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Addition of statins to the standard treatment in patients with cirrhosis:Safety and efficacy

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World Journal of Gastroenterology 2021年第28期27卷 4639-4652页

作者： Alberto E Muñoz Florencia D Pollarsky Mónica Marino Mariano Cartier Horacio Vázquez Pablo Salgado gustavo romero Sección Hepatología Hospital de Gastroenterología Dr.Carlos Bonorino UdaondoFacultad de MedicinaUniversidad de Buenos AiresCiudad Autónoma de Buenos Aires 1264Argentina Instituto de Investigaciones en Salud Pública Facultad de OdontologíaUniversidad de Buenos AiresCiudad Autónoma de Buenos Aires 1122Argentina Unidad Clínica Hospital de Gastroenterología Dr.Carlos Bonorino UdaondoInvestigador Asociado del Gobierno de la Ciudad Autónoma de Buenos AiresCiudad Autónoma de Buenos Aires 1264Argentina

This review summarizes the safety and efficacy of statins in patients with *** to concerns about the safety of statins in patients with impaired liver function,they have recently been investigated as a potential treatment option in *** most clinically significant adverse event is statin-related myopathy,and this may be related to the high serum statin concentrations in the setting of severely impaired liver *** is the most serious and potentially life-threatening *** has recently been demonstrated that the recommended dose of simvastatin in patients with decompensated cirrhosis would be 20 mg/d because higher values,such as 40 mg/d,are associated with many adverse events,especially muscle ***,simvastatin should not be administered to patients with Model for End-stage Liver Disease score>12 and/or Child-Pugh class C because of the high risk of severe muscle *** to the pleiotropic effects,the focus on statins has shifted from being considered harmful to something *** these effects,statins could prevent liver-related morbidity and mortality in cirrhotic *** studies in large populations of patients with cirrhosis have shown that treatment with statins to decrease high cholesterol levels was associated with a reduced risk of hepatic decompensation,hepatocellular carcinoma development and *** few randomized controlled trials in patients with cirrhosis and portal hypertension showed that statins lower portal pressure,quite likely through a reduction in hepatic *** large randomized controlled trial in patients with variceal bleeding showed that simvastatin in addition to standard of care did not prevent rebleeding but improved survival *** these encouraging outcomes,the quality of the evidence regarding the use of statins is low or very low due to the observational characteristics of most of the studies ***,it is advisable to per

关键词： Cirrhosis Liver disease Statins Safety Efficiency

Intermediate-advanced hepatocellular carcinoma in Argentina:Treatment and survival analysis

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World Journal of Gastroenterology 2019年第27期25卷 3607-3618页

作者： Federico Pinero Sebastián Marciano Nora Fernández Jorge Silva Margarita Anders Alina Zerega Ezequiel Ridruejo gustavo romero Beatriz Ameigeiras Claudia D’Amico Luis Gaite Carla Bermúdez Virginia Reggiardo Luis Colombato Adrián Gadano Marcelo Silva Hospital Universitario Austral Facultad de Ciencias BiomédicasUniversidad AustralBuenos Aires B1629HJArgentina Latin American Liver Research Educational and Awareness Network(LALREAN) Buenos Aires B1629HJArgentina Hospital Italiano de Buenos Cuidad Autónoma de Buenos AiresBuenos Aires C1424BYEArgentina Hospital Británico Cuidad Autonoma de Buenos AiresBuenos Aires C1280AEBArgentina Hospital G Rawson San Juan 5400Argentina Hospital Aleman Cuidad Autonoma de Buenos AiresBuenos Aires C1280AEBArgentina Sanatorio Allende from Córdoba Córdoba 5016Argentina Centro de Educación Médica e Investigaciones Clínicas“Norberto Quirno”(CEMIC) Ciudad de Buenos Aires 1431Argentina Hospital Udaondo Cuidad Autonoma de Buenos Aires C1264AAAArgentina Hospital Ramos Mejía Ciudad de Buenos Aires C1221ADCArgentina Centro Especialidades Medicas Ambulatorias(CEMA) Mar del PlataBuenos Aires 7600Argentina Clínica de Nefrología Santa Fe 3000Argentina Hospital del Centenario RosarioSanta Fe S2002KDTArgentina

BACKGROUND Hepatocellular carcinoma(HCC) represents the sixteenth most frequent cancer in Argentina. The rise of new therapeutic modalities in intermediate-advanced HCC opens up a new paradigm for the treatment of *** To describe real-life treatments performed in patients with intermediateadvanced HCC before the approval of new systemic *** This longitudinal observational cohort study was conducted between 2009 and2016 in 14 different regional hospitals from Argentina. Included subjects had intermediate-advanced Barcelona Clinic Liver Cancer(BCLC) HCC stages(BCLC B to D). Primary end point analyzed was survival, which was assessed for each BCLC stage from the date of treatment until last patient follow-up or *** Meier survival curves and Cox regression analysis were performed, with hazard ratios(HR) calculations and 95% confidence intervals(95%CI).RESULTS From 327 HCC patients, 41% were BCLC stage B, 20% stage C and 39% stage *** median survival were 15 mo(IQR 5-26 mo), 5 mo(IQR 2-13 mo)and 3 mo(IQR 1-13 mo)(P < 0.0001), respectively. Among BCLC-B patients(n =135), 57% received TACE with a median number of 2 sessions(IQR 1-3 sessions).Survival was significantly better in BCLC-B patients treated with TACE HR =0.29(CI: 0.21-0.40) than those without TACE. After tumor reassessment by RECIST 1.1 criteria following the first TACE, patients with complete response achieved longer survival (HR = 0.15(CI: 0.04-0.56, P = 0.005))Eighty-two patients were treated with sorafenib, mostly BCLC-B and C(87.8%). However,12.2% were BCLC-D. Median survival with sorafenib was 4.5 mo(IQR 2.3-11.7 mo);which was lower among BCLC-D patients 3.2 mo(IQR 2.0-14.1 mo). A total of 36 BCLC-B patients presented tumor progression after TACE. In these patients,treatment with sorafenib presented better survival when compared to those patients who received sorafenib without prior TACE [HR = 0.26(CI: 0.09-0.71);P= 0.013].CONCLUSION In this real setting, our results we

关键词： Hepatocellular carcinoma Therapeutics Survival Real-life

Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

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World Journal of Hepatology 2018年第1期10卷 41-50页

作者： Federico Pinero Josefina Pages Sebastián Marciano Nora Fernández Jorge Silva Margarita Anders Alina Zerega Ezequiel Ridruejo Beatriz Ameigeiras Claudia D’Amico Luis Gaite Carla Bermúdez Manuel Cobos Carlos Rosales gustavo romero Lucas McCormack Virginia Reggiardo Luis Colombato Adrián Gadano Marcelo Silva Hepatology and Liver Transplantation Unit Hospital Universitario AustralBuenos Aires 1629Argentina Hepatology Section Liver Transplant ProgramDepartment of Academic ResearchHospital Italiano from Buenos AiresBuenos Aires 1424Argentina Sanatorio Trinidad San Isidro Buenos Aires 1642Argentina Clínica Privada San Fernando Buenos Aires 2013Argentina Hepatology and Gastroenterology Hospital BritánicoBuenos Aires 1280Argentina Hepatobiliary Surgery Hospital G RawsonSan Juan 5400Argentina Department of Hepatology and Liver Transplant Program Hospital AlemanBuenos Aires 1118Argentina Department of Hepatology and Liver Transplantation Sanatorio AllendeCórdoba 5016Argentina Hepatology Section Department of MedicineCentro de Educación Médica e Investigaciones Clínicas Norberto Department of Hepatology Hospital Ramos MejíaBuenos Aires 1221Argentina Department of Hepatology Centro Especialidades Medicas Ambulatorias(CEMA)Mar del Plata 7600Argentina Department of Hepatology and Liver Transplantation Clínica de Nefrología de Santa FeSanta Fe 3000Argentina Department of Hepatology and Gastroenterology Hospital C Bonorino UdaondoBuenos Aires 1264Argentina Department of Hepatology and Gastroenterology Hospital CentenarioSanta Fe 2002Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical *** A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher *** The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

关键词： Hepatocellular carcinoma Etiology Fatty liver South America

Chlorophyll, anthocyanin, and gas exchange changes assessed by spectroradiometry in Fragaria chiloensis under salt stress

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Journal of Integrative Plant Biology 2014年第5期56卷 505-515页

作者： Miguel Garriga Jorge B. Retamales Sebastián romero-Bravo Peter D.S. Caligari gustavo A. Lobos Faculty of Agricultural Sciences Plant Breeding and Phenomic Center Universidad de Talca Instituto de Biología Vegetaly Biotecnología Universidad de Talca

Chlorophyll and anthocyanin contents provide a valuable indicator of the status of a plant’s physiology, but to be more widely utilized it needs to be assessed easily and non‐destructively. This is particularly evident in terms of assessing and exploiting germplasm for plant‐breeding programs. We report, for the first time, experiments with Fragaria chiloensis（L.）Duch. and the estimation of the effects of response to salinity stress（0, 30, and 60 mmol NaCl/L） in terms of these pigments content and gas exchange. It is shown that both pigments（which interestingly, themselves show a high correlation） give a good indication of stress response. Both pigments can be accurately predicted using spectral reflectance indices（SRI）;however, the accuracy of the predictions was slightly improved using multilinear regression analysis models and genetic algorithm analysis. Specifically for chlorophyll content, unlike other species, the use of published SRI gave better indications ofstress response than Normalized Difference Vegetation *** effect of salt on gas exchange is only evident at the highest concentration and some SRI gave better prediction performance than the known Photochemical Reflectance Index. This information will therefore be useful for identifying tolerant genotypes to salt stress for incorporation in breeding programs.

关键词： Gas exchange high‐throughput phenotyping pigment phenomic photosynthesis reflectance spectral reflectance indices

Wheat genotypic variability in grain yield and carbon isotope discrimination under Mediterranean conditions assessed by spectral reflectance

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Journal of Integrative Plant Biology 2014年第5期56卷 470-479页

作者： gustavo A. Lobos Iván Matus Alejandra Rodriguez Sebastián romero-Bravo José Luis Araus Alejandro del Pozo Plant Breeding and Phenomic Center Faculty of Agricultural Sciences University of Talca CRI-Quilamapu Agricultural Research Institute Plant Physiology Department Faculty of Biology University of Barcelona

A collection of 368 advanced lines and cultivars of spring wheat（Triticum aestivum L.） from Chile, Uruguay, and CIMMYT（Centro Internacional de Mejoramiento de Maíz y Trigo）, with good agronomic characteristics were evaluated under the Mediterranean conditions of central Chile. Three different water regimes were assayed： severe water stress（SWS, rain fed）, mild water stress（MWS; one irrigation around booting）, and full irrigation（FI; four irrigations： at tillering,flag leaf appearance, heading, and middle grain filling）. Traits evaluated were grain yield（GY）, agronomical yield components,days from sowing to heading, carbon isotope discrimination（△^13C） in kernels, and canopy spectral reflectance. Correlation analyses were performed for 70 spectral reflectance indices（SRI） and the other traits evaluated in the three trials. GY and △^13C were the traits best correlated with SRI, particularly when these indices were measured during grain filling. However,only GY could be predicted using a single regression, with ResearchNormalized Difference Moisture Index（NDMI2： 2,200; 1,100）having the best fit to the data for the three trials. For △^13C, only individual regressions could be forecast under FI（r^2： 0.25–0.37）and MWS（r^2： 0.45–0.59） but not under SWS（r^2： 0.03–0.09）.NIR‐based SRI proved to be better predictors than those that combine visible and NIR wavelengths.

关键词： Breeding drought dry matter index normalized difference moisture index vegetative index water index

Entanglement,Identical Particles and the Uncertainty Principle

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Communications in Theoretical Physics 2016年第8期65卷 201-206页

作者： gustavo Rigolin Departamento de Fisica Universidade Federal de Sao Carlos 13565-905 Sao Carlos SP Brazil

A new uncertainty relation(UR) is obtained for a system of N identical pure entangled particles if we use symmetrized observables when deriving the inequality. This new expression can be written in a form where we identify a term which explicitly shows the quantum correlations among the particles that constitute the system. For the particular cases of two and three particles, making use of the Schwarz inequality, we obtain new lower bounds for the UR that are different from the standard one.

关键词： quantum mechanics uncertainty relations identical and entangled particles

A Modern Approach to the Solution and Analysis of the Simha-Somcynsky Model for the Description of Pressure-Volume-Temperature Properties of Polymer Fluids

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Chinese Journal of Polymer Science 2015年第4期33卷 523-523,524-539页

作者： gustavo A.Carri Department of Polymer Science College of Polymer Science and Polymer EngineeringThe University of Akron

We revisit the Simha-Somcynsky model of polymer fluids with the purpose of developing novel theoretical and computational approaches to simplify and speed up its solution as well as the fitting of experimental data, and decrease its level of mathematical complexity. We report a novel method that allows us to solve one of the two equations of the model exactly, thus putting the level of mathematical difficulty on a par with the one of other models for polymer fluids. Moreover, we describe a computational algorithm capable of fitting all five parameters of the model in an unbiased way. The results obtained reproduce literature results and fit experimental pressure-volume-temperature and solubility parameter data for three polymers very accurately. Moreover, the new techniques allow for the investigation of the model at very low temperatures. Unexpectedly, the model predicts behaviors that could be interpreted as a glass transition, as routinely observed in dilatometry and differential scanning calorimetry, and a glass phase. We compared the predicted and experimental Tg＇s for cis poly（1,4-butadiene） and found an excellent quantitative agreement.

关键词： Simha-Somcynsky model PVT properties Polymer fluids.

Serum testosterone levels and excessive erythrocytosis during the process of adaptation to high altitudes

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Asian Journal of Andrology 2013年第3期15卷 368-374页

作者： gustavo F Gonzales High Altitude Research Institute and Department of Biological and Physiological Sciences Faculty of Sciences and Philosophy Universidad Peruana Cayetano Heredia Lima 31 Peru

Populations living at high altitudes （HAs）, particularly in the Peruvian Andes, are characterized by a mixture of subjects with erythrocytosis （16 g dl-1〈haemoglobin （Hb）≤21 gdl-1） and others with excessive erythrocytosis （EE）（Hb〉21 g dl-1）. Elevated haemoglobin values （EE） are associated with chronic mountain sickness, a condition reflecting the lack of adaptation to HA. According to current data, native men from regions of HA are not adequately adapted to live at such altitudes if they have elevated serum testosterone levels. This seems to be due to an increased conversion of dehydroepiandrosterone sulphate （DH EAS） to testosterone. Men with erythrocytosis at HAs show higher serum androstenedione levels and a lower testosterone/androstenedione ratio than men with EE, suggesting reduced 17beta-hydroxysteroid dehydrogenase （17beta-HSD） activity. Lower 17beta-HSD activity via A4-steroid production in men with erythrocytosis at HA may protect against elevated serum testosterone levels, thus preventing EE. The higher conversion of DHEAS to testosterone in subjects with EE indicates increased 17beta-HSD activity via the A5-pathway. Currently, there are various situations in which people live （human biodiversity） with low or high haemoglobin levels at HA. Antiquity could be an important adaptation component for life at HA, and testosterone seems to participate in this process.

关键词： chronic mountain sickness DHEA haemoglobin high altitudes men oestradiol women

AT1 receptor downregulation:A mechanism for improving glucose homeostasis

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World Journal of Diabetes 2023年第3期14卷 170-178页

作者： Diana L Lopez Oscar E Casillas Hiram J Jaramillo Tatiana romero-Garcia J.gustavo Vazquez-Jimenez Department of Internal Medicine General Hospital of MexicaliMexicali 21000Baja CaliforniaMexico Faculty of Medicine Autonomous University of Baja CaliforniaMexicali 21000Baja CaliforniaMexico Faculty of Sports Autonomous University of Baja CaliforniaMexicali 21289Baja CaliforniaMexico

There is a pathophysiological correlation between arterial hypertension and diabetes mellitus, established since the pre-diabetic state in the entity known as insulin resistance. It is known that high concentrations of angiotensin-Ⅱ enable chronic activation of the AT1 receptor, promoting sustained vasoconstriction and the consequent development of high blood pressure. Furthermore, the chronic activation of the AT1 receptor has been associated with the development of insulin resistance. From a molecular outlook, the AT1 receptor signaling pathway can activate the JNK kinase. Once activated, this kinase can block the insulin signaling pathway, favoring the resistance to this hormone. In accordance with the previously mentioned mechanisms, the negative regulation of the AT1receptor could have beneficial effects in treating metabolic syndrome and type 2diabetes mellitus. This review explains the clinical correlation of the metabolic response that diabetic patients present when receiving negatively regulatory drugs of the AT1 receptor.

关键词： Type 2 diabetes mellitus High blood pressure Insulin receptor Insulin signaling pathway AT1 receptor Angiotensin II signaling pathway