Arterial structure and function in children with inflammatory bowel disease.

Background and Aim: People with inflammatory bowel disease (IBD) have an increased risk of cardiovascular disease, including in younger adulthood. This may arise in part from chronic, systemic low-grade inflammation. The process of atherosclerosis may begin in childhood. We sought to determine whether pediatric IBD is associated with adverse changes in arterial structure and function as a marker of early increased cardiovascular risk. Methods: We performed a case-control study comparing children with IBD for a median disease duration of 2.49 (interquartile range 1.23, 4.38) years with healthy children. In a single visit, we collected baseline clinical and anthropometric data, and measured blood pressure, pulse wave velocity, carotid artery distensibility, and aortic and carotid intima-media thickness. High-sensitivity C-reactive protein and fasting lipids were measured. Results: We enrolled 81 children with IBD (40 with Crohn's disease, 40 with ulcerative colitis, and 1 with unspecified IBD) and 82 control participants. After adjusting for age, sex, body mass index z-score, blood pressure, and low-density lipoprotein cholesterol, there was no difference in measures of arterial structure and function in children with IBD compared with controls, nor between those with Crohn's disease or ulcerative colitis. Conclusion: We did not show any differences in arterial structure and function in children with a history of IBD for less than 5 years compared with healthy controls. IBD diagnosed in childhood may provide a window of opportunity to actively reduce standard cardiovascular risk factors and improve future cardiovascular outcomes.

Distinct diagnostic trajectories in NBAS-associated acute liver failure highlights the need for timely functional studies.

Variants of uncertain significance (VUS) are commonly found following genomic sequencing, particularly in ethnically diverse populations that are underrepresented in large population databases. Functional characterization of VUS may assist in variant reclassification, however these studies are not readily available and often rely on research funding and good will. We present four individuals from three families at different stages of their diagnostic trajectory with recurrent acute liver failure (RALF) and biallelic NBAS variants, confirmed by either trio analysis or cDNA studies. Functional characterization was undertaken, measuring NBAS and p31 levels by Western blotting, demonstrating reduced NBAS levels in two of three families, and reduced p31 levels in all three families. These results provided functional characterization of the molecular impact of a missense VUS, allowing reclassification of the variant and molecular confirmation of NBAS-associated RALF. Importantly, p31 was decreased in all individuals, including an individual with two missense variants where NBAS protein levels were preserved. These results highlight the importance of access to timely functional studies after identification of putative variants, and the importance of considering a range of assays to validate variants whose pathogenicity is uncertain. We suggest that funding models for genomic sequencing should consider incorporating capabilities for adjunct RNA, protein, biochemical, and other specialized tests to increase the diagnostic yield which will lead to improved medical care, increased equity, and access to molecular diagnoses for all patients.

Chronic diarrhoea in children: A practical algorithm-based approach.

Diarrhoea is a leading cause of morbidity and mortality world-wide. Most diarrhoeal episodes are acute and infectious in origin. Diarrhoea lasting for longer than 4 weeks with no discernible infectious aetiology warrants thorough evaluation. The aim of this review is to elucidate an approach to evaluation of diarrhoea based on its pathophysiologic mechanisms with focus on aetiology, investigation and management of chronic diarrhoea. It includes a brief description of normal fluid homeostasis in the gut and pathophysiology of diarrhoea. Further, diarrhoea is classified as 'watery', 'fatty' and 'bloody' based on stool characteristics. Relevant history, physical examination findings, first and second-line investigations which help in differentiating the different types of diarrhoea are listed and an algorithmic approach to individual types of diarrhoea has been devised. Principles of management and recent advances in diagnostics and therapeutics of diarrhoea are briefly discussed.

The burden of surgery and postoperative complications in children with inflammatory bowel disease.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) may be associated with a higher burden of surgery and postoperative complications. This study aimed to measure the burden in pediatric IBD over a 20-year period in a large tertiary referral center. METHODS: A retrospective review was conducted of children diagnosed with IBD between 1996 and 2015, with a focus upon operative intervention (excluding endoscopy) and postoperative outcomes. RESULTS: Of 786 IBD patients, 121/581 (20.8%) with Crohn's disease (CD) and 22/205 (10.7%) with ulcerative colitis (UC) underwent surgery during the study period. When comparing 10-year epochs for CD, median time from diagnosis to intervention decreased from 34 months to 3 months (P < 0.0001). Postoperative complications occurred in 16/121 (13%) CD patients (bowel obstruction: 10, anastomotic stricture: 4, stomal issues: 4, anastomotic leak: 1). Within the UC cohort, the median time from diagnosis to intervention decreased from 62 months to 6 months (P = 0.0019). Postoperative complications occurred in 9/22 (41%) UC patients (bowel obstruction: 7, stomal issues: 3, anastomotic stricture: 1). Compared with CD, complications were more frequent in UC patients (P = 0.004). CONCLUSION: Surgery and postoperative complications are common in pediatric IBD. The timing of intervention has trended towards earlier operations in both CD and UC. LEVEL OF EVIDENCE: Treatment study-level III (retrospective comparative study).

Secondary Loss of Response to Infliximab in Pediatric Crohn Disease: Does It Matter How and When We Start?

OBJECTIVES: A significant proportion of children with Crohn disease develop a secondary loss of response (LOR) to infliximab. Our aim was to study the impact of initial treatment strategies on secondary LOR. METHODS: We reviewed the medical records of children with Crohn disease who received scheduled maintenance infliximab therapy for at least 12 months. We compared children who developed LOR with those who did not; with regards to their clinical and laboratory parameters, disease phenotype, and treatment strategy before developing LOR. RESULTS: A total of 73 children (median age at diagnosis 11 (2-16) years, 41 boys) who had received a median duration of 33 (13-110) months of infliximab therapy were included in the final analysis. LOR was seen in 25(34.2%). Demographic variables, disease phenotype (age, disease location, and behavior), inflammatory parameters, and pediatric Crohn disease activity index at induction with infliximab were similar between both groups. Children with LOR had a significantly greater number of flares of the disease when compared to those who did not have LOR (4 [1-8] vs 2 [1-5] P = 0.03). The choice of the concomitant immunomodulator-methotrexate (11/29 [37.9%]) versus azathioprine (11/36 [30.5%]) (P = 0.6) did not affect LOR rates. The median time-lag between diagnosis and induction with infliximab was significantly longer in children with LOR as compared to those who did not have an LOR (28 [4-90] months vs 12.5 [1-121] months, P = 0.004). CONCLUSION: Early use of infliximab in pediatric Crohn disease is associated with a decrease in secondary LOR. The type of concomitant immunomodulator used does not make a difference to LOR rates.

Paediatric MRCP: 10 year experience with 195 patients.

PURPOSE: Magnetic resonance cholangiopancreatography (MRCP) has now largely substituted endoscopic retrograde cholangiopancreatography (ERCP) in evaluating the biliary tree in adults giving its high sensitivity and specificity. Whilst smaller series published to date suggests this may be extrapolated to the paediatric population, its routine use in children is still debatable. The aim of our study is therefore to review the utility of MRCP in a large series of paediatric patients. METHODS AND MATERIALS: All MRCPs performed in our institution were examined for diagnostic quality, spectrum of diagnoses and correlation with direct cholangiography (DC) were available. Correlation with histopathology results and final clinical diagnosis was made in the subset of patients in whom a MRCP had been performed to evaluate the presence of primary sclerosing cholangitis (PSC). RESULTS: There were 245 MRCP examinations performed on 195 patients and 219 were diagnostic. There was 100% MRCP and DC concordance in the 16 cases where both had been performed. MRCP yielded a sensitivity of 89% in the subset of patients with PSC. CONCLUSION: MRCP was a valuable diagnostic tool in our paediatric population. Image quality is sufficiently diagnostic and shows good correlation with clinical diagnosis in conditions encountered in our population, including primary sclerosing cholangitis, post liver transplant biliary strictures, post surgical complications, dilated common bile ducts, choledochal cysts, cholelithiasis and choledocholithaisis.

Cardiac cirrhosis and hepatocellular carcinoma in a 13-year-old treated with doxorubicin microbead transarterial chemoembolization.

Increasing numbers of children are surviving into adulthood following surgery to correct or palliate congenital heart disease. This surgery can occasionally result in long-standing elevated right heart pressures and chronic hepatic venous congestion leading to cardiac cirrhosis. We report the first paediatric case of hepatocellular carcinoma in the setting of cardiac cirrhosis. A 13-year-old girl developed inoperable hepatocellular carcinoma and was treated with transarterial embolization with lipiodol and doxorubicin eluting microbeads. Promoting awareness of this association, even in younger patients, will hopefully result in better surveillance and screening of hepatic complications in survivors of complex cardiac surgery.

Emerging management concepts for eosinophilic esophagitis in children.

Eosinophilic esophagitis (EoE) is a newly recognized condition that appears to be increasing in incidence for as yet unknown reasons. It can occur at any age and presents both to gastroenterologists and allergists. Clinical manifestations range from gastrointestinal symptoms (vomiting, feeding difficulties, dysphagia or food bolus impaction) to co-existing atopic conditions (asthma, allergic rhinitis or eczema). The diagnosis requires demonstration of at least 15 eosinophils per high power field on esophageal histology, usually in the context of resistance to proton pump inhibitor treatment or a normal 24-h esophageal pH monitoring study. The differential diagnosis between EoE and gastroesophageal reflux disease (GERD) can be problematic as there is significant clinical overlap between both conditions. Although difficult-to-manage esophageal strictures are well recognized in patients with long-standing EoE, little is known about risk factors for the development of this complication. There is a paucity of data on both the natural history and optimal long-term management of EoE. Current treatment options include food allergen elimination diets, use of topical aerosolized corticosteroids, or a combination of the two. Pediatric case studies have been provided to illustrate the complexity of decision points that often arise in the management of these patients. This paper aims to discuss the various strategies currently available to clinicians in the management of EoE and highlights gaps in the current evidence base that urgently require further research.

Drug rash with eosinophilia and systemic symptoms secondary to sulfasalazine.

A severe cutaneous eruption in an unwell patient can be a major cause of physician anxiety. With numerous differential diagnoses, an early accurate diagnosis can be challenging. infectious causes are the most important to exclude in a timely manner and drug rash and eosinophilia with systemic symptoms (DRESS) is another differential diagnosis that should be considered in children. This hypersensitivity reaction is associated with multisystem involvement. Children with underlying chronic diseases may have impairment of normal metabolic pathways and are also often on multiple medications. Therefore, drugs should always be considered in the aetiopathology of any new symptoms and signs. This case report informs readers of the association of sulfasalazine and DRESS in an 11-year-old with inflammatory bowel disease and discusses its pathogenesis and treatment. Increased awareness of this disorder will hopefully lead to increased reporting and consequently illuminate the syndrome more clearly and help guide its prevention and treatment.

Ursodeoxycholic acid's role in avoiding diversionary surgery in idiopathic fibrosing pancreatitis.

Obstructive jaundice in childhood is rare but a cause of great concern and warrants aggressive investigation into its aetiology. Idiopathic fibrosing pancreatitis (IFP) is a rare cause of this phenomenon and is presently a diagnosis of exclusion with lymphoma a main differential diagnosis. IFP appears to be a self limiting occurrence and as a result the previous gold standard of therapy of surgical diversion may ultimately be unnecessary. We describe ursodeoxycholic acid as a useful adjunct to treatment allowing more time for clinicians to evaluate the nature of the underlying disease process without hastily moving towards invasive surgery until clearly indicated.