Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver diseas...Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,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 childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It 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 impairments.However,comparable pediatric data remain limited.Given 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.展开更多
Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resi...Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.展开更多
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 mos...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.展开更多
One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease(NAFLD),which is the most common form of liver disease in children.NAFLD is defined by hepatic fat infiltration > 5%...One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease(NAFLD),which is the most common form of liver disease in children.NAFLD is defined by hepatic fat infiltration > 5% hepatocytes,as assessed by liver biopsy,in the absence of excessive alcohol intake,viral,autoimmune and drug-induced liver disease.It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis,which,in turn,can evolve into cirrhosis and end stage liver disease.Obesity and insulin resistance are the main risk factors for pediatric NAFLD.In fact,NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome,prediabetes and type 2 diabetes mellitus(T2D).In particular,it has been clearly shown in obese youth that the prevalence of metabolic syndrome,pre-diabetes and type 2 diabetes increaseswith NAFLD severity progression.Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition.Recently,a non-synonymous SNP(rs738409),characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene(PNPLA3),has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children.Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein.The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes,is aimed at acting upon specific targets involved in the pathogenesis.There are some therapeutic approaches that are being studied in children.This article reviews the current knowledge regarding the pediatric fatty liver disease,the new insights and the future directions.展开更多
Acute appendicitis is one of the most common indications for abdominal surgery in pediatrics with peak incidence in the second decade of life. Acute appendicitis in the first years of life is an uncommon event. The cl...Acute appendicitis is one of the most common indications for abdominal surgery in pediatrics with peak incidence in the second decade of life. Acute appendicitis in the first years of life is an uncommon event. The clinical presentation is often varied and the diagnosis may be overshadowed by other medical conditions.Gastroenteritis is the most common misdiagnosis, with a history of diarrhea present in 33% to 41% of patients. Pain is the most common presenting symptom in children less than 5 years old, followed by vomiting, fever, anorexia and diarrhea. The most common physical sign is focal tenderness(61% of the patients) followed by guarding(55%), diffuse tenderness(39%), rebound(32%), and mass(6%). Neonatal appendicitis is a very rare disease with high mortality; presenting symptoms are nonspecific with abdominal distension representing the main clinical presentation. The younger the patient, the earlier perforation occurs: 70% of patients less than 3 years develop a perforation within 48 h of onset of symptoms. A timely diagnosis reduces the risk of complications. We highlight the epidemiology, pathophysiology, clinical signs and laboratory clues of appendicitis in young children and suggest an algorithm for early diagnosis.展开更多
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) levels.AI...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) levels.AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.METHODS 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 dose.CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.展开更多
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 th...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 function.Recently the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology.In particular,it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children.AIM To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate(eGFR)in obese children.METHODS We enrolled 684 obese children(mean age 10.56±2.94 years;mean BMI-SDS 2.98±0.78)consecutively attending our Obesity Clinic.All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation.To detect hepatic steatosis,a liver ultrasound was performed.NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase(ALT)levels>40 IU/L.The study population was divided on the basis of the NAFLD presence.Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made.RESULTS 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 higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele(P value for intercepts=0.005;P value for slopes=0.94).The same effect was observed among patients without NAFLD(P value for intercepts=0.0012;P value for slopes=0.87).CONCLUSION Carriers of the HSD17B13 rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.展开更多
Due its close relationship with obesity,nonalcoholic fatty liver disease(NAFLD)has become a major worldwide health issue even in childhood.The most accepted pathophysiological hypothesis is represented by the“multipl...Due its close relationship with obesity,nonalcoholic fatty liver disease(NAFLD)has become a major worldwide health issue even in childhood.The most accepted pathophysiological hypothesis is represented by the“multiple hits”theory,in which both hepatic intracellular lipid accumulation and insulin resistance mainly contribute to liver injury through several factors.Among these,lipotoxicity has gained particular attention.In this view,the pathogenic role of different lipid classes in NAFLD(e.g.,sphingolipids,fatty acids,ceramides,etc.)has been highlighted in recent lipidomics studies.Although there is some contrast between plasma and liver findings,lipidomic profile in the NAFLD context provides novel insights by expanding knowledge in the intricate field of NAFLD pathophysiology as well as by suggesting innovative therapeutic approaches in order to improve both NAFLD prevention and treatment strategies.Selective changes of distinct lipid species might be an attractive therapeutic target for treating NAFLD.Herein the most recent evidence in this attractive field has been summarized to provide a comprehensive overview of the lipidomic scenario in paediatric NAFLD.展开更多
The relationship between nonalcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD)has gained considerable scientific interest in adults over the past few years.However,this association has recently emerge...The relationship between nonalcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD)has gained considerable scientific interest in adults over the past few years.However,this association has recently emerged in children.Several 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 diseases.In 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.展开更多
Severe acute respiratory syndrome coronavirus 2 infection was declared a pandemic in January 2020.Since then,several measures to limit virus transmission have been imposed;among them,home confinement has been the most...Severe acute respiratory syndrome coronavirus 2 infection was declared a pandemic in January 2020.Since 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 population.The“stay at home”rule has impaired healthcare service access,and patients with chronic conditions were the most exposed to the negative effects of this limitation.There is strong evidence of the worsening of obesity and diabetes mellitus in children during this period.To overcome these issues,healthcare providers have changed their clinical practice to ensure follow-up visits and medical consultation though the use of telemedicine.Telemedicine,including telephone calls,videocalls,data platforms of shared telemedicine data platforms mitigated the negative effect of pandemic restrictions.Published evidence has documented good metabolic control and weight management outcomes in centers that performed extensive telemedicine services last year during the pandemic.This review discusses studies that investigated the use of telemedicine tools for the management of pediatric obesity and diabetes.展开更多
Acute lobar nephritis(ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract ...Acute lobar nephritis(ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children.展开更多
BACKGROUND Patients affected by cystic fibrosis can present with metabolic alkalosis such as Bartter's syndrome.In this case report we want to underline this differential diagnosis and we aimed focusing on the sus...BACKGROUND Patients affected by cystic fibrosis can present with metabolic alkalosis such as Bartter's syndrome.In 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 screening.CASE 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 vomiting.Differential diagnosis between cystic fibrosis and tubulopathies causing metabolic alkalosis(Bartter's Syndrome)was considered.We started intravenous rehydration with subsequent improvement of clinical conditions and serum electrolytes normalization.We 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 exposure.CONCLUSION 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.展开更多
The rapid global spread of coronavirus disease 2019(COVID-19)infection has become a major health issue with higher morbidity and mortality rates.Besides respiratory symptoms,a growing body of evidence indicates a vari...The rapid global spread of coronavirus disease 2019(COVID-19)infection has become a major health issue with higher morbidity and mortality rates.Besides respiratory symptoms,a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement.In 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 evidence.In 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 diseases.The 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 supposed.Of note,patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection.This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients.Taking 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 recommended.We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.展开更多
In 2020,an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease(MAFLD).This recent proposal reflects the close association of fa...In 2020,an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease(MAFLD).This recent proposal reflects the close association of fatty liver with metabolic derangements,as demonstrated by previous robust data.Several factors[including genetics,inflammation,metabolic abnormalities,insulin resistance(IR),obesity,prenatal determinants,and gut–liver axis]have been found to be involved in MAFLD pathophysiology,but this tangled puzzle remains to be clearly understood.In particular,IR has been recognized as a key player in metabolic impairments development in children with fatty liver.On this ground,MAFLD definition focuses on the pathophysiological basis of the disease,by emphasizing the crucial role of metabolic impairments in this condition.Although primarily developed for adults,MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles,because of the increasing attention to cardiometabolic risk in childhood.To date,accumulating evidence is available on the feasibility of MAFLD definition in clinical practice,but some data are still conflicting in highly selected populations.Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk,early strategies for MAFLD identification,treatment and prevention are needed.Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging.We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.展开更多
AIM:To verify the prevalence of thyroid autoimmunity(TA) and the possible association between atopy and TA in children affected by skin disease.METHODS:Three hundred and twenty-four children consecutively referred due...AIM:To verify the prevalence of thyroid autoimmunity(TA) and the possible association between atopy and TA in children affected by skin disease.METHODS:Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled.One hundred and eighty-seven were diagnosed with atopic dermatitis(AD),95 with acute urticaria,40 with chronic urticaria(CU),and 2 with alopecia areata(AA).According to the work-up for atopy,the children were divided into two groups:Atopics and non-atopics.TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay.RESULTS:In all children with skin disease,a significant prevalence of TA in atopies compared with non-atopies(13.67%vs 2.67%,P=0.0016) and a significant association between TA and atopy(OR=5.76,95%CI:1.71-19.35) were observed.These findings were confirmed as significant in children with AD:TA in atopies was 11.5%,while TA in non-atopies was2.7%(P=0.03,OR=4.68,95%CI:1.02-21.38).In addition,atopics with CU showed a significantly higher prevalence of TA(26.9%),but none of the non-atopics showed CU(P=0.0326).On the other hand,atopies with AA showed a 100%(2 out of 2) prevalence of TA,compared with none of the non-atopies.CONCLUSION:In children with skin disease,atopy seems to be associated with an increased risk of TA.展开更多
As a result of the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)represents a global medical concern in childhood with a closely related increased cardiometabolic risk.Knowledge on NAFLD pathophysiology has...As a result of the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)represents a global medical concern in childhood with a closely related increased cardiometabolic risk.Knowledge on NAFLD pathophysiology has been largely expanded over the last decades.Besides the well-known key NAFLD genes(including the I148M variant of the PNPLA3 gene,the E167K allele of the TM6SF2,the GCKR gene,the MBOAT7-TMC4 rs641738 variant,and the rs72613567:TA variant in the HSD17B13 gene),an intriguing pathogenic role has also been demonstrated for the gut microbiota.More interestingly,evidence has added new factors involved in the“multiple hits”theory.In particular,omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment.In fact,different branches of omics including metabolomics,lipidomics(in particular sphingolipids and ceramides),transcriptomics(including micro RNAs),epigenomics(such as DNA methylation),proteomics,and glycomics represent the most attractive pathogenic elements in NAFLD development,by providing insightful perspectives in this field.In this perspective,we aimed to provide a comprehensive overview of NAFLD pathophysiology in children,from the oldest pathogenic elements(including genetics)to the newest intriguing perspectives(such as omics branches).展开更多
Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resis...Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resistance(IR)represents the key factor underlying the spectrum of these obesity consequences.As observed in adults,recent data supported the occurrence of microalbuminuria(MA)as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity.In fact,a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics.Based on the clinical and prognostic relevance of this relationship in daily practice(including an increased risk of chronic kidney disease development overtime),more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity.In this paper,we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity:(1)What is the prevalence of pediatric MA?(2)What is the state of art of MA in children with obesity?and(3)Is there a link between IR and MA in children with obesity?展开更多
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 angioten...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 receptor.Accumulating 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 known.During 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 diseases.Both organs are involved in the common mucosal immune system(including bronchus-associated and gut-associated lymphoid tissues)and their homeostasis is crucial for human health.In this framework,it has been found that the role of GI dysbiosis is affecting the homeostasis of the gutliver axis.Of note,a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects,but it remains to be clarified.Based 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 population.We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.展开更多
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 sustaine...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 data.Thus, 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.展开更多
AIM:To verify if subclinical hypothyroidism(SCH) could be associated to atopy in children.METHODS:Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled ...AIM:To verify if subclinical hypothyroidism(SCH) could be associated to atopy in children.METHODS:Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy,obesity,chronic low grade inflammation,and SCH work up.RESULTS:Four hundred and forty-five out of 705(63.12%) children affected by allergic disease were diagnosed as atopic and 260(36.88%) as not atopic.The SCH prevalence was 6.3%.Significant higher prevalence of SCH among atopic children with average(group 2) and high(group 3) low grade chronic inflammation compared to atopic children with mild(group 1)low grade chronic inflammation was present.Moreover,group 1 and group 2 presented an OR to show SCH of2.57(95%CI:1.55-6.26) and 2.96(95%CI:1.01-8.65),respectively.Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3respect to group 2 and group 1.Noteworthy,among atopic patients,also total immunoglobulin E(IgE) serum levels,were significantly higher in group 3 compared to group 2 and group 1 children.In atopic children,C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values,while in not atopic children this phenomenon was not evident.CONCLUSION:The possibility exists that an increasing atopic inflammation contributes to SCH occurrence.So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.展开更多
文摘Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,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 childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It 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 impairments.However,comparable pediatric data remain limited.Given 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.
文摘Classically, the non-alcoholic fatty liver disease(NAFLD) physiopathology and progression has been summarized in the two hits hypothesis. The first hit is represented by the action of hyperinsulinemia and insulin resistance, accompanying obesity, that leads to liver steatosis increasing the absolute non esterified fatty acids uptake in the liver and the esterification to form triacylglycerol. The oxidative stress is involved in the second hit leading to the progression to nonalcoholic steatohepatitis(NASH) because of its harmful action on steatosic hepatocytes. However, at the present time, the two hits hypothesis needs to be updated because of the discover of genetic polymorphisms involved both in the liver fat accumulation and progression to NASH that make more intriguing understanding the NAFLD pathophysiological mechanisms. In this editorial, we want to underline the role of PNPLA3 I148 M, GPR120 R270 H and TM6SF2 E167 K in the pediatric NAFLD development because they add new pieces to the comprehension of the NAFLD pathophysiological puzzle. The PNPLA3 I148 M polymorphism encodes for an abnormal protein which predisposes to intrahepatic triglycerides accumulation both for a loss-of-function of its triglyceride hydrolase activity and for a gain-of-function of its lipogenic activity.Therefore, it is involved in the first hit, such as TM6SF2 E167 K polymorphisms that lead to intrahepatic fat accumulation through a reduced very low density lipoprotein secretion. On the other hand, the GPR120 R270 H variant, reducing the anti-inflammatory action of the GPR120 receptor expressed by Kuppfer cells, is involved in the second hit leading to the liver injury.
基金Supported by The American Heart Association(13SDG14640038)2012 Yale Center for Clinical Investigation cholar award to Santoro NThis publication was also made possible by CTSA Grant Number UL1 RR024139 from the National Center for Advancing Translational Science,a component of the National Institutes of Health(NIH),and NIH roadmap for Medical Research,Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NIH
文摘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.
基金Supported by The American Heart Association(AHA),No.13SDG146400382012 Yale Center for Clinical Investigation(YCCI)scholar award to Santoro N+1 种基金CTSA Grant Number UL1 RR024139 from the National Center for Advancing Translational Science(NCATS),a component of the National Institutes of Health(NIH)NIH roadmap for Medical Research
文摘One of the most common complications of childhood obesity is the non-alcoholic fatty liver disease(NAFLD),which is the most common form of liver disease in children.NAFLD is defined by hepatic fat infiltration > 5% hepatocytes,as assessed by liver biopsy,in the absence of excessive alcohol intake,viral,autoimmune and drug-induced liver disease.It encompasses a wide spectrum of liver diseases ranging from simple steatosis to non-alcoholic steatohepatitis,which,in turn,can evolve into cirrhosis and end stage liver disease.Obesity and insulin resistance are the main risk factors for pediatric NAFLD.In fact,NAFLD is strongly associated with the clinical features of insulin resistance especially the metabolic syndrome,prediabetes and type 2 diabetes mellitus(T2D).In particular,it has been clearly shown in obese youth that the prevalence of metabolic syndrome,pre-diabetes and type 2 diabetes increaseswith NAFLD severity progression.Evidence that not all of the obese patients develop NAFLD suggests that the disease progression is likely to depend on complex interplay between environmental factors and genetic predisposition.Recently,a non-synonymous SNP(rs738409),characterized by a C to G substitution encoding an isoleucine to methionine substitution at the amino acid position 148 in the patatin like phospholipase containing domain 3 gene(PNPLA3),has been associated with hepatic steatosis in a multiethnic cohort of adults as well as in children.Another important polymorphisms that acts with PNPLA3 to convey susceptibility to fatty liver in obese youths is the rs1260326 polymorphism in the glucokinase regulatory protein.The pharmacological approach in NAFLD children poorly adherent to or being unresponsive/partially responsive to lifestyle changes,is aimed at acting upon specific targets involved in the pathogenesis.There are some therapeutic approaches that are being studied in children.This article reviews the current knowledge regarding the pediatric fatty liver disease,the new insights and the future directions.
文摘Acute appendicitis is one of the most common indications for abdominal surgery in pediatrics with peak incidence in the second decade of life. Acute appendicitis in the first years of life is an uncommon event. The clinical presentation is often varied and the diagnosis may be overshadowed by other medical conditions.Gastroenteritis is the most common misdiagnosis, with a history of diarrhea present in 33% to 41% of patients. Pain is the most common presenting symptom in children less than 5 years old, followed by vomiting, fever, anorexia and diarrhea. The most common physical sign is focal tenderness(61% of the patients) followed by guarding(55%), diffuse tenderness(39%), rebound(32%), and mass(6%). Neonatal appendicitis is a very rare disease with high mortality; presenting symptoms are nonspecific with abdominal distension representing the main clinical presentation. The younger the patient, the earlier perforation occurs: 70% of patients less than 3 years develop a perforation within 48 h of onset of symptoms. A timely diagnosis reduces the risk of complications. We highlight the epidemiology, pathophysiology, clinical signs and laboratory clues of appendicitis in young children and suggest an algorithm for early diagnosis.
文摘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) levels.AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels.METHODS 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 dose.CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.
文摘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 function.Recently the hydroxysteroid 17-beta dehydrogenase 13(HSD17B13)gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology.In particular,it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children.AIM To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate(eGFR)in obese children.METHODS We enrolled 684 obese children(mean age 10.56±2.94 years;mean BMI-SDS 2.98±0.78)consecutively attending our Obesity Clinic.All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation.To detect hepatic steatosis,a liver ultrasound was performed.NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase(ALT)levels>40 IU/L.The study population was divided on the basis of the NAFLD presence.Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made.RESULTS 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 higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele(P value for intercepts=0.005;P value for slopes=0.94).The same effect was observed among patients without NAFLD(P value for intercepts=0.0012;P value for slopes=0.87).CONCLUSION Carriers of the HSD17B13 rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.
文摘Due its close relationship with obesity,nonalcoholic fatty liver disease(NAFLD)has become a major worldwide health issue even in childhood.The most accepted pathophysiological hypothesis is represented by the“multiple hits”theory,in which both hepatic intracellular lipid accumulation and insulin resistance mainly contribute to liver injury through several factors.Among these,lipotoxicity has gained particular attention.In this view,the pathogenic role of different lipid classes in NAFLD(e.g.,sphingolipids,fatty acids,ceramides,etc.)has been highlighted in recent lipidomics studies.Although there is some contrast between plasma and liver findings,lipidomic profile in the NAFLD context provides novel insights by expanding knowledge in the intricate field of NAFLD pathophysiology as well as by suggesting innovative therapeutic approaches in order to improve both NAFLD prevention and treatment strategies.Selective changes of distinct lipid species might be an attractive therapeutic target for treating NAFLD.Herein the most recent evidence in this attractive field has been summarized to provide a comprehensive overview of the lipidomic scenario in paediatric NAFLD.
文摘The relationship between nonalcoholic fatty liver disease(NAFLD)and chronic kidney disease(CKD)has gained considerable scientific interest in adults over the past few years.However,this association has recently emerged in children.Several 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 diseases.In 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.
文摘Severe acute respiratory syndrome coronavirus 2 infection was declared a pandemic in January 2020.Since 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 population.The“stay at home”rule has impaired healthcare service access,and patients with chronic conditions were the most exposed to the negative effects of this limitation.There is strong evidence of the worsening of obesity and diabetes mellitus in children during this period.To overcome these issues,healthcare providers have changed their clinical practice to ensure follow-up visits and medical consultation though the use of telemedicine.Telemedicine,including telephone calls,videocalls,data platforms of shared telemedicine data platforms mitigated the negative effect of pandemic restrictions.Published evidence has documented good metabolic control and weight management outcomes in centers that performed extensive telemedicine services last year during the pandemic.This review discusses studies that investigated the use of telemedicine tools for the management of pediatric obesity and diabetes.
文摘Acute lobar nephritis(ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children.
文摘BACKGROUND Patients affected by cystic fibrosis can present with metabolic alkalosis such as Bartter's syndrome.In 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 screening.CASE 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 vomiting.Differential diagnosis between cystic fibrosis and tubulopathies causing metabolic alkalosis(Bartter's Syndrome)was considered.We started intravenous rehydration with subsequent improvement of clinical conditions and serum electrolytes normalization.We 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 exposure.CONCLUSION 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.
文摘The rapid global spread of coronavirus disease 2019(COVID-19)infection has become a major health issue with higher morbidity and mortality rates.Besides respiratory symptoms,a growing body of evidence indicates a variety of gastrointestinal manifestations including liver involvement.In 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 evidence.In 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 diseases.The 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 supposed.Of note,patients with previous metabolic comorbidities also had a higher risk of severe COVID-19 infection.This emphasizes the pathogenic interrelation of the inflammatory pathways with a dysregulated metabolic milieu in COVID-19 patients.Taking 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 recommended.We aimed to summarize the most recent evidence regarding the potential interplay between pediatric fatty liver and COVID-19.
文摘In 2020,an international group of experts proposed to replace the term of nonalcoholic fatty liver disease with metabolic-associated fatty liver disease(MAFLD).This recent proposal reflects the close association of fatty liver with metabolic derangements,as demonstrated by previous robust data.Several factors[including genetics,inflammation,metabolic abnormalities,insulin resistance(IR),obesity,prenatal determinants,and gut–liver axis]have been found to be involved in MAFLD pathophysiology,but this tangled puzzle remains to be clearly understood.In particular,IR has been recognized as a key player in metabolic impairments development in children with fatty liver.On this ground,MAFLD definition focuses on the pathophysiological basis of the disease,by emphasizing the crucial role of metabolic impairments in this condition.Although primarily developed for adults,MAFLD diagnostic criteria have been recently updated with an age-appropriate definition for sex and age percentiles,because of the increasing attention to cardiometabolic risk in childhood.To date,accumulating evidence is available on the feasibility of MAFLD definition in clinical practice,but some data are still conflicting in highly selected populations.Considering the growing prevalence worldwide of fatty liver and its close relationship with metabolic dysfunction both in children and adults with subsequent increased cardiovascular risk,early strategies for MAFLD identification,treatment and prevention are needed.Novel therapeutic insights for MAFLD based on promising innovative biological techniques are also emerging.We aimed to summarize the most recent evidence in this intriguing research area both in children and adults.
文摘AIM:To verify the prevalence of thyroid autoimmunity(TA) and the possible association between atopy and TA in children affected by skin disease.METHODS:Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled.One hundred and eighty-seven were diagnosed with atopic dermatitis(AD),95 with acute urticaria,40 with chronic urticaria(CU),and 2 with alopecia areata(AA).According to the work-up for atopy,the children were divided into two groups:Atopics and non-atopics.TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay.RESULTS:In all children with skin disease,a significant prevalence of TA in atopies compared with non-atopies(13.67%vs 2.67%,P=0.0016) and a significant association between TA and atopy(OR=5.76,95%CI:1.71-19.35) were observed.These findings were confirmed as significant in children with AD:TA in atopies was 11.5%,while TA in non-atopies was2.7%(P=0.03,OR=4.68,95%CI:1.02-21.38).In addition,atopics with CU showed a significantly higher prevalence of TA(26.9%),but none of the non-atopics showed CU(P=0.0326).On the other hand,atopies with AA showed a 100%(2 out of 2) prevalence of TA,compared with none of the non-atopies.CONCLUSION:In children with skin disease,atopy seems to be associated with an increased risk of TA.
文摘As a result of the obesity epidemic,non-alcoholic fatty liver disease(NAFLD)represents a global medical concern in childhood with a closely related increased cardiometabolic risk.Knowledge on NAFLD pathophysiology has been largely expanded over the last decades.Besides the well-known key NAFLD genes(including the I148M variant of the PNPLA3 gene,the E167K allele of the TM6SF2,the GCKR gene,the MBOAT7-TMC4 rs641738 variant,and the rs72613567:TA variant in the HSD17B13 gene),an intriguing pathogenic role has also been demonstrated for the gut microbiota.More interestingly,evidence has added new factors involved in the“multiple hits”theory.In particular,omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment.In fact,different branches of omics including metabolomics,lipidomics(in particular sphingolipids and ceramides),transcriptomics(including micro RNAs),epigenomics(such as DNA methylation),proteomics,and glycomics represent the most attractive pathogenic elements in NAFLD development,by providing insightful perspectives in this field.In this perspective,we aimed to provide a comprehensive overview of NAFLD pathophysiology in children,from the oldest pathogenic elements(including genetics)to the newest intriguing perspectives(such as omics branches).
文摘Childhood obesity represents a complex disease with a well-known cardiometabolic burden including fatty liver,type 2 diabetes,metabolic syndrome,and cardiovascular disease.From a pathogenic point of view,insulin resistance(IR)represents the key factor underlying the spectrum of these obesity consequences.As observed in adults,recent data supported the occurrence of microalbuminuria(MA)as marker of early kidney dysfunction and its potential link with cardiometabolic factors also in children with obesity.In fact,a well-documented pathophysiological hypothesis both in adults and children supported an intimate correlation with the major feature of obesity such as IR through the influence of insulin on renal hemodynamics.Based on the clinical and prognostic relevance of this relationship in daily practice(including an increased risk of chronic kidney disease development overtime),more scientific attention needs to be paid to the evaluation of early kidney damage in children with obesity.In this paper,we attempt to address three debated questions regarding the intriguing liaison between IR and MA in children with obesity:(1)What is the prevalence of pediatric MA?(2)What is the state of art of MA in children with obesity?and(3)Is there a link between IR and MA in children with obesity?
文摘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 receptor.Accumulating 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 known.During 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 diseases.Both organs are involved in the common mucosal immune system(including bronchus-associated and gut-associated lymphoid tissues)and their homeostasis is crucial for human health.In this framework,it has been found that the role of GI dysbiosis is affecting the homeostasis of the gutliver axis.Of note,a gut microbiome imbalance has been linked to COVID-19 severity in adult subjects,but it remains to be clarified.Based 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 population.We aimed to summarize the most recent evidence on this striking aspect of COVID-19 in childhood.
文摘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 data.Thus, 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.
文摘AIM:To verify if subclinical hypothyroidism(SCH) could be associated to atopy in children.METHODS:Seven hundred and thirty-two Caucasian children from South Italy presenting symptoms of allergic disease were enrolled and submitted to atopy,obesity,chronic low grade inflammation,and SCH work up.RESULTS:Four hundred and forty-five out of 705(63.12%) children affected by allergic disease were diagnosed as atopic and 260(36.88%) as not atopic.The SCH prevalence was 6.3%.Significant higher prevalence of SCH among atopic children with average(group 2) and high(group 3) low grade chronic inflammation compared to atopic children with mild(group 1)low grade chronic inflammation was present.Moreover,group 1 and group 2 presented an OR to show SCH of2.57(95%CI:1.55-6.26) and 2.96(95%CI:1.01-8.65),respectively.Both in atopic and not atopic children we found C3 serum levels significantly higher in group 3respect to group 2 and group 1.Noteworthy,among atopic patients,also total immunoglobulin E(IgE) serum levels,were significantly higher in group 3 compared to group 2 and group 1 children.In atopic children,C3 and total IgE serum values increased in parallel with the increase of C-reactive protein values,while in not atopic children this phenomenon was not evident.CONCLUSION:The possibility exists that an increasing atopic inflammation contributes to SCH occurrence.So far this is the first report in literature showing an association between SCH and atopy but further studies are needed to confirm our data.
