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1.
Eur J Gastroenterol Hepatol ; 34(4): 372-374, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34034281

RESUMO

There is a paucity of treatment options for patients who have failed multiple biologics. A drawback of biologic therapies is their selectivity in targeting a single pathway. We report the use of dual biologic therapy with vedolizumab and ustekinumab for three highly refractory patients who previously failed both of these medications as monotherapy. The dual biologic therapy led to the closure of a recto-vaginal fistula and restoration of continuity after takedown of a stoma.


Assuntos
Doença de Crohn , Ustekinumab , Anticorpos Monoclonais Humanizados , Terapia Biológica , Criança , Doença de Crohn/induzido quimicamente , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Ustekinumab/uso terapêutico
2.
J Pediatr Gastroenterol Nutr ; 72(6): 877-882, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587407

RESUMO

OBJECTIVES: Both the inflammatory burden of Crohn disease (CD) and corticosteroids have a negative effect on bone density. Exclusive enteral nutrition (EEN) avoids corticosteroids and promotes endoscopic healing. We aimed to explore the effect of nutritional therapy on bone health in pediatric CD. METHODS: This was a planned sub-study of a clinical trial enrolling children with new-onset mild-moderate CD. Children were randomized to either 6 weeks EEN followed by 6 weeks 25% partial enteral nutrition (PEN) or 6 weeks of 50% PEN with a CD exclusion diet followed by 6 weeks of 25% PEN with exclusion diet. Bone formation and resorption were measured at baseline, week 12 and week 24 by serum C-Propeptide of Type I Procollagen (CICP) and type I Collagen N-Telopeptide (NTX), respectively. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry (DXA) scan at baseline and week 24. RESULTS: Median CICP improved from 130 ng/mL (106-189) at baseline to 223 (143-258) at week 12 and 193 (143-252) at week 24 (P = 0.016 for both, n = 29 children). Median NTX remained unchanged (P = 0.45 and P = 0.45). Thirty-six children had DXA scans performed at diagnosis; 81% and 33% had z scores of <-1 and <-2, respectively. DXA z scores did not improve from baseline (adjusted total body less head [TBLH] BMD -1.62 ±â€Š0.87) to week 24 (-1.76 ±â€Š0.75; P = 0.30, n = 21 with both scans). CONCLUSIONS: Low bone density is common in new-onset mild-moderate pediatric CD. CICP, a sensitive marker of bone formation, improved following dietary intervention but this was not associated with improved BMD.


Assuntos
Densidade Óssea , Doença de Crohn , Absorciometria de Fóton , Biomarcadores , Criança , Doença de Crohn/terapia , Nutrição Enteral , Humanos
3.
J Crohns Colitis ; 12(3): 306-312, 2018 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-29165666

RESUMO

BACKGROUND: Exclusive enteral nutrition [EEN] and corticosteroids [CS] induce similar rates of remission in mild to moderate paediatric Crohn's disease [CD], but differ with regard to mucosal healing. Our goal was to evaluate if EEN at diagnosis was superior to CS for improving long-term outcomes. METHODS: We prospectively followed newly diagnosed children aged < 17 years, with mild to moderate CD at baseline, for 2 years in the GROWTH CD study. Patients were evaluated at baseline and at 8, 12, 78, and 104 weeks. Remission, relapses, complications [fibrostenotic disease, penetrating disease, and active perianal disease] and growth were recorded throughout the study. A propensity score analysis was performed. RESULTS: A total of 147 children [mean age 12.9 ± 3.2 years], treated by EEN [n = 60] or CS [n = 87] were included. New complications developed in 13.7% of CS [12/87] versus 11.6% of EEN [7/60], p = 0.29. Remission was achieved in 41/87 [47%] in CS and 38/60 [63%] EEN, p = 0.036. Median time to relapse did not differ [14.4 ± 1 months with CS, 16.05 ± 1.1 EEN, p = 0.28]. Mean height Z scores decreased from Week 0 to Week 78 with CS [-0.34 ± 1.1 to -0.51 ± 1.2, p = 0.01], but not with EEN [-0.32 ± 1.1 to -0.22 ± 0.9, p = 0.56]. In a propensity score analysis, EEN was superior to CS for inducing remission [p = 0.05] and trended to superiority for height Z score [p = 0.055]. CONCLUSIONS: Use of EEN was associated with higher remission rates and a trend toward better growth but with similar relapse and complication rates in new-onset mild to moderate paediatric CD.


Assuntos
Corticosteroides/uso terapêutico , Estatura , Doença de Crohn/terapia , Nutrição Enteral , Fístula Retal/etiologia , Indução de Remissão , Abscesso/etiologia , Adolescente , Produtos Biológicos/uso terapêutico , Criança , Constrição Patológica/etiologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Masculino , Pontuação de Propensão , Estudos Prospectivos , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
4.
J Crohns Colitis ; 11(8): 981-987, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28789473

RESUMO

BACKGROUND: The importance of a holistic approach with a comprehensive multidisciplinary team, including nutritional and psychosocial support, is becoming well recognised as a key contributor to optimal care in paediatric inflammatory bowel disease [IBD]. The Paediatric committee of ECCO [P-ECCO] aimed to determine important components that would contribute to quality of care in a paediatric IBD centre [henceforth 'quality items']. METHODS: First, a list of items has been generated by a Delphi group of 111 international paediatric IBD experts. Through an iterative process, the group graded and ranked the items according to their perceived relative contribution to quality care. We then surveyed 101 paediatric IBD centres affiliated with the Porto and Interest groups of ESPGHAN in Europe and with the ImproveCareNow registry in North America, exploring the availability of the retained items in their centres. RESULTS: A total of 68 items were generated and reduced to a list of 60 ranked order items, grouped in six domains: Facility, Personnel, Management, Supportive Services, Patient Support and Accessibility, and Academia and Communications. Of the retained items, 52 [88%] were present in most of the 101 high-performing paediatric IBD centres, and there was a trend for increased availability with increased patient volume at the centres. CONCLUSION: In this P-ECCO study, we attempted to tabulate, for the first time in paediatrics, 60 quality items that paediatric IBD referral centres may wish to include.


Assuntos
Instituições de Assistência Ambulatorial/organização & administração , Doenças Inflamatórias Intestinais/terapia , Instituições de Assistência Ambulatorial/normas , Criança , Técnica Delphi , Europa (Continente) , Humanos , Equipe de Assistência ao Paciente/organização & administração , Qualidade da Assistência à Saúde/normas , Sistema de Registros , Recursos Humanos
5.
J Crohns Colitis ; 11(8): 970-974, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28369299

RESUMO

BACKGROUND: Paediatric ulcerative colitis [UC] is more extensive than adult disease, and more often refractory to mesalamine. However, no prospective trials have evaluated mesalamine enemas for inducing remission in children. Our goal was to evaluate the ability of mesalamine enemas to induce remission in mild to moderate paediatric UC refractory to oral mesalamine. METHODS: This was an open-label arm of a previously reported randomised controlled trial of once-daily mesalamine in active paediatric UC [MUPPIT trial]. Children aged 4-18 years, with a Paediatric Ulcerative Colitis Activity Index [PUCAI] score of 10-55, were enrolled after failing at least 3 weeks of full-dose oral mesalamine. Patients treated with steroids or enemas in the previous month and those with isolated proctitis were excluded. Children received Pentasa® enemas 25 mg/kg [up to 1g] daily for 3 weeks with the previous oral dose. The primary endpoint was clinical remission by Week 3. RESULTS: A total of 38 children were enrolled (mean age 14.6 ± 2.3 years; 17/38 [45%] with extensive colitis). Clinical remission was obtained in 16 [42%] and response was obtained in 27 [71%] at Week 3. Eight children deteriorated and required steroids. There were no differences in baseline parameters between those who entered or failed to enter remission, including disease extent [43% in left-sided and 41% in extensive colitis] and disease activity [44% in mild and 41% in moderate activity]. CONCLUSION: Clinical remission can be markedly increased in children who are refractory to oral mesalamaine by adding mesalamine enemas for 3 weeks, before commencing steroids.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Mesalamina/administração & dosagem , Adolescente , Criança , Pré-Escolar , Enema , Feminino , Humanos , Masculino , Mesalamina/uso terapêutico , Estudos Prospectivos , Indução de Remissão/métodos , Método Simples-Cego , Falha de Tratamento
6.
Can J Gastroenterol Hepatol ; 29(7): 351-6, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26076398

RESUMO

The treatment armamentarium in pediatric Crohn disease (CD) is very similar to adult-onset CD with the notable exception of the use of exclusive enteral nutrition (EEN [the administration of a liquid formula diet while excluding normal diet]), which is used more frequently by pediatric gastroenterologists to induce remission. In pediatric CD, EEN is now recommended by the pediatric committee of the European Crohn's and Colitis Organisation and the European Society for Paediatric Gastroenterology Hepatology and Nutrition as a first-choice agent to induce remission, with remission rates in pediatric studies consistently >75%. To chart and address enablers and barriers of use of EEN in Canada, a workshop was held in September 2014 in Toronto (Ontario), inviting pediatric gastroenterologists, nurses and dietitians from most Canadian pediatric IBD centres as well as international faculty from the United States and Europe with particular research and clinical expertise in the dietary management of pediatric CD. Workshop participants ranked the exclusivity of enteral nutrition; the health care resources; and cost implications as the top three barriers to its use. Conversely, key enablers mentioned included: standardization and sharing of protocols for use of enteral nutrition; ensuring sufficient dietetic resources; and reducing the cost of EEN to the family (including advocacy for reimbursement by provincial ministries of health and private insurance companies). Herein, the authors report on the discussions during this workshop and list strategies to enhance the use of EEN as a treatment option in the treatment of pediatric CD in Canada.


Assuntos
Consenso , Doença de Crohn/terapia , Nutrição Enteral/normas , Gastroenterologia/educação , Canadá , Criança , Nutrição Enteral/economia , Humanos
7.
Curr Opin Gastroenterol ; 31(4): 303-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25887458

RESUMO

PURPOSE OF REVIEW: An increasing body of evidence has linked diet to inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis. Most of our current knowledge pertains to the link between diet and Crohn's disease. Exclusive enteral nutrition and partial enteral nutrition are the best known dietary intervention for the induction of remission and maintenance of remission in Crohn's disease both in children and in adults, but the mechanism whereby these interventions may cause or maintain remission and mucosal healing has remained elusive. RECENT FINDINGS: Recent studies have shed light on the possible mechanisms of response to dietary intervention. Epidemiological and rodent model studies over the last year have supplied us with several dietary candidates for an effect of diet on inflammation and disease pathogenesis. Others have shed insight into the effect of diet on dysbiosis and the microbiota. An elimination diet based on some of these candidates has shown clinical efficacy, and bridged the knowledge obtained from rodent models to a human intervention. SUMMARY: These studies may allow better understanding of the pathogenesis of IBD and provide new tools to treat these difficult diseases. Elimination diets based on the identification of deleterious dietary components may pave the way for an improved control of the disease in the future. VIDEO ABSTRACT: http://links.lww.com/COG/A10.


Assuntos
Nutrição Enteral/métodos , Doenças Inflamatórias Intestinais/terapia , Animais , Dieta/efeitos adversos , Modelos Animais de Doenças , Microbioma Gastrointestinal , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/etiologia , Doenças Inflamatórias Intestinais/microbiologia
8.
Isr Med Assoc J ; 10(7): 503-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18751627

RESUMO

BACKGROUND: A polymeric diet rich in transforming growth factor-beta 2 used as a single nutrient has been shown to induce remission in 79% of children with Crohn's disease. OBJECTIVES: To summarize the experience of several pediatric gastroenterology units in Israel using a TGFbeta2-enriched polymeric diet (Modulen IBD) supplementation in children and adolescents with Crohn's disease. METHODS: In a retrospective study we reviewed the charts of 28 children with Crohn's disease (10 girls, 18 boys) who received, in addition to conventional treatment, Modulen IBD as a supplement to their regular nutrition. These children were compared with 18 children supplemented with standard polymeric formula (Ensure Plus) and 18 children without formula supplementation. We recorded clinical manifestations, growth, and the Pediatric Crohn's Disease Activity Index before and after initiation of the polymeric diet. RESULTS: The Modulen-treated children showed a significant decrease in PCDAI from 34.3 to 15.7 (P< 0.0001). A significant decrease in PCDAI was recorded also in the Ensure Plus group, from 35 to 22 (P= 0.02) but not in the non-supplemented group. Significant improvements in body mass index (P = 0.01) and erythrocyte sedimentation rate (P= 0.03) were recorded at follow-up (median 3.4 months) only in the Modulen IBD group. CONCLUSIONS: In this cohort of children with Crohn's disease, supplementation of the diet with Modulen IBD as well as supplementation with Ensure Plus was associated with a decrease in PCDAI. The children supplemented with Modulen IBD also showed improvement in BMI, suggesting an additional advantage of nutritional therapy in children with this disease.


Assuntos
Doença de Crohn/dietoterapia , Dieta , Suplementos Nutricionais , Fator de Crescimento Transformador beta2/uso terapêutico , Adolescente , Adulto , Antropometria , Índice de Massa Corporal , Criança , Pré-Escolar , Doença de Crohn/fisiopatologia , Feminino , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
9.
Pediatr Res ; 51(5): 635-40, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11978889

RESUMO

There have been several reports implying a benefit for heparin therapy in patients with refractory ulcerative colitis. Although this effect has been attributed to the anti-inflammatory properties of heparin, other mechanisms have not been excluded. Heparin is a potent modulator of receptor binding of growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor, and heparin-binding epidermal growth factor (HB-EGF), that play a role in wound repair. We examined the effect of heparin on the functional levels of FGF and HB-EGF in a model of experimental colitis. Fifty-six Wistar rats were divided into four groups: group 1 was the control group, group 2 received s.c. heparin 50 units/kg/d, group 3 underwent induction of 3% iodoacetamide colitis, and group 4 underwent induction of colitis and heparin treatment. Rats were killed and evaluated for severity of colitis by macroscopic and microscopic colitis scores, area of inflammation, and myeloperoxidase levels. FGF and HB-EGF levels were functionally assessed in colonic tissue in each group. Heparin therapy resulted in significant improvement in macroscopic and microscopic features of colitis (p < 0.05), accompanied by a partial reduction in myeloperoxidase levels. FGF receptor binding activity was identical in groups 1 and 2 but increased more than 3-fold after colitis induction in group 3 (p < 0.05). Treatment with heparin caused a significant decrease in FGF concentration. Levels of HB-EGF binding activity were similar in groups 1 and 2 and decreased in group 3 (p < 0.01). Heparin caused a significant increase in HB-EGF content in group 4 (p < 0.05). Levels of growth factors are altered differently in experimental colitis. Colonic FGF binding activity increases with colitis, whereas HB-EGF binding decreases with colitis. These trends were reversed by heparin, concomitant with a clinical and pathologic improvement in colitis. We suggest that one mechanism of heparin-mediated improvement in colitis may involve tissue healing associated with changes in functional levels of colonic growth factors.


Assuntos
Colite/tratamento farmacológico , Fator de Crescimento Epidérmico/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Heparina/uso terapêutico , Animais , Colite/induzido quimicamente , Colite/metabolismo , Avaliação Pré-Clínica de Medicamentos , Heparina/farmacologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Peptídeos e Proteínas de Sinalização Intercelular , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Iodoacetamida/toxicidade , Masculino , Peroxidase/análise , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar
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