Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and ...the West. We aimed to evaluate disease-predisposing genes in Asian IBD patients.
A systematic review and meta-analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews.
In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western Crohn's disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio OR 0.97; 95% confidence interval CI 0.84-1.13). Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16-2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF) superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41; 95% CI 1.89-3.07) were associated with ulcerative colitis in Asians.
Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease-associated mechanisms in this population of rising incidence.
The purpose of our study was to compare the diagnostic performance of a digital selenium detector (Thoravision) with that of analog film-screen systems and digital luminescence radiography in ...skeletal radiography for the detection of fissures and lesions in porcine bones.
One hundred bones taken from domestic pigs (50 ribs and 50 femurs) were divided into two equal groups. Fissures and bone lesions were created in 50 bones and 50 served as controls. The bones were examined using film-screen systems, digital luminescence radiography, and digital selenium radiography at various doses. Digital selenium radiography exposure values were adapted to the image geometry differing from the reference methods with a detector focus distance of 2.15 m. Four radiologists independently evaluated image quality and detectability of fissures and lesions on a five-point scale of confidence. Statistical evaluation was based on receiver operating characteristic curve analysis.
Fissures and bone lesions were detected most reliably using the mammography film-screen system, but the difference in the results of the analog and digital reference images did not achieve statistical significance.
Compared with analog film-screen systems, the lower spatial resolution of the digital selenium and digital luminescence radiography systems does not affect detectability of fissures and bone lesions in porcine bone. Selenium is effective in skeletal radiography for detecting fissures and bone lesions. With digital selenium and digital luminescence radiography, the surface dose can be cut to half that required for 200-speed film-screen systems without losing any diagnostically relevant information.
To compare a large-area direct-readout flat-panel detector system with a conventional screen-film system and a storage-phosphor system in detecting small artificial osseous lesions simulating ...osteolytic disease and to assess diagnostic performance with decreasing exposure dose.
Artificial lesions (0.5-3.0 mm) were created in 100 of 200 predefined regions in 20 porcine femoral specimens. Specimens were enclosed in containers filled with water to create absorption and scatter radiation conditions comparable with those in a human extremity. Imaging was performed with a flat-panel detector system, a conventional screen-film system, and a storage-phosphor system. Levels of exposure equivalent to speed classes 400, 800, 1600, and 3200 were used. In all images, the presence or absence of a lesion was assessed by three radiologists using a five-point confidence scale. Receiver operating characteristic (ROC) analysis was performed for 4,800 observations (600 for each imaging modality and exposure level) and diagnostic performance estimated with the area under the ROC curve (A(z)). The significance of differences in diagnostic performance was tested with analysis of variance.
ROC analysis showed A(z) values of 0.820 (speed class 400), 0.780 (class 800), 0.758 (class 1600), and 0.676 (class 3200) for the flat-panel detector; 0.761 (class 400), 0.725 (class 800), and 0.662 (class 1600) for the storage-phosphor system; and 0.788 (class 400) for the conventional screen-film system. The A(z) value for the flat-panel detector at speed class 400 was significantly higher than that for all other systems (P <.05). A(z) values for the speed class 400 screen-film system and flat-panel detector system at speed class 800 were not significantly different.
The flat-panel detector has diagnostic performance superior to that of conventional screen-film and storage-phosphor radiography for detecting small artificial osseous lesions at clinical exposure settings. With the flat-panel detector, exposure dose can be reduced by 50% to obtain diagnostic performance comparable with that of a conventional speed class 400 screen-film system.
The purpose of the study was to examine the possibilities for reducing radiation exposure in uroradiology using digital flat-panel silicon X-ray detector radiography. We compared the subjectively ...determined image quality of abdominal radiographs and urograms obtained on a digital flat-panel detector radiography system with those obtained on a computed radiography system. SUBJECTS AND METHODS. Fifty patients who had a clinical indication for urography underwent unenhanced abdominal imaging that was alternately performed using flat-panel silicon X-ray detector radiography or computed radiography. For patients who required a second radiograph with contrast medium, the examination modality was changed to avoid exposing the patients to excess radiation. The images obtained on flat-panel X-ray detector radiography were obtained at half the radiation dose of the images obtained on computed radiography (800 speed vs 400 speed). The resulting 50 pairs of images were interpreted by four independent observers who rated the detectability of structures of bone and the efferent urinary tract relevant to diagnosis and compared the image quality.
At half the radiation dose, digital flat-panel X-ray detector radiography provided equivalent image quality of the liver and spleen, lumbar vertebrae 2 and 5, pelvis, and psoas margin on abdominal radiographs. The image quality obtained with digital flat-panel X-ray detector radiography of the kidneys, the hollow cavities of the upper efferent urinary tract, and the urinary bladder was judged to be statistically better than those obtained with computed radiography.
With half the exposure dose of computed radiography, the flat-panel X-ray detector produced urograms with an image quality equivalent to or better than computed radiography.
To evaluate the efficacy of adalimumab in the healing of draining fistulas in patients with active Crohn's disease (CD).
A phase III, multicentre, randomised, double-blind, placebo controlled study ...with an open-label extension was conducted in 92 sites.
A subgroup of adults with moderate to severely active CD (CD activity index 220-450) for >or=4 months who had draining fistulas at baseline.
All patients received initial open-label adalimumab induction therapy (80 mg/40 mg at weeks 0/2). At week 4, all patients were randomly assigned to receive double-blind placebo or adalimumab 40 mg every other week or weekly to week 56 (irrespective of fistula status). Patients completing week 56 of therapy were then eligible to enroll in an open-label extension.
Complete fistula healing/closure (assessed at every visit) was defined as no drainage, either spontaneous or with gentle compression.
Of 854 patients enrolled, 117 had draining fistulas at both screening and baseline (70 randomly assigned to adalimumab and 47 to placebo). The mean number of draining fistulas per day was significantly decreased in adalimumab-treated patients compared with placebo-treated patients during the double-blind treatment period. Of all patients with healed fistulas at week 56 (both adalimumab and placebo groups), 90% (28/31) maintained healing following 1 year of open-label adalimumab therapy (observed analysis).
In patients with active CD, adalimumab therapy was more effective than placebo for inducing fistula healing. Complete fistula healing was sustained for up to 2 years by most patients in an open-label extension trial.
For most applications, conventional film based methods may be replaced by digital imaging. This trend is influenced technically by the advent of more efficient detectors, improved image processing ...methods, faster computers, brighter and sharper displays and larger systems for image storage and archiving. The evolution of digital imaging reflects the fast development of information technology. Work in radiology departments will change. Information systems will organize the registration and administration of patient data, the scheduling of examinations, management of work flow and the generation of reports. Images will be taken without film cassettes and will be directly displayed on monitors for reporting. Digital imaging provides greater flexibility in processing, transmitting and displaying images. A larger dynamic range and improved contrast resolution lead to a consistently high image quality. This must lead to new rules of diagnosing images and quality assurance. Interfaces are interrelating imaging modalities, displays, the administration and the archive system to each other. The resulting net has to be safe, stable and fault-tolerant. Digital imaging systems will depend much more on the proper function of the interrelated systems in the network.
Evaluation of low-dose full spine radiographs using fluoroscopic images for the assessment of the Cobb angle measurement in patients with scoliosis.
Twenty-one consecutive patients (aged 10 - 27 ...years, mean age 14 years) with a conventional full spine examination (film speed class 800) underwent a follow-up exam using digital pulsed fluoroscopy (Multi Diagnost 4, Philips Medical Systems, Eindhoven, The Netherlands). The mean follow-up was 9 months. During a synchronized scan with a C-arm speed of 4 cm/sec fluoroscopic images were stored with a pulsed frequency of 3 images per second. The single images were merged and reconstructed to one image with the software Easy Spine (Philips medical Systems, Eindhoven, The Netherlands). The corresponding dose-area product values (DAP) of both methods were compared. Three independent observers assessed Cobb angles and image quality for each technique.
The mean DAP values for conventional imaging was 94.9 cGy x cm (2) and for fluoroscopy 7.8 cGy x cm (2), respectively. A significant dose reduction of 91.8 % (CI 91 % to 95 %) was calculated. The average absolute angle difference between the observers was found to be 2.7 degrees for conventional imaging and 2.4 degrees for the fluoroscopic method. Interobserver standard deviation of 2.9 degrees was lower than the 5.3 degrees for conventional images. Image quality was better in the conventional images.
Using the scanning method, we could achieve a mean reduction of the radiation dose of 92 %, while the accuracy of the Cobb angle measurements was comparable for both techniques despite of reduced image quality of digital fluoroscopy.
Background: “Probiotic” bacteria are effective in treating some inflammatory bowel diseases. However which bacteria confer benefit and mechanisms of action remain poorly defined. Dendritic cells, ...which are pivotal in early bacterial recognition, tolerance induction, and shaping of T cell responses, may be central in mediating the effects of these bacteria. Aims: To assess effects of different probiotic bacteria on dendritic cell function. Methods: Human intestinal lamina propria mononuclear cells, whole blood, or an enriched blood dendritic cell population were cultured with cell wall components of the eight bacterial strains in the probiotic preparation VSL#3 (four lactobacilli, three bifidobacteria, and one streptococcal strains). Dendritic cells were identified and changes in dendritic cell maturation/costimulatory markers and cytokine production in response to probiotic bacteria were analysed by multicolour flow cytometry, in addition to subsequent effects on T cell polarisation. Results: VSL#3 was a potent inducer of IL-10 by dendritic cells from blood and intestinal tissue, and inhibited generation of Th1 cells. Individual strains within VSL#3 displayed distinct immunomodulatory effects on dendritic cells; the most marked anti-inflammatory effects were produced by bifidobacteria strains which upregulated IL-10 production by dendritic cells, decreased expression of the costimulatory molecule CD80, and decreased interferon-γ production by T cells. VSL#3 diminished proinflammatory effects of LPS by decreasing LPS induced production of IL-12 while maintaining IL-10 production. Conclusions: Probiotic bacteria differ in their immunomodulatory activity and influence polarisation of immune responses at the earliest stage of antigen presentation by dendritic cells.
Background & Aims Inflammatory bowel diseases (IBD) are becoming more common in Asia, but epidemiologic data are lacking. The Asia-Pacific Crohn’s and Colitis Epidemiology Study aimed to determine ...the incidence and phenotype of IBD in 8 countries across Asia and in Australia. Methods We performed a prospective, population-based study of IBD incidence in predefined catchment areas, collecting data for 1 year, starting on April 1, 2011. New cases were ascertained from multiple overlapping sources and entered into a Web-based database. Cases were confirmed using standard criteria. Local endoscopy, pathology, and pharmacy records were searched to ensure completeness of case capture. Results We identified 419 new cases of IBD (232 of ulcerative colitis UC, 166 of Crohn’s disease CD, and 21 IBD-undetermined). The crude annual overall incidence values per 100,000 individuals were 1.37 for IBD in Asia (95% confidence interval: 1.25−1.51; 0.76 for UC, 0.54 for CD, and 0.07 for IBD-undetermined) and 23.67 in Australia (95% confidence interval: 18.46−29.85; 7.33 for UC, 14.00 for CD, and 2.33 for IBD-undetermined). China had the highest incidence of IBD in Asia (3.44 per 100,000 individuals). The ratios of UC to CD were 2.0 in Asia and 0.5 in Australia. Median time from symptom onset to diagnosis was 5.5 months (interquartile range, 1.4−15 months). Complicated CD (stricturing, penetrating, or perianal disease) was more common in Asia than Australia (52% vs 24%; P = .001), and a family history of IBD was less common in Asia (3% vs 17%; P < .001). Conclusions We performed a large-scale population-based study and found that although the incidence of IBD varies throughout Asia, it is still lower than in the West. IBD can be as severe or more severe in Asia than in the West. The emergence of IBD in Asia will result in the need for specific health care resources, and offers a unique opportunity to study etiologic factors in developing nations.
Summary
Background
Crohn's disease recurs in the majority of patients after intestinal resection.
Aim
To compare the relative efficacy of thiopurines and anti‐TNF therapy in patients at high risk of ...disease recurrence.
Methods
As part of a larger study comparing post‐operative management strategies, patients at high risk of recurrence (smoker, perforating disease, ≥2nd operation) were treated after resection of all macroscopic disease with 3 months metronidazole together with either azathioprine 2 mg/kg/day or mercaptopurine 1.5 mg/kg/day. Thiopurine‐intolerant patients received adalimumab induction then 40 mg fortnightly. Patients underwent colonoscopy at 6 months with endoscopic recurrence assessed blind to treatment.
Results
A total of 101 patients 50% male; median (IQR) age 36 (25–46) years were included. There were no differences in disease history between thiopurine‐ and adalimumab‐treated patients. Fifteen patients withdrew prior to 6 months, five due to symptom recurrence (of whom four were colonoscoped). Endoscopic recurrence (Rutgeerts score i2–i4) occurred in 33 of 73 (45%) thiopurine vs. 6 of 28 (21%) adalimumab‐treated patients intention‐to‐treat (ITT); P = 0.028 or 24 of 62 (39%) vs. 3 of 24 (13%) respectively per‐protocol analysis (PPA); P = 0.020. Complete mucosal endoscopic normality (Rutgeerts i0) occurred in 17/73 (23%) vs. 15/28 (54%) (ITT; P = 0.003) and in 27% vs. 63% (PPA; P = 0.002). The most advanced disease (Rutgeerts i3 and i4) occurred in 8% vs. 4% (thiopurine vs. adalimumab).
Conclusions
In Crohn's disease patients at high risk of post‐operative recurrence adalimumab is superior to thiopurines in preventing early disease recurrence.
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