Transmural Healing Is Associated with Improved Long-term Outcomes of Patients with Crohn's Disease.

BACKGROUND: Mucosal healing (MH) is currently accepted as one of the best treatment targets in Crohn's disease. However, even in patients with sustained MH, residual bowel wall inflammation can still be detected by cross-sectional imaging. The long-term benefits of obtaining transmural healing (TH) have not been previously assessed. METHODS: We performed an observational study including 214 patients with Crohn's disease with a magnetic resonance enterography (MRE) and colonoscopy performed within a 6-month interval. Patients were classified as having TH (inactive MRE and colonoscopy), MH (active MRE with inactive colonoscopy), or no healing (active colonoscopy). Need for surgery, hospital admission, and therapy escalation were evaluated at 12 months of follow-up. RESULTS: Patients with TH presented lower rates of hospital admission, therapy escalation, and surgery than patients with MH or no healing. In logistic regression analysis, endoscopic remission (odds ratio 0.331 95% confidence interval [0.178-0.614], P < 0.001) and MRE remission (odds ratio 0.270 95% confidence interval [0.130-0.564], P < 0.001) were independently associated with a lower likelihood of reaching any unfavorable outcome. CONCLUSIONS: TH is associated with improved long-term outcomes in Crohn's disease and may be a more suitable target than MH.

Impact of Early Surgery and Immunosuppression on Crohn's Disease Disabling Outcomes.

BACKGROUND AND AIMS: The definition of early therapeutic strategies to control Crohn's disease aggressiveness and prevent recurrence is key to improve clinical practice. This study explores the impact of early surgery and immunosuppression onset in the occurrence of disabling outcomes. METHODS: This was a multicentric and retrospective study with 754 patients with Crohn's disease, who were stratified according to the need for an early surgery (group S) or not (group I) and further divided according to the time elapsed from the beginning of the follow-up to the start of immunosuppression therapy. RESULTS: The rate of disabling events was similar in both groups (S: 77% versus I: 76%, P = 0.700). The percentage of patients who needed surgery after or during immunosuppression therapy was higher among group S, both for first surgeries after the index event (38% of groups S versus 21% of group I, P < 0.001) and for reoperations (38% of groups S versus 12% of group I, P < 0.001). The time elapsed to reoperation was shorter in group I (HR = 2.340 [1.367-4.005]), stratified for the onset of immunosuppression. Moreover, reoperation was far more common among patients who had a late start of immunosuppression (S36: 50% versus S0-6: 27% and S6-36: 25%, P < 0.001) and (I36: 16% versus I0-6: 5% and I6-36: 7%, P < 0.001). CONCLUSIONS: Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.

What is new in genetics and osteogenesis imperfecta classification? / O que há de novo em genética e classificação de osteogênese imperfeita?

OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference. .

OBJETIVO: Revisão da literatura sobre novos genes relacionados à osteogênese imperfeita (OI) e atualização da sua classificação. FONTE DOS DADOS : Revisão nas bases de dados do PUBMED e OMIM com seleção de referências relevantes. SÍNTESE DOS DADOS: Sillence et al., em 1979, desenvolveram uma classificação dos subtipos de OI baseada em características clínicas e gravidade da doença: OI tipo I, forma leve, comum, com escleras azuladas; OI tipo II, forma perinatal letal; OI tipo III, forma grave e progressivamente deformante com esclera normal; e OI tipo IV, forma de gravidade moderada com esclera normal. Cerca de 90% dos indivíduos com OI são heterozigotos para mutações em COL1A1 e COL1A2, com padrão de herança dominante ou esporádico. A partir de 2006 foram identificadas mutações nos genes CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1 e TMEM38B associadas à OI recessiva e mutação em IFITM5 associada à OI dominante. Mutações em PLS3 foram identificadas recentemente em famílias com osteoporose e fraturas, com padrão de herança ligado ao X. Além da complexidade genética das bases moleculares das OI, extensa variabilidade fenotípica resultante de loci individuais também tem sido documentada. CONCLUSÕES: Face à descoberta de novos genes e à correlação genótipo-fenótipo limitada, o uso de ferramentas de sequenciamento de nova geração torna-se útil no estudo molecular de casos de OI. A recomendação do Grupo de Nosologia da Sociedade Internacional de Displasias Esqueléticas é manter a classificação de Sillence como a forma prototípica e universalmente aceita para classificar o grau de gravidade na OI, e libertá-la de referência ...

What is new in genetics and osteogenesis imperfecta classification?

OBJECTIVE: Literature review of new genes related to osteogenesis imperfecta (OI) and update of its classification. SOURCES: Literature review in the PubMed and OMIM databases, followed by selection of relevant references. SUMMARY OF THE FINDINGS: In 1979, Sillence et al. developed a classification of OI subtypes based on clinical features and disease severity: OI type I, mild, common, with blue sclera; OI type II, perinatal lethal form; OI type III, severe and progressively deforming, with normal sclera; and OI type IV, moderate severity with normal sclera. Approximately 90% of individuals with OI are heterozygous for mutations in the COL1A1 and COL1A2 genes, with dominant pattern of inheritance or sporadic mutations. After 2006, mutations were identified in the CRTAP, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, and TMEM38B genes, associated with recessive OI and mutation in the IFITM5 gene associated with dominant OI. Mutations in PLS3 were recently identified in families with osteoporosis and fractures, with X-linked inheritance pattern. In addition to the genetic complexity of the molecular basis of OI, extensive phenotypic variability resulting from individual loci has also been documented. CONCLUSIONS: Considering the discovery of new genes and limited genotype-phenotype correlation, the use of next-generation sequencing tools has become useful in molecular studies of OI cases. The recommendation of the Nosology Group of the International Society of Skeletal Dysplasias is to maintain the classification of Sillence as the prototypical form, universally accepted to classify the degree of severity in OI, while maintaining it free from direct molecular reference.

Complete resolution of enterocolic fistulas with infliximab.

Fistulas are a frequent and serious complication of Crohn's disease. Most of the literature has been focused on perianal fistulas, which are by far the most frequent. The effectiveness of treatment with infliximab in fistulizing Crohn's disease was demonstrated in the ACCENT II trial. In that study, however, all patients had external fistulas, and the majority of those were perianal fistulas. The response to fistula treatment in other locations was not evaluated.

Flavonóides O-glicosilados de Croton campestris St. Hill. (Euphorbiaceae) / Glycosyl flavonoids from Croton campestris St. Hill. (Euphorbiaceae)

Do extrato butanólico de Croton campestris St. Hill. (Euphorbiaceae) foram isolados quatro flavonóides, todos O-glicosídeos da quercetina. Estas substâncias foram identificadas como 3-O-b-D-apiofuranosil-(1®2)-galactopiranosil quercetina (1), 3-O-b-D-galactopiranosil quercetina (hiperina) (2), 3-O-a-L-arabinopiranosil quercetina (guaijaverina) (3) e 3-O-a-L-ramnopiranosil quercetina (quercitrina) (4).O presente trabalho relata a presença destas substâncias pela primeira vez para esta espécie de Croton, cuja elucidação estrutural deu-se por espectroscopia em UV, EM e RMN, incluindo as técnicas bidimensionais: ¹H-¹H (2D NOESY, 2D COSY), ¹H-13C (2D HETCOR) e 13C (APT), além de comparações com os dados da literatura.

Four flavonoids were isolated from the butanolic extract of the aerial parts of Croton campestris St. Hill. (Euphorbiaceae). These compounds were identified as 3-O-b-D-apiofuranosyl-(1®2)-galactopyranoside quercetin (1), 3-O-b-D-galactopyranoside quercetin (hyperin) (2), 3-O-a-L-arabinopyranoside quercetin (guaijaverin) (3) and 3-O-a-L-ramnopyranoside quercetin (quercitrin) (4). They have been isolated for the first time from Croton campestris. Their structures were elucidated by UV, MS and NMR experiments including ¹H-¹H (2D NOESY, 2D COSY), ¹H-13C (2D HETCOR), 13C (APT) and by comparison of the spectral data with those reported in the literature.

Lack of effect of colchicine in alcoholic cirrhosis: final results of a double blind randomized trial.

BACKGROUND: Colchicine, an inhibitor of collagen synthesis, has been suggested as potentially beneficial in cirrhosis. OBJECTIVE: This long-term, randomized, double blind, placebo controlled trial was conducted in order to evaluate the efficacy of colchicine in alcoholic cirrhosis. METHODS: Ambulatory patients with biopsy proven alcoholic cirrhosis, presenting from 1989 to 1997, with no exclusion criteria (e.g. Child-Pugh C, bilirubin > 10 mg/dl and gastrointestinal bleeding in the previous 15 days), were randomized to receive orally, 5 days/week, 1 mg/day of colchicine or placebo. MAIN OUTCOME MEASURES: Results were analysed on an intention to treat basis, for survival, incidence of complications, biochemical liver tests and safety. RESULTS: Twenty-nine patients received colchicine and 26 placebo; characteristics of both groups were similar. The median follow-up was 40.6 (1.4-126.3) months in the colchicine versus 42.4 (5.7-118.2) months in the placebo group (NS). No significant side effects were reported. During follow-up, there were no significant differences in compliance and alcohol abstinence (86% vs 85%). Overall survival was not statistically different (P = 0.38). Cumulative 3-year survival rates were 74.9% in the colchicine versus 91.4% in placebo group (NS). The annual incidence rate of complications was similar with colchicine or placebo: gastrointestinal bleeding, 1.5% vs 1.2%; ascites, 3.7% vs 3.7%; and encephalopathy, 1.0% vs 0.9%. The comparison of changes in biochemical parameters between groups did not show any significant difference. CONCLUSIONS: Although well tolerated, colchicine does not appear to overcome the progression and natural history of long-established alcoholic cirrhosis.