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Digesting gluten with oral endopeptidases to improve the management of celiac disease

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World Journal of gastroenterology 2024年第26期30卷 3201-3205页

作者： Katelin Durham Mirac Nedim Ince Department of Internal Medicine Division of Gastroenterology and HepatologyUniversity of IowaCarver College of Medicineand the Iowa City Veterans Affairs Medical CenterIowa CityIA 52242United States

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed *** avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel *** villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid *** administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under *** article is about the utility of one endopeptidase isolated from Aspergillus *** critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

关键词： Celiac disease Gluten-free diet Endopeptidase Villous atrophy Aspergillus niger Adjunct therapy

Drug repurposing for cancer therapy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1981-2013页

作者： Ying Xia Ming Sun Hai Huang Wei-Lin Jin center for clinical Laboratories The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550004PR China The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Guiyang 550001PR China School of clinical Laboratory Science Guizhou Medical UniversityGuiyang 550004PR China Division of gastroenterology and hepatology Department of Medicine andDepartment of OncologySidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreMD 21287USA Institute of Cancer Neuroscience Medical Frontier Innovation Research CenterThe First Hospital of Lanzhou UniversityThe First Clinical Medical College of Lanzhou UniversityLanzhou 730000PR China

Cancer,a complex and multifactorial disease,presents a significant challenge to global *** significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic ***,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer *** promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved *** repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety *** light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat *** describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor *** addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug *** also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy *** conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.

关键词： drugs integrating spite

Hepatocellular carcinoma and musculoskeletal system: A narrative literature review

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World Journal of gastroenterology 2024年第15期30卷 2109-2117页

作者： Jelena Jadzic Danijela Djonic center of Bone Biology Faculty of MedicineUniversity of BelgradeBelgrade 11000Serbia

Musculoskeletal alterations in hepatocellular carcinoma(HCC)are less common than liver-related ***,they can significantly impact the quality of life and overall prognosis of patients with *** main obstacle in the clinical assessment of HCC-induced musculoskeletal alterations is related to effective and timely diagnosis because these complications are often asym-ptomatic and unapparent during routine clinical *** narrative literature review aimed to provide a comprehensive overview of the contem-porary literature related to the changes in the musculoskeletal system in patients with HCC,focusing on its clinical implications and underlying etiopathogenetic *** bone metastases are the most common skeletal alterations associated with HCC,which could be associated with an increased risk of low-trauma bone ***,previous studies reported that osteopenia,sarcopenia,and myosteatosis are associated with poor clinical outcomes in patients with *** though low bone mineral density and sarcopenia are consistently reported as reliable predictors of pretransplantation and post-transplantation mortality in HCC patients,these complications are frequently overlooked in the clinical management of patients with *** together,contemporary literature suggests that a multidisciplinary approach is essential for early recognition and clinical management of HCC-associated musculoskeletal alterations to improve patient *** research into the mechanisms and treatment options for musculoskeletal complications is warranted to enhance our understanding and clinical management of this aspect of HCC.

关键词： Hepatocellular carcinoma Osteopenia Osteoporosis Sarcopenia Bone metastases Bone fragility

Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?

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World Journal of gastroenterology 2024年第10期30卷 1368-1376页

作者： Nobukazu Agatsuma Takahiro Utsumi Yoshitaka Nishikawa Takahiro Horimatsu Takeshi Seta Yukitaka Yamashita Yukari Tanaka Takahiro Inoue Yuki Nakanishi Takahiro Shimizu Mikako Ohno Akane Fukushima Takeo Nakayama Hiroshi Seno Department of gastroenterology and hepatology Kyoto University Graduate School of MedicineKyoto 606-8507Japan Department of gastroenterology and hepatology Japanese Red Cross Wakayama Medical CenterWakayama 640-8558Japan Department of Health Informatics Kyoto University School of Public HealthKyoto 606-8501Japan Institute for Advancement of clinical and Translational Science(iACT) Kyoto University HospitalKyoto 606-8507Japan Medical Support Section Medical Affairs DivisionKyoto University HospitalKyoto 606-8507Japan

BACKGROUND Colorectal cancer(CRC)is a global health concern,with advanced-stage diagnoses contributing to poor *** efficacy of CRC screening has been well-established;nevertheless,a significant proportion of patients remain unscreened,with>70%of cases diagnosed outside *** identifying specific subgroups for whom CRC screening should be particularly recommended is crucial owing to limited resources,the association between the diagnostic routes and identification of these subgroups has been less *** the Japanese cancer registry,the diagnostic routes for groups discovered outside of screening are primarily categorized into those with comorbidities found during hospital visits and those with CRC-related *** To clarify the stage at CRC diagnosis based on diagnostic *** We conducted a retrospective observational study using a cancer registry of patients with CRC between January 2016 and December 2019 at two *** diagnostic routes were primarily classified into three groups:Cancer screening,follow-up,and *** early-stage was defined as Stages 0 or *** and univariate logistic regressions were exploited to determine the odds of early-stage diagnosis in the symptomatic and cancer screening groups,referencing the follow-up *** adjusted covariates were age,sex,and tumor *** Of the 2083 patients,715(34.4%),1064(51.1%),and 304(14.6%)belonged to the follow-up,symptomatic,and cancer screening groups,*** the 2083 patients,CRCs diagnosed at an early stage were 57.3%(410 of 715),23.9%(254 of 1064),and 59.5%(181 of 304)in the follow-up,symptomatic,and cancer screening groups,*** symptomatic group exhibited a lower likelihood of early-stage diagnosis than the follow-up group[P<0.001,adjusted odds ratio(aOR),0.23;95%confidence interval(95%CI):0.19-0.29].The likelihood of diagnosis at an early stage was similar between the follow-up and cancer screening gro

关键词： Colorectal neoplasms Cancer registry Diagnostic route Cancer screening Stage at diagnosis

clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China Organ Transplantation center The Affiliated Hospital of Qingdao UniversityQingdao 266000China Institute of Organ Donation and Transplantation of Qingdao University Qingdao 266000China Department of gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

Diagnostic and therapeutic role of endoscopic ultrasound in liver diseases:A systematic review and meta-analysis

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World Journal of gastroenterology 2024年第7期30卷 742-758页

作者： Eyad Gadour Abeer Awad Zeinab Hassan Khalid Jebril Shrwani Bogdan Miutescu Hussein Hassan Okasha Department of gastroenterology and hepatology King Abdulaziz Hospital-National GuardAhsa 31982Saudi Arabia Department of Internal Medicine Faculty of MedicineZamzam University CollegeKhartoum 11113Sudan Department of Hepatogastroenterology Kasar Alainy HospitalFaculty of MedicineCairo UniversityCairo 11451Egypt Department of Internal Medicine Stockport Hospitals NHS Foundation TrustManchester SK27JEUnited Kingdom Public Health Authority Saudi Center for Disease Prevention and ControlJazan 45142Saudi Arabia Department of clinical Infection Microbiology and ImmunologyInstitute of Infection and Global HealthSchool of Medicine and Life SciencesUniversity of LiverpoolLiverpoolUnited Kingdom Department of gastroenterology and hepatology Victor Babes University of Medicine and PharmacyTimisoara 300041Romania Advanced Regional Research center in gastroenterology and hepatology Victor Babes University of Medicine and PharmacyTimisoara 30041Romania Department of Internal Medicine Division of Gastroenterology and HepatologyKasr Al-Aini School of MedicineCairo UniversityCairo 11562Egypt

BACKGROUND In hepatology,the clinical use of endoscopic ultrasound(EUS)has experienced a notable increase in recent *** applications range from the diagnosis to the treatment of various liver ***,this systematic review summarizes the evidence for the diagnostic and therapeutic roles of EUS in liver *** To examine and summarize the current available evidence of the possible roles of the EUS in making a suitable diagnosis in liver diseases as well as the therapeutic accuracy and *** PubMed,Medline,Cochrane Library,Web of Science,and Google Scholar databases were extensively searched until October *** methodological quality of the eligible articles was assessed using the Newcastle-Ottawa scale or Cochrane Risk of Bias *** addition,statistical analyses were performed using the Comprehensive Meta-Analysis *** Overall,45 articles on EUS were included(28 on diagnostic role and 17 on therapeutic role).Pooled analysis demonstrated that EUS diagnostic tests had an accuracy of 92.4%for focal liver lesions(FLL)and 96.6%for parenchymal liver ***-guided liver biopsies with either fine needle aspiration or fine needle biopsy had low complication rates when sampling FLL and parenchymal liver diseases(3.1%and 8.7%,respectively).Analysis of data from four studies showed that EUS-guided liver abscess had high clinical(90.7%)and technical success(90.7%)without significant ***,EUS-guided interventions for the treatment of gastric varices(GV)have high technical success(98%)and GV obliteration rate(84%)with few complications(15%)and rebleeding events(17%).CONCLUSION EUS in liver diseases is a promising technique with the potential to be considered a first-line therapeutic and diagnostic option in selected cases.

关键词： Focal liver lesion Liver abscess drainage Fine needle aspiration Gastric varices Endoscopic ultrasound

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

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World Journal of Transplantation 2024年第1期14卷 141-153页

作者： Hirak Pahari Amruth Raj Ambreen Sawant Dipak S Ahire Raosaheb Rathod Chetan Rathi Tushar Sankalecha Sachin Palnitkar Vikram Raut Department of Liver Transplant and HPB Surgery Medicover HospitalsNavi Mumbai 410210MaharashtraIndia Department of Liver Transplant Anaesthesia Medicover HospitalsNavi Mumbai 410210MaharashtraIndia Department of gastroenterology and hepatology Medicover HospitalsNavi Mumbai 410210India Department of gastroenterology and hepatology Medicover HospitalsNavi Mumbai 410210MaharashtraIndia Department of gastroenterology and hepatology Medicover HospitalsAurangabad 431003India Department of gastroenterology and hepatology Medicover HospitalsNashik 422009India Department of gastroenterology and hepatology Medicover HospitalsPune 411026India

BACKGROUND Liver transplantation(LT)for hepatocellular carcinoma(HCC)has been widely researched and is well established *** cornerstone of this treatment lies in the various criteria formulated by expert consensus and *** variations among the criteria are staggering,and the short-and long-term outcomes are *** To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the *** We conducted a survey of major centers in India that performed LT in December 2022.A total of 23 responses were *** centers were classified as high-and low-volume,and the current trend of care for patients undergoing LT for HCC was *** Of the 23 centers,35%were high volume center(>500 Liver transplants)while 52%were high-volume centers that performed more than 50 transplants/*** 39%of centers had performed>50 LT for HCC while the percent distribution for HCC in LT patients was 5%–15%in approximately 73%of the *** a few,most centers were divided equally between University of California,San Francisco(UCSF)and center-specific criteria when choosing patients with HCC for LT,and most(65%)did not have separate transplant criteria for deceased donor LT and living donor LT(LDLT).Most centers(56%)preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC ***-emission tomography-computed tomography(CT)was the modality of choice for metastatic workup in the majority of centers(74%).Downstaging was the preferred option for over 90%of the centers and included transarterial chemoembolization,transarterial radioembolization,stereotactic body radiotherapy and atezolizumab/bevacizumab with varied *** alphafetoprotein(AFP)cut-off was used by 74%of centers to decide on transplantation as well as to downstage tumors,even if they met the *** criteria for successful downstaging v

关键词： Hepatocellular carcinoma Liver transplant India Downstaging Survey Milan University of California,San Francisco Portal vein tumor thrombus Expanded criteria

Transjugular Intrahepatic Portosystemic Shunt Linked to Increased Risk of Hepatocellular Carcinoma:A VA Matched Cohort Study

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Journal of clinical and Translational hepatology 2024年第5期12卷 534-538页

作者： Shalini Bansal Tamar Taddei Rebecca Wells Marina Serper Theresa Bittermann Nadim Mahmud David E.Kaplan Sidney Kimmel Medical College at Thomas Jefferson University PhiladelphiaPAUSA Division of gastroenterology and hepatology Perelman School of Medicine University of PennsylvaniaPhiladelphiaPAUSA Corporal Michael J.Crescenz VA Medical center PhiladelphiaPAUSA Division of gastroenterology and hepatology Yale University School of MedicineNew HavenCTUSA VA Connecticut Healthcare System West HavenCTUSA

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and often evolves from regenerating nodules in liver *** there have been significant advances in the treatment of HCC,the overall prognosis in patients with a large tumor burden,vascular invasion,or extrahepatic spread remains poor.1 The magnitude of liver stiffness in cirrhosis has been consistently associated with an increased risk of development of HCC.

关键词： Carcinoma invasion cirrhosis

Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

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Journal of clinical and Translational hepatology 2024年第10期12卷 845-856页

作者： Naweed Mohammad Regina Oshins Tongjun Gu Virginia Clark Jorge Lascano Naziheh Assarzadegan George Marek Mark Brantly Nazli Khodayari Division of Pulmonary Critical Care and Sleep MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Interdisciplinary center for Biotechnology Research Bioinformatics CoreUniversity of FloridaGainesvilleFLUSA Division of gastroenterology Hepatology and NutritionCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of Pathology Immunologyand Laboratory MedicineCollege of MedicineUniversity of FloridaGainesvilleFLUSA Division of gastroenterology and hepatology Mayo ClinicRochesterMNUSA

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue *** results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the *** goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene ***:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional *** used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver *** observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those ***:A total of 339 genes were differentially *** pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with *** analysis also revealed higher levels of fibrosis and hepatocellular damage in these ***:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is *** believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

关键词： Alpha-1 antitrypsin deficiency Chronic obstructive pulmonary disease Liver fibrosis Liver biopsy Liver histology Transcriptomics