Depósito Académico
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Results
- EchoBrush may be superior to standard EUS-guided FNA in the evaluation of cystic lesions of the pancreas(2011) Lozano, M.D. (María Dolores); Álvarez-Cienfuegos, J. (Javier); Subtil, J.C. (José Carlos); Echeveste, J.I. (José I.); Labiano, T. (Tania); Idoate, M.A. (Miguel Ángel); Prieto-Frías, C. (Cesár); Betes, M.T. (María Teresa)BACKGROUND: Cystic lesions of the pancreas are being detected with increasing frequency. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is one of the most precise methods of diagnosis but still has limited accuracy. A new, through-the-needle cytologic brush system (EchoBrush; Cook Medical, Bloomington, Ind) has been approved for use during EUS evaluation of cystic pancreatic lesions. METHODS: Data from 127 EUS-FNAs of pancreatic cystic lesions were analyzed to compare the cytologic yield of EchoBrush with conventional EUS-FNA. An attending cytopathologist was present on site to assess specimen adequacy in all the cases. Diagnostic yields of both procedures, as well as related adverse events, were recorded. Statistical analysis was performed with the SPSS 15.0 version software (SPSS, Chicago, Ill). RESULTS: A total of 127 cystic lesions of the pancreas from 120 patients (42 men and 78 women, mean age of 62.17 ± 12.17 years) were included in the study. Mean size of lesions was 23.58 ± 21.69 mm. Adequacy of the samples and diagnostic yield were higher using EchoBrush. In 80 (63 %) cases, conventional EUS-FNA was performed, whereas in 47 (37%), we used EchoBrush. Diagnostic material was obtained in 85.1% (40 of 47) of cases using EchoBrush and in 66.3% (53 of 80) with conventional EUS-FNA. (P < .05). There were very few clinically relevant complications related to EUS-FNA and EUS-EchoBrush techniques. CONCLUSIONS: This study suggests that cytological specimens from pancreatic cystic lesions obtained using EchoBrush at the time of EUS are superior to conventional EUS-FNA mainly because of the higher yield of epithelial cells. Larger studies are needed to compare both methods. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society.
- FNDC4 reduces hepatocyte inflammatory cell death via AMPKa in metabolic dysfunction-associated steatotic liver disease(Elsevier Ltd., 2024) Neira, G. (Gabriela); Valenti, V. (Víctor); Colina, I. (Inmaculada); Catalan, V. (Victoria); Becerril, S. (Sara); Frühbeck, G. (Gema); Moncada, R. (Rafael); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Escalada, J. (Javier)Background: The molecular mediators responsible for the progression of metabolic dysfunction- associated steatotic liver disease (MASLD) to steatohepatitis (MASH) have not yet been completely disentangled. We sought to analyze whether FNDC4, an hepatokine and adipokine with anti-inflammatory properties, is involved in TNF-a-induced inflammatory cell death in patients with MASLD. Methods: Plasma FNDC4 (n 1⁄4 168) and hepatic FNDC4 and inflammatory cell death (n 1⁄4 65) were measured in samples from patients with severe obesity with available liver biopsy-proven MASLD diagnosis. The effect of FNDC4 on TNF-a-induced pyroptosis, apoptosis and necroptosis (PANoptosis) and mitochondrial dysfunction was studied in vitro using human HepG2 hepatocytes. Results: Compared with individuals with normal liver, patients with type 2 diabetes and MASLD exhibited decreased hepatic FNDC4 mRNA and protein levels, which were related to liver inflammation. An overexpression of TNF-a, its receptor TNF-R1 and factors involved in inflammatory cell death was also found in the liver of these patients. FNDC4-knockdown in HepG2 hepatocytes increased apoptotic cell death, while FNDC4 treatment blunted NLRP3 inflammasome-induced pyroptosis, apoptosis and necroptosis in TNF-a-stimulated hepatocytes. Moreover, FNDC4 improved TNF-a-induced hepatocyte mitochondrial dysfunction by enhancing mitochondrial DNA (mtDNA) copy number and OXPHOS complex subunits I, II, III and V protein expression. Mechanistically, AMP-activated protein kinase a (AMPKa) was required for the FNDC4-mediated inhibition of cell death and increase in mtDNA content. Conclusions: FNDC4 acts as a hepatocyte survival factor favouring mitochondrial homeostasis and decreasing inflammatory cell death via AMPKa. Collectively, our study identifies FNDC4 as an attractive target to prevent hepatocellular damage in patients with MASLD.
- Cardiometabolic risk stratification using a novel obesity phenotyping system based on body adiposity and waist circumference(Elsevier B.V., 2024) Marugan-Pinos, R. (Rocío); Perdomo-Zelaya, C.M. (Carolina M.); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Aguas-Ayesa, M. (Maite); Becerril, S. (Sara); Frühbeck, G. (Gema); Olazarán, L. (Laura); Salmón-Gómez, L. (Laura); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Escalada, J. (Javier); Yárnoz-Esquiroz, P. (Patricia)Background: The estimation of obesity-associated cardiometabolic risk does not usually take into account body composition or the distribution of adiposity. The aim of the present study was to assess the clinical usefulness of a novel obesity phenotyping system based on the combination of actual body fat percentage (BF%) and waist circumference (WC) according to the cardiometabolic risk estimation. Methods: A classification matrix combining BF% and WC as measures of both amount and distribution of adiposity establishing nine body phenotypes (3 BF% x 3 WC) was developed. Individuals were grouped in five different cardiometabolic risk phenotypes. We conducted a validation study in a large cohort of White subjects from both genders representing a wide range of ages and adiposity (n = 12,754; 65 % females, aged 18–88 years). Results: The five risk groups using the matrix combination of BF% and WC exhibited a robust linear distribution regarding cardiometabolic risk, estimated by the Metabolic Syndrome Severity Score, showing a continuous increase between groups with significant differences (P < 0.001) among them, as well as in other cardiometabolic risk factors. An additional 24 % of patients at very high risk was detected with the new classification system proposed (P < 0.001) as compared to an equivalent matrix using BMI and WC instead of BF% and WC. Conclusions: A more detailed phenotyping should be a priority in the diagnosis and management of patients with obesity. Our classification system allows to gradually estimate the cardiometabolic risk according to BF% and WC, thus representing a novel and useful tool for both research and clinical practice.
- Comment on: “Pregnancy outcomes after bariatric surgery: importance of maternal ferritin on birth weight”(Springer, 2024) Aguas-Ayesa, M. (Maite); Frühbeck, G. (Gema); Gomez-Ambrosi, J. (Javier)Of all the available therapies, in adequately selected patients, bariatric surgery (BS) is the most efective treatment for severe obesity and its complications. Despite the numerous benefits of BS, even in reproductive performance, women who have undergone BS have higher rates of small-for-gestational age (SGA) fetuses and preterm births than non-intervened women with the same body mass index (BMI). The mechanisms involved are not known, but nutritional defciencies, common after BS, have been identifed as one of the factors that could contribute to these pregnancy complications.
- Revisiting the beyond BMI paradigm in excess weight diagnosis and management: A call to action(John Wiley & Sons, 2024) Aguas-Ayesa, M. (Maite); García-Almeida, J.M. (José Manuel); Frühbeck, G. (Gema); Olazarán, L. (Laura); Perdomo, C. (Carolina); Gomez-Ambrosi, J. (Javier); Vegas-Aguilar, I.M. (Isabel María); Yárnoz-Esquiroz, P. (Patricia)Adolphe Quételet, a 19th-century Belgian sociologist and statistician, pioneered the incorporation of statistics into social sciences. He initiated the development of anthropometry since he was interested in identifying the proportions of the 'ideal man'. He devised a ratio between weight and height, originally termed the Quételet Index, and today widely known and used as the body mass index or BMI. In 1835, he demonstrated that a normal curve accommodates the distribution of human traits articulating his reasoning on human variance around the average. Quételet's long-lasting legacy of the establishment of a simple measure to classify people's weight relative to an ideal for their height endures today with minor variations having dramatically influenced public health agendas. While being very useful, the limitations of the BMI are well known. Thus, revisiting the beyond BMI paradigm is a necessity in the era of precision medicine with morphofunctional assessment representing the way forward via incorporation of body composition and functionality appraisal. While healthcare systems were originally designed to address acute illnesses, today's demands require a radical rethinking together with an original reappraisal of our diagnosis and treatment approaches from a multidimensional perspective. Embracing new methodologies is the way forward to advance the field, gain a closer look at the underlying pathophysiology of excess weight, keep the spotlight on improving diagnostic performance and demonstrate its clinical validity. In order to provide every patient with the most accurate diagnosis together with the most appropriate management, a high degree of standardization and personalization is needed.
- Tracking dynamic evolution of low‐ and intermediate‐risk differentiated thyroid cancer: Identification of individuals at risk of recurrence(John Wiley & Sons, 2024) Alegre, E. (Estibaliz); Lozano, M.D. (María Dolores); Volpi, F. (Federico); Colombo, C. (Carla); Argueta, A. (Allan); Larrache, J. (Javier); Alcalde, J. (Juan); Galofre, J.C. (Juan Carlos)Objective: The generally good prognosis of low- and intermediate-risk differentiated thyroid cancer (DTC) underscored the need to identify those few patients who relapse. Design: Records of 299 low- or intermediate-risk DTC patients (mean follow-up 8.2 ± 6.2 years) were retrospectively reviewed. The sample was classified following the American Thyroid Association (ATA) dynamic risk stratification (DRS) system. Patients and measurement: After classifying patients according to DRS at the first visit following initial therapy (FU1), structural recurrence occurred in 2/181 (1.1%), 5/81 (6.2%) and 13/26 (50.0%) with excellent, indeterminate and biochemical incomplete response to treatment, respectively. All relapses but one happened within 5 years from FU1. Univariate analysis comparing excellent, indeterminate and biochemical incomplete with structural incomplete responses at the end of the follow-up, identified tumour size (p < .001), T status (<0.001), positive lymph nodes (N) (p < .01), multifocality (p < .004), need of additional radioactive iodine (RAI) (p < .0001) and first DRS status (p < .0003) as risk factors of recurrence. In the multivariate analysis, only RAI remained statistically significant (p < .02). Comparison between excellent and indeterminate with biochemical and structural incomplete responses, identified tumour size (p < .0004), T (p < .01), N (p < .0001), bilaterality (p < .03), first DRS status (p < .0001) and RAI (p < .001) as recurrence risk factors. T (p < .01) and first DRS (p < .0006) were confirmed in the multivariate analysis. Conclusions: Patients with DTC classified as low- or intermediate-risk of recurrence with excellent response to treatment at FU1 rarely develop structural disease and this occurs almost exclusively in the first 5 years. Initial DRS status is an accurate tool for determining the risk of recurrence.
- Antagonic effect of ghrelin and LEAP-2 on hepatic stellate cell activation and liver fibrosis in obesity-associated nonalcoholic fatty liver disease(Oxford University Press, 2023) Landecho, M.F. (Manuel F.); Valenti, V. (Víctor); Ezquerro-Ezquerro, S. (Silvia); Hanley, K.P. (Karen Piper); Catalan, V. (Victoria); Becerril, S. (Sara); Frühbeck, G. (Gema); Tuero, C. (Carlota); Mocha, F. (Fátima); Silva, C. (Camilo); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia); Escalada, J. (Javier); Moncada-Durruti, R. (Rafael)Background: Growing evidence suggests the key role of ghrelin in the onset and progression of nonalcoholic fatty liver disease (NAFLD). The potential participation of ghrelin and the ghrelin receptor antagonist, LEAP-2, in the onset of liver fibrosis in patients with severe obesity and NAFLD through the regulation of TGF-β1-induced hepatic stellate cell (HSC) activation was investigated.
- Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD(2020) Sánchez-Infantes, D. (David); Bartrons, R. (Ramon); Valenti, V. (Víctor); Domínguez-Castellano, M. (María); Weber, M. (Minéia); Frühbeck, G. (Gema); Zorzano, A. (Antonio); Fucho, R. (Raquel); Casals, N. (Núria); Llorente-Cortes, V. (Vicenta); Mera, P. (Paula); Soler-Vázquez, M.C. (M. Carmen); Serra, D. (Dolors); Herrero, L. (Laura); Mir, J.F. (Joan Francesc); Rodriguez, A. (Amaia); Sebastián, D. (David); Montironi, C. (Carla); Casas, J. (Josefina); Alonso, S. (Sergio); Recalde, S. (Sandra); Escola-Gil, J.C. (Joan Carles)The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.
- Autonomous cortisol secretion in patients with primary aldosteronism: prevalence and implications on cardiometabolic profile and on surgical outcomes(European Society of Endocrinology, 2023) Díaz-Guardiola, P. (Patricia); Morales, M. (Manuel); Calatayud, M. (Maria); Ferreira, R. (Rui); Sampedro-Nuñez, M.A. (Miguel Antonio); Meneses, D. (Diego); Percovich, J.C. (Juan Carlos); Ruiz-Sanchez, J.G. (Jorge Gabriel); Del-Castillo-Tous, M; Serrano, J. (Joaquín); Manjón, L. (Laura); Picón-César, M.J. (María José); González-Boillos, M. (Marga); Martín-Rojas-Marcos, P. (Patricia); Hanzu, F. (Felicia); Gonzalvo-Diaz, C. (César); Gracia-Gimeno, P. (Paola); Gómez-Hoyos, E. (Emilia); Perdomo, C. (Carolina); García-Sanz, I. (Íñigo); Pla-Peris, B. (Begoña); Michalopoulou, T. (Theodora); Recasens, M. (Mónica); Araujo-Castro, M. (Marta); Pascual-Corrales, E. (Eider); Parra-Ramírez, P. (Paola); García-Centeno, R. (Rogelio); Rebollo-Román, A. (Angel); Escudero-Quesada, V. (Verónica); García-Cano, A.M. (Ana María); Vicente, A. (Almudena); Sanmartín-Sánchez, A. (Alicia); Paja, M. (Miguel); Moya-Mateo, E.M. (Eva María); Barahona-San-Millan, R. (Rebeca); Lamas, C. (Cristina); Furio-Collao, S.A. (Simone Andree); Mena-Ribas, E. (Elena); Guerrero-Vázquez, R. (Raquel); Robles-Lázaro, C. (Cristina)Purpose The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8–5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS–PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS–PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS–PA group. When comparing the ACS–PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64–22.32)) and cardiovascular events (OR 5.0 (2.29–11.07)) was higher in ACS–PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS–PA and PA-only groups. Conclusion Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS–PA and PA-only are similar.
- Single anastomosis duodeno-ileal bypass with sleeve gastrectomy generates sustained improvement of glycemic control compared with sleeve gastrectomy in the diet-induced obese rat model(Springer, 2024) Unamuno, X. (Xabier); Valenti, V. (Víctor); Ramirez, B. (Beatriz); Catalan, V. (Victoria); Álvarez-Cienfuegos, J. (Javier); Becerril, S. (Sara); Frühbeck, G. (Gema); Moncada, R. (Rafael); Gomez-Ambrosi, J. (Javier); Rodriguez, A. (Amaia)Bariatric surgery has become a recognized and effective procedure for treating obesity and type 2 diabetes (T2D). Our objective was to directly compare the caloric intake-independent effects of sleeve gastrectomy (SG) and single anastomosis duodenoileal bypass with SG (SADI-S) on glucose tolerance in rats with diet-induced obesity (DIO) and to elucidate the differences between bariatric surgery and caloric restriction.A total of 120 adult male Wistar rats with DIO and insulin resistance were randomly assigned to surgical (sham operation, SG, and SADI-S) and dietary (pair-feeding the amount of food eaten by animals undergoing the SG or SADI-S surgeries) interventions. Body weight and food intake were weekly monitored, and 6 weeks after interventions, fasting plasma glucose, oral glucose and insulin tolerance tests, plasma insulin, adiponectin, GIP, GLP-1, and ghrelin levels were determined.The body weight of SADI-S rats was significantly (p < 0.001) lower as compared to the sham-operated, SG, and pair-fed groups. Furthermore, SADI-S rats exhibited decreased whole body fat mass (p < 0.001), lower food efficiency rates (p < 0.001), and increased insulin sensitivity, as well as improved glucose and lipid metabolism compared to that of the SG and pair-fed rats.SADI-S was more effective than SG, or caloric restriction, in improving glycemic control and metabolic profile, with a higher remission of insulin resistance as well as long-term weight loss.