Evaluation of exclusive enteral nutrition and corticosteroid induction treatment in new-onset moderate-to-severe luminal paediatric Crohn's disease

To induce remission in luminal paediatric Crohn's disease (CD), the ESPGHAN/ECCO guideline recommends treatment with exclusive enteral nutrition (EEN) or oral corticosteroids. In newly diagnosed moderate-to-severe paediatric CD patients, we determined the proportion of patients in which EEN or corticosteroids induced remission and maintained remission on azathioprine monotherapy. We included patients from the "TISKids" study assigned to the conventional treatment arm. Patients were aged 3-17 years and had new-onset, untreated luminal CD with weighted paediatric CD activity index (wPCDAI)> 40. Induction treatment consisted of EEN or oral corticosteroids; all received azathioprine maintenance treatment from start of treatment. The primary outcome of this study was endoscopic remission defined as a SES-CD score Conclusion: In children with moderate-to-severe newly diagnosed CD, induction treatment with EEN or CS regularly is insufficient to achieve endoscopic remission without treatment escalation at week 10.Peer reviewe

Best packing of rods into boxes

AbstractWe determine the maximum number of 1 × 1 x … × 1 × n rods which will fit inside an arbitrary d-dimensional rectangular box, on condition that they be packed parallel to the edges of the box

First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn's disease: An open-label multicentre randomised controlled trial

Objective: In newly diagnosed paediatric patients with moderate-to-severe Crohn's disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment. Design: In this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3-17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI <12.5 at week 52, without need for treatment escalation, using intention-to-treat analysis. Results: 100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was no

Targeted expression of a lumican transgene rescues corneal deficiencies in lumican-null mice.

To investigate whether targeted expression of lumican in the mouse cornea rescued the Lum(-/-) phenotype.Lum(-/-)/Kera-Lum mice were generated by crossing Lum(-/-) mice with Kera-Lum transgenic mice that overexpressed lumican under the control of the keratocan promoter. Mouse eyes were analyzed in vivo by confocal microscopy through focusing (CMTF) to determine corneal sublayer thickness and haze. Subsequently, one cornea from each mouse was processed for SDS-PAGE/western blotting while the other was used for either electron microscopy (EM) or real-time polymerase chain reaction (RT-PCR).Overall, corneas of Lum(-/-)/Kera-Lum mice showed significant improvement over Lum(-/-) but were still deficient when compared to wildtype (WT) mice. Specifically, analysis of Lum(-/-)/Kera-Lum mouse eyes by CMTF showed a similar stromal but slightly increased epithelial thickness compared to matching Lum(-/-) mice. Analysis of the CMTF scans for light backscattering revealed a small yet significant reduction in corneal haze in Lum(-/-)/Kera-Lum mice as compared to Lum(-/-) mice. At the EM level, the pronounced disarray of the posterior fibrillar matrix seen in Lum(-/-) mice was not observed in Lum(-/-)/Kera-Lum mice. Moreover, analyses of collagen fibril diameter distributions showed a significant reduction in the number of large-diameter (&gt;40 nm) fibrils in Lum(-/-)/Kera-Lum mice as compared to Lum(-/-) mice. No significant differences in keratocan expression were found at the mRNA level, but western blot analysis detected an approximately twofold increase in keratocan protein levels in Lum(-/-)/Kera-Lum over Lum(-/-) mice.Together these data suggest that despite the low keratocan promoter activity driving the transgene in Lum(-/-) cornea, transgenic lumican expression was sufficient to partially rescue corneal phenotypic deficiencies

Targeted expression of a lumican transgene rescues corneal deficiencies in lumican-null mice.

To investigate whether targeted expression of lumican in the mouse cornea rescued the Lum(-/-) phenotype.Lum(-/-)/Kera-Lum mice were generated by crossing Lum(-/-) mice with Kera-Lum transgenic mice that overexpressed lumican under the control of the keratocan promoter. Mouse eyes were analyzed in vivo by confocal microscopy through focusing (CMTF) to determine corneal sublayer thickness and haze. Subsequently, one cornea from each mouse was processed for SDS-PAGE/western blotting while the other was used for either electron microscopy (EM) or real-time polymerase chain reaction (RT-PCR).Overall, corneas of Lum(-/-)/Kera-Lum mice showed significant improvement over Lum(-/-) but were still deficient when compared to wildtype (WT) mice. Specifically, analysis of Lum(-/-)/Kera-Lum mouse eyes by CMTF showed a similar stromal but slightly increased epithelial thickness compared to matching Lum(-/-) mice. Analysis of the CMTF scans for light backscattering revealed a small yet significant reduction in corneal haze in Lum(-/-)/Kera-Lum mice as compared to Lum(-/-) mice. At the EM level, the pronounced disarray of the posterior fibrillar matrix seen in Lum(-/-) mice was not observed in Lum(-/-)/Kera-Lum mice. Moreover, analyses of collagen fibril diameter distributions showed a significant reduction in the number of large-diameter (&gt;40 nm) fibrils in Lum(-/-)/Kera-Lum mice as compared to Lum(-/-) mice. No significant differences in keratocan expression were found at the mRNA level, but western blot analysis detected an approximately twofold increase in keratocan protein levels in Lum(-/-)/Kera-Lum over Lum(-/-) mice.Together these data suggest that despite the low keratocan promoter activity driving the transgene in Lum(-/-) cornea, transgenic lumican expression was sufficient to partially rescue corneal phenotypic deficiencies