Imaging and endoscopic tools in pediatric inflammatory bowel disease: What’s new?

Pediatric inflammatory bowel disease(IBD)is a chronic inflammatory disorder,with increasing incidence and prevalence worldwide.There have been recent advances in imaging and endoscopic technology for disease diagnosis,treatment,and monitoring.Intestinal ultrasound,including transabdominal,transperineal,and endoscopic,has been emerging for the assessment of transmural bowel inflammation and disease complications(e.g.,fistula,abscess).Aside from surgery,IBD-related intestinal strictures now have endoscopic treatment options including through-the-scope balloon dilatation,injection,and needle knife stricturotomy and new evaluation tools such as endoscopic functional lumen imaging probe.Unsedated transnasal endoscopy may have a role in patients with upper gastrointestinal Crohn’s disease or those with IBD with new upper gastrointestinal symptoms.Improvements to dysplasia screening in pediatric patients with longstanding colonic disease or primary sclerosing cholangitis hold promise with the addition of virtual chromoendoscopy and ongoing research in the field of artificial intelligence-assisted endoscopic detection.Artificial intelligence and machine learning is a rapidly evolving field,with goals of further personalizing IBD diagnosis and treatment selection as well as prognostication.This review summarized these advancements,focusing on pediatric patients with IBD.

Pediatric stricturing Crohn's disease

Crohn’s disease(CD)is a chronic inflammatory disease of the digestive tract.The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide.Notably,approximately 25%of children with CD develop stricturing CD(SCD)that requires intervention.Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions.Non-pharmacological therapeutic strategies include endoscopic balloon dilatation,stricturoplasty,and surgical resection of the strictured seg-ment.However,strictures tend to recur postoperatively regardless of treatment modality.The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%.Thus,new and emerging strategies,advanced diagnostic tools,and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Health Systems Strengthening to Tackle the Global Burden of Pediatric and Congenital Heart Disease: A Diagonal Approach

1 Background Congenital heart disease(CHD)is the most common major congenital anomaly,affecting approximately one in every 100 live births[1].Among congenital anomalies,66%of preventable deaths are due to CHD,and 58%of the avertable morbidity and mortality due to congenital anomalies would result from scaling congenital heart surgery services[2].Every year,nearly 300,000 children and adults die from CHD,the majority of whom live in low-and middle-income countries(LMICs)[3].Approximately 49%of all individuals with CHD will require surgical or interventional care at some point in their lifetime[4];as a result of advances in access to and the delivery of such services,over 95%of children born with CHD in high-income countries now live into adulthood[3].Here,adults have surpassed children in the number of CHD cases at a ratio of 2:1[5].

Inpatient management of iron deficiency anemia in pediatric patients with inflammatory bowel disease: A single center experience

BACKGROUND Screening for iron deficiency anemia(IDA)is important in managing pediatric patients with inflammatory bowel disease(IBD).Concerns related to adverse reactions may contribute to a reluctance to prescribe intravenous(IV)iron to treat IDA in this population.AIM To track the efficacy and safety of IV iron therapy in treating IDA in pediatric IBD patients admitted to our center.METHODS A longitudinal observational cohort study was performed on 236 consecutive pediatric patients admitted to our tertiary IBD care center between September 2017 and December 2019.92 patients met study criteria for IDA,of which 57 received IV iron,17 received oral iron,and 18 were discharged prior to receiving iron therapy.RESULTS Patients treated with IV iron during their hospitalization experienced a significant increase of 1.9(±0.2)g/dL in mean(±SE)hemoglobin(Hb)concentration by the first ambulatory follow-up,compared to patients who received oral iron 0.8(±0.3)g/dL or no iron 0.8(±0.3)g/dL(P=0.03).One out of 57(1.8%)patients that received IV iron therapy experienced an adverse reaction.CONCLUSION Our findings demonstrate that treatment with IV iron therapy is safe and efficacious in improving Hb and iron levels in pediatric patients with IDA and active IBD.

Fecal calprotectin in pediatric gastrointestinal diseases:Pros and cons

BACKGROUND Fecal calprotectin is a valuable biomarker for assessing intestinal inflammation in pediatric gastrointestinal diseases.However,its role,pros,and cons in various conditions must be comprehensively elucidated.AIM To explore the role of fecal calprotectin in pediatric gastrointestinal diseases,including its advantages and limitations.METHODS A comprehensive search was conducted on PubMed,PubMed Central,Google Scholar,and other scientific research engines until February 24,2024.The review included 88 research articles,56 review articles,six metaanalyses,two systematic reviews,two consensus papers,and two letters to the editors.RESULTS Fecal calprotectin is a non-invasive marker for detecting intestinal inflammation and monitoring disease activity in pediatric conditions such as functional gastrointestinal disorders,inflammatory bowel disease,coeliac disease,coronavirus disease 2019-induced gastrointestinal disorders,gastroenteritis,and cystic fibrosis-associated intestinal pathology.However,its lack of specificity and susceptibility to various confounding factors pose challenges in interpretation.Despite these limitations,fecal calprotectin offers significant advantages in diagnosing,monitoring,and managing pediatric gastrointestinal diseases.CONCLUSION Fecal calprotectin holds promise as a valuable tool in pediatric gastroenterology,offering insights into disease activity,treatment response,and prognosis.Standardized protocols and guidelines are needed to optimize its clinical utility and mitigate interpretation challenges.Further research is warranted to address the identified limitations and enhance our understanding of fecal calprotectin in pediatric gastrointestinal diseases.

Home-Nebulized Inhaled Glucocorticoid Therapy in Pediatric Respiratory Diseases

Objective:To evaluate the therapeutic effect of home-nebulized inhaled glucocorticoid therapy in pediatric respiratory diseases.Methods:60 cases of children with respiratory diseases admitted between October 2022 and October 2023 were selected as study subjects and randomly divided into the control group and the observation group,30 cases each.The control group was provided with conventional treatment only,while the observation group was provided with home-nebulized inhalation glucocorticosteroid treatment,and the treatment effects,clinical symptom relief time,disease recurrence rate,and treatment satisfaction of the children’s families were recorded and compared between the two groups.Results:A comparison of the two groups in terms of gender and age showed that the differences were not statistically significant(P>0.05).In terms of clinical efficacy,the total effective rate of the observation group was 90.00%,which was significantly higher than that of the control group of 66.67%(P<0.05).Compared with the control group,the disappearance time of the clinical symptoms of the observed group was significantly shortened(P<0.05).In addition,the satisfaction scores of the families of the children in the observation group were significantly higher than those of the control group(P<0.05).Conclusion:Home-nebulized inhalation glucocorticoid therapy shows significant clinical efficacy in pediatric respiratory diseases,significantly reduces the time of disappearance of clinical symptoms,and improves the satisfaction of patients’families,which provides an effective treatment option for children.

Response to strict and liberalized specific carbohydrate dietin pediatric Crohn's disease

AIM: To investigate the specific carbohydrate diet(SCD) as nutritional therapy for maintenance of remission in pediatric Crohn's disease(CD). METHODS: Retrospective chart review was conducted in 11 pediatric patients with CD who initiated the SCD as therapy at time of diagnosis or flare. Two groups defined as SCD simple(diet alone, antibiotics or 5-ASA) or SCD with immunomodulators(corticosteroids and/or stable thiopurine dosing) were followed for one year and compared on disease characteristics, laboratory values and anthropometrics.RESULTS: The mean age at start of the SCD was 11.8 ± 3.0 years(range 6.6-17.6 years) with five patients starting the SCD within 5 wk of diagnosis. Three patients maintained a strict SCD diet for the study period and the mean time for liberalization was 7.7 ± 4.0 mo(range 1-12) for the remaining patients. In both groups, hematocrit, albumin and ESR values improved while on strict SCD and appeared stable after liberalization(P-value 0.006, 0.002, 0.002 respectively). The majority of children gained in weight and height percentile while on strict SCD, with small loss in weight percentile documented with liberalization. CONCLUSION: Disease control may be attainable with the SCD in pediatric CD. Further studies are needed to assess adherence, impact on mucosal healing and growth.

Transmission Dynamics and Optimal Control Strategies of a Hand-Foot-Mouth Disease Model with Treatment and Vaccination Interventions

In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.

Efficacy of early treatment with infliximab in pediatric Crohn’s disease

AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and maintenance therapy for the first year, and were treated with azathioprine after 1 year. All patients were followed for at least 24 mo. Efficacy was determined by the relapse rate using the pediatric Crohn’s disease activity index score in each group at 12 and 24 mo. RESULTS: At the 1 year follow-up, the relapse ratee, Mi Jin Kim, Hae Jeong Lee, Yon Ho Choe (23.1%, 3 of 13 patients) in group C was lower than that (61.5%, 8 of 13 patients) in group B (P = 0.047). At the 2 years follow-up, the relapse rate (38.5%, 5 of 13 patients) in group C was lower than that (76.9%, 10 of 13 patients) in group B (P = 0.047). Adverse events in group C were fewer than in groups A and B. CONCLUSION: Early induction with infliximab at diagnosis, known as "top-down" therapy, was effective for reducing the relapse rate compared to conventional therapies for at least 2 years.

Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review

Upper gastrointestinal(UGI) tract involvement of inflammatory bowel disease(IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis(UC), atypical UC, Crohn's disease(CD) and IBD unclassified.Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid(non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD,is histologically characterized by increased intraepithelial lymphocytes(> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis,villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.

Inflammatory bowel disease in pediatric and adolescent patients:A biomolecular and histopathological review

Crohn&#x02019;s disease (CD) and ulcerative colitis (UC) are the two main forms of inflammatory bowel disease (IBD) with both overlapping and distinct clinical, pathological and biomolecular features. It has been suggested that pediatric IBD is a distinct disease entity, with probably different disease subtypes.The aim of this study is to review and summarize the evolution of the current concept of pediatric IBD. The results of this review reinforce the idea that pediatric CD and UC may be further classified in various clinicopathologic entities. For clinicians and pathologists convenience, practical algorithms for the distinction of the various subphenotypes of pediatric IBD are also provided.

Understanding the pathophysiological mechanisms in the pediatric non-alcoholic fatty liver disease: The role of genetics

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.

Beyond the Pediatric end-stage liver disease system: Solutions for infants with biliary atresia requiring liver transplant

Biliary atresia(BA), a chronic progressive cholestatic disease of infants, is the leading cause for liver transplant in children, especially in patients under two years of age. BA can be successfully treated with the Kasai portoenterostomy; however most patients still require a liver transplant, with up to one half of BA children needing a transplant by age two. In the current pediatric end-stage liver disease system, children with BA face the risk of not receiving a liver in a safe and timely manner. In this review, we discuss a number of possible solutions to help these children. We focus on two general approaches:(1) preventing/delaying need for transplantation, by optimizing the success of the Kasai operation; and(2) expediting transplantation when needed, by performing techniques other than the standard deceased-donor, whole, ABO-matched organ transplant.

Pediatric inflammatory bowel disease

Inflammatory bowel disease is an important cause of gastrointestinal pathology in children and adolescents. The incidence of pediatric inflammatory bowel disease is increasing; therefore, it is important for the clinician to be aware of the presentation of this disease in the pediatric population. Laboratory tests, radiology studies, and endoscopic procedures are helpful in diagnosing inflammatory bowel disease and differentiating between Crohn＇s disease and ulcerative colitis. Once diagnosed, the goal of medical management is to induce remission of disease while minimizing the side effects of the medication. Specific attention needs to be paid to achieving normal growth in this susceptible population. Surgical management is usually indicated for failure of medical management, complication, or malignancy. Algorithms for diagnostic evaluation and treatment of pediatric inflammatory bowel disease are presented. The specific psychosocial issues facing these patients are also discussed in this review as are the future goals of research in the complex problem of pediatric inflammatory bowel disease.

Dietary supplements and pediatric non-alcoholic fatty liver disease: Present and the future

Non-alcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in children.High prevalence of pediatric obesity and sedentary lifestyle has augmented the incidence of NAFLD in children.Obesity is associated with an increased risk of NAFLD through various mechanisms such as intensification of insulin resistance and increased levels of inflammatory markers.There is no approved medical intervention for treatment of pediatric NAFLD;the only proven strategy in management of pediatric NAFLD is lifestyle modification.Recently,the effects of nutritional supplements have been examined in the management of pediatric NAFLD.The purpose of this review is to summarize the studies evaluating the effects of nutritional supplements on pediatric NAFLD and explain the future direction in this field.

Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn&#x02019;s disease (CD) and the effect of transforming growth factor-&#x003b2; (TGF-&#x003b2;) on these miRs in duodenal epithelial and fibroblast cells.METHODS: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-&#x003b2; (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as well.RESULTS: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 &#x000b1; 0.50 vs CD intact: 0.62 &#x000b1; 0.26, P &#x02264; 0.01) and to the control group (CD inflamed: 3.21 &#x000b1; 0.50 vs C: 1.00 &#x000b1; 0.33, P &#x02264; 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 &#x000b1; 1.02 vs Control: 1.00 &#x000b1; 0.40, P &#x02264; 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-&#x003b2; treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-&#x003b2;: 0.7 &#x000b1; 0.083 vs Control: 1 &#x000b1; 0.09, P &#x02264; 0.05) and also the expression of miR-146a (TGF-&#x003b2;: 0.67 &#x000b1; 0.04 vs Control: 1 &#x000b1; 0.15, P &#x02264; 0.01) and miR-155 (TGF-&#x003b2;: 0.72 &#x000b1; 0.09 vs Control: 1 &#x000b1; 0.06, P &#x02264; 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated controls. TGF-&#x003b2; treatment did not influence the expression of miR-122.CONCLUSION: The elevated expression of miR-146a and -155 in the inflamed duodenal mucosa of CD patients suggests the role of these miRs in the pathomechanism of inflammatory bowel disease. Anti-inflammatory TGF-&#x003b2; plays an important role in the regulation of the expression of these miRs.

Cardiac biomarkers in pediatric heart disease:A state of art review

Every year there are more than 11000 hospitalizations related to heart failure in children resulting in significant morbidity and mortality.Over the last two decades,our understanding,diagnosis and management of pediatric heart failure is evolving but our ability to prognosticate outcomes in pediatric heart acute heart failure is extremely limited due to lack of data.In adult heart failure patients,the role of cardiac biomarkers has exponentially increased over the last two decades.Current guidelines for management of heart failure emphasize the role of cardiac biomarkers in diagnosis,management and prognostication of heart failure.It is also noteworthy that these biomarkers reflect important biological processes that also open up the possibility of therapeutic targets.There is however,a significant gap present in the pediatric population with regards to biomarkers in pediatric heart failure.Here,we seek to review available data regarding cardiac biomarkers in the pediatric population and also explore some of the emerging biomarkers from adult literature that may be pertinent to pediatric heart failure.

Recent management of urinary stone disease in a pediatric population

The incidence of stone disease has been increasing and the risk of recurrent stone formation is high in a pediatric population. It is crucial to use the most effective method with the primary goal of complete stone removal to prevent recurrence from residual fragments. While extracorporeal shock wave lithotripsy(ESWL) is still considered first line therapy in many clinics for urinary tract stones in children, endoscopic techniques are widely preferred due to miniaturization of instruments and evolution of surgical techniques. The standard procedures to treat urinary stone disease in children are the same as those used in an adult population. These include ESWL, ureterorenoscopy, percutaneous nephrolithotomy(standard PCNL or mini-perc), laparoscopic and open surgery. ESWL is currently the procedure of choice for treating most upper urinary tract calculi in a pediatric population. In recent years, endourological management of pediatric urinary stone disease is preferred in many centers with increasing experience in endourological techniques and decreasing sizes of surgical equipment. The management of pediatric stone disease has evolved with improvements in the technique and a decrease in the size of surgical instru-ments. Recently, endoscopic methods have been safely and effectively used in children with minor complications. In this review, we aim to summarize the recent management of urolithiasis in children.

Fecal microbial transplant for the treatment of pediatric inflammatory bowel disease

The role of fecal microbial transplant(FMT) in the treatment of pediatric gastrointestinal disease has become increasingly popular among pediatric practitioners, patients, and parents. The success of FMT for the treatment of recurrent Clostridium difficile infection(RCDI) has bolstered interest in its potential application to other disease states, such as inflammatory bowel disease(IBD). FMT has particular interest in pediatrics, given the concerns of patients and parents about rates of adverse events with existing therapeutic options, and the greater cumulative medication burden associated with childhoodonset disease. Published literature on the use of FMT in pediatrics is sparse. Only 45 pediatric patients treated for RCDI have been reported, and only 27 pediatric patients with pediatric IBD. The pediatric microbiome may uniquely respond to microbial-based therapies. This review will provide a comprehensive overview of fecal microbial transplant and its potential role in the treatment of pediatric inflammatory bowel disease. We will discuss the microbiome in pediatric inflammatory bowel disease, existing adult and pediatric literature on the use of FMT in IBD treatment, and pediatric FMT trials that are currently recruiting patients. This review will also discuss features of the microbiome that may be associated with host response in fecal transplant, and potential challenges and opportunities for the future of FMT in pediatric IBD treatment.

MicroRNA-15a-cell division cycle 42 signaling pathway in pathogenesis of pediatric inflammatory bowel disease

AIM To determine whether cell division cycle(Cdc)42 is regulated by microRNA(miR)-15 a in the development of pediatric inflammatory bowel disease(IBD).METHODS We cultured 293 T cells, used plasmids and performed dual-luciferase assay to determine whether Cdc42 is a miR-15 a target gene. We cultured Caco-2 cells, and stimulated them with tumor necrosis factor(TNF)-α. We then employed lentiviruses to alter the expression of miR-15 a and Cdc42. We performed quantitative reverse transcription polymerase chain reaction(qRTPCR) and immunofluorescence to determine whether Cdc42 is regulated by miR-15 a in Caco-2 cells. Finally, we collected ileocecal tissue by endoscopy from patients and performed qRT-PCR to examine the expression of miR-15 a and Cdc42 in pediatric IBD patients.RESULTS Target Scan and dual-luciferase assay revealed thatCdc42 was a miR-15 a target gene. MiR-15 a expression increased(P = 0.0038) and Cdc42 expression decreased(P = 0.0013) in cells stimulated with TNF-α, and the expression of the epithelial junction proteins zona occludens(ZO)-1(P < 0.05) and E-cadherin(P < 0.001) decreased. Cdc42 levels decreased in miR-15 a-mimic cells(P < 0.001) and increased in miR-15 a inhibitor cells(P < 0.05). ZO-1 and E-cadherin decreased in mi R-15 a-mimic cells(P < 0.001) but not in the miR-15 a inhibitor + TNF-α cells. In Lv-Cdc42 + TNF-α cells, ZO-1 and E-cadherin expression increased compared to the Lv-Cdc42-NC + TNF-α(P < 0.05) or miR-15 a-mimic cells(P < 0.05). Fifty-four pediatric IBD patients were included in this study, 21 in the control group, 19 in the Crohn's disease(CD) active(AC) group, seven in the CD remission(RE) group, and seven in the ulcerative colitis(UC) group. MiR-15 a increased and Cdc42 decreased in the CD AC group compared to the control group(P < 0.05). miR-15 a decreased and Cdc42 increased in the CD RE group compared to the CD AC group(P < 0.05). miR-15 a was positively correlated with the Pediatric Crohn's disease Activity Index(PCDAI)(P = 0.006), while Cdc42 was negatively correlated with PCDAI(P = 0.0008). Finally, miR-15 a expression negatively correlated with Cdc42 in pediatric IBD patients(P = 0.0045).CONCLUSION Mi R-15 a negatively regulates epithelial junctions through Cdc42 in Caco-2 cells and pediatric IBD patients.