., Results: Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%., Conclusions: Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.
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- 2016
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19. Differential Antitumoral Properties and Renal-Associated Tissue Damage Induced by Tacrolimus and Mammalian Target of Rapamycin Inhibitors in Hepatocarcinoma: In Vitro and In Vivo Studies.
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Navarro-Villarán E, Tinoco J, Jiménez G, Pereira S, Wang J, Aliseda S, Rodríguez-Hernández MA, González R, Marín-Gómez LM, Gómez-Bravo MA, Padillo FJ, Álamo-Martínez JM, and Muntané J
- Subjects
- Animals, Apoptosis drug effects, Cell Cycle drug effects, Cell Differentiation drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Enzyme Inhibitors adverse effects, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use, Everolimus adverse effects, Everolimus pharmacology, Everolimus therapeutic use, Fibrosis, Humans, Immunosuppressive Agents adverse effects, Immunosuppressive Agents pharmacology, Immunosuppressive Agents therapeutic use, Kidney pathology, Male, Mice, Neovascularization, Pathologic drug therapy, Tacrolimus therapeutic use, Carcinoma, Hepatocellular pathology, Kidney drug effects, Liver Neoplasms pathology, TOR Serine-Threonine Kinases antagonists & inhibitors, Tacrolimus adverse effects, Tacrolimus pharmacology, Xenograft Model Antitumor Assays
- Abstract
Orthotopic liver transplantation (OLT) is the recommended treatment for patients at early stages of hepatocarcinoma (HCC) with potential portal hypertension and/or bilirubinemia, but without vascular-associated diseases. The patients are receiving immunosuppressive therapy to reduce graft rejection, but differential side effects have been related to calcineurin and mTOR inhibitor administration regarding tumor recurrence and nephrotoxicity. The in vitro studies showed that Tacrolimus exerted a more potent pro-apoptotic effect than Everolimus (Huh 7>Hep 3B>HepG2), being sirolimus only active in Hep3B cell line. Tacrolimus and Everolimus exerted potent antiproliferative properties in Huh 7 and Hep3B in which cells Sirolimus was inactive. Interestingly, Tacrolimus- and Everolimus-dependent G0/G1 cell accumulation occurred as a consequence of drastic reduction in S, as well as in S and G2+M phases, respectively. The in vivo studies support data on the more effective antitumoral properties of Everolimus, eventual risk of pro-angiogenic tumoral properties and nephrotoxicity of Tacrolimus, and pro-proliferative properties of Sirolimus in tumors developed in nude mice.
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- 2016
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20. Point-of-care haemostasis monitoring during liver transplantation reduces transfusion requirements and improves patient outcome.
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Leon-Justel A, Noval-Padillo JA, Alvarez-Rios AI, Mellado P, Gomez-Bravo MA, Álamo JM, Porras M, Barrero L, Hinojosa R, Carmona M, Vilches-Arenas A, and Guerrero JM
- Subjects
- Acute Kidney Injury etiology, Acute Kidney Injury pathology, Erythrocyte Transfusion economics, Erythrocyte Transfusion statistics & numerical data, Female, Fibrinogen metabolism, Hemoglobins metabolism, Hemorrhage etiology, Hemorrhage pathology, Hemorrhage therapy, Hemostasis, Humans, Male, Middle Aged, Platelet Transfusion economics, Platelet Transfusion statistics & numerical data, Point-of-Care Systems, Prospective Studies, Risk, Treatment Outcome, Acute Kidney Injury prevention & control, Hemorrhage prevention & control, Hemostatic Techniques, Liver Transplantation adverse effects, Postoperative Complications
- Abstract
Background: Optimal haemostasis management can improve patient outcomes and reduce blood loss and transfusion volume in orthotopic-liver-transplant (OLT)., Methods: We performed a prospective study including 200 consecutive OLTs. The first 100 patients were treated according to the clinic's standards and the next 100 patients were treated using the new point-of-care (POC)-based haemostasis management strategy. Transfusion parameters and other outcomes were compared between groups., Results: Transfusion requirements were reduced in the POC group. The median and IQR of red-blood-cells (RBC) transfusion units were reduced from 5 [2-8] to 3 [0-5] (p < 0.001), plasma from 2 [0-4] to 0 (p < 0.001), and platelets from 1 [0-4] to 0 [0-1] (p < 0.001), into the POC group only four patients received tranexamic acid and fibrinogen transfusion rate was 1.13 ± 1.44 g (p = 0.001). We also improved the incidence of transfusion avoidance, 5% vs. 24% (p < 0.001) and reduced the incidence of massive transfusion (defined as the transfusion of more than 10 RBC units), 13% vs. 2% (p = 0.005). We also observed a relationship between RBC transfusion requirements and preoperative haemoglobin, and between platelet transfusion and preoperative fibrinogen levels. The incidence of postoperative complications, such as, reoperation for bleeding, acute-kidney-failure or haemodynamic instability was significantly lower (13.0% vs. 5%, p = 0.048, 17% vs. 2%, p < 0.001, and 29% vs. 16%, p = 0.028). Overall, blood product transfusion was associated with increased risk of postoperative complications., Conclusions: A haemostatic therapy algorithm based on POC monitoring reduced transfusion and improved outcome in OLT., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
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21. Monitoring of transplanted liver health by quantification of organ-specific genomic marker in circulating DNA from receptor.
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Macher HC, Suárez-Artacho G, Guerrero JM, Gómez-Bravo MA, Álvarez-Gómez S, Bernal-Bellido C, Dominguez-Pascual I, and Rubio A
- Subjects
- Adult, Aged, Chromosomes, Human, Y genetics, DNA isolation & purification, Female, Humans, Male, Middle Aged, Organ Specificity, Sex-Determining Region Y Protein blood, beta-Globins metabolism, DNA blood, Genetic Markers, Genomics, Liver Transplantation, Transplant Recipients
- Abstract
Background: Health assessment of the transplanted organ is very important due to the relationship of long-term survival of organ transplant recipients and health organ maintenance. Nowadays, the measurement of cell-free DNA from grafts in the circulation of transplant recipients has been considered a potential biomarker of organ rejection or transplant associated complications in an attempt to replace or reduce liver biopsy. However, methods developed to date are expensive and extremely time-consuming. Our approach was to measure the SRY gene, as a male organ biomarker, in a setting of sex-mismatched female recipients of male donor organs., Methods: Cell-free DNA quantization of the SRY gene was performed by real-time quantitative PCR beforehand, at the moment of transplantation during reperfusion (day 0) and during the stay at the intensive care unit. Beta-globin cell-free DNA levels, a general cellular damage marker, were also quantified., Results: Beta-globin mean values of patients, who accepted the graft without any complications during the first week after surgery, diminished from day 0 until patient stabilization. This decrease was not so evident in patients who suffered some kind of post-transplantation complications. All patients showed an increase in SRY levels at day 0, which decreased during hospitalization. Different complications that did not compromise donated organs showed increased beta-globin levels but no SRY gene levels. However, when a donated organ was damaged the patients exhibited high levels of both genes., Conclusion: Determination of a SRY gene in a female recipient's serum is a clear and specific biomarker of donated organs and may give us important information about graft health in a short period of time by a non-expensive technique. This approach may permit clinicians to maintain a close follow up of the transplanted patient.
- Published
- 2014
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22. Bioabsorbable implant as a tracheal wall substitute in young developing canines.
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Soriano-Rosales RE, Perez-Guille BE, Arch-Tirado E, Alfaro-Rodriguez A, Villegas-Alvarez F, Gonzalez-Zamora JF, Jimenez-Bravo MA, Zaragoza-Huerta S, Gonzalez-Maciel A, Ramos-Morales A, Reynoso-Robles R, and Mota-Rojas D
- Subjects
- Animals, Disease Models, Animal, Dogs, Longitudinal Studies, Polylactic Acid-Polyglycolic Acid Copolymer, Absorbable Implants, Lactic Acid, Polyglycolic Acid, Prosthesis Design, Tracheal Stenosis surgery
- Abstract
This study evaluated a polylactic and polyglycolic acid (PLA/PGA) implant as a partial tracheal substitute in young developing canines. This experimental and longitudinal study included local stray pups that received substitution of a short cervical tracheal segment with a PLA 85%/PGA 15% plaque. We measured clinical, endoscopic, and tomographic variables for 1 year, at which time we performed histomorphological evaluations of the implant using light and electron microscopy. There were no adverse events throughout the clinical progression. On endoscopic evaluation, the implant was covered with mucosal tissue beginning in the first month, without granulation or stenosis, and the circular shape of the trachea was altered. Tomographic images of the tracheal area at the implant site were similar to adjacent healthy areas (p = 0.423). At the end of the follow-up period, the plaque had biodegraded, and the space was covered by pseudostratified epithelium and ciliated cells similar to the neighboring tissue. Implantation of a PLA/PGA plaque constituted an effective (functional) replacement of a short semicircular cervical tracheal segment without limiting the growth of the recipient. Additional studies are required to prove the efficacy of these implants for larger tracheal segment replacements and in subjects at different stages of development.
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- 2014
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23. Deficient long-term response to pandemic vaccine results in an insufficient antibody response to seasonal influenza vaccination in solid organ transplant recipients.
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Cordero E, Aydillo TA, Perez-Ordoñez A, Torre-Cisneros J, Lara R, Segura C, Gentil MA, Gomez-Bravo MA, Lage E, Pachon J, and Perez-Romero P
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Influenza Vaccines therapeutic use, Male, Middle Aged, Young Adult, Antibodies, Viral immunology, Influenza A Virus, H1N1 Subtype immunology, Influenza Vaccines immunology, Influenza, Human epidemiology, Influenza, Human prevention & control, Organ Transplantation, Pandemics
- Abstract
Background: Little is known about the long-term antibody response to the 2009-H1N1 vaccine in solid organ transplant recipients (SOTR) and its clinical repercussion on the efficacy of following 2010-2011 influenza vaccine., Methods: We performed a multicenter prospective study in SOTR receiving one dose of the nonadjuvant 2010-2011 seasonal influenza vaccine and determined the immunological response at 5 weeks after vaccination., Results: One hundred SOTR were included. Long-term antibody titers to the previous vaccine were only detected in one third of the patients. Patients with baseline titers had significantly higher seroprotection for the 2009-H1N1 strain (100% vs. 73%, relative risks [RR] 1.37, 95% confidence intervals [CI] 1.19-1.57; P=0.006), for H3N2 strain (100% vs. 62.2%, RR 1.61, 95% CI 1.36-1.90; P=0.005), and for B strain (100% vs. 69%; P=0.02). The seroconversion rate in patients with baseline titers was 90.9% vs. 73% (RR 2.97, 95% CI 0.75-11.74; P=0.07) for the 2009-H1N1 strain, 92.2% vs. 62.2% (RR 5.29, 95% CI 0.8-35.7; P=0.02) for the H3N2 strain, and 58.3% vs. 69% (P=0.45) for the B strain., Conclusions: SOTR response to the 2010-2011 influenza vaccine was not optimal. The response was related to baseline titers; however, most of the patients did not exhibit detectable antibodies at vaccination lacking long-term response. New strategies are necessary to improve vaccination efficacy.
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- 2012
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24. Therapeutic effect of the acquisition of cytomegalovirus-specific immune response during preemptive treatment.
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Benmarzouk-Hidalgo OJ, Cisneros JM, Cordero E, Martín-Peña A, Sanchez B, Martin-Gandul C, Gentil MA, Gomez-Bravo MA, Lage E, and Perez-Romero P
- Subjects
- Adult, Aged, Cytokines metabolism, Cytomegalovirus genetics, Cytomegalovirus growth & development, Cytomegalovirus immunology, Cytomegalovirus Infections diagnosis, Cytomegalovirus Infections immunology, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents adverse effects, Linear Models, Male, Middle Aged, Prospective Studies, Spain, T-Lymphocytes immunology, T-Lymphocytes virology, Time Factors, Treatment Outcome, Viral Load, Virus Replication, Adaptive Immunity drug effects, Antiviral Agents administration & dosage, Cytomegalovirus drug effects, Cytomegalovirus Infections prevention & control, Organ Transplantation adverse effects
- Abstract
Background: It has been suggested that preemptive therapy against cytomegalovirus (CMV) infection after transplantation promotes a CMV-specific immune response. Our objective was to determine whether solid-organ transplant patients at high risk for CMV infection treated preemptively acquire a CMV-specific immune response and whether the acquired immune response confers immunity by controlling subsequent CMV replication episodes and by protecting from late-onset CMV disease., Methods: Patients were followed up for 18 months after transplantation. CMV viral load was determined using real-time polymerase chain reaction assays, and the T-cell immune response was characterized by intracellular cytokine staining., Results: The 21 patients studied developed CMV replication episodes at a median of 4 weeks (range 2-8 weeks) after transplantation and a CMV-specific T-cell response within a median of 12 weeks (range 10-20 weeks). The decline in the incidence of CMV replication episodes is inversely correlated with the acquisition of the CMV-specific T-cell response (linear regression r=0.781, Pearson correlation=-0.883; P=0.001). There were no CMV replication episodes after week 47 of transplantation. In addition, after acquisition of the immune response, 42 replication episodes were cleared without treatment. The time taken for immune clearance of replication correlated with the peak viral load (P=0.01). No incidence of CMV early or late-onset disease was detected., Conclusions: Our results demonstrate that preemptive therapy is a safe and an effective strategy for the control of CMV infection in solid-organ transplant recipients at high risk for CMV infection. This is the first study that reports a therapeutic effect of the acquisition of CMV-specific immune response during preemptive treatment., (© 2011 by Lippincott Williams & Wilkins)
- Published
- 2011
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25. Choice of calcineurin inhibitor may influence the development of de novo immune hepatitis associated with anti-GSTT1 antibodies after liver transplantation.
- Author
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Aguilera I, Sousa JM, Praena JM, Gómez-Bravo MA, and Núñez-Roldan A
- Subjects
- Adolescent, Adult, Aged, Female, Humans, Male, Middle Aged, Survival Rate, Young Adult, Antibodies, Anti-Idiotypic adverse effects, Calcineurin adverse effects, Glutathione Transferase immunology, Hepatitis, Autoimmune etiology, Immunosuppressive Agents adverse effects, Liver Transplantation adverse effects
- Abstract
In 2004, we defined the genetic mismatch in the glutathione S-transferase T1 (GSTT1) gene positive donor/null recipient as a risk factor to develop de novo immune hepatitis (IH) after liver transplant (LT), which is always associated with production of donor-specific anti-GSTT1 antibodies. However, there are several unresolved questions, such as why some of these patients produce antibodies, why others do not and why not all of the patients with antibodies develop the disease. The aim of this study was to evaluate the influence of several variables in the production of anti-GSTT1 antibodies and/or de novo IH. The study group included 35 liver-transplanted patients. The number of patients not producing antibodies was significantly higher in the group treated with Tac-based immunosuppression compared with the CsA-based group (94.1% vs. 5.9%, p = 0.001). Additionally, a protective effect of the Tac-based therapy vs. the CsA-based therapy was observed with regard to development of de novo IH (80.8% vs. 19.2%, p = 0.003). In conclusion, the choice of calcineurin inhibitor may influence the development of de novo IH mediated by anti-GSTT1 antibodies., (© 2010 John Wiley & Sons A/S.)
- Published
- 2011
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26. Metal contamination in interstitial waters of Doñana Park.
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Tovar-Sanchez A, Huerta-Diaz MA, Negro JJ, Bravo MA, and Sañudo-Wilhelmy SA
- Subjects
- Accidents, Environmental Monitoring, Spain, Industrial Waste, Iron, Metals analysis, Mining, Rivers chemistry, Sulfides, Water Pollutants, Chemical analysis
- Abstract
The composition of interstitial waters in Spain's Doñana National Park was assessed 4 years after a major pyrite slurry spill occurred from the Aznalcollar Mine. Metal and nutrient concentrations in pore waters from two of the most important watercourses traversing Doñana Park were measured: Guadiamar River (affected by the accident) and Partido Stream (unimpacted by the accident). Concentrations of dissolved constituents in interstitial waters varied according to land use in the two watersheds and to the effects of the mine spill. Levels of dissolved Co, Cu, Mo, Ti, and Zn were higher in pore waters from the Guadiamar River than in the Partido Stream, suggesting that concentrations of trace elements are still influenced by the spill. In contrast, concentrations of dissolved nutrients (NH4+, NO2-, NO3-, PO4(-3)) and some trace metals used in fertilizers (e.g. Al and Cr) were higher in the Partido Stream. Levels of dissolved As, Cs, DOC, Ge, Hg, Rb and V in the interstitial waters were equal in both watercourses. Metal concentrations in interstitial waters of the Guadiamar River floodplain were between 0.3 (As) and 16,000 (Zn) times lower than those previously reported in the river and groundwater a few weeks after the mine spill. Although metals in pore water appear to have reached levels characteristic of the area before the accident, concentrations are 60-150 times higher than those in pore waters from other regions. Metal:Al ratios in Doñana's pore waters suggest a transport of contaminants from the Iberian Pyrite Belt into Doñana Park.
- Published
- 2006
- Full Text
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