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Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 101-109页

作者： Mariarosaria D'Amato Gennaro Iengo Nicola Massa Chiara Carlomagno Department of Oncology Ospedale San Rocco ASL CasertaSessa Aurunca 81037CampaniaItaly Department of Clinical Medicine and Surgery University of Naples Federico IINaples 80131CampaniaItaly

BACKGROUND Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase(DPD),encoded by the DPYD *** 7%of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme *** To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal *** A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts:(1)149 patients who started fluoropyrimidines after DPYD testing;and(2)151 patients treated without DPYD *** the patients in cohort A,15%tested only the DPYD2A polymorphism,19%tested four polymorphisms(DPYD2A,HapB3,c.2846A>T,and DPYD13),and 66%tested five polymorphisms including *** Overall,14.8%of patients were found to be carriers of a DPYD variant,the most common being DPYD6(12.1%).Patients in cohort A reported≥G3 toxicities(P=0.00098),particularly fewer nonhematological toxicities(P=0.0028)compared with cohort B,whereas there was no statistically significant difference between the two cohorts in hematological toxicities(P=0.6944).Significantly fewer chemotherapy dose reductions(P=0.00002)were observed in cohort A compared to cohort B,whereas there was no statistically significant differences in chemotherapy *** Although this study had a limited sample size,it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.

关键词： Dihydropyrimidine dehydrogenase DPYD polymorphisms Fluoropyrimidine Caucasian population Gastrointestinal cancers

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Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro Federico Department of Precision Medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Precision Medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic *** on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),*** Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these ***,due to its invasiveness and costs,CSPH is almost never evaluated in clinical ***,recognizing noninvasively predicting tools still have more appeal across healthcare *** red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been *** In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD *** Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 *** baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were *** FUP,DEs(timing and modaities)were *** was assessed at the baseline and on DE occurrence according to the available Clinical Practice *** Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve a

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational Medicine Prognostic biomarker

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Micro-RNAs in hepatitis B virus-related chronic liver diseases and hepatocellular carcinoma

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World Journal of Hepatology 2018年第9期10卷 558-570页

作者： Evangelista Sagnelli Nicoletta Potenza Lorenzo Onorato Caterina Sagnelli Nicola Coppola Aniello Russo Department of Mental Health and Public Medicine Section of Infectious DiseasesUniversity of Campania Luigi Vanvitelli DISTABIF University of Campania "Luigi Vanvitelli"

MicroRNAs(miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level by affecting both the stability and translation of complementary mRNAs. Several studies have shown that mi RNAs are important regulators in the conflicting efforts between the virus(to manipulate the host for its successful propagation) and the host(to inhibit the virus),culminating in either the elimination of the virus or its persistence. An increasing number of studies report a role of miRNAs in hepatitis B virus(HBV) replication and pathogenesis. In fact,HBV is able to modulate different host miRNAs,particularly through the transcriptional transactivator HBx protein and,conversely,different cellular miRNAs can regulate HBV gene expression and replication by a direct binding to HBV transcripts or indirectly targeting host factors. The present review will discuss the role of miRNAs in the pathogenesis of HBVrelated diseases and their role as a biomarker in the management of patients with HBV-related disease and as therapeutic targets.

关键词： Hepatitis B virus infection MicroRNAs Hepatitis B virus pathogenesis Molecular mechanisms

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Melanocortin 3,5 receptors immunohistochemical expression in colonic mucosa of inflammatory bowel disease patients:A matter of disease activity?

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World Journal of Gastroenterology 2024年第9期30卷 1132-1142页

作者： Antonietta Gerarda Gravina Iacopo Panarese Maria Consiglia Trotta Michele D'Amico Raffaele Pellegrino Franca Ferraraccio Marilena Galdiero Roberto Alfano Paolo Grieco Alessandro Federico Hepatogastroenterology Division Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Pathology Division Department of Mental and Physical Health and Preventive MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Experimental Medicine Division of PharmacologyUniversity of Campania Luigi VanvitelliNaples 80138Italy Department of Advanced Medical and Surgical Sciences(DAMSS) University of Campania Luigi VanvitelliNaples 80138Italy Department of Pharmacy University of Naples Federico IINaples 80131Italy

BACKGROUND Melanocortin 3 and 5 receptors(i.e.,MC3R and MC5R)belong to the melanocortin ***,data regarding their role in inflammatory bowel diseases(IBD)are currently *** This study aims to ascertain their expression profiles in the colonic mucosa of Crohn’s disease(CD)and ulcerative colitis(UC),aligning them with IBD disease endoscopic and histologic *** Colonic mucosal biopsies from CD/UC patients were sampled,and immunohisto-chemical analyses were conducted to evaluate the expression of MC3R and *** sampling was performed on both traits with endoscopic scores(Mayo endoscopic score and CD endoscopic index of severity)consistent with inflamed mucosa and not consistent with disease activity(i.e.,normal appearing mucosa).RESULTS In both CD and UC inflamed mucosa,MC3R(CD:+7.7 fold vs normal mucosa,P<0.01;UC:+12 fold vs normal mucosa,P<0.01)and MC5R(CD:+5.5 fold vs normal mucosa,P<0.01;UC:+8.1 fold vs normal mucosa,P<0.01)were significantly more expressed compared to normal *** MC3R and MC5R are expressed in the colon of IBD ***,expression may differ according to disease endoscopic activity,with a higher degree of expression in the traits affected by disease activity in both CD and UC,suggesting a potential use of these receptors in IBD pharmacology.

关键词： Melanocortin 3 receptor Melanocortin 5 receptor Ulcerative colitis Crohn's disease Inflammatory bowel disease

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May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

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World Journal of Gastroenterology 2024年第1期30卷 17-33页

作者： Antonietta Gerarda Gravina Raffaele Pellegrino Marina Cipullo Giovanna Palladino Giuseppe Imperio Andrea Ventura Salvatore Auletta Paola Ciamarra Alessandro Federico Division of Hepatogastroenterology Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy

Artificial intelligence is increasingly entering everyday *** language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM *** hype generated by such systems may lead to unweighted patient trust in these ***,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for *** review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their *** the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some *** studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bowel disease Chat Generative Pre-trained Transformer Large language model Artificial intelligence

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Reactivation of hepatitis B virus infection in patients with hemolymphoproliferative diseases, and its prevention

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World Journal of Gastroenterology 2019年第26期25卷 3299-3312页

作者： Caterina Sagnelli Mariantonietta Pisaturo Federica Calò Salvatore Martini Evangelista Sagnelli Nicola Coppola Department of Mental Health and Public Medicine Section of Infectious Diseases University of Campania Luigi Vanvitelli

Reactivation of hepatitis B virus(HBV)replication is characterized by increased HBV-DNA serum values of about 1 log or by HBV DNA turning positive if previously undetectable in serum,possibly associated with liver damage and seldom *** to HBV reactivation,hepatitis B surface antigen(HBsAg)-negative/anti-HBc-positive subjects may revert to *** patients with hemo-lymphoproliferative disease,the frequency of HBV reactivation depends on the type of lymphoproliferative disorder,the individual's HBV serological status and the potency and duration of *** particular,it occurs in 10%-50%of the HBsAg-positive and in 2%-25%of the HBsAg-negative/anti-HBc-positive,the highest incidences being registered in patients receiving rituximab-based *** reactivation can be prevented by accurate screening of patients at risk and by a pharmacological prophylaxis with anti-HBV nucleo(t)sides starting 2-3 wk before the beginning of immunosuppressive treatment and covering the entire period of administration of immunosuppressive drugs and a long subsequent period,the duration of which depends substantially on the degree of immunodepression *** with significant HBV replication before immunosuppressive therapy should receive anti-HBV nucleo(t)sides as a long-term(may be life-long)*** review article is mainly directed to doctors engaged every day in the treatment of patients with onco-lymphoproliferative diseases,so that they can broaden their knowledge on HBV infection and on its reactivation induced by the drugs with high immunosuppressive potential that they use in the care of their patients.

关键词： Hepatitis B virus reactivation Hepatitis B virus infection Hemolymphoproliferative diseases Immunosuppressive therapy Hepatitis B virus therapy Hepatitis B virus prophylasis

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Numerical simulation of mud-flows impacting structures

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Journal of Mountain Science 2019年第2期16卷 364-382页

作者： GRECO Massimo DI CRISTO Cristiana IERVOLINO Michele VACCA Andrea DICEA Università di Napoli Federico II DI Università della Campania Luigi Vanvitelli

The study of the interaction of mud-flows with obstacles is important to define inundation zones in urban areas and to design the possible structural countermeasures. The paper numerically investigates the impact of a mud-flow on rigid obstacles to evaluate the force acting on them using two different depth-integrated theoretical models, Single-Phase Model(SPM) and Two-Phase Model(TPM), to compare their performance and limits. In the first one the water-sediment mixture is represented as a homogeneous continuum described by a shearthinning power-law rheology. Alternatively, the twophase model proposed by Di Cristo et al in 2016 is used, which separately accounts for the liquid and solid phases. The considered test cases are represented by a 1D landslide flowing on a steep slope impacting on a rigid wall and a 2D mud dam-break flowing on a horizontal bottom in presence of single and multiple rigid obstacles. In the 1D test case, characterized by a very steep slope, the Two-Phase Model predicts the separation between the two phases with a significant longitudinal variation of the solid concentration. In this case the results indicate appreciable differences between the two models in the estimation of both the wave celerity and the magnitude of the impact, with an overestimation of the peak force when using the Single-Phase Model. In the 2D test-cases, where the liquid and solid phases remain mixed, even if the flow fields predicted by the two models present some differences, the essential features of the interaction with the obstacles, along with the maximum impact force, are comparable.

关键词： Mud-Flow Impact force Two-phase model Power-law

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Covariation between plant biodiversity and soil systems in a European beech forest and a black pine plantation:the case of Mount Faito,(campania,Southern Italy)

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Journal of Forestry Research 2022年第1期33卷 239-252页

作者： Tiziana Danise Michele Innangi Elena Curcio Antonietta Fioretto Department of Environmental Biological and Pharmaceutical Sciences and TechnologiesUniversity of Campania“Luigi Vanvitelli”Via Vivaldi 4381100 CasertaItaly

Both climate and land-use changes,including the introduction and spread of allochthonous species,are forecast to affect forest ***,forests will be affected in terms of species composition as well as their soil chemical and biological *** possible changes in both tree cover and soil system might impact the amount of carbon that is stored in living plants and dead biomass and within the soil ***,such alterations can have a strong impact on the detrital food web that is linked to litter *** there are studies on the infuence of plant diversity on soil physical and chemical characteristics,the effects on soil biological activity and carbon storage processes remain largely *** aim of this study was to investigate and compare chemical and biological variables in covariation with plant communities in an autochthonous beech forest(Fagus sylvatica L.)and a black pine plantation(Pinus nigra *** ***).Our results confirmed that the two communities were considerably different,with the old-growth beech community having a lower number of plant species and the pine community was in development as a consequence of anthropogenic *** aspects of the two communities were also refected in the soil,with the beech soil having higher nitrogen levels and a more specialized microbial community compared to the pine soil,with most extracellular enzymes(such as peroxidase and chitinase)showing lower activity in the pine soil.

关键词： 2B-PLS Plant and soil Vegetation Soil enzymes

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Bone alterations in inflammatory bowel diseases

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World Journal of Clinical Cases 2019年第15期7卷 1908-1925页

作者： Dolores Sgambato Francesca Gimigliano Cristiana De Musis Antimo Moretti Giuseppe Toro Emanuele Ferrante Agnese Miranda Domenico De Mauro Lorenzo Romano Giovanni Iolascon Marco Romano Departments of Precision Medicine and Polyspecialistic Internal Medicine University of Campania "Luigi Vanvitelli" and University HospitalNaples 80131Italy Department of Physical and Mental Health University of Campania“Luigi Vanvitelli”Naples 80131Italy Department of Medical and Surgical Specialties and Dentistry University of Campania“Luigi Vanvitelli”Naples 80131Italy Surgical Digestive Endoscopy Department of Clinical Medicine and SurgeryFederico Ⅱ UniversityNaples 80131Italy

Inflammatory bowel diseases(IBDs)are characterized by a multifactorial partially unknown etiology that involves genetic,immunological and environmental *** to 50%of IBD patients experience at least one extraintestinal manifestation;among them is the involvement of bone density which is referred to as metabolic bone disease(MBD),including osteopenia and *** alterations in IBDs population appear to have a multifactorial etiology:Decreased physical activity,inflammation-related bone resorption,multiple intestinal resections,dietary malabsorption of minerals and vitamin D deficiency,genetic factors,gut-bone immune signaling interaction,steroid treatment,microbiota and pathogenic micro-organisms interaction,and dietary malabsorption of minerals,that,all together or individually,may contribute to the alteration of bone mineral *** review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone *** also want to underline the role of the screening and prophylaxis of bone alterations in Crohn’s disease and ulcerative colitis patients and the importance of treating appropriately MBD.

关键词： Inflammatory bowel diseases Bone alterations Bone mineral density Osteoporosis Osteopenia Ulcerative colitis Crohn’s disease

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COVID-19 and pediatric fatty liver disease:Is there interplay?

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World Journal of Gastroenterology 2021年第22期27卷 3064-3072页

作者： Anna Di Sessa Francesca Lanzaro Sarah Zarrilli Vittorio Picone Stefano Guarino Emanuele Miraglia del Giudice Pierluigi Marzuillo Department of Woman Childand General and Specialized SurgeryUniversity of Campania“Luigi Vanvitelli”Naples 80138Italy

The rapid global spread of coronavirus disease 2019(COVID-19)infection has become a major health issue with higher morbidity and mortality *** respiratory symptoms,a growing body of evidence indicates a variety of gastrointestinal manifestations including liver *** this regard,several data supported an association between COVID-19 infection and liver injury in adults,while in children there is compelling but currently limited *** particular,patients with COVID-19 have shown a higher risk of liver injury(mainly expressed as increased transaminase levels or hepatic steatosis).Conversely,a greater risk of more severe forms of COVID-19 infection has been observed in subjects with pre-existing chronic liver *** dramatic interplay between COVID-19 and liver damage has been related to the inflammatory pathways chronically active in patients with nonalcoholic fatty liver disease and acutely in those affected by COVID-19,but other different pathogenic mechanisms have also been *** note,patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 *** emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 *** into account the prognostic role of fatty liver in COVID-19 patients and its intrinsic relationship with metabolic abnormalities even in childhood,a strict monitoring of this condition is *** aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.

关键词： COVID-19 Children Adults Nonalcoholic fatty liver disease

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