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Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease:A crosssectional study

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World Journal of Gastroenterology 2025年第7期31卷 63-73页

作者： Yolanda Real Martinez Carlos Ernesto Fernandez-Garcia Esther Fuertes-Yebra Mario Calvo Soto Angela Berlana Vicente Barrios Maria Caldas Leticia Gonzalez Moreno Luisa Garcia-Buey Begoña Molina Baena Miguel Sampedro-Nuñez Maria J Beceiro C García-Monzón Águeda González-Rodríguez servicio Aparato Digestivo Hospital Universitario La PrincesaInstituto de Investigación Sanitaria La PrincesaUniversidad Autónoma de MadridMadrid 28006Spain Unidad de Investigación Hospital Universitario Santa CristinaInstituto de Investigación Sanitaria La PrincesaMadrid 28009Spain department of Endocrinology Department of PediatricsHospital Infantil Universitario Niño JesúsInstituto de Investigación La PrincesaMadrid 28009Spain Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición Instituto de Salud Carlos IIIMadrid 28029Spain servicio de Endocrinología y Nutrición Hospital Universitario La PrincesaInstituto de Investigación Sanitaria La PrincesaUniversidad Autónoma de MadridMadrid 28006Spain Instituto de Investigaciones Biomédicas Sols-Morreale(IIBM) CSIC-UAMMadrid 28029Spain Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas Madrid 28029Spain

BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these ***,their actual prevalence and pathophysiology remain to be *** To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with *** Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level *** degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional *** and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD *** analysis was performed comparing results according to liver fibrosis and *** No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver ***,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD *** serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.

关键词： Skeletal muscle alterations Myokines Metabolic dysfunction-associated steatotic liver disease Liver fibrosis Hepatosteatosis

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Cardiovascular prevention in elderly patients

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Journal of Geriatric Cardiology 2022年第5期19卷 377-392页

作者： Clara Bonanad Rosa Fernández-Olmo Sergio García-Blas Jose Antonio Alarcon Pablo Díez-Villanueva Carmen Rus Mansilla Héctor García-Pardo Pablo Toledo Ana Ayesta Eva Pereira Antoni Carol Almudena Castro-Conde Carmen de Pablo-Zarzoso Manuel Martínez-Sellés Vicente Arrarte Raquel Campuzano Albert Ariza-Solé servicio de Cardiología Hospital Clínico Universitario de ValenciaValenciaSpain Instituto de Investigación Sanitaria INCLIVA ValenciaSpain servicio Cardiología.hospital universitario de Jaén Spain servicio Cardiología.hospital de Donosti Spain servicio de Cardiología Hospital Universitario La Princesa de MadridSpain servicio de Cardiología Hospital Alto Gudalquivir de AndújarJaénSpain servicio de Cardiología Hospital Rio Hortega de ValladolidSpain servicio Cardiología.hospital Clínico San Cecilio de Granada Spain servicio de Cardiología Hospital Universitario Central de AsturiasSpain servicio de Cardiologia Hospital de LugoSpain servicio de Cardiología Hospital Moisés Broggi de BarcelonaSpain servicio de Cardiología.hospital universitario de la Paz de Madrid Spain servicio de Cardiología Hospital Ramón y Cajal de MadridSpain department of Cardiology.hospital universitario Gregorio Marañón CIBERCV.Universidad EuropeaUniversidad Compluten servicio de Cardiología del hospital General de Alicante Spain servicio de Cardiología.hospital Universitario Fundación de Alcorcón de MadridSpain servicio de Cardiología Hospital Bellvitge de BarcelonaBioheartGrup de Malalties CardiovascularsInstitut d’InvestigacióBiomèdica de BellvitgeIDIBELLL’Hospitalet de LlobregatBarcelonaSpain

In recent decades,life expectancy has been increasing *** this scenario,health interventions are ne-cessary to improve prognosis and quality of life of elderly with cardiovascular risk factors and cardiovascular ***,the number of elderly patients included in clinical trials is low,thus current clinical practice guidelines do not include specific *** document aims to review prevention recommendations focused in patients≥75 years with high or very high cardiovascular risk,regarding objectives,medical treatment options and also including physical exercise and their inclusion in cardiac rehabilitation ***,we will show why geriatric syndromes such as frailty,dependence,cognitive impair-ment,and nutritional status,as well as comorbidities,ought to be considered in this population regarding their important pro-gnostic impact.

关键词： prevention patients cardiovascular

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Effectiveness of sacubitril-varsartan versus angiotensin converting enzyme inhibitors in patients hospitalized for acute heart failure:a retrospective cohort study of the RICA registry

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Journal of Geriatric Cardiology 2022年第11期19卷 802-810页

作者： Llanos Soler-Rangel Manuel Méndez-Bailón JoséPérez-Silvestre JoséMaría Fernández-Rodríguez Beatriz Cuesta García Adrián Argüelles-Curto Álvaro González-Franco Alicia Conde-Martel Sara Carrascosa-García Marta Sánchez-Marteles JoséManuel Cerqueiro-González Noel Lorenzo-Villalba Manuel Montero-Pérez-Barquero Llanos Soler-Rangel Servicio de Medicina InternaHospital Universitario Infanta SofíaFIIB HUIS HHENMadridSpain servicio de Medicina Interna Hospital Clínico San CarlosInstituto de Investigación San Carlos(IdISSC)Spain servicio de Medicina Interna Consorcio Hospital General Universitario de ValenciaSpain servicio de Medicina Interna Hospital Carmen y Severo OchoaCangas del NarceaAsturiasSpain servicio de Medicina Interna Hospital Universitario Central de AsturiasOviedoSpain servicio de Medicina Interna Hospital Universitario de Gran Canaria Dr NegrínSpain servicio de Medicina Interna Hospital Clínico Universitario Lozano Blesa de ZaragozaZaragozaSpain hospital universitario Lucus Augusti de Lugo LugoSpain Service de Médecine Interne Diabète et Maladies MétaboliquesHôpitaux Universitaires de StrasbourgFrance servicio de Medicina Interna IMIBIC/Hospital Universitario Reina SofíaCórdobaSpain

BACKGROUND Sacubitril-valsartan has been shown to reduce hospitalizations and mortality in patients with heart failure(HF)and reduced ejection *** PIONEER-HF trial demonstrated that initiation of the drug during acute HF hospitalization reduced NT-proBNP levels and a post-hoc analysis of the trial found a reduction in HF hospitalizations and ***-life studies in the elderly population are *** aim of our study was to assess the effectiveness of sacubitril-valsartan versus angiotensin converting enzyme inhibitors(ACEI)in elderly patients who initiate this treatment during hospitalization for acute *** We conducted a retrospective cohort study using the Spanish acute heart failure registry(RICA)comparing rehospitalizations and deaths at 3 months and 1 year among patients aged 70 years or older who had initiated treatment with sacubitrilvalsartan during hospitalization for acute HF versus those treated with *** One hundred and ninety-nine patients hospitalized between October 2016 and November 2020 were included,with a median age of 82 years and high rate of *** these,107 were treated with sacubitril-valsartan and 92 with *** adjusted OR for readmission for HF at 3 months was 0.906(95%CI:0.241-3.404)and for the combined variable readmission for HF or death at 3 months was 0.696(95%CI:0.224-2.167).The adjusted OR for HF readmission at one year was 0.696(95%CI:0.224-2.167).and for the combined variable HF readmission or death at one year 0.724(95%CI:0.325-1.612).CONCLUSION Treatment with sacubitril-valsartan initiated early in hospitalization for HF in elderly patients with high comorbidity was associated with a trend towards a reduction in readmissions and death due to HF compared to treatment with ACEI,which did not reach statistical significance either at 3 months or 1 year of follow-up.

关键词： patients initiated admission

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Thrombin activation and liver inflammation in advanced hepatitis C virus infection

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World Journal of Gastroenterology 2016年第18期22卷 4427-4437页

作者： Emilio González-Reimers Geraldine Quintero-Platt Candelaria Martín-González Onán Pérez-Hernández Lucía Romero-Acevedo Francisco Santolaria-Fernández servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna

Hepatitis C virus(HCV) infection is associated with increased thrombotic risk. Several mechanisms are involved including direct endothelial damage by the HCV virus, with activation of tissue factor, altered fibrinolysis and increased platelet aggregation and activation. In advanced stages, chronic HCV infection may evolve to liver cirrhosis, a condition in which alterations in the portal microcirculation may also ultimately lead to thrombin activation, platelet aggregation, and clot formation. Therefore in advanced HCV liver disease there is an increased prevalence of thrombotic phenomena in portal vein radicles. Increased thrombin formation may activate hepatic stellate cells and promote liver fibrosis. In addition, ischemic changes derived from vascular occlusion by microthrombi favor the so called parenchymal extinction, a process that promotes collapse of hepatocytes and the formation of gross fibrous tracts. These reasons may explain why advanced HCV infection may evolve more rapidly to end-stage liver disease than other forms of cirrhosis.

关键词： Coagulation Liver cirrhosis Hepatitis C virus Fibrogenesis Parenchymal extinction Portal thrombosis Protein C

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New antimyeloma drugs in spinal cord infiltration for multiple myeloma. determination of lenalidomide in cerebrospinal fluid with ultrasensitive high-performance liquid chromatography

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Modern Chemotherapy 2012年第2期1卷 11-13页

作者： Inmaculada Rapado Juan José Lahuerta Laura Montejano María ángeles Montalbán Laura Pares Joaquín Martínez- López servicio de Bioquímica Hospital Universitario 12 de Octubre Madrid Spain servicio de Hematología Hospital Universitario 12 de Octubre Madrid Spain

A 64-year-old woman with IgA kappa multiple myeloma was treated with thalidomide-dexa- methasone. Due to progression of the disease, bortezomib, doxorubicin and dexamethasone were administered, followed by autologous stem cell transplantation. Although near-complete remission was achieved, 5 months later, neuro- logical symptoms appeared and the patient was diagnosed with multiple myeloma with cells in- filtrating the spinal cord. Bis-chloronitrosourea, bortezomib and lenalidomide were then admin- istered and although the patient remained neu- rologically asymptomatic, she died 3 months later becausee of disease progression. Lena- lidomide entered into the cerebrospinal fluid (confirmed by ultrasensitive high-performance liquid chromatography), although did not im- prove the poor prognosis of multiple myeloma involving the central nervous system.

关键词： Lenalidomide Multiple Myeloma Spinal Cord Infiltration High-Performance Liquid Chromatography

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Bone marrow-derived mononuclear stem cells in the treatment of retinal degenerations

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Neural Regeneration Research 2022年第9期17卷 1937-1944页

作者： Diego García-Ayuso Johnny Di Pierdomenico David García-Bernal Manuel Vidal-Sanz María P.Villegas-Pérez departamento de oftalmología Facultad de MedicinaUniversidad de MurciaCampus de Ciencias de la saludMurciaSpain Instituto Murciano de Investigación Biosanitaria.hospital Virgen de la Arrixaca(IMIB-Virgen de la Arrixaca) MurciaSpain servicio de Hematología Hospital Clínico Universitario Virgen de la ArrixacaMurciaSpain

Retinal degenerative diseases affecting the outer retina in its many forms(inherited,acquired or induced)are characterized by photoreceptor loss,and represent currently a leading cause of irreversible vision loss in the *** present,there are very few treatments capable of preventing,recovering or reversing photoreceptor degeneration or the secondary retinal remodeling,which follows photoreceptor loss and can also cause the death of other retinal ***,these diseases are nowadays one of the greatest challenges in the field of ophthalmological *** marrow derived-mononuclear stem cell transplantation has shown promising results for the treatment of photoreceptor *** cells may have the potential to slow down photoreceptor loss,and therefore should be applied in the early stages of photoreceptor ***,because of their possible paracrine effects,they may have a wide range of clinical applications,since they can potentially impact on several retinal cell types at once and photoreceptor degenerations can involve different cells and/or begin in one cell type and then affect adjacent *** intraocular injection of bone marrow derived-mononuclear stem cells also enhances the outcomes of other treatments aimed to protect ***,it is likely that future investigations may combine bone marrow derived-mononuclear stem cell therapy with other systemic or intraocular treatments to obtain greater therapeutic effects in degenerative retinal diseases.

关键词： age-related macular degeneration bone marrow stem cells intravitreal injection macroglia microglia photoreceptor degeneration retinal ganglion cells retinitis pigmentosa subretinal injection transplant

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Management of betablocked patients after sustained virological response in hepatitis C cirrhosis

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World Journal of Gastroenterology 2019年第21期25卷 2665-2674页

作者： Marta Abadía María Luisa Montes Dolores Ponce Consuelo Froilán Miriam Romero Joaquín Poza Teresa Hernández Rubén Fernández-Martos Antonio Olveira Antonio Olveira Servicio de Aparato DigestivoHospital Universitario La PazMadrid 28046Spain Unidad VIH Servicio de Medicina InternaHospital Universitario La PazMadrid 28046Spain servicio de Radiología Hospital Universitario La PazMadrid 28046Spain CIBERehd IdiPAZ Madrid 28029Spain

BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after directacting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 103/μL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was

关键词： Hepatitis C virus Oesophageal varices Portal hypertension Betablocker Variceal bleeding

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Alcoholism: A systemic proinflammatory condition

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World Journal of Gastroenterology 2014年第40期20卷 14660-14671页

作者： Emilio González-Reimers Francisco Santolaria-Fernández María Candelaria Martín-González Camino María Fernández-Rodríguez Geraldine Quintero-Platt servicio de Medicina Interna Hospital Universitario de Canarias Universidad de La Laguna Tenerife 38320 Canary Islands Spain

Excessive ethanol consumption affects virtually any organ,both by indirect and direct *** research in the last two decades has widened the knowledge about the paramount importance of proinflammatory cytokines and oxidative damage in the pathogenesis of many of the systemic manifestations of *** cytokines derive primarily from activated Kupffer cells exposed to Gram-negative intestinal bacteria,which reach the liver in supra-physiological amounts due to ethanol-mediated increased gut *** oxygen species(ROS)that enhance the inflammatory response are generated both by activation of Kupffer cells and by the direct metabolic effects of *** effects of this increased cytokine secretion and ROS generation lie far beyond liver *** addition to the classic consequences of endotoxemia associated with liver cirrhosis that weredescribed several decades ago,important research in the last ten years has shown that cytokines may also induce damage in remote organs such as brain,bone,muscle,heart,lung,gonads,peripheral nerve,and *** effects are even seen in alcoholics without significant liver ***,alcoholism can be viewed as an inflammatory condition,a concept which opens the possibility of using new therapeutic weapons to treat some of the complications of this devastating and frequent *** this review we examine some of the most outstanding consequences of the altered cytokine regulation that occurs in alcoholics in organs other than the liver.

关键词： Alcoholism Cytokines Brain Bone Muscle Oxidative damage Atherosclerosis Sepsis Lung Chronic pancreatitis Alcoholic liver disease

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development and postnatal neurogenesis in the retina: a comparison between altricial and precocial bird species

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Neural Regeneration Research 2021年第1期16卷 16-20页

作者： Guadalupe Álvarez-Hernán José Antonio de Mera-Rodríguez Yolanda Gañán Jorge Solana-Fajardo Gervasio Martín-Partido Joaquín Rodríguez-León Javier Francisco-Morcillo Área de Biología Celular Departamento de AnatomíaBiología Celular y ZoologíaFacultad de CienciasUniversidad de ExtremaduraBadajozSpain Área de Anatomía Humana Departamento de AnatomíaBiología Celular y ZoologíaFacultad de MedicinaUniversidad de ExtremaduraBadajozSpain servicio de oftalmología Complejo Hospitalario Universitario de BadajozBadajozSpain

The visual system is affected by neurodegenerative diseases caused by the degeneration of specific retinal neurons,the leading cause of irreversible blindness in *** vertebrate phylogeny,the retina has two kinds of specialized niches of constitutive neurogenesis:the retinal progenitors located in the circumferential marginal zone and Müller *** proliferative activity in the retinal progenitors located in the circumferential marginal zone in precocial birds such as the chicken,the commonest bird model used in developmental and regenerative studies,is very *** region adds only a few retinal cells to the peripheral edge of the retina during several months after hatching,but does not seem to be involved in retinal regeneration.Müller cells in the chicken retina are not proliferative under physiological conditions,but after acute damage some of them undergo a reprogramming event,dedifferentiating into retinal stem cells and generating new retinal ***,regenerative response after injury occurs with low efficiency in the precocial avian *** contrast,it has recently been shown that neurogenesis is intense in the retina of altricial birds at *** particular,abundant proliferative activity is detected both in the circumferential marginal zone and in the outer half of the inner nuclear ***,stem cell niches are very active in the retina of altricial *** more extensive research is needed to assess the potential of proliferating cells in the adult retina of altricial birds,it emerges as an attractive model for studying different aspects of neurogenesis and neural regeneration in vertebrates.

关键词： altricial birds circumferential marginal zone Müller glia postnatal neurogenesis precocial regeneration retinogenesis

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Gastrointestinal disorders associated with migraine: A comprehensive review

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World Journal of Gastroenterology 2016年第36期22卷 8149-8160页

作者： Carlos R Cámara-Lemarroy Rene Rodriguez-Gutierrez Roberto Monreal-Robles Alejandro Marfil-Rivera servicio de Neurología Hospital Universitario "Dr. José E. González" Universidad Autónoma de Nuevo León servicio de Endocrinología Hospital Universitario "Dr. José E. González" Universidad Autónoma de Nuevo León servicio de Gastroenterología Hospital Universitario "Dr. José E. González" Universidad Autónoma de Nuevo León

Migraine is a recurrent and commonly disabling primary headache disorder that affects over 17% of women and 5%-8% of men. Migraine susceptibility is multifactorial with genetic, hormonal and environmental factors all playing an important role. The physiopathology of migraine is complex and still not fully understood. Many different neuropeptides, neurotransmitters and brain pathways have been implicated. In connection with the myriad mechanisms and pathways implicated in migraine, a variety of multisystemic comorbidities(e.g., cardiovascular, psychiatric and other neurological conditions) have been found to be closely associated with migraine. Recent reports demonstrate an increased frequency of gastrointestinal(GI) disorders in patients with migraine compared with the general population. Helicobacter pylori infection, irritable bowel syndrome, gastroparesis, hepatobiliary disorders, celiac disease and alterations in the microbiota have been linked to the occurrence of migraine. Several mechanisms involving the gut-brain axis, such as a chronic inflammatory response with inflammatory and vasoactive mediators passing to the circulatory system, intestinal microbiota modulation of the enteric immunological milieu and dysfunction of the autonomic and enteric nervous system, have been postulated to explain these associations. However, the precise mechanisms and pathways related to the gut-brain axis in migraine need to be fully elucidated. In this review, we survey the available literature linking migraine with GI disorders. We discuss the possible physiopathological mechanisms, and clinical implications as well as several future areas of interest for research.

关键词： Migraine Headache Microbiota Review Gastrointestinal diseases

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