Functional constipation in children:What physicians should know

Functional constipation(FC)is considered the most common functional gastrointestinal disorder in children with a pooled global prevalence of 14.4%(95%confidence interval:11.2-17.6)when diagnosed based on the Rome IV criteria.Its pathophysiological mechanisms are thought be multifactorial and complicated,resulting in difficult management.Currently,the most effective medication,when used in parallel with toilet training,is osmotic laxatives.Children’s adherence to medication and parental concern regarding long-term laxative use are the main contributors to treatment failure.Recently,novel therapies with a high safety profile have been developed,such as probiotics,synbiotics,serotonin 5-hydroxytryptamine 4 receptor agonists,chloride channel activators,and herbal and transitional medicines;nonetheless,well-designed research to support the use of these therapies is needed.This review aims to focus on multiple aspects of FC in children,including global prevalence,pathogenesis,diagnostic criteria,tools,as well as conventional and novel treatment options,such as non-pharmacological management,including adequate fiber and fluid intake,physiotherapy,or neuromodulators.We also report that in very difficult cases,surgical intervention may be required.

Cohort analysis of pediatric intussusception score to diagnose intussusception

BACKGROUND Intussusception is a primary cause of intestinal obstruction in young children.Delayed diagnosis is associated with increased morbidity.Ultrasonography(USG)is the gold standard for diagnosis,but it is operator dependent and often unavailable in limited resource areas.AIM To study the clinical characteristics of intussusception including management and evaluation of the diagnostic accuracy of abdominal radiography(AR)and the promising parameters found in the pediatric intussusception score(PIS).METHODS Children with suspected intussusception in our center from 2006 to 2018 were recruited.Clinical manifestations,investigations,and treatment outcomes were recorded.AR images were interpreted by a pediatric radiologist.Diagnosis of intussusception was composed of compatible USG and response with reduction.The diagnostic value of the proposed PIS was evaluated.RESULTS Ninety-seven children were diagnosed with intussusception(2.06±2.67 years,62.9%male),of whom 74%were<2 years old and 37.1%were referrals.The common manifestations of intussusception were irritability or abdominal pain(86.7%)and vomiting(59.2%).Children aged 6 mo to 2 years,pallor,palpable abdominal mass,and positive AR were the parameters that could discriminate intussusception from other mimics(P<0.05).Referral case was the only significant parameter for failure to reduce intussusception(P<0.05).AR to diagnose intussusception had a sensitivity of 59.2%.The proposed PIS,a combination of clinical irritability or abdominal pain,children aged 6 mo to 2 years,and compatible AR,had a sensitivity of 85.7%.CONCLUSION AR alone provides poor screening for intussusception.The proposed PIS in combination with common manifestations and AR data was shown to increase the diagnostic sensitivity,leading to timely clinical management.

Gastroesophageal reflux disease in children: What’s new right now?

Gastroesophageal reflux(GER)in children is very common and refers to the involuntary passage of gastric contents into the esophagus.This is often physiological and managed conservatively.In contrast,GER disease(GERD)is a less common pathologic process causing troublesome symptoms,which may need medical management.Apart from abnormal transient relaxations of the lower esophageal sphincter,other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense,impaired esophageal and gastric motility and clearance,as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia.The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation.Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD.The following review focuses on up-to-date information regarding of the pathogenesis,diagnostic evaluation and management of GERD in children.

Prevalence of gastroesophageal reflux disease in children with extraesophageal manifestations using combined-video,multichannel intraluminal impedance-pH study

BACKGROUND Gastroesophageal reflux disease(GERD)might be either a cause or comorbidity in children with extraesophageal problems especially as refractory respiratory symptoms,without any best methods or criterion for diagnosing it in children.AIM To evaluate the prevalence of extraesophageal GERD using conventional and combined-video,multichannel intraluminal impedance-pH(MII-pH),and to propose novel diagnostic parameters.METHODS The study was conducted among children suspected of extraesophageal GERD at King Chulalongkorn Memorial Hospital between 2019 and 2022.The children underwent conventional and/or combined-video MII-pH.The potential parameters were assessed and receiver operating characteristic was used for the significant parameters.RESULTS Of 51 patients(52.9%males),aged 2.24 years were recruited.The common problems were cough,recurrent pneumonia,and hypersecretion.Using MII-pH,35.3%of the children were diagnosed with GERD by reflux index(31.4%),total reflux events(3.9%),and symptom indices(9.8%)with higher symptom recorded in the GERD group(94 vs 171,P=0.033).In the video monitoring group(n=17),there were more symptoms recorded(120 vs 220,P=0.062)and more GERD(11.8%vs 29.4%,P=0.398)by symptom indices.Longest reflux time and mean nocturnal baseline impedance were significant parameters for diagnosis with receiver operating characteristic areas of 0.907(P=0.001)and 0.726(P=0.014).CONCLUSION The prevalence of extraesophageal GERD in children was not high as expected.The diagnostic yield of symptom indices increased using video monitoring.Long reflux time and mean nocturnal baseline impedance are novel parameters that should be integrated into the GERD diagnostic criteria in children.

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.

Immunization status and hospitalization for vaccine-preventable and non-vaccine-preventable infections in liver-transplanted children

BACKGROUND Infections and associated morbidity and mortality may be more frequent in children who have undergone liver transplant than in healthy children.Immunization strategies to prevent vaccine-preventable infections(VPIs)can effectively minimize this infection burden.However,data on age-appropriate immunization and VPIs in children after liver transplant in Asia are limited.AIM To evaluate the immunization status,VPIs and non-VPIs requiring hospitalization in children who have undergone a liver transplant.METHODS The medical records of children who had a liver transplant between 2004 and 2018 at King Chulalongkorn Memorial Hospital(Bangkok,Thailand)were retrospectively reviewed.Immunization status was evaluated via their vaccination books.Hospitalization for infections that occurred up to 5 years after liver transplantation were evaluated,and divided into VPIs and non-VPIs.Hospitalizations for cytomegalovirus and Epstein-Barr virus were excluded.Severity of infection,length of hospital stay,ventilator support,intensive care unit requirement,and mortality were assessed.RESULTS Seventy-seven children with a mean age of 3.29±4.17 years were included in the study,of whom 41(53.2%)were female.The mean follow-up duration was 3.68±1.45 years.Fortyeight children(62.3%)had vaccination records.There was a significant difference in the proportion of children with incomplete vaccination according to Thailand’s Expanded Program on Immunization(52.0%)and accelerated vaccine from Infectious Diseases Society of America(89.5%)(P<0.001).Post-liver transplant,47.9%of the children did not catch up with ageappropriate immunizations.There were 237 infections requiring hospitalization during the 5 years of follow-up.There were no significant differences in hospitalization for VPIs or non-VPIs in children with complete and incomplete immunizations.The risk of serious infection was high in the first year after receiving a liver transplant,and two children died.Respiratory and gastrointestinal systems were common sites of infection.The most common pathogens that caused VPIs were rotavirus,influenza virus,and varicella-zoster virus.CONCLUSION Incomplete immunization was common pre-and post-transplant,and nearly all children required hospitalization for non-VPIs or VPIs within 5 years posttransplant.Infection severity was high in the first year post-transplant.

Immunophenotyping of hematopoietic progenitor cells: Comparison between cord blood and adult mobilized blood grafts

AIM:To study the immunophenotype of hematopoietic progenitor cells from cord blood (CB) grafts (n = 39) in comparison with adult apheresis grafts (AG, n = 229) and pre-apheresis peripheral blood (PAPB) samples (n = 908) using flow cytometry analysis.METHODS: First, we performed a qualitative analysis of CD34+ cell sub-populations in both CB and PAPB grafts using the standardized ISHAGE protocol and a wide panel of 20 monoclonal antibodies. Next, we stud-ied some parameters, such as the age of mothers and the weight of newborns, which can influence the qual-ity and the quantity of CD34+ cells from CB. RESULTS: We found that the percentage of apoptotic cells was high in CB in comparison to PAPB (PAPB: 4.6% ± 2.6% vs CB: 53.4% ± 5.2%, P < 0.001). In CB, the weight of newborn and the age of the mother have the influence on CD34+ cells. The follow-up of Ag CD133in the ISHAGE double platform protocol in association with CD45, CD34 and the 7’AAD shows an equal rate between the two cell populations CD133+CD45+CD34+ high and CD34+CD45+ high with a higher percentage. So, is the inclusion of Ac CD133 necessary in the pres-ent panel included in the ISHAGE methodflLast part, we showed a signif icant presence of interferon γ in CB in comparison to PAPB, the annexin showing the high number of apoptotic cells in CB. CONCLUSION: This study demonstrates that many different obstetric factors must be taken into account when processing and cryo-banking umbilical CB units for transplantation.

Liver tumors in children with chronic liver diseases

Liver tumors are rare in children,but the incidence may increase in some circumstances and particularly in chronic liver diseases.Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma.Other liver tumors include hepatoblastoma,focal nodular hyperplasia,adenoma,pseudotumor,and nodular regenerative hyperplasia.Screening of suspected cases is beneficial.Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance.However,liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings.Once the malignant liver tumor is detected in children with cirrhosis,liver transplantation is currently considered the preferred option and achieves favorable outcomes.Based on the current evidence,this review focuses on liver tumors with underlying chronic liver disease,their epidemiology,pathogenesis,early recognition,and effective management.

Role of microRNA in regulation of myeloma-related angiogenesis and survival

Multiple myeloma(MM)is a malignant disease causedby clonal proliferation of plasma cells that result in monoclonal gammopathy and severe end organ damage.Despite the uniform clinical signs,the disease is very diverse in terms of the nature and sequence of the underlying molecular events.Multiple cellular processes are involved in helping the malignant cells to remain viable and maintain proliferative properties in the hypoxic microenvironment of the bone marrow.Specifically,the process of angiogenesis,triggered by the interactions between the malignant MM cells and the stroma cells around them,was found to be critical for MM progression.In this review we highlight the current understanding about the epigenetic regulation of the proliferation and apoptosis of MM cells and its dependency on angiogenesis in the bone marrow that is carried out by different micro RNAs.

Cytomegalovirus infection in liver-transplanted children

Cytomegalovirus (CMV) infection is a common complication of liver transplantationin children. The CMV serostatus of recipients and donors is theprimary risk factor, and prophylaxis or pre-emptive strategies are recommendedfor high-risk patients. Graft rejection, coinfection and Epstein-Bar virusreactivation, which can lead to post-transplant lymphoproliferative disease, areindirect effects of CMV infection. Assessment of CMV infection viral load shouldbe routinely performed upon clinical suspicion. However, tissue-invasive CMVdisease is not associated with CMV viraemia and requires confirmation by tissuepathology. Oral valganciclovir and intravenous ganciclovir are equivalenttreatments, and the duration of treatment depends on factors including CMV viralload, tissue pathology, and clinical response. Risk stratification by donor andrecipient status prior to transplantation and post-transplantation antiviralprophylaxis or pre-emptive therapy are recommended. Adult guidelines havebeen established but additional study of the effectiveness of the preventiveguidelines in children is needed. This review summarizes the burden, risk factors,clinical manifestations, laboratory evaluation, treatment, and prevention of CMVinfection in children after liver transplantation.

Pediatric liver transplantation outcomes from a single center in Thailand

BACKGROUND Liver transplantation(LT)has become an acceptable curative method for children with several liver diseases,especially irreversible acute liver failure and chronic liver diseases.King Chulalongkorn Memorial Hospital is one of Thailand’s largest liver transplant centers and is responsible for many pediatric cases.AIM To report the experience with pediatric LT and evaluate outcomes of livingrelated vs deceased-donor grafts.METHODS This evaluation included children who underwent LT between August 2004 and November 2019.Data were retrospectively reviewed,including demographics,diagnoses,laboratory values of donors and recipients,the pediatric end-stage liver disease(PELD)or model for end-stage liver disease(MELD)score,graft source,wait time,perioperative course,postoperative complications,and survival rates.Continuous data were reported using the median and interquartile range.The Mann–Whitney U-test was used to compare the wait time between the living-related and deceased-donor groups.The chi-square or Fisher's exact test were used to compare the frequencies of between-group complications.Survival rates were calculated using the Kaplan–Meier method.RESULTS Ninety-four operated pediatric liver transplant patients were identified(54%were females).The median age at transplantation was 1.2(0.8-3.8)years.The median PELD and MELD scores were 20(13-26.8)and 19.5(15.8-26.3),respectively.Most grafts(81.9%)were obtained from living-related donors.The median wait time for the living donors was significantly shorter compared with the deceased donors at 1.6(0.3-3.1)mo vs 11.2(2.1-33.3)mo(P=0.01).Most patients were diagnosed with biliary atresia(74.5%),and infection was the most common complication within 30 d posttransplantation(14.9%).Without a desensitization protocol,9%of transplants were ABOincompatible.Eight hepatitis B core antibodies(anti-HBc)-negative recipients received positive anti-HBc grafts without different observed complications.The overall survival rate was 93.6%and 90.3%at 1 and 5 years,respectively.No graft loss during follow-up was noted among survivors.CONCLUSION A significant number of pediatric LT cases were reported in Thailand.Based on relatively comparable outcomes,ABO-incompatible and HBc antibody-positive grafts may be considered in an organ shortage situation.

Historical evolution,overview,and therapeutic manipulation of costimulatory molecules

Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved.

Serum levels of chemokines in adolescents with major depression treated with fluoxetine

BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.The inflammatory response contributes to the onset of depression,and in adult MDD patients,symptom severity has been linked to chemokine levels.AIM To determine the differences in circulatory levels of chemokines in healthy volunteers(HVs)and adolescents with MDD,and assess the changes induced by fluoxetine consume.METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale(HDRS).The serum levels of monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP)-1α,MIP-1β,interleukin(IL)-8,interferon gamma-induced protein(IP)-10,and eotaxin were measured in patients and HVs.RESULTS In all cases,significant differences were detected in circulating chemokine levels between patients before treatment and HVs(P<0.0001).All chemokines decreased at 4 wk,but only MCP-1 and IL-8 significantly differed(P<0.05)between 0 wk and 4 wk.In the patients,all chemokines rose to their initial concentrations by 8 wk vs 0 wk,but only IP-10 did so significantly(P<0.05).All patients experienced a significant decrease in HDRS scores at 4 wk(P<0.0001)and 8 wk(P<0.0001)compared with 0 wk.CONCLUSION Despite the consumption of fluoxetine,patients had significantly higher chemokine levels,even after considering the improvement in HDRS score.The high levels of eotaxin,IP-10,and IL-8 partially explain certain aspects that are affected in MDD such as cognition,memory,and learning.