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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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Characterization of Gromov Hyperbolic Short Graphs

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Acta Mathematica Sinica,English Series 2014年第2期30卷 197-212页

作者： José Manuel RODRIGUEZ Departamento de Matemticas Universidad Carlos III de MadridAvenida de la Universidad 30

To decide when a graph is Gromov hyperbolic is,in general,a very hard *** this paper,we solve this problem for the set of short graphs（in an informal way,a graph G is r-short if the shortcuts in the cycles of G have length less than r）：an r-short graph G is hyperbolic if and only if S9r（G）is finite,where SR（G）：=sup{L（C）：C is an R-isometric cycle in G}and we say that a cycle C is R-isometric if dC（x,y）≤dG（x,y）＋R for every x,y∈C.

关键词： Short graph Gromov hyperbolicity Gromov hyperbolic graph infinite graphs geodesics

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Prevalence of hepatocarcinoma-related hepatitis B virus mutants in patients in grey zone of treatment

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World Journal of Gastroenterology 2019年第38期25卷 5883-5896页

作者： Ana Isabel Gil-García Antonio Madejón Irene Francisco-Recuero Ana López-López Emiliana Villafranca Miriam Romero Araceli García Antonio Olveira Rocío Mena Juan Ramón larrubia Javier García-Samaniego Hepatology Unit Hospital Universitario La PazMadrid 28046Spain Centro de Investigación Biomédica en Red Instituto de Salud Carlos IIIMadrid 28029Spain Instituto de Investigación del hospital Universitario la paz Madrid 28046Spain Biochemistry Department Faculty of MedicineUniversidad Autónoma de MadridMadrid 28029Spain Instituto de Genética Médica y Molecular Hospital Universitario La PazMadrid 28046Spain Translational Hepatology Unit Hospital General Universitario de GuadalajaraGuadalajara 19002Castilla-La ManchaSpain

BACKGROUND Antiviral treatment of patients with chronic hepatitis B(CHB)in the grey zone of treatment comands risk management in order to optimize the health *** this sense,the identification of HBV mutants related with an increased risk of hepatocellular carcinoma(HCC)could be useful to identify subpopulations with potential indication of antiviral *** To analyze the prevalence/persistence of hepatitis B virus(HBV)preS and basal core promoter(BCP)/precore/core variants associated to HCC development in CHB patients in the grey *** Work was designed as a longitudinal retrospective study,including 106 plasma samples from 31 patients with CHB in the grey zone of treatment:Hepatitis B e antigen negative,HBV-DNA levels between 12-20000 IU/mL,normal or discordant transaminase levels during follow up and mild/moderate necroinflammatory activity in liver biopsy or Fibroscan(up to 9.5 kPa).Serum HBVDNA was tested using the Abbott Real Time HBV Assay and the BCP/precore/core and the hepatitis B surface antigen(HBsAg)coding regions were analyzed in positive samples by PCR/bulk-sequencing to identify the HCCrelated HBV *** High-risk HCC related mutants were detected in 24(77%)patients:19(61%)in the BCP/precore/core,and 7(23%)in the HBsAg coding region(2 preS1 and 5 preS2 deletions).The prevalence of preS deletions was genotype-dependent:3/5(60%)patients with preS2 deletions and 1/2 with preS1 deletions were infected with the HBV-E *** HBV-E was the most prevalent in sub-Saharan patients,a correlation between preS deletions and ethnicity was also found:6/8(75%)sub-Saharan vs 1/19(5%)Caucasian patients had preS deletions(P=0.00016).Remarkably,this correlation was maintained in those patients infected with HBV-A,a minor genotype in sub-Saharan patients:2/2 patients infected with HBV-A from West Africa vs 0/6 of Caucasian origin had preS *** HCC related variants were the major strains and persisted over time(up to 48 mo).Pa

关键词： Hepatitis B virus Hepatocellular carcinoma PreS deletions Hepatitis B virus treatment Grey zone

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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 latelets 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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Properdin deficiency associated with systemic meningococcal disease due to a novel ***337Arg pathogenic variant

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Genes & Diseases 2024年第6期11卷 43-46页

作者： laura Gonzalez-Sanchez Ana Mei Agudo Anne Van Den Rym Maria Isabel Begiristain Alazne Saizar Rebeca Perez de Diego Pilar Nozal Alberto Lopez-Lera Margarita Lopez-Trascasa Fernando Corvillo Complement Research Group Hospital La Paz Institute for Health Research(ldiPAZ)La Paz University HospitalMadrid 28046Spain Center for Biomedical Network Research on Rare Diseases MadridSpain laboratory of Immunogenetics of Human Diseases IdiPAz Institute for Health ResearchLa Paz University HospitalMadrid 28046Spain Ormaiztegui Clinic Guipuzcoa 20216Spain Immunology Unit La Paz University HospitalMadrid 28046Spain Departamento de Medicina Universidad Autonoma de MadridMadrid28029Spain

Properdin(FP)is a soluble glycoprotein with a key role in the regulation of the alternative pathway(AP)of the complement system.1 Neutrophils are the main source of FP,although monocytes,bone marrow progenitors,and T cells also synthesize this complement *** is codified by the gene CFP,located at Xp11.23-p11.3,and formed by 10 exons,of which exons 2 to 10 are translated conforming six thrombospondin type 1 repeats(TSR1-6).

关键词： Xp11.2 glycoprotein progenitor

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Understanding the immune response and the current landscape of immunotherapy in pancreatic cancer

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World Journal of Gastroenterology 2021年第40期27卷 6775-6793页

作者： Lorena Ostios-Garcia Julia Villamayor Esther Garcia-Lorenzo David Vinal Jaime Feliu Department of Oncology La Paz University HospitalIDIPAZCIBERONCCátedra UAMAMGENMadrid 28046Spain

Pancreatic ductal adenocarcinoma(PDAC)is an aggressive tumor with high *** with surgery,radiotherapy,chemotherapy,and other locoregional or systemic therapies,the survival rates for PDAC are low and have not significantly changed in the past *** special characteristics of the PDAC’s microenvironment and its complex immune escape mechanism need to be considered when designing novel therapeutic approaches in this *** is characterized by chronic inflammation with a high rate of tumor-associated macrophages and myeloid-derived suppressor cells and a low rate of natural killer and effector T *** pancreatic microenvironment is a fibrotic,microvascularized stroma that isolates the tumor from systemic ***,a novel approach that has demonstrated effectiveness in certain solid tumors,has failed to show any practice-changing results in pancreatic cancer,with the exception of PDACs with mismatch repair deficiency and high tumor mutational burden,which show prolonged survival rates with ***,numerous clinical trials are attempting to assess the efficacy of immunotherapeutic strategies in PDAC,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell transfer,alone or in combination with other immunotherapeutic agents,chemoradiotherapy,and other targeted therapies.A deep understanding of the immune response will help in the development of new therapeutic strategies leading to improved clinical outcomes for patients with PDAC.

关键词： Pancreatic cancer Immunity Immune evasion Tumor microenvironment Immunotherapy Cancer vaccines

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Secondary male hypogonadism： a prevalent but overlooked comorbidity of obesity

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Asian Journal of Andrology 2018年第6期20卷 531-538页

作者： Maria Molina-Vega Araceli Mufioz-Garach Miguel Damas-Fuentes JosO carlos Fernfindez-Garcia Francisco J inahones Department of Endocrinology and Nutrition Virgen de la Victoria Universitary HospitalMalaga 29010Spain Institute of Biomedical Research in Malaga（IBIMA） Virgen de la Victoria Universitary HospitalMalaga 29010Spain CIBER Pathophysiology of Obesity and Nutrition（CB06/003） Institute of Health Carlos III（ISClII）Madrid 28029Spain.

Male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. Male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.

关键词： adipose tissue male hypogonadism obesity testosterone

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Impact of HIV on the health-related quality of life in youth with perinatally acquired HIV

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World Journal of Pediatrics 2019年第5期15卷 492-498页

作者： Isabel Cuéllar-Flores Talís Saínz carlos Velo María Isabel González-Tomé Cristina García-Navarro Caroclina Fernández-Mcphee Sara Guillén JoséTomás Ramos Pilar Miralles Rafae Rubio JoséIgnacio Bernardino Luis Prieto Pablo Rojo Santiago Jiménez de Ory Maria Luisa Navarro CoRiSpe(FARO and NeuroCoRISpeS projects,RITIP-Traslational Research Network in Pediatric Infectious Diseases) Pediatric Department Hospital Clínico San CarlosMadridSpain Infectious Diseases Service Paed DepartmentHospital La PazMadridSpain la paz Research Institute(Idipaz) MadridSpain Infectious Diseases Service Paed DepartmentHospital 12 de OctubreMadridSpain Infectious Diseases Service Paed DepartmentH.Gregorio MaranónMadridSpain Paed Department Hospital de GetafeMadridSpain Infectious Diseases Service H.Gregorio MaranónMadridSpain HIV Service Hospital 12 de OctubreMadridSpain Infectious Diseases Service Hospital La PazMadridSpain Instituto de Investigación Sanitaria.hospital Gregorio Maranón(IiSGM) MadridSpain Universidad Complutense de Madrid MadridSpain Translational Research Network in Pediatric Infectious Diseases(RITIP) MadridSpain 不详

Background Studies investigating health-related quality of life(HRQoL)in youth with perinatally acquired HIV(PHIV+)are *** study aimed to compare HRQoL of PHIV+to sociodemographic-matched youth not living with HIV(HIV-),Spanish general youth population,and to explore associations between sociodemographic variables,drug consumption,and *** PHIV+youth were randomly selected from CoRISpe database(Cohort of the Spanish Pediatric HIV Network).HRQoL was evaluated by *** Thirty-nine PHIV+youth(mean age:23.36 years,SD=3.83)and thirty-nine HIV-youth(mean age:22.97 years,SD=3.80)participated in this ***+obtained lower scores in SF-12 physical health subscale(PCS)than HIV-(P=0.001)and Spanish general youth population(P=0.006).PHIV+had lower scores on the mental health subscale(MCS)than the Spanish general youth population(P<0.001).PHIV+who were at school obtained better scores than those were not at ***+youth who had used cocaine and cannabis had lower scores in MCS(P=0.002).Conclusions There is a need for HRQoL management in the associated medical follow-up.

关键词： Drug consumption Health-related quality of life Mental health Perinatally acquired HIV youth

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Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

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World Journal of Gastroenterology 2016年第11期22卷 3165-3174页

作者： Antonio Madejón Míriam Romero ángela Hernández Araceli García-Sánchez Marta Sánchez-Carrillo Antonio Olveira Javier García-Samaniego Hepatology Section Gastroenterology Department Hospital Universitario La Paz 28046 Madrid Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticasy Digestivas (CIBERehd) 28046 Madrid Spain Instituto de Investigación del hospital Universitario la paz (Idipaz) 28046 Madrid Spain

AIM: To study the hepatitis B virus(HBV) and hepatitis D virus(HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV ***: We conducted a transversal study including 68 chronic hepatitis delta(CHD)(37 HIVpositive) patients and a control group of 49 chronic hepatitis B(CHB)(22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B(HBs Ag) serum titers were analyzed with the Monolisa HBs Ag Ultra system(Bio-Rad), using as quantification standard a serial dilution curve of an international HBs Ag standard. Serum HBV-DNA titers were analyzed using the Roche Cobas Taq Man(Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time q RT-PCR method, with Taq Man probes. HBV genotype was determined with the line immunoassay Li PA HBV genotyping system(Innogenetics, Ghent, Belgium). In those patients negative for Li PA assay, a nested PCR method of complete HBs Ag coding region, followed by sequence analysis was ***: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median(IQR): 1.25(1.00-1.35) vs 2.95(2.07-3.93) log10(copies/m L), P = 0.013] and HIV positive patients [2.63(1.24-2.69) vs 7.25(4.61-7.55) log10(copies/m L), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with Li PA assay. Finally, the HBs Ag titers reflected no significant differences in CHD patients infected with HBV-A or ***: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

关键词： Hepatitis D virus Hepatitis B virus Delta hepatitis Replication interference Viral replication

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Clinical characteristics and type of antithrombotic treatment in a Spanish cohort of elderly patients with atrial fibrillation according to dependency, frailty and cognitive impairment

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Journal of Geriatric Cardiology 2018年第4期15卷 268-274页

作者： Jose Maria Mostaza Manuel Jesús Romero Jiménez Fernando José Ruiz laiglesia José Antonio Díaz Peromingo Manuel Beltrán Robles Ernesto Guevara Sierra Ana Santander Bilbao Carmen Suárez hospital carlos iii Madrid Spain hospital Infanta Elena Huelva Spain hospital Clínico Universitario Lozano Blesa Zaragoza Spain Complejo hospitalario Universitario de Santiago Santiago de Compostela Spain hospital Virgen del Camino Sanlucar-Cádiz Spain Centro Socio-Sanitario Vallparadís Terrassa Spain hospital de Basurto Bilbao Spain hospital Universitario de la Princesa Madrid Spain

Background Available data regarding clinical profile and management of elderly patients with atrial fibrillation （AF） according to dependency, fragility and cognitive impairment are scarce. The objective of the study was to analyze the biodemographic data, clinical profile and antithrombotic treatment according to dependency, fragility and cognitive impairment in elderly AF patients. Methods Cross- sectional and multi-center study performed in consecutive AF patients ≥ 75 years treated with oral anticoagulants ≥ 3 months attended in Internal Medicine Departments in Spain. Results A total of 837 patients （83.0 ± 5.0 years; CHA2DS2-VASc： 5.0 ± 1.4; HAS-BLED： 2.1 ± 0.9） were included. 44.4% of patients had some degree of dependency, 43.3% were fragile, and 32.3% had cognitive impairment. Patients with any of these conditions were older, had a worse clinical profile, with more comorbidities and higher risks of thromboembolic and bleeding events. All these conditions were independently associated among them. Overall, 70.8% of patients were taking vitamin K antagonists, the remaining 29.2% direct oral anticoagulants and 9.7% oral antiplatelets. This distribution was independent of the presence of dependency or fragility, but there was a trend to a higher prescription of vitamin K antagonists in those patients with cognitive impairment （75.2% vs. 68.8%; P = 0.05）. Conclusions Approximately 32%-44% of elderly anticoagulated AF patients attended have some degree of dependency, fragility and/or cognitive impairment. Patients with any of these conditions are older and have a worse clinical profile. Ap？proximately 71% of patients are taking vitamin K antagonists, regardless dependency or frailty, but with a trend to higher prescription in patients with cognitive impairment.

关键词： Atrial fibrillation Cognitive impairment Dependency Fragility Oral anticoagulants

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