Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease

<p>Abstract</p> <p>Background</p> <p>Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients.</p> <p>Methods</p> <p>One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT).</p> <p>Results</p> <p>Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO.</p> <p>Conclusion</p> <p>SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors.</p

Inter-comparison of MAX-DOAS measurements of tropospheric HONO slant column densities and vertical profiles during the CINDI-2 campaign

We present the inter-comparison of delta slant column densities (SCDs) and vertical profiles of nitrous acid (HONO) derived from measurements of different multi-axis differential optical absorption spectroscopy (MAX-DOAS) instruments and using different inversion algorithms during the Second Cabauw Inter-comparison campaign for Nitrogen Dioxide measuring Instruments (CINDI-2) in September 2016 at Cabauw, the Netherlands (51.97∘ N, 4.93∘ E). The HONO vertical profiles, vertical column densities (VCDs), and near-surface volume mixing ratios are compared between different MAX-DOAS instruments and profile inversion algorithms for the first time. Systematic and random discrepancies of the HONO results are derived from the comparisons of all data sets against their median values. Systematic discrepancies of HONO delta SCDs are observed in the range of ±0.3×1015 molec. cm−2, which is half of the typical random discrepancy of 0.6×1015 molec. cm−2. For a typical high HONO delta SCD of 2×1015 molec. cm−2, the relative systematic and random discrepancies are about 15 % and 30 %, respectively. The inter-comparison of HONO profiles shows that both systematic and random discrepancies of HONO VCDs and near-surface volume mixing ratios (VMRs) are mostly in the range of ∼±0.5×1014 molec. cm−2 and ∼±0.1 ppb (typically ∼20 %). Further we find that the discrepancies of the retrieved HONO profiles are dominated by discrepancies of the HONO delta SCDs. The profile retrievals only contribute to the discrepancies of the HONO profiles by ∼5 %. However, some data sets with substantially larger discrepancies than the typical values indicate that inappropriate implementations of profile inversion algorithms and configurations of radiative transfer models in the profile retrievals can also be an important uncertainty source. In addition, estimations of measurement uncertainties of HONO dSCDs, which can significantly impact profile retrievals using the optimal estimation method, need to consider not only DOAS fit errors, but also atmospheric variability, especially for an instrument with a DOAS fit error lower than ∼3×1014 molec. cm−2. The MAX-DOAS results during the CINDI-2 campaign indicate that the peak HONO levels (e.g. near-surface VMRs of ∼0.4 ppb) often appeared in the early morning and below 0.2 km. The near-surface VMRs retrieved from the MAX-DOAS observations are compared with those measured using a co-located long-path DOAS instrument. The systematic differences are smaller than 0.15 and 0.07 ppb during early morning and around noon, respectively. Since true HONO values at high altitudes are not known in the absence of real measurements, in order to evaluate the abilities of profile inversion algorithms to respond to different HONO profile shapes, we performed sensitivity studies using synthetic HONO delta SCDs simulated by a radiative transfer model with assumed HONO profiles. The tests indicate that the profile inversion algorithms based on the optimal estimation method with proper configurations can reproduce the different HONO profile shapes well. Therefore we conclude that the features of HONO accumulated near the surface derived from MAX-DOAS measurements are expected to represent the ambient HONO profiles well

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre

BACKGROUND: Celiac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period. METHODS: To diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient. RESULTS: In our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22-67), 6/8 Crohn's disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn's disease patients are B1, 2/6 Crohn's disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients. CONCLUSIONS: Within our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population

Intercomparison of NO2, O4, O3 and HCHO slant column measurements by MAX-DOAS and zenith-sky UV¿visible spectrometers during CINDI-2

40 pags., 22 figs., 13 tabs.In September 2016, 36 spectrometers from 24 institutes measured a number of key atmospheric pollutants for a period of 17¿d during the Second Cabauw Intercomparison campaign for Nitrogen Dioxide measuring Instruments (CINDI-2) that took place at Cabauw, the Netherlands (51.97¿¿N, 4.93¿¿E). We report on the outcome of the formal semi-blind intercomparison exercise, which was held under the umbrella of the Network for the Detection of Atmospheric Composition Change (NDACC) and the European Space Agency (ESA). The three major goals of CINDI-2 were (1) to characterise and better understand the differences between a large number of multi-axis differential optical absorption spectroscopy (MAX-DOAS) and zenith-sky DOAS instruments and analysis methods, (2) to define a robust methodology for performance assessment of all participating instruments, and (3) to contribute to a harmonisation of the measurement settings and retrieval methods. This, in turn, creates the capability to produce consistent high-quality ground-based data sets, which are an essential requirement to generate reliable long-term measurement time series suitable for trend analysis and satellite data validation. The data products investigated during the semi-blind intercomparison are slant columns of nitrogen dioxide (NO2), the oxygen collision complex (O4) and ozone (O3) measured in the UV and visible wavelength region, formaldehyde (HCHO) in the UV spectral region, and NO2 in an additional (smaller) wavelength range in the visible region. The campaign design and implementation processes are discussed in detail including the measurement protocol, calibration procedures and slant column retrieval settings. Strong emphasis was put on the careful alignment and synchronisation of the measurement systems, resulting in a unique set of measurements made under highly comparable air mass conditions. The CINDI-2 data sets were investigated using a regression analysis of the slant columns measured by each instrument and for each of the target data products. The slope and intercept of the regression analysis respectively quantify the mean systematic bias and offset of the individual data sets against the selected reference (which is obtained from the median of either all data sets or a subset), and the rms error provides an estimate of the measurement noise or dispersion. These three criteria are examined and for each of the parameters and each of the data products, performance thresholds are set and applied to all the measurements. The approach presented here has been developed based on heritage from previous intercomparison exercises. It introduces a quantitative assessment of the consistency between all the participating instruments for the MAX-DOAS and zenith-sky DOAS techniques.CINDI-2 received funding from the Netherlands Space Office (NSO). Funding for this study was provided by ESA through the CINDI-2 (ESA contract no. 4000118533/16/ISbo) and FRM4DOAS (ESA contract no. 4000118181/16/I-EF) projects and partly within the EU 7th Framework Programme QA4ECV project (grant agreement no. 607405). The BOKU MAX-DOAS instrument was funded and the participation of Stefan F. Schreier was supported by the Austrian Science Fund (FWF): I 2296-N29. The participation of the University of Toronto team was supported by the Canadian Space Agency (through the AVATARS project) and the Natural Sciences and Engineering Research Council (through the PAHA project). The instrument was primarily funded by the Canada Foundation for Innovation and is usually operated at the Polar Environment Atmospheric Research Laboratory (PEARL) by the Canadian Network for the Detection of Atmospheric Change (CANDAC). Funding for CISC was provided by the UVAS (“Ultraviolet and Visible Atmospheric Sounder”) projects SEOSAT/INGENIO, ESP2015-71299- R, MINECO-FEDER and UE. The activities of the IUP-Heidelberg were supported by the DFG project RAPSODI (grant no. PL 193/17-1). SAOZ and Mini-SAOZ instruments are supported by the Centre National de la Recherche Scientifique (CNRS) and the Centre National d’Etudes Spatiales (CNES). INTA recognises support from the National funding projects HELADO (CTM2013-41311-P) and AVATAR (CGL2014-55230-R). AMOIAP recognises support from the Russian Science Foundation (grant no. 16-17-10275) and the Russian Foundation for Basic Research (grant nos. 16-05- 01062 and 18-35-00682). Ka L. Chan received transnational access funding from ACTRIS-2 (H2020 grant agreement no. 654109). Rainer Volkamer recognises funding from NASA’s Atmospheric Composition Program (NASA-16-NUP2016-0001) and the US National Science Foundation (award AGS-1620530). Henning Finkenzeller is the recipient of a NASA graduate fellowship. Mihalis Vrekoussis recognises support from the University of Bremen and the DFG Research Center/Cluster of Excellence “The Ocean in the Earth System-MARUM”. Financial support through the University of Bremen Institutional Strategy in the framework of the DFG Excellence Initiative is gratefully appreciated for Anja Schönhardt. Pandora instrument deployment was supported by Luftblick through the ESA Pandonia Project and NASA Pandora Project at the Goddard Space Flight Center under NASA Headquarters’ Tropospheric Composition Program. The article processing charges for this open-access publication were covered by BK Scientific

Cost effectiveness of ibandronate for the prevention of fractures in inflammatory bowel disease-related osteoporosis: Cost-utility analysis using a Markov model.

Osteoporosis is a frequent complication in patients with inflammatory bowel disease. Recent studies have shown bisphosphonates to considerably reduce fracture risk in patients with osteoporosis, and preventing fractures with bisphosphonates has been reported to be cost effective in older populations. However, no studies of the cost effectiveness of these agents in preventing fractures in patients with inflammatory bowel disease are available. OBJECTIVE: To investigate the cost effectiveness of the bisphosphonate ibandronate combined with calcium/colecalciferol (&#39;ibandronate&#39;) in patients with osteopenia or osteoporosis due to inflammatory bowel disease in Germany. Treatment strategies used for comparison were sodium fluoride combined with calcium/colecalciferol (&#39;fluoride&#39;) and calcium/colecalciferol (&#39;calcium&#39;) alone. STUDY DESIGN AND METHODS: A cost-utility analysis was conducted using data from a randomized controlled trial (RCT). Changes in bone mineral density (BMD) were adjusted and predicted for a standardized population receiving each respective treatment. A Markov model was developed, with probabilities of transition to fracture states consisting of BMD-dependent and -independent components. The BMD-dependent component was assessed using predicted change in BMD from the RCT. The independent component captured differences in bone quality and micro-architecture resulting from prevalent fractures or treatment with anti-resorptive drugs.The analysis was conducted for a population with a mean age of the RCT patients (women aged 36 years, men aged 38 years) with osteopenia (T-score about -2.0 at baseline), a population of the same age with osteoporosis (T-score of -3.0 at baseline) and for an older population (both sexes aged 65 years) with osteoporosis (T-score of -3.0). Outcomes were measured as costs per QALY gained from a societal perspective. The treatment duration in the RCT was 42 months. A 5-year period was assumed to follow, during which the treatment effects linearly declined to 0. The simulation time was 10 years.Prices for medication and treatment were presented as year 2004 values; costs and effects were discounted at 5%. To test the robustness of the results, univariate and probabilistic sensitivity analyses (Monte Carlo simulation) were conducted. RESULTS: The calcium strategy dominated the fluoride strategy. When the ibandronate strategy was compared with the calcium strategy, the base-case cost-effectiveness ratios (costs per QALY gained) were between euro 407 375 for an older female population with osteoporosis and euro 6 516 345 for a younger female population with osteopenia. Univariate sensitivity analyses resulted in variations between 4% of base-case results and dominance of calcium. In Monte Carlo simulations, conducted for the various populations, the probability of an ICER of ibandronate below euro 50 000 per QALY was never greater than 20.2%. CONCLUSION: The ibandronate strategy is unlikely to be considered cost effective by decision makers in men or women with characteristics of those in the target population of the RCT, or in older populations with osteoporosis

Bones and Crohn's: Estradiol deficiency in men with Crohn's disease is not associated with reduced bone mineral density

<p>Abstract</p> <p>Background</p> <p>Reduced bone mineral density (BMD) and osteoporosis are frequent in Crohn's disease (CD), but the underlying mechanisms are still not fully understood. Deficiency of sex steroids, especially estradiol (E2), is an established risk factor in postmenopausal osteoporosis.</p> <p>Aim</p> <p>To assess if hormonal deficiencies in male CD patients are frequent we investigated both, sex steroids, bone density and bone metabolism markers.</p> <p>Methods</p> <p>111 male CD patients underwent osteodensitometry (DXA) of the spine (L1–L4). Disease related data were recorded. Disease activity was estimated using Crohn's disease activity index (CDAI). Testosterone (T), dihydrotestosterone (DHT), estradiol (E2), sex hormone binding globulin (SHBG), Osteocalcin and carboxyterminal cross-linked telopeptids (ICTP) were measured in 111 patients and 99 age-matched controls.</p> <p>Results</p> <p>Patients had lower T, E2 and SHBG serum levels (p < 0.001) compared to age-matched controls. E2 deficiency was seen in 30 (27.0%) and T deficiency in 3 (2.7%) patients but only in 5 (5.1%) and 1 (1%) controls. Patients with E2 deficiency had significantly decreased T and DHT serum levels. Use of corticosteroids for 3 of 12 months was associated with lower E2 levels (p < 0.05). Patients with life-time steroids >10 g had lower BMD. 32 (28.8%) patients showed osteoporosis, 55 (49.5%) osteopenia and 24 (21.6%) had normal BMD. Patients with normal or decreased BMD showed no significant difference in their hormonal status. No correlation between markers of bone turnover and sex steroids could be found. ICTP was increased in CD patients (p < 0.001), and patients with osteoporosis had higher ICTP levels than those with normal BMD.</p> <p>Conclusion</p> <p>We found an altered hormonal status – i.e. E2 and, to a lesser extent T deficiency – in male CD patients but failed to show an association to bone density or markers of bone turnover. The role of E2 in the negative skeletal balance in males with CD, analogous to E2 deficiency in postmenopausal females, deserves further attention.</p