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Ursodeoxycholic acid as adjuvant treatment to phototherapy for neonatal hyperbilirubinemia:a systematic review and meta‑analysis

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World Journal of pediatrics 2022年第9期18卷 589-597页

作者： Ilari Kuitunen Panu Kiviranta Ulla Sankilampi Marjo Renko Institute of Clinical Medicine Department of PediatricsUniversity of Eastern FinlandKuopioFinland department of pediatrics Mikkeli Central HospitalPorrassalmenkatu 35-3750100 MikkeliFinland department of pediatrics Kuopio University HospitalKuopioFinland

Background Neonatal hyperbilirubinemia is observed in most newborns,and 5–15%of neonates require phototherapy.Phototherapy is efective but often prolongs hospitalization and has both short-term and potential long-term harms.The aim of this systematic review and meta-analysis was to evaluate the role of ursodeoxycholic acid(UDCA)combined with phototherapy in neonatal hyperbilirubinemia.Methods A literature search was conducted on September 1,2021;590 studies were screened,and 17 full texts were assessed by two authors.We included randomized controlled trials with or without placebo intervention.Primary outcomes were changes in total bilirubin levels at 24 hours and phototherapy duration.We calculated mean diferences with 95%confdence intervals(CI).Results Six studies with 880 neonates were included.Of these studies,only two used a placebo-controlled double-blinded design.The overall risk of bias was high in one and moderate in four of the included studies.The mean decrease in the total bilirubin level during the frst 24 hours was 2.06 mg/dL(95%CI 0.82–3.30;six studies)greater in the UDCA treatment group.The phototherapy duration was 19.7 hours(95%CI 10.4–29.1;fve studies)shorter in the UDCA treatment group.Conclusions We found low-quality evidence that UDCA as an adjuvant to phototherapy seems to decrease total bilirubin faster and shorten phototherapy duration compared to standard treatment.Further studies are needed to confrm the efcacy,acute and long-term outcomes,and safety before implementing UDCA as an adjuvant to phototherapy in neonatal hyperbilirubinemia.

关键词： Jaundice Phototherapy Unconjugated hyperbilirubinemia Ursodeoxycholic acid

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Variation in SARS-CoV-2 seroprevalence in children in the region of Asturias,Northern Spain

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World Journal of pediatrics 2022年第12期18卷 835-844页

作者： Elisa García-García Mercedes Rodríguez-Pérez David Pérez-Solís Carlos Pérez-Méndez Cristina Molinos-Norniella Ángeles Cobo-Ruisánchez Eva María Fernández Fernández Noelia García González Laura Calle-Miguel Pediatrics Department Centro de Salud LaviadaCalle Juanín de Mieres833207GijónSpain Microbiology department Hospital Universitario Central de AsturiasOviedoSpain Pediatrics Department Hospital Universitario San AgustínAvilésSpain Pediatrics Department Hospital Universitario de CabueñesGijónSpain Pediatrics Department Hospital Carmen y Severo Ochoa.Cangas del NarceaSpain Pediatrics Department Centro de Salud TeatinosOviedoSpain Pediatrics Department Hospital Universitario Central de AsturiasOviedoSpain

Background Updated seroprevalence estimates are important to describe the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)landscape and to guide public health decisions.The aims are to describe longitudinal changes in seroprevalence in children in a region in Northern Spain and to analyze factors associated with SARS-CoV-2 seropositivity.Methods Prospective multicenter longitudinal study with subjects recruited from July to September 2020.Children(up to 14 years old)were included and followed up until September 2021.Venous blood samples were collected every six months during three testing rounds and were analyzed for SARS-CoV-2 antibodies.The data regarding epidemiological features,contact tracing,symptoms,and virological tests were collected.The evolution of SARS-CoV-2 seroprevalence during the study and the differences between children with positive and negative SARS-CoV-2 antibody tests were analyzed.Results Two hundred children were recruited(50.5%girls,median age 9.7 years).The overall seroprevalence increased from round 1[1.5%,95%confidence interval(CI)0.3%–4.3%]to round 2(9.1%,95%CI 4.6%–12.7%)and round 3(16.6%,95%CI 9.5%–19.6%)(P<0.001).Main changes occurred in children aged zero to four years(P=0.001)who lived in urban areas(P<0.001).None of the children who were previously positive became seronegative.Following multivariable analysis,three variables independently associated with SARS-CoV-2 seropositivity were identified:close contact with coronavirus disease 2019(COVID-19)confirmed or suspected cases[odds ratio(OR)=3.9,95%CI 1.2–12.5],previous positive virological test(OR=17.1,95%CI 3.7–78.3)and fatigue(OR=18.1,95%CI 1.7–193.4).Conclusions SARS-CoV-2 seroprevalence in children has remarkably increased during the time of our study.Fatigue was the only COVID-19-compatible symptom that was more frequent in seropositive than in seronegative children.

关键词： Antibodies Child COVID-19 Seroepidemiologic studies

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Height and body mass index trajectories from 1975 to 2015 and prevalence of stunting,underweight and obesity in 2016 among children in Chinese cities:findings from five rounds of a national survey

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World Journal of pediatrics 2024年第4期20卷 404-412页

作者： Xin‑Nan Zong Hui Li Ya‑Qin Zhang department of Growth and Development Capital Institute of PediatricsBeijing 100020China

Background A more comprehensive assessment of growth and nutrition in children is required in China due to rapid socioeconomic processes.We aimed to investigate height and body mass index(BMI)trajectories from 1975 to 2015 and the prevalence of stunting and obesity in 2016 among children in Chinese cities.Methods A total of 904,263 children from birth to 6.9 years were collected from a series of nationally representative surveys in China.Height and BMI trajectories and prevalence of stunting,underweight,overweight and obesity were assessed.Results The average height level of Chinese urban children under 7 years presented a positive secular trend from 1975 to 2015;however,a slowing tendency occurred in 2005‒2015.An apparent increase was observed at the 5th,50th and 95th percentiles of BMI in urban children aged 3 years and older,with a more prominent increase at the 95th percentile.The total prevalence of stunting and underweight under 7 years was 1.4%and 2.0%,respectively.The total prevalence of overweight and obesity under 7 years was 12.6%and 4.3%,respectively,with 12.7%and 4.9%for boys,12.6%and 3.6%for girls,12.1%and 4.0%in urban areas and 13.1%and 4.5%in suburban rural areas.Conclusions The average height level of Chinese urban children has reached World Health Organization child growth standards since 2005 and presented a slowing tendency in secular trend in 2005‒2015.More attention and efforts and public health interventions should be urgently made to combat overweight and obesity among preschool children.

关键词： Body mass index Children Height Obesity Stunting

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Molecular docking studies of human MCT8 protein with soy isoflavones in Allan-Herndon-Dudley syndrome(AHDS)

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Journal of Pharmaceutical Analysis 2018年第5期8卷 318-323页

作者： Divya Shaji department of pediatrics Aichi Medical University

Monocarboxylate transporter-8 （MCT8） is a specific thyroid hormone transporter, essential for the uptake of thyroid hormone into target tissues. Mutations in the MCT8 gene have been identified as the cause of Allan-Herndon-Dudley syndrome （AHDS）. It has been reported that soy isoflavones influence thyroid hormone system and can interact with thyroid hormone transporter proteins. Therefore, the present study aimed to find out whether soy isoflavones （genistein, daidzein and glycitein） can be used as a natural inhibitor to target MCT8 in AHDS. Docking studies were performed for soy isoflavones in order to evaluate their binding affinity to MCT8 protein using AutoDock4 （version 4.2.6） and AutoDock Vina. After docking, the ligands were ranked according to their binding energy and the best lead compound was selected based on the least binding energy. The docking results indicated that daidzein possesses the lowest binding energy against MCT8. Moreover, it was found that the residues PRO-338, HIS-341, and GLU-348 were involved in hydrogen bond interactions with genistein and daidzein. This study suggests that daidzein is a promising natural inhibitor to target MCT8 in AHDS.

关键词： Molecular docking MCT8 AHDS Soy isoflavones Daidzein Genistein

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Intensive phototherapy vs.exchange transfusion for the treatment of neonatal hyperbilirubinemia:a multicenter retrospective cohort study

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Chinese Medical Journal 2022年第5期135卷 598-605页

作者： Meng Zhang Yang He Jun Tang Wenbin Dong Yong Zhang Benjin Zhang Hong Wan Quanmin Deng Lirong Guan Bin Xia Zhong Chen Min Ge Jing Zhao Wenxing Li Jingjun Pei Yi Qu Dezhi Mu department of pediatrics West China Second HospitalSichuan UniversityChengduSichuan 610041China Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University) Ministry of EducationChengduSichuan 610041China department of pediatrics The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646099China department of pediatrics Sichuan Maternal and Child Health HospitalChengduSichuan 610045China department of pediatrics Dazhou Central HospitalDazhouSichuan 635000China department of pediatrics Leshan Maternal and Child Health HospitalLeshanSichuan 614000China department of pediatrics People’s Hospital of DeyangDeyangSichuan 618000China department of pediatrics Mianyang Central HospitalMianyangSichuan 621000China

Background:Intensive phototherapy(IPT)and exchange transfusion(ET)are the main treatments for extreme hyperbilirubinemia.However,there is no reliable evidence on determining the thresholds for these treatments.This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.Methods:This retrospective cohort study was conducted in seven centers from January 2015 to January 2018.Patients with extreme hyperbilirubinemia that met the criteria of ET were included.Patients were divided into three subgroups(low-,medium-,and high-risk)according to gestational week and risk factors.Propensity score matching(PSM)was performed to balance the data before treatment.Study outcomes included the development of bilirubin encephalopathy,duration of hospitalization,expenses,and complications.Mortality,auditory complications,seizures,enamel dysplasia,ocular motility disorders,athetosis,motor,and language development were evaluated during follow-up at age of 3 years.Results:A total of 1164 patients were included in this study.After PSM,296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-,medium-,and high-risk subgroups with 188,364,and 40 matched patients,respectively.No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity,complications,and sequelae.Hospitalization duration and expenses were lower in the low-and medium-risk subgroups in the IPT only group.Conclusions:In this study,our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia.The indication of ET for patients with hyperbilirubinemia could be stricter.However,it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors.If IPT can be guaranteed and proved to be therapeutic,ET should be avoided as much as possible.

关键词： Neonatal hyperbilirubinemia Exchange transfusion Intensive phototherapy

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Treatment of primary sclerosing cholangitis in children

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World Journal of Hepatology 2019年第1期11卷 19-35页

作者： Trevor J Laborda M Kyle Jensen Marianne Kavan Mark Deneau department of pediatrics University of Utah

Primary sclerosing cholangitis(PSC) is a rare disease of stricturing and destruction of the biliary tree with a complex genetic and environmental etiology.Most patients have co-occurring inflammatory bowel disease. Children generally present with uncomplicated disease, but undergo a variable progression to endstage liver disease. Within ten years of diagnosis, 50% of children will develop clinical complications including 30% requiring liver transplantation.Cholangiocarcinoma is a rare but serious complication affecting 1% of children.Ursodeoxycholic acid and oral vancomycin therapy used widely in children as medical therapy, and may be effective in a subset of patients. Gamma glutamyltransferase is a potential surrogate endpoint for disease activity, with improved survival in patients who achieve a normal value. Endoscopic retrograde cholangiopancreatography is a necessary adjunct to medical therapy to evaluate mass lesions or dominant strictures for malignancy, and also to relieve biliary obstruction. Liver transplantation remains the only option for patients who progress to end-stage liver disease. We review special considerations for patients before and after transplant, and in patients with inflammatory bowel disease. There is presently no published treatment algorithm or guideline for the management of children with PSC. We review the evidence for drug efficacy, dosing, duration of therapy, and treatment targets in PSC, and provide a framework for endoscopic and medical management of this complex problem.

关键词： Liver transplant Pediatric Ursodeoxycholic acid Oral vancomycin Oral vancomycin therapy Endoscopic retrograde cholangiopancreatography

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Clinical spectrum and currently available treatment of typeⅠinterferonopathy Aicardi-Goutières syndrome

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World Journal of pediatrics 2023年第7期19卷 635-643页

作者： Giovanni Battista Dell'Isola Gianluca Dini Kaleb Logan Culpepper Katherin Elizabeth Portwood Pietro Ferrara Giuseppe Di Cara Alberto Verrotti Mauro Lodolo department of pediatrics University of PerugiaGiorgio Menghini Square06129 PerugiaItaly department of Neurology Jacksonville University of FloridaFloridaUSA department of pediatrics Division of Child NeurologyUniversity of FloridaUF Health Shands Children's HospitalGainesvilleFLUSA Unit of pediatrics Campus Bio-Medico UniversityRomeItaly

Background Aicardi-Goutières syndrome(AGS)is a genetically determined disorder with a variable phenotype.Since the original description of AGS,advances in gene sequencing techniques have resulted in a significant broadening of the phenotypic spectrum associated with AGS genes,and new clinical pictures have emerged beyond the classic presentation.The aim of this review is to provide a comprehensive analysis of the clinical spectrum of AGS and report currently available treatments and new immunosuppressive strategies.Data sources Literature reviews and original research articles were collected from databases,including PubMed and Clini-calTrials.gov.Relevant articles about AGS were included.Results The involvement of the nervous system certainly represents the major cause of mortality and morbidity in AGS patients.However,other clinical manifestations,such as chilblains,hepatosplenomegaly,and hematological disturbances,may lead to the diagnosis and considerably impact the prognosis and overall quality of life of these patients.Therapeutic approaches of AGS are limited to interventions aimed at specific symptoms and the management of multiple comorbidities.However,advances in understanding the pathogenesis of AGS could open new and more effective therapies.Conclusions The over-activation of innate immunity due to upregulated interferon production plays a critical role in AGS,leading to multi-organ damage with the main involvement of the central nervous system.To date,there is no specific and effective treatment for AGS.New drugs specifically targeting the interferon pathway may bring new hope to AGS patients.

关键词： Aicardi-Goutieres syndrome Immunosuppressive drugs Interferon-α Neuroinflammation Systemic lupus erythematosus

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Hypoallergenicity of a thickened hydrolyzed formula in children with cow’s milk allergy

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World Journal of Clinical Cases 2019年第16期7卷 2256-2268页

作者： Danilo Rossetti Salvatore Cucchiara AlessANDra Morace Beatrice Leter Salvatore Oliva department of pediatrics Sapienza University of Rome

BACKGROUND Allergy to cow’s milk is the most frequent allergy occurring in infants and young children.The dietary management of these patients consists of the elimination of any cow’s milk proteins from the diet,and for formula-fed infants,the substitution of the usual infant formula with an adapted formula that is generally based on extensively hydrolyzed cow’s milk proteins.The American Academy of pediatrics has established specific criteria to confirm the hypoallergenicity of a formula intended for these children.AIM To assess the hypoallergenicity of a new thickened extensively hydrolyzed casein-based formula (TeHCF) in children with cow’s milk allergy (CMA).METHODS Children diagnosed with CMA through a double-blind placebo-controlled food challenge (DBPCFC) were randomly administered increased doses of a placebo formula or the TeHCF [Allernova,new thickener including fibres (Novalac)] under double-blind conditions and medical surveillance on two separate days.Otherwise,both of these formulas and a cow’s milk-based formula were randomly introduced to children who were highly suspected of having CMA on three separate days.Immediate and late reactions occurring after the introduction of any of these formulas were thoroughly recorded by the physician at the hospital and reported by parents to the physician after hospital discharge,respectively.If the children tolerated the TeHCF during the DBPCFC,they were exclusively fed this formula during a 3-mo period where potential allergic symptoms,anthropometric parameters,as secondary outcomes,and adverse events were registered.The Cow’s Milk-related Symptoms Score (CoMiSSTM) was assessed and anthropometric parameters were compared to World Health Organization (WHO) reference data.RESULTS Of the 30 children included in the study,the CMA diagnosis of 29 (mean age: 8.03 ± 7.43 mo) patients was confirmed by a DBPCFC.The children all tolerated the TeHCF during both the challenge and the subsequent 3-mo feeding period,which they all completed.During the latter period,the CoM

关键词： Cow's milk allergy Hypoallergenicity Tolerance Thickened extensively hydrolyzed formula Digestive comfort Dietary management

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Rapid transport of insulin to the brain following intranasal administration in rats

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Neural Regeneration Research 2019年第6期14卷 1046-1051页

作者： Lir-Wan Fan Kathleen Carter Abhay Bhatt Yi Pang department of pediatrics University of Mississippi Medical Center

We previously reported that intranasal insulin protects substantia nigra dopaminergic neurons against6-hydroxydopamine neurotoxicity in rats. This study aimed to assess insulin pharmacokinetics in the rat brain following intranasal application. Recombinant human insulin(rh-Ins) or phosphate buffer solution was administered to both nostrils of rats. Animals were sacrificed at 15 minutes, 1, 2, and 6 hours to determine insulin levels in different brain regions by an ultrasensitive, human-specific enzyme-linked immunosorbent assay kit. For fluorescence tracing study, rats were administered with intranasal florescence-tagged insulin(Alex546-Ins), and brains were fixed at 10 and 30 minutes to prepare sagittal sections.rh-Ins was detected in all brain regions examined except the cerebral cortex. The highest levels were detected in the brainstem, followed by the cerebellum, substantia nigra/ventral tegmental area, olfactory bulb,striatum, hippocampus, and thalamus/hypothalamus. Insulin levels reached a peak at 15 minutes and then declined gradually overtime, but remained significantly higher than baseline levels at 6 hours in most regions.Consistently, widespread Alex546-Ins-binding cells were detected in the brain at 10 and 30 minutes, with the olfactory bulb and brainstem showing the highest while the cerebral cortex showing lowest fluorescence signals. Double-immunostaining showed that Alex546-Ins-bindings were primarily co-localized with neuronal nuclei-positive neurons. In the subtantia nigra, phospho-Akt was found to be activated in a subset of Alex546-Ins and tyrosine hydroxylase double-labeled cells, suggesting activation of the Akt/PI3 K pathway in these dopaminergic neurons. Data from this study suggest that intranasal insulin could effectively reach deep brain structures including the nigrostriatal pathways, where it binds to dopaminergic neurons and activates intracellular cell survival signaling. This study was approved by the Institutional Animal Care Committee at the University of Mississippi Medical Cent

关键词： dopaminergic neurons striatum substantia nigra brainstem olfactory bulb glia trigeminal nerve pharmacokinetics axonal transport pAkt

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Treatment of hepatitis C in children and adolescents:how far have we reached?

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World Journal of pediatrics 2023年第2期19卷 107-119页

作者： Vybhav Venkatesh Keerthivasan Seetharaman Neha Anushree department of Gastroenterology and Hepatobiliary Sciences IMS and SUM HospitalSOA UniversityBhubaneswarIndia department of pediatrics Sri Manakula Vinayagar Medical College and HospitalPuducherryIndia department of pediatrics Command Hospital-Southern CommandPune411040India

Background Hepatitis C virus(HCV)infection is a global public health problem and also generates a significant case load in children and adolescents.With the introduction of directly acting antivirals(DAA),the treatment and care of HCV-infected patients have progressed significantly.The available treatment options in children are limited,and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens.Data sources This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV,directly acting antivirals/DAA,natural history,treatment,pediatrics,children,and adolescents as keywords.Results Combination therapies with highly effective DAA regimes,such as sofosbuvir/ledipasvir,sofosbuvir/velpatasvir,glecaprevir/pibrentasvir,sofosbuvir/daclatasvir,sofosbuvir/ribavirin and others,are available for use in children.Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents.Pan-genotypic regimens are also available in children and adolescents,and these regimens can be used while skipping genotype testing.Conclusion The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.

关键词： Children Directly acting antivirals Hepatitis C

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