Wolfgang Miehsler

Inflammatory Bowel Disease Is a Risk Factor for Recurrent Venous Thromboembolism

BACKGROUND & AIMSnPatients with inflammatory bowel disease (IBD) are at increased risk of a first venous thromboembolism (VTE), yet their risk of recurrent VTE is unknown. We performed a cohort study to determine the risk for recurrent VTE among patients with IBD compared with subjects without IBD.nnnMETHODSnWe assessed 2811 patients with IBD for a history of VTE, recruited from outpatient clinics at 14 referral centers (June 2006-December 2008). Patients with VTE before a diagnosis of IBD or those not confirmed to have VTE, cancer, or a VTE other than deep vein thrombosis or pulmonary embolism, were excluded. Recurrence rates were compared with 1255 prospectively followed patients without IBD that had a first unprovoked VTE (not triggered by trauma, surgery, or pregnancy). The primary end point was symptomatic, objectively confirmed, recurrent VTE after discontinuation of anticoagulation therapy after a first VTE.nnnRESULTSnOverall, of 116 IBD patients who had a history of first VTE, 86 were unprovoked. The probability of recurrence 5 years after discontinuation of anticoagulation therapy was higher among patients with IBD than patients without IBD (33.4%; 95% confidence interval [CI]: 21.8-45.0 vs 21.7%; 95% CI: 18.8-24.6; P = .01). After adjustment for potential confounders, IBD was an independent risk factor of recurrence (hazard ratio = 2.5; 95% CI: 1.4-4.2; P = .001).nnnCONCLUSIONSnPatients with IBD are at an increased risk of recurrent VTE compared to patients without IBD.

Endoscopy and MR enteroclysis: Equivalent tools in predicting clinical recurrence in patients with Crohn's disease after ileocolic resection

Background: Ileocolonoscopy poses the gold standard in the evaluation of postoperative recurrence of Crohns disease (CD) at the site of ileocolonic anastomosis. Magnetic resonance enteroclysis (MRE) on the other hand is a promising technique for small bowel imaging. The aim was to compare MRE and ileocolonoscopy for predicting clinical recurrence in CD patients who have undergone ileocolonic resection. Methods: We included 29 patients in the study. The median time since index operation was 35 months and between ileocolonoscopy and MRE was 3 days. Patients were followed up for a maximum of 2 years unless clinical recurrence occurred earlier. Endoscopic findings were evaluated on a 5‐grade scale (i0–i4), whereas MRE findings on the neoterminal ileum and anastomosis were assessed according to a previously validated 4‐grade scale MR score (MR0‐MR3). Results: By classifying patients into subgroups of endoscopic severity of postoperative recurrence using as a threshold an endoscopic score of i3, we found that 10% of patients in the i0 to i2 group had a clinical recurrence during the 2‐year follow‐up period as compared to 52.6% of subjects with i3 to i4 (P = 0.043). The corresponding clinical exacerbation rates in the subgroups based on MRE severity assessment were 12.5% for MR0 to MR1 and 50% for MR2 to MR3 (P = 0.09). Conclusions: Our data suggest that colonoscopy and MR enteroclysis are of similar value to predict the risk of clinical recurrence in postoperative patients with Crohns disease. Inflamm Bowel Dis 2009

Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding ☆

BACKGROUNDnRecommendations on breastfeeding under thiopurines are inconsistent due to limited data.nnnAIMnTo assess the risk of infections in offspring breastfed by mothers receiving azathioprine (AZA) for inflammatory bowel disease (IBD).nnnMETHODSnBabies, who were breastfed from their mothers treated either with or without AZA were included from a local pregnancy-registry. Women were asked by structured personal interview on general development, infections, hospitalisations and vaccinations of their offspring.nnnRESULTSnA group of 11 mothers taking AZA (median 150 mg/d) during pregnancy and lactation and another of 12 patients without using any immunosuppressive therapy breastfed 15 babies each for median 6 months and 8 months, respectively. Median age of children at time of interview was 3.3 and 4.7 years, respectively. All offspring showed age-appropriate mental and physical development. Infections were commonly seen childhood diseases. Similar rates were observed for most of the various infections between offspring with and without azathioprine exposure during breastfeeding. However, common cold more than two episodes/year and conjunctivitis were numerically more often reported in the group without AZA exposure. In an exploratory analysis no difference in the rate of hospitalisations was seen between exposed (0.06 hospitalisations/patient year) versus non-exposed children (0.12 hospitalisations/patient year, p=0.8)nnnCONCLUSIONnOur study which reports the largest number of babies breastfed with exposure to AZA suggests that breastfeeding does not increase the risk of infections.

The Impact of Thiopurines on the Risk of Surgical Recurrence in Patients With Crohn's Disease After First Intestinal Surgery

OBJECTIVES:Smoking and a lack of immunosuppressive (IS) therapy are considered risk factors for intestinal surgery in Crohns disease (CD). Good evidence for the latter is lacking. The objective of this study was to evaluate the impact of thiopurine treatment on surgical recurrence in patients after first intestinal resection for CD and its possible interaction with smoking.METHODS:Data on 326 patients after first intestinal resection were retrieved retrospectively, and subjects were grouped according to their postoperative exposure to thiopurines. Treatment with either azathioprine (AZA) or 6-mercaptopurine (6-MP) was recorded on 161 patients (49%). Smoking status was assessed by directly contacting the patients.RESULTS:Surgical recurrence occurred in 151/326 (46.3%) patients after a median time of 71 (range 3–265) months. Cox regression revealed a significant reduction of re-operation rate in patients treated with AZA/6-MP for ⩾36 months as compared with patients treated for 3–35 months, for less than 3 months, and to those without postoperative treatment with AZA/6-MP (P=0.004). Cox regression analysis revealed treatment with thiopurines for ⩾36 months (hazard ratio (HR) 0.41; 95% confidence interval (CI) 0.23–0.76, P=0.004) and smoking (HR 1.6; 95% CI 1.14–2.4, P=0.008) as independent predictors for surgical recurrence. Furthermore, longer duration of disease tended to be protective (HR 0.99; 95% CI 0.99–1.0, P=0.067).CONCLUSIONS:Long-term maintenance treatment with AZA/6-MP reduces the risk of surgical recurrence in patients with CD. We also identified smoking as a risk factor for surgical recurrence.

A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease

Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.

Factors impacting the results of interferon‐γ release assay and tuberculin skin test in routine screening for latent tuberculosis in patients with inflammatory bowel diseases

Background: Screening for latent tuberculosis (LTB) including chest x‐ray, tuberculin skin test (TST), and facultative whole blood interferon‐&ggr; assay (IGRA) is part of routine management in inflammatory bowel disease (IBD) patients before starting therapy with tumor necrosis factor (TNF)‐&agr; inhibitors. However, in patients with immunomodulators (IM) TST and IGRA might show limitations. Methods: We aimed to evaluate the results from an IGRA (QuantiFERON‐TB Gold in Tube) and TST as well as their concordance in 208 consecutive IBD patients with indications for anti‐TNF‐&agr; therapy. Associations of both tests with risk factors for LTB were determined by logistic regression. Results: During screening, 149 patients (71.6%) were under IM therapy. In 26 (12.5%) patients TST was positive, whereas 15 (7.2%) patients showed a positive result from IGRA. IGRA failed on samples from 16/208 (7.7%) patients, resulting in 192/208 (92.3%) patients in whom results from both screening tests were available. Correlation between IGRA and TST results was fair (84.9%, &kgr; = 0.21). The presence of risk factors for LTB showed association with positive results of TST (odds ratio [OR] 3.7, 1.5–9.6) and IGRA (OR 3.5, 1.2–11.3). TST was associated furthermore with age (OR 1.06, 1.02–1.10) and signs indicative of LTB in chest x‐ray (OR 4.9, 1.1–19.9). The IGRA was negatively influenced by IM therapy (OR 0.3, 0.1–0.9). Conclusion: Our study reveals that results of IGRA are negatively affected by IM therapy. Thus, current guidelines for TB screening prior anti‐TNF‐&agr; therapy appear inaccurate in patients under IM. Therefore, LTB screening might be best performed prior to initiation of IM treatment. (Inflamm Bowel Dis 2011;)

Comparison of a new unguided self-advancing jejunal tube with the endoscopic guided technique: a prospective, randomized study

ObjectiveTo compare the success rate of correct jejunal placement of a new self-advancing jejunal tube with the gold standard, the endoscopic guided technique, in a comparative intensive care unit (ICU) patient population.DesignProspective, randomized study.SettingTwo medical ICUs at a university hospital.PatientsForty-two mechanically ventilated patients with persisting intolerance of intragastric enteral nutrition despite prokinetic therapy.MethodsPatients were randomly assigned to receive an unguided self-advancing jejunal feeding tube (Tiger Tube™) or an endoscopic guided jejunal tube (Freka® Trelumina). Primary outcome measure was the success rate of correct jejunal placement after 24xa0h.ResultsCorrect jejunal tube placement was reached in all 21 patients using the endoscopic guided technique whereas the unguided self-advancing jejunal tube could be placed successfully in 14 out of 21 patients (100% versus 67%; Pxa0=xa00.0086). In the remaining seven patients, successful endoscopic jejunal tube placement was performed subsequently. Duration of tube placement was longer in the unguided self-advancing tube group (20xa0±xa012xa0min versus 597xa0±xa0260xa0min; Pxa0<xa00.0001). Secondary outcome parameters (complication rate, number of attempts, days in correct position with accurate functional capability, days with high gastric residual volume, length of ICU stay, ICU mortality) were not statistically different between the two groups. No potentially relevant parameter predicting the failure of correct jejunal placement of the self-advancing tube could be identified.ConclusionsSuccess rate of correct jejunal placement of the new unguided self-advancing tube was significantly lower than the success rate of the endoscopic guided technique.

Impact of Interobserver Disagreement on Phenotype-Genotype Associations in Crohn's Disease

Background Nonvalidated definitions of disease‐related parameters in inflammatory bowel disease cause variations in diagnosis and disease classification. We determined interobserver agreement on applications of definitions of the Vienna Classification variables and computed the potential influence of misclassification on genotype/phenotype associations. Methods Ten records of patients with Crohns disease (CD) were independently evaluated by 19 observers using a standardized inflammatory bowel disease documentation system, which included the Vienna Classification. Interobserver agreement (IOA) was calculated as a percentage of the observers agreement with a predetermined reference observer and by Cohens kappa. Randomized reclassifications were then computed with 10,000 simulation runs using the IOA results and published NOD2/CARD15 gene status. A chi‐square independence test was calculated for each simulation run. Results IOA for location and behavior was 70% (&kgr; = 0.57) and 95% (&kgr; = 0.91), respectively. IOA for location subgroups ranged from 48% to 88% and for behavior from 91% to 97%. By including the results of histopathology into the evaluation of location, the overall IOA increased significantly, to 80% (P = 0.019). Assuming a true genotype/phenotype association, the proportion of studies with nonsignificant findings (P > 0.05) because of the observed misclassification of location ranged from 13.3% to 63.8% and of behavior from 0.2% to 22.2%, depending on a study sample size of 500 or 150 patients respectively. Conclusions We concluded that there is appreciable interobserver disagreement on the location of CD according to the original Vienna Classification that may obscure true genotype/phenotype associations. Definitions of disease parameters have to be validated before being used as the bases for classifications. (Inflamm Bowel Dis 2007)

Mortality, morbidity and special issues of obese ICU patients

ZusammenfassungAdipositas ist in den westlichen Industrienationen auf dem Vormarsch und daher auch für die Intensivmedizin zunehmend von Bedeutung. Entgegen der landläufigen Meinung, dass adipöse Intensiv-Patienten wohl eine erhöhte Mortalität haben dürften, zeigen überzeugende Meta-Analysen dass dem nicht so ist. Nichtsdestotrotz sind adipöse Intensiv-Patienten eine Herausforderung. Insbesondere die Beatmung dieser Patienten ist erwähnenswert: neben den anatomischen Besonderheiten, die die Intubation adipöser Patienten erschweren können, sind obstruktive Schlafapnoe, das Adipositas-Hypoventilations-Syndrom und der erhöhte intraabdominale Druck in Hinblick auf Beatmung, Entwöhnung und erfolgreiche Extubation zu nennen. Auch das Risiko für Infektionen ist bei adipösen Intensivpatienten erhöht, wenngleich damit kein erhöhtes Sepsisrisiko einherzugehen scheint. Unabhängig davon ist die mögliche Interaktion von Adipositas und Sepsis faszinierend, wenngleich die Rolle der Adipokine in der Sepsis des adipösen Patienten noch nicht aufgeklärt ist.SummaryObesity is on the advance in western industrialised countries and is therefore increasingly relevant also to intensive care medicine. In contrast to the common prejudice that obese patients probably have a higher ICU mortality than lean patients, convincing meta-analyses have revealed that this is not the case. Nevertheless, obese ICU patients are challenging. Especially mechanic ventilation has to be addressed: besides obesity-related anatomical problems that may complicate intubation, obstructive sleep apnoea, obesity hypoventilation syndrome and increased intra-abdominal pressure are of major relevance concerning ventilation, weaning and successful extubation. Also the risk of infections is increased in obese ICU patients, although this does not seem to increase the risk of sepsis. Nevertheless, the interplay of obesity and sepsis is a fascinating field in that adipous tissue is not just a passive reservoir of energy but an active endocrine and immunomodulating organ. However, the way of how adipokines interact with inflammation and coagulation in sepsis has yet to be clarified.

Are inherited thrombotic risk factors associated with fibrostenosis in Crohn's disease?

Background: Fibrostenotic lesions are common complications in Crohns disease (CD) often requiring surgery. Inherited thrombotic risk factors are associated with fibrosis in other chronic inflammatory diseases. The aim of the study was to assess whether inherited thrombotic risk factors are associated with fibrostenosis in CD. Methods: Clinical data on 529 CD patients were collected retrospectively. Subjects were tested for and grouped according to the presence of factor V Leiden (FVL), the prothrombin G20210A, and the methylenetetrahydrofolate reductase C677T mutation (MTHFR). Patients who underwent CD‐related intestinal surgery were assessed for the presence of fibrostenosis, which was the primary endpoint. The diagnosis of fibrostenosis was based on surgical, pathological, and histopathological reports. A Cox proportional hazards model was used for statistical analysis. Results: Thirty‐two (6.1%, heterozygous 30, homozygous 2) patients were carriers of FVL, 19 (3.6%, all heterozygous) carried the prothrombin variant, and 318 (60.1%) the MTHFR variant (243 heterozygous, 75 homozygous). In all, 303 (57.3%) patients underwent intestinal surgery. Fibrostenosis was identified in 219 (72.3%) surgical specimens. The rate of first intestinal surgeries with fibrostenosis tended to be more frequent in patients with the homozygous 677TT MTHFR mutation (hazard ratio, HR 1.39; 95% confidence interval [CI]: 0.98–1.97; P = 0.067). After adjustment for potential confounders homozygous 677TT MTHFR mutation did not remain a risk factor for intestinal surgery with fibrostenosis (HR 1.23; 95% CI: 0.77–1.98; P = 0.387). FVL and the prothrombin variant had no influence on the primary endpoint. Conclusions: The MTHFR 677TT mutation, factor V Leiden, and the prothrombin G20210A mutation are not associated with fibrostenosis in CD.