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Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第19期30卷 2512-2522页

作者： juan jose Urquijo-Ponce Carlos Alventosa-Mateu Mercedes Latorre-Sánchez Inmaculada Castelló-Miralles Moisés Diago Hepatology Unit Department of Digestive Diseases Consorcio Hospital General Universitario of ValenciaValencia 46014Spain

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

关键词： Hepatocellular carcinoma Early stage Intermediate stage Neoadjuvant Adjuvant Systemic therapy

A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： Marcio jose Concepcion-Zavaleta juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vasquez Elman Rolando Gamarra-Osorio juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon Elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca Elena Zavaleta-Gutierrez Luis Alberto Concepcion-Urteaga jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru Division of Medicine Hospital de Apoyo ChepénChepenPeru Division of Family Medicine Hospital de Apoyo ChepénChepenPeru Division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Division of Pediatrics Hospital de Apoyo ChepenChepenPeru Division of Internal Medicine Hospital de Apoyo ChepenChepenPeru Division of Genetics Universidad Nacional de TrujilloTrujilloPeru Division of Neonatology Hospital Belen de TrujilloTrujilloPeru Division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide prevalence.Genetic causes account for 7%of the cases in children with extreme obesity.Data sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 articles.The search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case reports.Results The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body weight.However,several important aspects of the pathophysiology of obesity remain unknown.Genetic causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this purpose.There are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric surgery.Conclusions Genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

Muscle strength deficits are associated with low bone mineral density in young pediatric cancer survivors:The iBoneFIT project

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Journal of Sport and Health Science 2024年第3期13卷 419-427页

作者： Andres Marmol-Perez jose J.Gil-Cosano Esther Ubago-Guisado Francisco J.Llorente-Cantarero juan Francisco Pascual-Gázquez Kirsten K.Ness Vicente Martinez-Vizcaino Jonatan R.Ruiz Luis Gracia-Marco Department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18011Spain Department of Epidemiology and Cancer Control St.Jude Children's Research HospitalMemphisTN 38105USA Department of Communication and Education Loyola University AndalusiaSeville 41704Spain Biosanitary Research Institute ibs.GranadaGranada 18012Spain Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Cordoba 14004Spain CIBEROBN Biomedical Research Networking Center for Physiopathology of Obesity and NutritionCarlos III Health InstituteMadrid 28029Spain Department of Specific Didactics Faculty of EducationUniversity of CordobaCordoba 14071Spain Pediatric and adolescent hematology and oncology service Pediatrics and Pediatric Surgery Clinical Management UnitVirgen de las Nieves University HospitalGranada 18014Spain Health and Social Research Center Universidad de Castilla-La ManchaCuenca 13001Spain

Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added ben

关键词： Bone health Childhood cancer DXA Lean mass Resistance training

Portal vein arterialization in 25 liver transplant recipients:A Latin American single-center experience

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World Journal of Transplantation 2024年第2期14卷 135-147页

作者： Nicolas Andres Cortes-Mejia Diana Fernanda Bejarano-Ramirez juan jose Guerra-Londono Diego Rymel Trivino-Alvarez Raquel Tabares-Mesa Alonso Vera-Torres Division of Anesthesiology Critical Care Medicineand Pain MedicineThe University of Texas MD Anderson Cancer CenterHoustonTX 77030United States Transplant and Hepatobiliary Surgery Department Fundacion Santa Fe de BogotaBogota 110111Colombia General Surgery Department Fundacion Santa Fe de BogotaBogota 110111Colombia

BACKGROUND Portal vein arterialization(PVA)has been used in liver transplantation(LT)to maximize oxygen delivery when arterial circulation is compromised or has been used as an alternative reperfusion technique for complex portal vein thrombosis(PVT).The effect of PVA on portal perfusion and primary graft dysfunction(PGD)has not been assessed.All patients receiving PVA and LT at the Fundacion Santa Fe de Bogota between 2011 and 2022 were analyzed.To account for the time-sensitive effects of graft perfusion,patients were classified into two groups:prereperfusion(pre-PVA),if the arterioportal anastomosis was performed before graft revascularization,and postreperfusion(post-PVA),if PVA was performed afterward.The pre-PVA rationale contemplated poor portal hemodynamics,severe vascular steal,or PVT.Post-PVA was considered if graft hypoperfusion became evident.Conservative interventions were attempted before PVA.

关键词： Liver transplantation Portal vein arterialization Arteriovenous anastomoses Portal hypertension Portal vein thrombosis Spontaneous portosystemic shunts Vascular steal phenomenon Primary graft dysfunction Early allograft dysfunction

Z-line examination by the PillCam^(TM) SB:Prospective comparison of three ingestion protocols

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World Journal of Gastroenterology 2010年第1期16卷 63-68页

作者： Ignacio Fernandez-Urien Erika Borobio Inmaculada Elizalde Rebeca Irisarri juan jose vila Jesus Maria Urman Javier Jimenez Department of Gastroenterology Hospital of Navarra

AIM:To evaluate the Z-line visualization by the PillCamTM SB2 using three different ingestion protocols. METHODS:Ninety consecutive patients undergoing small bowel capsule endoscopy(SBCE)between January and May 2008 were included in the study. They swallowed the capsule in the standing(Group A= 30),supine(Group B=30)and right supine positions (Group C=30).Baseline patient characteristics, difficulties in capsule ingestion,esophageal transit times(ETT)and Z-line visualization were noted. RESULTS:No significant differences were found between the groups with regard to baseline patient characteristics,ingestion difficulties and complete SB examinations(P>0.05).At least 1 frame of the Z-line was detected in 15.8%,46.7%and 90%of patients in groups A,B and C,respectively(P<0.001).The average number of Z-line images was 0.21±0.53,3.23 ±6.59 and 5.53±7.55 and the mean%of the Z-linedetected was 71.3,25.1 and 8.3,in groups A,B and C, respectively(both P<0.001).ETT times were longer in the supine group followed by the right supine and the standing groups(median of 237 s vs 64 s and 39 s, respectively;P<0.001). CONCLUSION:Z-line visualization in patients undergoing SBCE can be accurately achieved in most cases when the capsule is swallowed in the right supine position.

关键词： Barrett Capsule endoscopy Esophagus Gastroesophageal reflux disease Ingestion Varices Z-line

Role of endoscopic ultrasound in the diagnosis of pancreatic cancer

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World Journal of Gastrointestinal Oncology 2014年第9期6卷 360-368页

作者： juana Gonzalo-Marin juan jose vila Manuel Perez-Miranda Unit of Endoscopy Department of GastroenterologyQuirón Hospital Unit of Endoscopy Department of GastroenterologyComplejo Hospitalario de Navarra Department of Gastroenterology Hospital Universitario Rio Hortega

Endoscopic ultrasonography(EUS) with or without fine needle aspiration has become the main technique for evaluating pancreatobiliary disorders and has proved to have a higher diagnostic yield than positron emission tomography,computed tomography(CT) and transabdominal ultrasound for recognising early pancreatic tumors.As a diagnostic modality for pancreatic cancer,EUS has proved rates higher than 90%,especially for lesions less than 2-3 cm in size in which it reaches a sensitivity rate of 99% vs 55% for CT.Besides,EUS has a very high negative predictive value and thus EUS can reliably exclude pancreatic cancer.The complication rate of EUS is as low as 1.1%-3.0%.New technical developments such as elastography and the use of contrast agents have recently been applied to EUS,improving its diagnostic capability.EUS has been found to be superior to the recent multidetector CT for T stagingwith less risk of overstaying in comparison to both CT and magnetic resonance imaging,so that patients are not being ruled out of a potentially beneficial resection.The accuracy for N staging with EUS is 64%-82%.In unresectable cancers,EUS also plays a therapeutic role by means of treating oncological pain through celiac plexus block,biliary drainage in obstructive jaundice in patients where endoscopic retrograde cholangiopancreatography is not affordable and aiding radiotherapy and chemotherapy.

关键词： modality staging potentially diagnostic transabdominal celiac retrograde plexus chemotherapy adenocarcinoma

Male genitourinary schistosomiasis-related symptoms among long-term Western African migrants in Spain: a prospective population-based screening study

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贫困所致传染病(英文) 2024年第2期13卷 1-10页

作者： Roure Sílvia Vallès Xavier Pérez-Quílez Olga López-Mu?oz Israel Chamorro Anna Abad Elena Valerio Lluís Soldevila Laura Espa?a Sergio Hegazy Alaa H. A. Fernández-Rivas Gema Gorriz Ester Herena Dolores Oliveira Mário Miralles Maria Carme Conde Carmen Montero-Alia juan José Fernández-Pedregal Elia Miranda-Sánchez jose Llibre josep M. Isnard Mar Bonet josep Maria Estrada Oriol Prat Núria Clotet Bonaventura The Schisto-Stop study group Primary Health Care Unit Mataró-(Rocafonda-Palau) Barcelona North Metropolitan Health Directorate Catalan Institute for Health Camí Ral el Ravalet Mataró Barcelona Spain Barcelona North Metropolitan Primary Care Directorate Catalan Institute for Health Ctra. de Barcelona Sabadell Barcelona Spain Directorate for Innovation and Interdisciplinary Cooperation Barcelona North Metropolitan Health Directorate Catalan Institute for Health C/Can Ruti S/N Badalona Spain IrsiCaixa-AIDS Research Institute Hospital Universitari Germans Trias i Pujol University Hospital c/Can Ruti s/n Badalona Spain Infectious Diseases Directorate Barcelona North Metropolitan Health Directorate Catalan Institute for Health C/Can Ruti S/N Badalona Spain International Health Program (PROSICS) Barcelona North Metropolitan Territorial Directorate for Infectious Diseases Catalan Institute for Health CAP La Salut Passatge dels Encants S/N Badalona Spain Fundació Lluita contra les Infeccions c/Can Ruti s/n Badalona Spain Infectious Diseases Department Hospital Universitari Germans Trias i Pujol c/Can Ruti s/n Badalona Spain Germans Trias i Pujol Research Institute c/Can Ruti s/n Badalona Spain Microbiology Department Germans Trias i Pujol University Hospital c/Can Ruti s/n Badalona Spain Department of Genetics and Microbiology Universitat Autònoma de Barcelona c/Can Ruti s/n Badalona Spain Faculty of Medicine University of Asyut El Fateh Assiut Governorate Egypt Department of Urology Germans Trias i Pujol University Hospital c/Can Ruti s/n Badalona Spain Canovelles Primary Health Care Unit Barcelona North Metropolitan Health Directorate Catalan Institute for Health C/Indústria Canovelles Spain

Background Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test.Methods We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain.Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire.Results We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18–76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11–21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive forSchistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positiveSchistosoma serology results: pelvic pain (45.2%;OR = 1.57, 95%CI: 1.0–2.4), pain on ejaculation (14.5%;OR = 1.85, 95%CI: 1.0–3.5), dyspareunia (12.4%;OR = 2.45, 95%CI: 1.2–5.2), erectile dysfunction (9.5%;OR = 3.10, 95%CI: 1.3–7.6), self-reported episodes of infertility (32.1%;OR = 1.69, 95%CI: 1.0–2.8), haematuria (55.2%;OR = 2.37, 95%CI: 1.5–3.6), dysuria (52.1%;OR = 2.01, 95%CI: 1.3–3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%;OR = 1.81, 95%CI: 1.0–3.1). Clinical signs tended to cluster.Conclusions Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positiveSchistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis.

关键词： Schistosomiasis Chronic schistosomiasis Urogenital schistosomiasis Male genital schistosomiasis Longterm migrant

A Tutorial on Federated Learning from Theory to Practice:Foundations,Software Frameworks,Exemplary Use Cases,and Selected Trends

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 824-850页

作者： M.Victoria Luzón Nuria Rodríguez-Barroso Alberto Argente-Garrido Daniel Jiménez-López jose M.Moyano Javier Del Ser Weiping Ding Francisco Herrera Department of Software Engineering Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Computer Science and Artificial Intelligence Andalusian Research Institute in Data Science and Computational Intelligence(DaSCI)University of GranadaGranada 18071Spain Department of Communications Engineering University of the Basque Country(UPV/EHU)and also with TECNALIABasque Research&Technology Alliance(BRTA)Spain School of Information Science and Technology Nantong UniversityNantong 226019China

When data privacy is imposed as a necessity,Federated learning(FL)emerges as a relevant artificial intelligence field for developing machine learning(ML)models in a distributed and decentralized environment.FL allows ML models to be trained on local devices without any need for centralized data transfer,thereby reducing both the exposure of sensitive data and the possibility of data interception by malicious third parties.This paradigm has gained momentum in the last few years,spurred by the plethora of real-world applications that have leveraged its ability to improve the efficiency of distributed learning and to accommodate numerous participants with their data sources.By virtue of FL,models can be learned from all such distributed data sources while preserving data privacy.The aim of this paper is to provide a practical tutorial on FL,including a short methodology and a systematic analysis of existing software frameworks.Furthermore,our tutorial provides exemplary cases of study from three complementary perspectives:i)Foundations of FL,describing the main components of FL,from key elements to FL categories;ii)Implementation guidelines and exemplary cases of study,by systematically examining the functionalities provided by existing software frameworks for FL deployment,devising a methodology to design a FL scenario,and providing exemplary cases of study with source code for different ML approaches;and iii)Trends,shortly reviewing a non-exhaustive list of research directions that are under active investigation in the current FL landscape.The ultimate purpose of this work is to establish itself as a referential work for researchers,developers,and data scientists willing to explore the capabilities of FL in practical applications.

关键词： Data privacy distributed machine learning federated learning software frameworks

Stay in touch with the endoplasmic reticulum

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Science China(Life Sciences) 2024年第2期67卷 230-257页

作者： Sha Sun Gan Zhao Mingkang Jia Qing Jiang Shulin Li Haibin Wang Wenjing Li Yunyun Wang Xin Bian Yan G.Zhao Xun Huang Ge Yang Huaqing Cai jose C.Pastor-Pareja Liang Ge Chuanmao Zhang Junjie Hu National Laboratory of Biomacromolecules Institute of BiophysicsUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking UniversityBeijing 100871China State Key Laboratory of Membrane Biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Laboratory of Computational Biology&Machine Intelligence School of Artificial IntelligenceUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Medicinal Chemical Biology College of Life SciencesNankai UniversityTianjin 300071China Brain Research Center Department of BiologySchool of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Institute of Neurosciences Consejo Superior de Investigaciones Científicas-Universidad Miguel HernándezSan Juan de Alicante 03550Spain

The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic cells.As a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling events.Here,we systematically review recent advances and converging themes on ER-involved organellar contact.The molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.

关键词： endoplasmic reticulum nuclear envelope mitochondria Golgi apparatus endosome lysosome lipid droplets autophagosome plasma membrane membrane contact site