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World Journal of Gastroenterology 2024年第15期30卷 2081-2086页

作者： Michele Nardolillo Fabiola Rescigno Mario Bartiromo Dario Piatto Stefano Guarino pierluigi marzuillo Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Naples 80138Italy

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant ***,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since *** recently,this term has been further replaced with metabolic associated steatotic liver *** is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic ***,comparable pediatric data remain *** the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

关键词： Metabolic(dysfunction)associated fatty liver disease Renal Function Children Obesity

Pediatric fatty liver disease:Role of ethnicity and genetics

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World Journal of Gastroenterology 2014年第23期20卷 7347-7355页

作者： pierluigi marzuillo Emanuele Miraglia del Giudice Nicola Santoro Department of Women and Children and General and Specialized Surgery Seconda Università degli Studi di Napoli80138 NaplesItaly Department of Pediatrics Yale University School of MedicineNew HavenCT 06520United States

Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver.

关键词： Non alcoholic fatty liver disease Ethnicity Patatin like phospholipase containing domain 3 gene Obesity Insulin resistance Glucokinase regulatory protein Apolipoprotein C3 gene Farnesyl-diphosphate farnesyltransferase 1

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

Telemedicine in the COVID-19 era:Taking care of children with obesity and diabetes mellitus

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World Journal of Diabetes 2021年第5期12卷 651-657页

作者： Giuseppina Rosaria Umano Anna Di Sessa Stefano Guarino Giuseppina Gaudino pierluigi marzuillo Emanuele Miraglia del Giudice Department of Woman Childand of General and Specialized SurgeryUniversity of Campania“Luigi Vanvitelli”Naples 80138Italy

Severe acute respiratory syndrome coronavirus 2 infection was declared a pandemic in January *** then,several measures to limit virus transmission have been imposed;among them,home confinement has been the most severe,with drastic changes in the daily routines of the general ***“stay at home”rule has impaired healthcare service access,and patients with chronic conditions were the most exposed to the negative effects of this *** is strong evidence of the worsening of obesity and diabetes mellitus in children during this *** overcome these issues,healthcare providers have changed their clinical practice to ensure follow-up visits and medical consultation though the use of ***,including telephone calls,videocalls,data platforms of shared telemedicine data platforms mitigated the negative effect of pandemic *** evidence has documented good metabolic control and weight management outcomes in centers that performed extensive telemedicine services last year during the *** review discusses studies that investigated the use of telemedicine tools for the management of pediatric obesity and diabetes.

关键词： COVID-19 Pandemic Children and adolescents Obesity Diabetes Telemedicine

Relationship between nonalcoholic fatty liver disease and chronic kidney disease could start in childhood

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World Journal of Gastroenterology 2021年第34期27卷 5793-5795页

作者： Anna Di Sessa Stefano Guarino Rosa Melone Rossella Francesca De Simone pierluigi marzuillo Emanuele Miraglia del Giudice Department of Woman Childand General and Specialized SurgeryUniversity of Campania Luigi VanvitelliNaples 80138Italy

The relationship between nonalcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD)has gained considerable scientific interest in adults over the past few ***,this association has recently emerged in *** published studies have suggested a role for NAFLD as a risk factor for CKD from the earliest age,with a potential influence of the major NAFLD risk polymorphisms,resulting in an increased risk of both cardiovascular and metabolic *** view of the progressive course and increased cardiometabolic risk closely related to NAFLD and CKD,we focused on the link between these diseases in childhood.

关键词： Nonalcoholic fatty liver disease Chronic kidney disease Children Liver

Omics era in type 2 diabetes:From childhood to adulthood

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World Journal of Diabetes 2021年第12期12卷 2027-2035页

作者： Antonio Paride Passaro pierluigi marzuillo Stefano Guarino Federica Scaglione Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Napoli 80138Italy

Parallel to the dramatic rise of pediatric obesity, estimates reported an increasedprevalence of type 2 diabetes (T2D) already in childhood. The close relationshipbetween obesity and T2D in children is mainly sustained by insulin resistance(IR). In addition, the cardiometabolic burden of T2D including nonalcoholic fattyliver disease, cardiovascular disease and metabolic syndrome is also strictlyrelated to IR. Although T2D pathophysiology has been largely studied in anattempt to improve therapeutic options, molecular mechanisms are still not fullyelucidated. In this perspective, omics approaches (including lipidomics,metabolomics, proteomics and metagenomics) are providing the most attractivetherapeutic options for T2D. In particular, distinct both lipids and metabolites areemerging as potential therapeutic tools. Of note, among lipid classes, thepathogenic role of ceramides in T2D context has been supported by several ***, selective changes of ceramides expression might represent innovativetherapeutic strategies for T2D treatment. More, distinct metabolomics pathwayshave been also found to be associated with higher T2D risk, by providing novelpotential T2D biomarkers. Taken together, omics data are responsible for theexpanding knowledge of T2D pathophysiology, by providing novel insights toimprove therapeutic strategies for this tangled disease. We aimed to summarizethe most recent evidence in the intriguing field of the omics approaches in T2Dboth in adults and children.

关键词： Omics Diabetes Children Adults Type 2 diabetes

Dehydrated patient without clinically evident cause:A case report

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World Journal of Clinical Cases 2020年第20期8卷 4838-4843页

作者： Federica Palladino Maria Cristina Fedele Marianna Casertano Laura Liguori Tiziana Esposito Stefano Guarino Emanuele Miraglia del Giudice pierluigi marzuillo Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania“Luigi Vanvitelli”Naples 80138Italy

BACKGROUND Patients affected by cystic fibrosis can present with metabolic alkalosis such as Bartter's *** this case report we want to underline this differential diagnosis and we aimed focusing on the suspect of cystic fibrosis,also in case of a negative newborn *** SUMMARY In a hot August–with a mean environmental temperature of 36℃–an 8-mo-old female patient presented with severe dehydration complicated by hypokalemic metabolic alkalosis,in absence of fever,diarrhea and *** diagnosis between cystic fibrosis and tubulopathies causing metabolic alkalosis(Bartter's Syndrome)was *** started intravenous rehydration with subsequent improvement of clinical conditions and serum electrolytes *** diagnosed a mild form of cystic fibrosis(heterozygous mutations:G126 D and F508 del in the cystic fibrosis transmembrane conductance regulator gene).The trigger factor of this condition had been heat *** When facing a patient with hypokalemic metabolic alkalosis,cystic fibrosis presenting with Pseudo-Bartter's syndrome should be considered in the differential diagnosis,even if the newborn screening was negative.

关键词： Metabolic alkalosis Dehydration Cystic fibrosis Pseudo-Bartter syndrome Heat exposure Children Case report

Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values

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World Journal of Clinical Cases 2019年第9期7卷 1021-1027页

作者： pierluigi marzuillo Stefano Guarino Tiziana Esposito Anna Di Sessa Sara Immacolata Orsini Daniela Capalbo Emanuele Miraglia del Giudice Angela La Manna Department of Woman Child and of General and Specialized Surgery Università degli Studi della Campania "Luigi Vanvitelli"

BACKGROUND In paediatric patients with complicated nephrotic syndrome(NS), rituximab(RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G(IgG) *** To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG *** We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation(SD)].RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients(55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two "starting doses" experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth *** RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.

关键词： Nephrotic syndrome Rituximab IgG hypogammaglobulinemia Immunoglobulin

Gut microbiota and COVID-19: An intriguing pediatric perspective

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World Journal of Clinical Cases 2022年第23期10卷 8076-8087页

作者： Maria Sole Valentino Claudia Esposito Simone Colosimo Angela Maria Caprio Simona Puzone StefanoGuarino pierluigi marzuillo Emanuele Miraglia del Giudice Anna Di Sessa Department of Woman Childand General and Specialized SurgeryUniversity of Campania Luigi VanvitelliNaples 80138Italy

Gastrointestinal(GI)involvement has been reported in approximately 50%of patients with coronavirus disease 2019(COVID-19),which is due to the pathogenic role of inflammation and the intestinal function of the angiotensinconverting enzyme 2 and its *** adult data has pointed out that gut dysbiosis might occur in these patients with a potential impact on the severity of the disease,however the role of gut microbiota in susceptibility and severity of COVID-19 disease in children is still poorly *** the last decades,the crosstalk between gut and lung has been largely recognized resulting in the concept of“gut-lung axis”as a central player in modulating the development of several *** organs are involved in the common mucosal immune system(including bronchus-associated and gut-associated lymphoid tissues)and their homeostasis is crucial for human *** this framework,it has been found that the role of GI dysbiosis is affecting the homeostasis of the gutliver *** note,a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects,but it remains to be *** on the increased risk of inflammatory diseases in children with COVID-19,the potential correlation between gut microbiota dysfunction and COVID-19 needs to be studied in this *** aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.

关键词： Gut Microbiota Dysbiosis Microbiome COVID-19 Children

Pediatric non-alcoholic fatty liver disease and kidney function: Effect of HSD17B13 variant

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World Journal of Gastroenterology 2020年第36期26卷 5474-5483页

作者： Anna Di Sessa Giuseppina Rosaria Umano Grazia Cirillo Antonio Paride Passaro Valentina Verde Domenico Cozzolino Stefano Guarino pierluigi marzuillo Emanuele Miraglia del Giudice Department of Woman Child and of General and Specialized SurgeryUniversitàdegli Studi della Campania Luigi VanvitelliNapoli 80138Italy Department of Internal Medicine Universitàdegli Studi della Campania Luigi VanvitelliNapoli 80138Italy

BACKGROUND Growing evidence supports a genetic link between non-alcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD).Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in the patatin like phospholipase containing domain 3(PNPLA3)and the E167K allele in the transmembrane 6 superfamily member 2 gene(TM6SF2)affect renal *** the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene has been recognized as a novel genetic variant involved in NAFLD *** particular,it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and *** To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate(eGFR)in obese *** We enrolled 684 obese children(mean age 10.56±2.94 years;mean BMI-SDS 2.98±0.78)consecutively attending our Obesity *** the patients underwent a careful clinical assessment and a comprehensive biochemical *** detect hepatic steatosis,a liver ultrasound was *** was defined by ultrasound detected liver steatosis and/or alanine aminotransferase(ALT)levels>40 IU/*** study population was divided on the basis of the NAFLD *** for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also *** Patients carrying the HSD17B13 rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD.A general linear model confirmed a direct and significant association of eGFR values with HSD17B13 genotype independently of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD.A comparison of regression line confirmed the influence of HSD17B13 genotype on the relationship between eGFR and age both among patients with and without NAFLD.H omozygous patients for HSD17B13 genotype with NAFLD showed a significantly h

关键词： Hydroxysteroid Dehydrogenase Fatty Liver Renal Function Obese Children