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.
Homozygous familial hypercholesterolaemia (FH) causes severe cardiovascular disease from childhood. Conventional drug therapy is usually ineffective; lipoprotein apheresis (LA) is often required. ...Liver transplantation (LT) can correct the metabolic defect but is considered a treatment of last resort. Newer drugs including lomitapide and evinacumab might reduce the need for apheresis and LT. We sought to determine the long-term outcomes following LT in Australia and New Zealand.
We analysed demographic, biochemical and clinical data from all patients in Australia and New Zealand who have received LT for homozygous FH, identified from the Australia and New Zealand Liver and Intestinal Transplant Registry.
Nine patients (five female; one deceased; seven aged between 3 and 6 years at the time of LT and two aged 22 and 26 years) were identified. Mean follow-up was 14.1 years (range 4-27). Baseline LDL-cholesterol off all treatment was 23 ± 4.1 mmol/L. Mean LDL-cholesterol on medical therapy (including maximal statin therapy in all patients, ezetimibe in three and LA in five) was 11 ± 5.7 mmol/L (p < 0.001). After LT, mean LDL-cholesterol was 2.6 ± 0.9 mmol/L (p = 0.004) with three patients remaining on statin therapy and none on LA. One patient died from acute myocardial infarction (AMI) three years after LT. Two patients required aortic valve replacement, more than 10 years after LT. The remaining six patients were asymptomatic after eight to 21 years of follow-up. No significant adverse events associated with immunosuppression were reported.
LT for homozygous FH was highly effective in achieving substantial long-term reduction in LDL-cholesterol concentrations in all nine patients. LT remains an option for severe cases of homozygous FH where drug therapy combined with apheresis is ineffective or unfeasible.
Children with liver disease can develop severe bleeding episodes and thrombosis. Liver failure usually results in decreased levels of procoagulant and anticoagulant factors. Additional risk factors, ...including changes in vascular flow and endothelial function, are of importance for the development of bleeding or thrombosis in individual vascular beds. Detailed studies of haemostatic disturbances in the setting of paediatric liver disease are sparse and extrapolation from adult studies is common. The spectrum of liver diseases and the haemostatic system differs between children and adults. Specific paediatric liver diseases are reported to have more distinctive effects on haemostasis and the risk of bleeding and/or thrombosis. Conclusion: we propose a model regarding haemostasis in paediatric liver disease, taking into account a number of specific variables and mechanisms, as well as the type of liver disease, which will provide a framework for clinical decision-making in these complex patients.
Achalasia: Outcome in children Meyer, Anell; Catto-Smith, Anthony; Crameri, Joe ...
Journal of gastroenterology and hepatology
32, Številka:
2
Journal Article
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Odprti dostop
Oesophageal achalasia is well-recognized but relatively rare in children, occasionally appearing as the "triple A" syndrome (with adrenal insufficiency and alacrima). Treatment modalities, as in ...adult practice, are not curative, often needing further interventions and spurring the search for better management. The outcome for syndromic variants is unknown. We sought to define the efficacy of treatments for children with achalasia with and without triple A syndrome.
We conducted a retrospective analysis of presentation and outcomes for 42 children with achalasia presenting over three decades to a major pediatric referral center. Long term impact of the diagnosis was assessed by questionnaire.
We identified 42 children including six with triple A syndrome. The median overall age at diagnosis was 10.8 years and median follow-up 1593 days. Initial Heller myotomy in 17 required further interventions in 11 (65%), while initial treatment with botulinum toxin (n = 20) was ultimately followed by myotomy in 17 (85%). Ten out of 35 patients who underwent myotomy required a repeat myotomy (29%). Patients with triple A syndrome developed symptoms earlier, but had delayed diagnosis, were more underweight at diagnosis and at last follow up. Questionnaire results suggested a significant long term deleterious impact on the quality of life of children and their families.
Many children with achalasia relapse after initial treatment, undergoing multiple, different procedures, despite which symptoms persist and impact on quality of life. Symptoms develop earlier in patients with triple A syndrome, but the diagnosis is delayed and this has substantial nutritional impact.
NOTCH2 mutations in Alagille syndrome Kamath, Binita Maya; Bauer, Robert C; Loomes, Kathleen M ...
Journal of medical genetics,
02/2012, Letnik:
49, Številka:
2
Journal Article
Recenzirano
Alagille syndrome (ALGS) is a dominant, multisystem disorder caused by mutations in the Jagged1 (JAG1) ligand in 94% of patients, and in the NOTCH2 receptor in <1%. There are only two NOTCH2 families ...reported to date. This study hypothesised that additional NOTCH2 mutations would be present in patients with clinical features of ALGS without a JAG1 mutation.
The study screened a cohort of JAG1-negative individuals with clinical features suggestive or diagnostic of ALGS for NOTCH2 mutations.
Eight individuals with novel NOTCH2 mutations (six missense, one splicing, and one non-sense mutation) were identified. Three of these patients met classic criteria for ALGS and five patients only had a subset of features. The mutations were distributed across the extracellular (N=5) and intracellular domains (N=3) of the protein. Functional analysis of four missense, one nonsense, and one splicing mutation demonstrated decreased Notch signalling of these proteins. Subjects with NOTCH2 mutations demonstrated highly variable expressivity of the affected systems, as with JAG1 individuals. Liver involvement was universal in NOTCH2 probands and they had a similar prevalence of ophthalmologic and renal anomalies to JAG1 patients. There was a trend towards less cardiac involvement in the NOTCH2 group (60% vs 100% in JAG1). NOTCH2 (+) probands exhibited a significantly decreased penetrance of vertebral abnormalities (10%) and facial features (20%) when compared to the JAG1 (+) cohort.
This work confirms the importance of NOTCH2 as a second disease gene in ALGS and expands the repertoire of the NOTCH2 related disease phenotype.
INTRODUCTION:Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been describeda pediatric-onset and an ...adult-onset type. The adult-onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date.
OBJECTIVE:We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition.
METHODS:A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Childrenʼs Hospital, Melbourne, was performed. A literature review was also conducted.
RESULTS:A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine.
CONCLUSIONS:Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the “‘adult” phenotype at a very young age. Patients with collagenous gastritis require long-term follow-up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.
Bright rectal bleeding in a neonate is most commonly due to necrotising enterocolitis, gastrointestinal infection or cows milk protein intolerance. We present here an infant who developed PR bleeding ...after cardiac surgery. Bleeding persisted despite presumptive treatment for the most common causes. A colonic intramural haematoma was identified on colonoscopy most likely related to anticoagulation in the setting of cardiac surgery.
Pediatric Collagenous Gastritis and Colitis Matta, Judy; Alex, George; Cameron, Donald J.S. ...
Journal of pediatric gastroenterology and nutrition,
September 2018, Letnik:
67, Številka:
3
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Introduction:
Collagenous gastritis is a rare disease characterized by the subepithelial deposition of collagen bands. Two phenotypes of the disease have been described: a pediatric‐onset ...and an adult‐onset type. The adult‐onset form is associated with collagenous colitis and autoimmune disorders. No effective treatment has been identified to date.
Objective:
We aim to describe the clinical features and outcomes of patients in our cohort and provide a summary of published pediatric cases with collagenous gastritis and colitis reported to date to gather information that will contribute to improved knowledge of this rare condition.
Methods:
A retrospective chart review of all patients with collagenous gastritis and/or colitis who were treated at the Royal Children's Hospital, Melbourne, was performed. A literature review was also conducted.
Results:
A total of 12 cases of collagenous gastritis were reviewed. Three of 12 (25%) patients had associated collagenous colitis. The most common clinical presentation was iron deficiency anemia. Nine (75%) patients were followed up, and repeat endoscopies were performed in 8 (67%). Iron deficiency anemia resolved in all patients on oral iron supplementation. Histologic improvement was only identified in one patient with the adult phenotype who had been treated with oral corticosteroids and azathioprine.
Conclusions:
Collagenous gastritis is a rare condition in children. A small proportion of children develop features of the “‘adult” phenotype at a very young age. Patients with collagenous gastritis require long‐term follow‐up and monitoring of their disease. Further randomized clinical trials are needed to establish an effective therapeutic strategy.
Nourishing children with liver disease is a challenging task; however, appropriate assessment and well‐timed nutritional interventions are paramount for a good long‐term outcome in these patients. An ...appropriate balance of macronutrients, micronutrients, and vitamins is important, as is the route of administration. This review aims to highlight the practical points in nutrition assessment and also provides a guide to the various nutritional interventions available for children with chronic liver disease.
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