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Early tacrolimus exposure does not impact long-term outcomes after liver transplantation

World Journal of Hepatology 2021年第3期13卷 362-374页

作者： Mikel Gastaca patricia ruiz Javier Bustamante Lorea Martinez-Indart Alberto Ventoso JoséRamón Fernandez Ibone Palomares Mikel Prieto Milagros Testillano patricia Salvador Maria Senosiain Maria Jesus Suárez Andres Valdivieso Department of HPB Surgery and Liver Transplantation Unit Hospital Universitario CrucesBilbao 48903Spain Department of Hepatology Unit Hospital Universitario CrucesBilbao 48903Spain Department of Bioinformatics and Statistics Platform Biocruces Bizkaia Health Research InstituteHospital Universitario CrucesBilbao 48903Spain

BACKGROUND Tacrolimus trough levels(TTL)during the first weeks after liver transplantation(LT)have been related with long-term renal function and hepatocellular carcinoma recurrence.Nevertheless,the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate AIM To evaluate the effect of TTL during the first month on the long-term outcomes after LT.METHODS One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied.Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy.Patients were classified into 2 groups according to their mean TTL within the first month after transplantation:≤10(n=98)and>10 ng/mL(n=57).Multivariate analyses were performed to assess risk factors for patient mortality.RESULTS Mean levels within the first month post-transplant were 7.4±1.7 and 12.6±2.2 ng/mL in the≤10 and>10 groups,respectively.Donor age was higher in the high TTL group 62.9±16.8 years vs 45.7±17.5 years(P=0.002)whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7%vs 15.8%(P=0.02).Recipient features were generally similar across groups.After a median follow-up of 52.8 mo(range 2.8-81.1),no significant differences were observed in:Mean estimated glomerular filtration rate(P=0.69),hepatocellular carcinoma recurrence(P=0.44),de novo tumors(P=0.77),new-onset diabetes(P=0.13),or biopsy-proven acute rejection rate(12.2%and 8.8%,respectively;P=0.50).Eighteen patients died during the follow-up and were evenly distributed across groups(P=0.83).Five-year patient survival was 90.5%and 84.9%,respectively(P=0.44),while 5-year graft survival was 88.2%and 80.8%,respectively(P=0.42).Early TTL was not an independent factor for patient mortality in multivariate analyses.CONCLUSION Differences in tacrolimus levels restricted to the first month after transplant did not result in sig

关键词： Liver transplantation Tacrolimus levels Prolonged released tacrolimus Oncedaily tacrolimus Renal function Survival Outcomes

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Impact of an acute hemodynamic response-guided protocol for primary prophylaxis of variceal bleeding

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World Journal of Clinical Cases 2018年第13期6卷 611-623页

作者： José Ignacio Fortea ángela Puente patricia ruiz Iranzu Ezcurra Javier Vaquero Antonio Cuadrado María Teresa Arias-Loste Joaquín Cabezas Susana Llerena Paula Iruzubieta Carlos Rodríguez-Lope patricia Huelin Fernando Casafont Emilio Fábrega Javier Crespo Servicio de Aparato Digestivo Hospital Universitario Marques? de Valdecilla Instituto de Investigación Sanitaria Marqués de Valdecilla Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas Laboratorio de Investigación en Hepatología y Gastroenterología Hospital General Universitario Gregorio Mara?ón-Instituto de Investigación Sanitaria Gregorio Mara?ón

AIM To evaluate the long-term outcome of an acute hemodynamic response-guided protocol in which acute responders to intravenous propranolol received traditional nonselective beta-blockers(NSBBs) and acute nonresponders received carvedilol.METHODS Retrospective review of a protocol for primary prophylaxis of variceal bleeding guided by the acute hemodynamic response to intravenous propranolol. Fifty-two acute responders treated with traditional NSBB(i.e. propranolol or nadolol) were compared with 24 acute nonresponders receiving carvedilol. A second hemodynamic study was performed in 27 and 13 patients, respectively. The primary endpoint was development of first or further decompensation. Secondary endpoints included death from any cause, association between acute and chronic hemodynamic response, and baseline clinical and laboratory variables related to the acute hemodynamic response.RESULTS Acute responders and acute nonresponders presented similar 1, 2, and 3-year probabilities of first decompensation(NSBB: 0%, 13.7%, 26.1% vs carvedilol: 0%, 20%, 20%, P = 0.968) or further decompensation(21.2%, 26.1%, 40.9% vs 21.2%, 50.0%, 50.0%, P = 0.525). A previous episode of hepatic encephalopathy was the only independent predictor of decompensation [hazard ratio(95% confidence interval): 8.03(2.76-23.37)]. Mortality rates were similar in acute responders and acute nonresponders with compensated(P = 0.428) or decompensated cirrhosis(P = 0.429). No clinical, laboratory, endoscopic or hemodynamic parameter predicted the acute hemodynamic response. In patients receiving traditional NSBB, the acute and chronic changes of hepatic venous pressure gradient were correlated(r = 0.59, P = 0.001). Up to 69.2% of acute nonresponders gained chronic response with carvedilol.CONCLUSION Early identification and treatment with carvedilol of acute nonresponders to intravenous propranolol improves the clinical outcome of this high-risk group of patients, probably due to its greater effects for reducing portal pressure.

关键词： Gastrointestinal hemorrhage Propranolol Carvedilol Liver cirrhosis Portal hypertension

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高灵敏度液相色谱/串联质谱分析河水中内分泌干扰物

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环境化学 2008年第1期27卷 131-133页

作者： patricia Revilla-ruiz Gordon Kearney Daniel McMillan Encarnacion Rodriguez-Gonzalo 萨拉曼卡大学西班牙萨拉曼卡沃特世公司英国曼彻斯特

来自野生动物和实验室的证据表明,一些化学物质可能对内分泌系统有干扰作用.内分泌干扰物（EDCs）包括农药、多氯联苯（PCBs）、二噁英、呋喃、烷基酚以及甾醇类雌激素（天然生成及人工合成）.由于甾醇类雌激素对人体潜在的干扰性,人们... 详细信息

来自野生动物和实验室的证据表明,一些化学物质可能对内分泌系统有干扰作用.内分泌干扰物（EDCs）包括农药、多氯联苯（PCBs）、二噁英、呋喃、烷基酚以及甾醇类雌激素（天然生成及人工合成）.由于甾醇类雌激素对人体潜在的干扰性,人们对其特别关注.天然的性激素———雌二醇及其代谢产物（雌酮和雌三醇）以及合成的甾醇类乙烯雌二醇是由哺乳动物泌尿排泄,在表层水和地下水中均有发现.其它内分泌干扰物,如烷基酚、壬基酚、双酚A以及五氯酚是工业和家庭活动的代谢产物,在环境水体中也时有发现.[第一段]

关键词：内分泌干扰物质谱分析液相色谱高灵敏度河水串联类雌激素人工合成

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Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： Emily P.Laveriano-Santos Sara Castro-Barquero Camila Arancibia-Riveros Ana María ruiz-León Rosa Casas Ramón Estruch patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús Martínez-Gómez Gloria Santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute Icahn School of Medicine at Mount Sinai Department de Nutrició Ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i Ciències de l'alimentació Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de Barcelona Department of Internal Medicine Hospital Clínic Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of Barcelona Consorcio CIBER M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn) Instituto de Salud Carlos III (ISCIII) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. Hospital Universitario Clínico San Carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in adolescents.Objective: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health parameters.Results: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend <0.001)， and the highest quintile of stilbene intake with lower BG (β=-1.83， 95%CI= -3.103;-0.64， P-for trend <0.001) and TG (β=-3.22， 95%CI= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%CI= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. Conclusion: A higher intake of (poly)phenols， especially flavonoids， phenolic acids， and stilbenes

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Advances in spray products for skin regeneration

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Bioactive Materials 2022年第10期7卷 187-203页

作者： Paula Pleguezuelos-Beltran patricia Galvez-Martín Daniel Nieto-Garcí Juan Antonio Marchal Elena Lopez-ruiz Biopathology and Regenerative Medicine Institute(IBIMER) Centre for Biomedical Research(CIBM)University of GranadaGranadaSpain Department of Human Anatomy and Embryology Faculty of MedicineUniversity of GranadaGranadaSpain BioFab i3D Lab-Biofabrication and 3D(bio)printing Laboratory GranadaSpain Excellence Research Unit“Modeling Nature”(MNat) University of GranadaGranadaSpain Biosanitary Research Institute of Granada(ibs.GRANADA) University Hospitals of Granada-University of GranadaGranadaSpain R&D Human Health Bioib´erica S.A.UBarcelonaSpain Department of Pharmacy and Pharmaceutical Technology Faculty of PharmacyUniversity of GranadaGranadaSpain Complex Tissue Regeneration Department MERLN Institute for Technology Inspired Regenerative MedicineUniversiteitssingel 406229ER Maastrichtthe Netherlands Department of Health Sciences University of Ja´enJa´enSpain

To date,skin wounds are still an issue for healthcare professionals.Although numerous approaches have been developed over the years for skin regeneration,recent advances in regenerative medicine offer very promising strategies for the fabrication of artificial skin substitutes,including 3D bioprinting,electrospinning or spraying,among others.In particular,skin sprays are an innovative technique still under clinical evaluation that show great potential for the delivery of cells and hydrogels to treat acute and chronic wounds.Skin sprays present significant advantages compared to conventional treatments for wound healing,such as the facility of application,the possibility to treat large wound areas,or the homogeneous distribution of the sprayed material.In this article,we review the latest advances in this technology,giving a detailed description of investigational and currently commercially available acellular and cellular skin spray products,used for a variety of diseases and applying different experimental materials.Moreover,as skin sprays products are subjected to different classifications,we also explain the regulatory pathways for their commercialization and include the main clinical trials for different skin diseases and their treatment conditions.Finally,we argue and suggest possible future trends for the biotechnology of skin sprays for a better use in clinical dermatology.

关键词： Skin Spray Tissue engineering Fibrin Hydrogel

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Immunotherapy in triple-negative breast cancer:A literature review and new advances

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World Journal of Clinical Oncology 2022年第3期13卷 219-236页

作者： Guillermo Arturo Valencia patricia Rioja Zaida Morante Rossana ruiz Hugo Fuentes Carlos A Castaneda Tatiana Vidaurre Silvia Neciosup Henry L Gomez Department of Medical Oncology Instituto Nacional de Enfermedades NeoplásicasLima 15036Peru

Triple-negative breast cancer(TNBC)is a highly complex,heterogeneous disease and historically has limited treatment options.It has a high probability of disease recurrence and rapid disease progression despite adequate systemic treatment.Immunotherapy has emerged as an important alternative in the management of this malignancy,showing an impact on progression-free survival and overall survival in selected populations.In this review we focused on immunotherapy and its current relevance in the management of TNBC,including various scenarios(metastatic and early-neoadjuvant,adjuvant-),new advances in this subtype and the research of potential predictive biomarkers of response to treatment.

关键词： Triple-negative breast cancer Early disease Immunotherapy Biomarkers Metastatic disease

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Sex-specific pathways in early cardiac response to pressure overload in mice

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世界最新医学信息文摘 2015年第99期 1-1页

作者： Henning Witt Carola Schubert Juliane Jaekel Daniela Fliegner Adam Penkalla Klaus Tiemann Joerg Stypmann Stefan Roepcke Sebastian Brokat Shokoufeh Mahmoodzadeh Eva Brozova Mercy M.Davidson patricia ruiz Noppinger Christian Grohé Vera Regitz-Zagrosek

Pressure overload(PO) first causes cardiac hypertrophy and then heart failure(HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction(TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology(GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes(α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function(PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males(collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF.

关键词： Pressure overload Hypertrophy Gene expression Sex Heart

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Sex-specific pathways in early cardiac response to pressure overload in mice

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世界最新医学信息文摘 2015年第A期 8-8页

Pressure overload(PO) first causes cardiac hypertrophy and then heart failure(HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction(TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology(GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes(α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function(PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-Co A dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males(collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and Hf.

关键词： Pressure overload Hypertrophy Gene expression Sex Heart

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Sex-specific pathways in early cardiac response to pressure overload in mice

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世界最新医学信息文摘 2016年第2期 8-8页

Pressure overload(PO) first causes cardiac hypertrophy and then heart failure(HF),which are associated with sex differences in cardiac morphology and function.We aimed to identify genes that may cause HF-related sex differences.We used a transverse aortic constriction(TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks,but with sex differences in hypertrophy 6 and 9 weeks after TAC.Cardiac gene expression was analyzed 2 weeks after surgery.Deregulated genes were classified into functional gene ontology(GO) categories and used for pathway analysis.Classical marker genes of hypertrophy were similarly upregulated in both sexes(α-actin,ANP,BNP,CTGF).Thirty-five genes controlling mitochondrial function(PGC-1,cytochrome oxidase,carnitine palmitoyl transferase,acyl-CoA dehydrogenase,pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC.Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males(collagen 3,matrix metalloproteinase 2,TIMP2,and TGFβ2,all about twofold) after TAC.We confirmed 87% of the gene expression by real-time polymerase chain reaction.By GO classification,female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis.Promoter studies confirmed the upregulation of PGC-1 by E2.Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO.These differences could contribute to subsequent sex differences in cardiac function and HF.

关键词： Pressure overload Hypertrophy Gene expression Sex Heart

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Survival after curative pancreaticoduodenectomy for ampullary adenocarcinoma in a South American population:A retrospective cohort study

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World Journal of Gastrointestinal Surgery 2022年第1期14卷 24-35页

作者： Ramiro Manuel Fernandez-Placencia Paola Montenegro Melvy Guerrero Mariana Serrano Emperatriz Ortega Mercedes Bravo Lourdes Huanca Stéphane Bertani Juan Manuel Trejo patricia Webb Jenny Malca-Vasquez Luis Taxa Alberto Lachos-Davila Juan Celis-Zapata Carlos Luque-Vasquez Eduardo Payet Eloy ruiz Francisco Berrospi Hepato-Pancreato-Biliary Section Department of Abdominal SurgeryInstituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Medical Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Pathology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru International Joint Laboratory of Molecular Anthopological Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Unite Pharmacochim&Pharmacol Dev UMR152F-31062 ToulouseFrance Department of Radiation Oncology Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru Department of Abdominal Surgery Instituto Nacional de Enfermedades NeoplasicasLima 15038Peru

BACKGROUND Ampullary adenocarcinoma(AAC)is a rare neoplasm that accounts for only 0.2%of all gastrointestinal cancers.Its incidence rate is lower than 6 cases per million people.Different prognostic factors have been described for AAC and are associated with a wide range of survival rates.However,these studies have been exclusively conducted in patients originating from Asian,European,and North American countries.AIM To evaluate the histopathologic predictors of overall survival(OS)in South American patients with AAC treated with curative pancreaticoduodenectomy(PD).METHODS We analyzed retrospective data from 83 AAC patients who underwent curative(R0)PD at the National Cancer Institute of Peru between January 2010 and October 2020 to identify histopathologic predictors of OS.RESULTS Sixty-nine percent of patients had developed intestinal-type AAC(69%),23%had pancreatobiliary-type AAC,and 8%had other subtypes.Forty-one percent of patients were classified as Stage I,according to the AJCC 8 th Edition.Recurrence occurred primarily in the liver(n=8),peritoneum(n=4),and lung(n=4).Statistical analyses indicated that T3 tumour stage[hazard ratio(HR)of 6.4,95%confidence interval(CI)of 2.5-16.3,P<0.001],lymph node metastasis(HR:4.5,95%CI:1.8-11.3,P=0.001),and pancreatobiliary type(HR:2.7,95%CI:1.2-6.2,P=0.025)were independent predictors of OS.CONCLUSION Extended tumour stage(T3),pancreatobiliary type,and positive lymph node metastasis represent independent predictors of a lower OS rate in South American AAC patients who underwent curative PD.

关键词： Gastrointestinal neoplasms Adenocarcinoma Ampulla Pancreaticoduodenectomy Survival South America

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