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1.
Aliment Pharmacol Ther ; 48(5): 523-537, 2018 09.
Article in English | MEDLINE | ID: mdl-29984520

ABSTRACT

BACKGROUND: Risk benefit strategies in managing inflammatory bowel diseases (IBD) are dependent upon understanding the risks of uncontrolled inflammation vs those of treatments. Malignancy and mortality in IBD have been associated with disease-related inflammation and immune suppression, but data are limited due to their rare occurrence. AIM: To identify and describe the most common causes of mortality, types of cancer and previous or current therapy among children and young adults with paediatric-onset IBD. METHODS: Information on paediatric-onset IBD patients diagnosed with malignancy or mortality was prospectively collected via a survey in 25 countries over a 42-month period. Patients were included if death or malignancy occurred after IBD diagnosis but before the age of 26 years. RESULTS: In total, 60 patients were identified including 43 malignancies and 26 fatal cases (9 due to cancer). Main causes of fatality were malignancies (n = 9), IBD or IBD-therapy related nonmalignant causes (n = 10; including 5 infections), and suicides (n = 3). Three cases, all fatal, of hepatosplenic T-cell lymphoma were identified, all were biologic-naïve but thiopurine-exposed. No other haematological malignancies were fatal. The 6 other fatal cancer cases included 3 colorectal adenocarcinomas and 3 cholangiocarcinomas (CCAs). Primary sclerosing cholangitis (PSC) was present in 5 (56%) fatal cancers (1 colorectal carcinoma, 3 CCAs and 1 hepatosplenic T-cell lymphoma). CONCLUSIONS: We report the largest number of paediatric-onset IBD patients with cancer and/or fatal outcomes to date. Malignancies followed by infections were the major causes of mortality. We identified PSC as a significant risk factor for cancer-associated mortality. Disease-related adenocarcinomas were a commoner cause of death than lymphomas.


Subject(s)
Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/mortality , Neoplasms/complications , Neoplasms/mortality , Adolescent , Adult , Age of Onset , Child , Child, Preschool , Europe/epidemiology , Female , Humans , Infant , Infant, Newborn , Inflammatory Bowel Diseases/epidemiology , Male , Neoplasms/epidemiology , Prospective Studies , Risk Assessment , Risk Factors , Young Adult
2.
Pathol Biol (Paris) ; 61(3): e61-4, 2013 Jun.
Article in French | MEDLINE | ID: mdl-22037405

ABSTRACT

Celiac disease (CD) is a chronic inflammatory enteropathy caused by the ingestion of gluten. A safe and efficient but unpleasant treatment exists for CD in form of a strict gluten-free diet. Thus, there is a need for new treatment strategies, which are based on the improved and advanced understanding of the pathophysiology of CD. The first strategy consists in reducing or even eliminating major antigenic motifs in gluten, responsible for the inflammatory reaction. The use of less immunogenic wheat was suggested but this seems rather difficult to realize. However, a complete digestion of the immunogenic parts of gluten looks very promising. This can be obtained by the use of polymers, capable to sequester gluten proteins or even better via the exogenous administration of propyl-endopeptidases, with two different enzymes under development. Another approach could be the use of inhibitors of tissue transglutaminase, a strategy which is under clinical investigation. Alternatively, inhibition of the site of liaison of immunostimulatory peptides with HLA molecules was suggested and is also under investigation in vivo. For patients suffering from refractory sprue, the inhibition of IL15 might be of therapeutic interest with the hope to improve the fatal outcome of many of these patients. However, the ultimate treatment approach is in form of prevention and the role of infectious agents, such as Rotavirus, in disease onset has to be considered.


Subject(s)
Celiac Disease/therapy , Celiac Disease/prevention & control , Diet, Gluten-Free/methods , Enzyme Inhibitors/therapeutic use , GTP-Binding Proteins/antagonists & inhibitors , Humans , Molecular Targeted Therapy , Peptides/therapeutic use , Plants, Genetically Modified , Preventive Medicine/methods , Preventive Medicine/trends , Protein Glutamine gamma Glutamyltransferase 2 , Therapies, Investigational/methods , Therapies, Investigational/trends , Transglutaminases/antagonists & inhibitors , Triticum/genetics
3.
Aliment Pharmacol Ther ; 33(12): 1332-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21507029

ABSTRACT

BACKGROUND: Nutritional therapy has an established role as induction therapy in paediatric Crohn's disease. However, compliance is the main difficulty and may be greatly influenced by the administration route. AIM: To analyse the efficiency of exclusive nutrition to induce remission in children with Crohn's disease comparing fractionated oral vs. continuous enteral feeding. METHODS: The medical records of 106 patients treated by exclusive nutritional therapy [Modulen IBD (R)] by either oral or continuous enteral route were reviewed retrospectively. Comparative analyses of remission rates, changes in anthropometry, Paediatric Crohn's disease Activity Index (PCDAI), laboratory indices and compliance rates were performed. RESULTS: On exclusive enteral nutrition, at 8 weeks, 34/45 patients achieved remission in the oral group (75% on intention-to-treat analysis) and 52/61 (85%) in the enteral nutrition group (P = 0.157). All patients showed a significant decrease in disease severity assessed by PCDAI (P < 0.0001) and significant improvements in anthropometric measures and inflammatory indices. No difference was observed whether Modulen IBD was administered orally or by continuous enteral feeding, apart from weight gain, which was greater in the enteral group (P = 0.041). In a subgroup of patients, mucosal healing was evidenced on follow-up endoscopies showing a clear correlation to remission. Compliance rates (87% and 90%) were similar. Nevertheless, noncompliant patients had lower mucosal healing and remission rates. CONCLUSIONS: These retrospective data suggest that the use of fractionated oral nutritional therapy might be as efficacious as continuous enteral administration to induce remission and mucosal healing in children with Crohn's disease. However, appropriate prospective clinical trials are needed to confirm these findings.


Subject(s)
Crohn Disease/diet therapy , Enteral Nutrition/methods , Patient Compliance/statistics & numerical data , Body Weight , Child , Crohn Disease/physiopathology , Crohn Disease/psychology , Female , Humans , Male , Nutritional Support , Patient Compliance/psychology , Remission Induction/methods , Retrospective Studies , Treatment Outcome
4.
Arch Pediatr ; 16(10): 1364-73, 2009 Oct.
Article in French | MEDLINE | ID: mdl-19683904

ABSTRACT

Alcohol consumption during pregnancy is a major cause of mental retardation in Western countries. Fetal alcohol syndrome (FAS) is mainly characterized by pre- and postnatal stunted growth, neurocognitive disorders, and facial dysmorphism. It compromises the intellectual and behavioral prognosis of the child. Prevention tools exist, through better information of health professionals, for optimal care of high-risk women before, during, and after pregnancy, which would decrease the incidence of SAF in the future.


Subject(s)
Alcoholism , Fetal Alcohol Spectrum Disorders , Pregnancy Complications , Female , Fetal Alcohol Spectrum Disorders/diagnosis , Fetal Alcohol Spectrum Disorders/physiopathology , Humans , Infant, Newborn , Practice Guidelines as Topic , Pregnancy , Prenatal Diagnosis , Time Factors
5.
Arch Pediatr ; 15(4): 456-61, 2008 Apr.
Article in French | MEDLINE | ID: mdl-18400480

ABSTRACT

Since the 1990's, the widespread use of very sensitive and specific serological tests has completely changed the conditions of the diagnosis of celiac disease (CD). The active form of the disease is now only the tip of the iceberg representing it. Currently, CD is evoked either in front of mild digestive symptoms at the usual age or in the course of screening in siblings of an index case or in patients at risk (insulin dependent diabetes for example) at a later age using IgA anti-endomysium or anti-tissue transglutaminase antibodies, the sensitivities and specificities of which exceed 90%. In some cases, HLA typing is helpful in allowing to exclude a patient who is neither DQ2 nor DQ8. The intestinal biopsy remains the "gold standard" of the diagnosis showing villous atrophy; the latter, however, is less and less often severe as the disease is milder and milder. The diagnosis of CD then rests on the confrontation of the clinical, biological and histological data. Once CD has been diagnosed, it can be classified either as active or silent (positive serology with isolated villous atrophy), or latent (positive serology with a normal mucosa) and the appropriate therapeutic decision can be taken.


Subject(s)
Celiac Disease/epidemiology , Celiac Disease/diagnosis , Celiac Disease/enzymology , Celiac Disease/pathology , Child , Diagnosis, Differential , France/epidemiology , Humans , Immunoassay , Transglutaminases/blood
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