Diagnostic delay in inflammatory bowel diseases in a German population.

BACKGROUND: Early diagnosis is key to prevent bowel damage in inflammatory bowel disease (IBD). Risk factor analyses linked with delayed diagnosis in European IBD patients are scarce and no data in German IBD patients exists. AIM: To identify risk factors leading to prolonged diagnostic time in a German IBD cohort. METHODS: Between 2012 and 2022, 430 IBD patients from four Berlin hospitals were enrolled in a prospective study and asked to complete a 16-item questionnaire to determine features of the path leading to IBD diagnosis. Total diagnostic time was defined as the time from symptom onset to consulting a physician (patient waiting time) and from first consultation to IBD diagnosis (physician diagnostic time). Univariate and multivariate analyses were performed to identify risk factors for each time period. RESULTS: The total diagnostic time was significantly longer in Crohn's disease (CD) compared to ulcerative colitis (UC) patients (12.0 vs 4.0 mo; P < 0.001), mainly due to increased physician diagnostic time (5.5 vs 1.0 mo; P < 0.001). In a multivariate analysis, the predominant symptoms diarrhea (P = 0.012) and skin lesions (P = 0.028) as well as performed gastroscopy (P = 0.042) were associated with longer physician diagnostic time in CD patients. In UC, fever was correlated (P = 0.020) with shorter physician diagnostic time, while fatigue (P = 0.011) and positive family history (P = 0.046) were correlated with longer physician diagnostic time. CONCLUSION: We demonstrated that CD patients compared to UC are at risk of long diagnostic delay. Future efforts should focus on shortening the diagnostic delay for a better outcome in these patients.

Integrating the Patient Perspective to Validate a Measure of Disease Severity in Inflammatory Bowel Disease: Online Survey of Patients and Their Physicians.

BACKGROUND: The patient perspective is essential for assessing disease severity, but it is not always adequately considered. We describe how a comprehensive clinical disease severity index (DSI) for inflammatory bowel disease (IBD) correlates with patient global self-assessment (PGSA). METHODS: In an individually linked parallel online survey, physicians provided the DSI, and patients provided self-assessed severity using a global question and visual analog scale (0-100) (PGSA). Mean DSI values by PGSA were calculated with 95% confidence intervals. Pearson correlation (r) and the intraclass correlation coefficient were calculated for PGSA vs DSI. Positive predictive values for identifying severe disease with PGSA categories as a reference were based on a threshold >22 points. RESULTS: The primary analysis included 89 pairs (46 Crohn's disease [CD], 43 ulcerative colitis [UC]) with strict criteria and 147 pairs when less stringent. Common reasons for exclusion were missing values for albumin or colonoscopy. Mean DSI values showed no clear trend with increasing PGSA in CD but good discrimination between moderate, severe, and very severe PGSA in UC. For PGSA on the visual analog scale, r was 0.54 for CD and 0.59 for UC (difference in means: CD 27.7, UC 13.8; intraclass correlation coefficient: CD 0.48, UC 0.58). A high DSI predicted severe disease in 76.2% of CD and 65.2% of UC. CONCLUSIONS: The DSI showed good discrimination for patient-reported disease severity in UC but performed unsatisfactorily in CD. Correlations were moderate. Further refinement of the DSI is suggested to better reflect the patient perspective.

The performance of an inflammatory bowel disease severity score was compared with self-perceived severity based on an individually linked online survey of patients and their physicians. Agreement and prediction of severe disease were moderate and should be improved by integrating the patients' perspective.

Results from the German registry for refractory celiac disease.

Refractory celiac disease (RCD) refers to a rare subgroup of patients with celiac disease who show clinical signs of malabsorption despite a gluten-free diet. RCD is divided into an autoimmune phenotype (RCD type I) and pre-lymphoma (RCD type II). To reflect the clinical reality in managing this disease in Germany, a national register was established based on a questionnaire developed specifically for this purpose. Between 2014 and 2020, a total of 53 patients were registered. The diagnosis of RCD was confirmed in 46 cases (87%). This included 27 patients (59%) with RCD type I and 19 patients (41%) with RCD type II. A wide range of diagnostic and therapeutic measures was used. Therapeutically, budesonide was used in 59% of the RCD patients regardless of the subtype. Nutritional therapy was used in only 5 patients (11%). Overall mortality was 26% (12 patients) with a clear dominance in patients with RCD type II (9 patients, 47%). In summary, RCD needs to become a focus of national guidelines to increase awareness, establish standards, and thus enable the treating physician to make the correct diagnosis in a timely manner. Moreover, we concluded that when treating such patients, contacting a specialized center is recommended to ensure sufficient management.

Improving treatment of patients with inflammatory bowel diseases: a controlled trial of a multifaceted intervention in two German cities.

PURPOSE: Many recommendations from clinical practice guidelines are not implemented. We aimed to develop and evaluate a multifaceted strategy for the implementation of guidelines for Crohn's disease (CD) and ulcerative colitis (UC). METHODS: In the intervention region (Berlin, Germany), a continuing medical education course was held, brief guidelines for practice were distributed to all family physicians and gastroenterologists, and patient guidelines were distributed to all surveyed patients. Educational outreach visits with local opinion leaders were also conducted. No specific interventions were performed in the control region (Hamburg, Germany). Prior to the intervention and 1 year later, 1900 members of three statutory sickness funds were asked about their treatment according to guidelines with (1) long-term aminosalicylates and (2) immunosuppressants, (3) whether they took long-term glucocorticoids for maintenance of remission, (4) if they smoked, in CD patients, and (5) about the surveillance colonoscopies, in UC patients. RESULTS: Response rate after implementation was 20.1%. Responders differed between intervention and control region by age and by distribution between patients with UC or CD. After 1 year, more patients were treated according to clinical practice guidelines in the control region than in the intervention region. More patients in the intervention region took immunosuppressants after 1 year, and fewer had a surveillance colonoscopy. However, no before-after comparison was statistically significant. CONCLUSIONS: This implementation strategy of UC and CD guidelines did not result in a statistically significant effect. Future implementation of guidelines for inflammatory bowel disease might need thorough evaluation of barriers and the support of theory-based concepts.

Low Sensitivity of Simtomax Point of Care Test in Detection of Celiac Disease in a Prospective Multicenter Study.

BACKGROUND & AIMS: Point of care tests (POCTs) might be used to identify patients with undiagnosed celiac disease who require further evaluation. We performed a large multicenter study to determine the performance of a POCT for celiac disease and assessed celiac disease prevalence in endoscopy centers. METHODS: We performed a prospective study of 1055 patients (888 adults; median age, 48 yrs and 167 children; median age, 10 yrs) referred to 8 endoscopy centers in Germany, for various indications, from January 2016 through June 2017. Patients were tested for celiac disease using Simtomax, which detects immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides (DGP). Results were compared with findings from histologic analyses of duodenal biopsies (reference standard). The primary aim was to determine the accuracy of this POCT for the detection of celiac disease, to identify candidates for duodenal biopsy. A secondary aim was to determine the prevalence of celiac disease in adult and pediatric populations referred for outpatient endoscopic evaluation. RESULTS: The overall prevalence of celiac disease was 4.1%. The POCT identified individuals with celiac disease with 79% sensitivity (95% CI, 64%-89%) and 94% specificity (95% CI, 93%-96%). Positive and negative predictive values were 37% and 99%. When we analyzed the adult and pediatric populations separately, we found the test to identify adults with celiac disease (prevalence 1.2%) with 100% sensitivity and 95% specificity. In the pediatric population (celiac disease prevalence 19.6%), the test produced false-negative results for 9 cases; the test therefore identified children with celiac disease with 72% sensitivity (95% CI 53%-86%). Analyses of serologic data revealed significantly lower DGP titers in the false-negative vs the true-positive group. CONCLUSIONS: In a study of more than 1000 adults and children, we found the Simtomax POCT to detect celiac disease with lower overall levels of sensitivity than expected. Although the test identifies adults with celiac disease with high levels of sensitivity and specificity, the prevalence of celiac disease was as low as 1.2% among adults. The test's lack of sensitivity might be due to the low intensity of the POCT bands and was associated with low serum DGP titers. Study ID no: DRKS00012499.

Guideline recommendations for treatment of patients with inflammatory bowel diseases are not implemented in clinical practice-results of a non-representative survey.

PURPOSE: There is a growing evidence for over-, under-, or misuse of health care in patients with inflammatory bowel disease. Most studies looked at treatment variability or used quality measures, which mostly capture supportive interventions rather than treatment of IBD in itself. We aimed to evaluate if current recommendations in clinical practice guidelines regarding the medical treatment of patients with inflammatory bowel diseases are being followed in Germany. METHODS: A questionnaire was sent to 1901 patients insured with two large German statutory sickness funds and an ICD 10 diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). The questionnaire asked about drug treatment, indications for drug treatment, provision of surveillance endoscopies in ulcerative colitis patients, and smoking status in Crohn's disease patients. RESULTS: Out of 460 evaluable patients, 62.4% of UC patients and 53.9% of CD patients were treated with mesalamine according to guidelines, 91.3% of all patients were treated with glucocorticoids according to guideline recommendations, while only 75.6% received recommended immunosuppressive treatment. Of UC patients, 94.5% had surveillance colonoscopies at the recommended interval and 58.8% of CD patients were non-smokers. No predictor for overall treatment according to guidelines could be found while being of age older than 60 or being treated outside of a dedicated IBD clinic was associated with less immunosuppressive treatment. CONCLUSIONS: A large proportion of patients with IBD do not receive drug treatment in accordance with clinical practice guidelines. Quality improvement measures are much needed.

Restless legs syndrome is a relevant comorbidity in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: In patients with inflammatory bowel disease (IBD), restless legs syndrome (RLS) may occur as an extraintestinal disease manifestation. Iron deficiency (ID) or folate deficiency/vitamin B12 deficiency (FD/VB12D) has previously been described to cause RLS. Here, we determined the prevalence and severity of RLS in IBD patients and evaluated the effect of iron and/or folic acid/vitamin B12 supplementation. METHODS: Patients were screened for ID and RLS by a gastroenterologist. If RLS was suspected, a neurologist was consulted for definitive diagnosis and severity. Patients with RLS and ID, FD, or VB12D received supplementation and were followed-up at weeks 4 and 11 after starting supplementation. RESULTS: A total of 353 IBD patients were included. Prevalence for RLS was 9.4% in Crohn's disease (CD) and 8% in ulcerative colitis (UC). Prevalence for the subgroup of clinically relevant RLS (symptoms ≥ twice/week with at least moderate distress) was 7.1% (n = 16) for CD and 4.8% (n = 6) for UC. 38.7% of RLS patients presented with ID, FD, and/or VB12D. Most frequently ID was seen (25.8%; n = 8). Iron supplementation resulted in RLS improvement (p = 0.029) at week 4 in seven out of eight patients. CONCLUSION: Although the overall prevalence of RLS in IBD did not differ to the general population, clinically relevant RLS was more frequent in IBD patients and, therefore, it is important for clinicians to be aware of RLS symptoms. Though for definite diagnosis and proper treatment of RLS, a neurologist must be consulted. Additionally, iron supplementation of IBD patients with ID can improve RLS symptoms. TRIAL REGISTRATION: ClinicalTrials.gov No. NCT03457571.

Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease.

BACKGROUND: Ustekinumab (CNTO 1275) and briakinumab (ABT-874) are monoclonal antibodies that target the standard p40 subunit of the cytokines interleukin-12 and interleukin-23 (IL-12/23p40), which are involved in the pathogenesis of Crohn's disease. OBJECTIVES: The objectives of this review were to assess the efficacy and safety of anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease. SEARCH METHODS: The following databases were searched from inception to September 16, 2014: PubMed, MEDLINE, EMBASE, and the Cochrane Library (CENTRAL). References and conference abstracts were searched to identify additional studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) trials in which monoclonal antibodies against IL-12/23p40 were compared to placebo or another active comparator in patients with active Crohn's disease were included.  DATA COLLECTION AND ANALYSIS: Two authors independently screened  studies for inclusion and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome was failure to induce clinical remission, defined as a Crohn's disease activity index (CDAI) of < 150 points. Secondary outcomes included failure to induce clinical improvement, serious adverse events, and withdrawals due to adverse events. Clinical improvement was defined as decreases of > 70 or > 100 points in the CDAI from baseline. We calculated the risk ratio (RR) and 95% confidence intervals (95% CI) for each outcome. A fixed-effect model was used to pool data. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. MAIN RESULTS: Four randomized controlled trials (n = 955 patients) met the inclusion criteria. A low risk of bias was assigned to all studies. The two briakinumab trials were not pooled due to differences in doses and time points for analysis. In both studies there was no statistically significant difference in remission rates. One study (n = 79) compared doses of 1 mg/kg and 3 mg/kg to placebo. In the briakinumab group 70% (44/63) of patients failed to enter clinical remission at 6 or 9 weeks compared to 81% (13/16) of placebo patients (RR 0.86, 95% CI 0.65 to 1.14). Subgroup analysis revealed no significant differences by dose. The other briakinumab study (n = 230) compared intravenous doses of 200 mg, 400 mg and 700 mg with placebo. Eighty-four per cent (154/184) of briakinumab patients failed to enter clinical remission at six weeks compared to 91% (42/46) of placebo patients (RR 0.92, 95% CI 0.83 to 1.03). Subgroup analysis revealed no significant differences by dose. GRADE analyses of the briakinumab studies rated the overall quality of the evidence for the outcome clinical remission as low due. Based on the results of these two studies the manufacturers of briakinumab stopped production of this medication. The two ustekinumab studies (630 patients) were pooled despite differences in intravenous doses (i.e. 1mg/kg, 3 mg/kg, 4.5 mg/kg, and 6 mg/kg), however the subcutaneous dose group was not included in the analysis, as it was unclear if subcutaneous was equivalent to intravenous dosing. There was no statistically significant difference in remission rates. At week six, 85% (356/420) of ustekinumab patients failed to enter remission compared to 89% (142/159) of placebo patients (RR 0.94, 95% CI 0.88 to 1.01). Subgroup analysis showed no statistically significant difference by dose. There were statistically significant differences in clinical improvement between ustekinumab and placebo-treated patients. In the ustekinumab group, 55% (230/420) of patients failed to improve clinically (i.e. 70-point decline in CDAI score), compared to 72% (115/159) of placebo patients (RR 0.75, 95% CI 0.66 to 0.86). Subgroup analysis revealed significant differences compared to placebo for the 1 mg/kg, 4.5 mg/kg and 6 mg/kg dosage subgroups. Similarly for a 100-point decline in CDAI, 62% (262/420) of patients in the ustekinumab group failed to improve clinically compared to 78% (124/159) of placebo patients (RR 0.79, 95% CI 0.71 to 0.89). Subgroup analysis showed a significant difference compared to placebo for the 4.5 mg/kg dose group. GRADE analyses of the ustekinumab studies rated the overall quality of the evidence for the outcomes clinical remission and clinical response as moderate. There were no statistically significant differences in the incidence of adverse events, serious adverse events or withdrawal due to adverse events. Sixty-seven per cent (316/473) of ustekinumab patients developed at least one adverse event compared to 73% (135/184) of placebo patients (RR 0.92, 95% CI 0.83 to 1.03). A GRADE analysis indicated that the overall quality of the evidence for this outcome was high. Six per cent (29/473) of ustekinumab patients had a serious adverse event compared to 8% (14/184) of placebo patients (RR 0.81, 95% CI 0.44 to 1.49). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low. The most common adverse events in briakinumab patients were injection site reactions and infections. Infections were the most common adverse event in ustekinumab patients. Worsening of Crohn's disease and serious infections were the most common serious adverse events. AUTHORS' CONCLUSIONS: Although we are uncertain about the efficacy of ustekinumab for induction of remission, moderate quality evidence suggests that ustekinumab may be effective for induction of clinical improvement in patients with moderate to severe CD. Due to small numbers of patients in dose subgroups the optimal dosage of ustekinumab is unclear. Briakinumab and ustekinumab appear to be safe. Due to sparse data we were unable to determine the risk of serious adverse events. Further studies are required to determine the efficacy and safety of ustekinumab in patients with moderate to severe CD. The results of three phase III trials that are currently underway will provide important new information.

Cerebrovascular events in inflammatory bowel disease patients treated with anti-tumour necrosis factor alpha agents.

BACKGROUND AND AIMS: Cerebrovascular accidents [CVA] have rarely been reported in inflammatory bowel disease [IBD] patients treated with anti-tumour necrosis alpha [anti-TNF alpha] agents. Our aim here was to describe the clinical course of CVA in these patients. METHODS: This was a European Crohn's and Colitis Organisation [ECCO] retrospective observational study, performed as part of the CONFER [COllaborative Network For Exceptionally Rare case reports] project. A call to all ECCO members was made to report on IBD patients afflicted with CVA during treatment with anti-TNF alpha agents. Clinical data were recorded in a standardised case report form and analysed for event association with anti-TNF alpha treatment. RESULTS: A total of 19 patients were identified from 16 centres: 14 had Crohn's disease, four ulcerative colitis and one IBD colitis unclassified [median age at diagnosis: 38.0 years, range: 18.6-62.5]. Patients received anti-TNF alpha for a median duration of 11.8 months [range: 0-62] at CVA onset; seven had previously been treated with at least one other anti-TNF alpha agent. Complete neurological recovery was observed in 16 patients. Anti-TNF alpha was discontinued in 16/19 patients. However, recurrent CVA or neurological deterioration was not observed in any of the 11 patients who received anti-TNF alpha after CVA [eight resumed after temporary cessation, three continued without interruption] for a median follow-up of 39.8 months [range: 5.6-98.2]. CONCLUSION: These preliminary findings do not unequivocally indicate a causal role of anti-TNF alpha in CVA complicating IBD. Resuming or continuing anti-TNF alpha in IBD patients with CVA may be feasible and safe in selected cases, but careful weighing of IBD activity versus neurological status is prudent.

Results of the 2nd scientific workshop of the ECCO (IV): therapeutic strategies to enhance intestinal healing in inflammatory bowel disease.

Evidence supporting the importance of assessment of mucosal healing in inflammatory bowel disease has increased in the last years. Mucosal healing has been integrated in the assessment of treatment efficacy in ulcerative colitis, but in Crohn's disease this thought has arised after biological agents have been evaluated in clinical trials. Although a validated definition of mucosal healing still does not exist, its use is also assuming an increasingly important role in the follow-up of individual patients in clinical practice. Corticosteroids induce mucosal healing in a small proportion of patients with Crohn's disease and are of no benefit to maintain it. By contrast, mucosal healing in Crohn's disease can be achieved and maintained, with varying degrees of evidence and success, with thiopurines and biological agents. In ulcerative colitis, the ability of corticosteroids to induce mucosal healing is well recognized. 5-aminosalicylates, thiopurines and biological agents are also able to induce mucosal healing and, additionally, to maintain it. Mucosal healing assessment should be considered in clinical practice when symptoms persist despite therapy or when treatment discontinuation is being considered. Conversely, in patients whose clinical remission is not associated with mucosal healing, intensification of treatment is not currently recommended because of lack of evidence.

Predictors for subsequent need for immunosuppressive therapy in early Crohn's disease.

BACKGROUND AND AIMS: The clinical course of Crohn's disease (CD) is highly variable with a subgroup of patients developing a progressive disease course necessitating immunosuppressive therapy (IT). However, reliable, stable and non-invasive individual clinical parameters in order to identify patients at risk for undergoing subsequent IT have not been sufficiently established. We therefore aimed to identify such clinical parameters. METHODS: A retrospective, multicenter analysis of CD patients from 6 German tertiary IBD centers was performed. Patients were classified into two groups depending on requiring IT or not. Personal data, clinical and laboratory parameters during the first 3 months after CD diagnosis and effects of initial medical therapy were compared between these two groups. RESULTS: In 218 (61.8%) of the 353 patients the CD course necessitated IT. Those patients were significantly younger at symptom onset and diagnosis, and required significantly more often a systemic corticosteroid therapy. Furthermore, significant differences in serological markers of inflammation were observed. Age, gender and the effect of initial steroid therapy were used to develop a prognostic model predicting the individual probability of necessitating IT. CONCLUSIONS: The simple clinical items age at diagnosis, gender, and need for systemic steroid therapy can predict a progressive disease course in early CD. Our model based on these parameters allows an individualized estimation of each patient's risk to develop a progressive disease course. Thereby, our model can help in deciding if patients will need immunosuppressive drugs early in the disease course or if a careful watch and wait strategy is justified.

Psychological interventions for treatment of inflammatory bowel disease.

BACKGROUND: The effect of psychological interventions in inflammatory bowel diseases (IBD) is controversial. OBJECTIVES: To assess the effects of psychological interventions (psychotherapy, patient education, relaxation techniques) on health related quality of life, coping, emotional state and disease activity in IBD. SEARCH STRATEGY: We searched the specialized register of the IBD/FBD Group, CENTRAL (Issue 5, 2010) and from inception to April 2010: Medline, Embase, LILACS, Psyndex, CINAHL, PsyInfo, CCMed, SOMED and Social SciSearch. Conference abstracts and reference lists were also checked. SELECTION CRITERIA: Randomized, quasi-randomized and non randomized controlled trials of psychological interventions in children or adults with IBD with a minimum follow up time of 2 months. DATA COLLECTION AND ANALYSIS: Data were extracted and study quality was independently assessed by two raters. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random effects model. MAIN RESULTS: Twenty-one studies were eligible for inclusion (1745 participants, 8 RCT, 4 QRCT, 8 NRCT; 19 in adults, 2 in adolescents). Most studies used multimodular approaches. The risk of bias was high for all studies.In adults, psychotherapy had no effect on quality of life at around 12 months (3 studies, 235 patients, SMD -0.07; 95% CI -0.33 to 0.19), emotional status (depression, 4 studies, 266 patients, SMD 0.03; 95% CI -0.22 to 0.27) or proportion of patients not in remission (5 studies, 287 patients, OR 0.85; 95% CI 0.48 to 1.48). Results were similar at 3 to 8 months. There was no evidence for statistical heterogeneity or subgroup effects based on type of disease or intensity of the therapy. In adolescents, there were positive short term effects of psychotherapy on most outcomes assessed including quality of life (2 studies, 71 patients, SMD 0.70; 95% CI 0.21 to 1.18) and depression (1 study, 41 patients, SMD -0.62; 95% CI -1.25 to 0.01).Educational interventions were ineffective with respect to quality of life at 12 months (5 studies, 947 patients, SMD 0.11; 95% CI -0.02 to 0.24), depression (3 studies, 378 patients, SMD -0.08; 95% CI -0.29 to 0.12) and proportion of patients not in remission (3 studies, 434 patients, OR 1.00; 95% CI 0.65 to 1.53). AUTHORS' CONCLUSIONS: There is no evidence for efficacy of psychological therapy in adult patients with IBD in general. In adolescents, psychological interventions may be beneficial, but the evidence is limited. Further evidence is needed to assess the efficacy of these therapies in subgroups identified as being in need of psychological interventions, and to identify what type of therapy maybe most useful.

Randomized, placebo-controlled, double-blind trial of Boswellia serrata in maintaining remission of Crohn's disease: good safety profile but lack of efficacy.

BACKGROUND: Complementary therapies are frequently used by patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the efficacy and safety of long-term therapy with a new Boswellia serrata extract (Boswelan, PS0201Bo) in maintaining remission in patients with Crohn's disease (CD). METHODS: In 22 German centers a double-blind, placebo-controlled, randomized, parallel study was performed. In all, 108 outpatients with CD in clinical remission were included. Patients were randomized to Boswelan (3×2 capsules/day; 400 mg each) or placebo for 52 weeks. The primary endpoint was the proportion of patients in whom remission was maintained throughout the 52 weeks. Secondary endpoints were time to relapse, changes of Crohn's Disease Activity Index (CDAI), and IBD Questionnaire (IBDQ) scores. RESULTS: The trial was prematurely terminated due to insufficient discrimination of drug and placebo with regard to the primary efficacy endpoint. A total of 82 patients were randomized to Boswelan (n=42) or placebo (n=40). Sixty-six patients could be analyzed for efficacy. 59.9% of the actively treated patients and 55.3% of the placebo group stayed in remission (P=0.85). The mean time to diagnosis of relapse was 171 days for the active group and 185 days for the placebo group (P=0.69). With respect to CDAI, IBDQ, and laboratory measurements of inflammation, no advantages in favor of active treatment were detected. Regarding safety concerns, no disadvantages of taking the drug compared to placebo were observed. CONCLUSIONS: The trial confirmed good tolerability of a new Boswellia serrata extract, Boswelan, in long-term treatment of CD. However, superiority versus placebo in maintenance therapy of remission could not be demonstrated.

[Clinical practice guideline on diagnosis and treatment of Crohn's disease - summary for the general practitioner]. / Leitlinie "Diagnostik und Therapie des Morbus Crohn" - Kurzfassung für Internisten und Hausärzte.

The German clinical practice guideline on diagnosis and therapy of Crohn's disease is the result of an evidence-based consensus conference under the auspices of the German Gastroenterologic Society and the Competence Network IBD. This article will summarize the recommendations most important for the general practitioner.Crohn's disease is diagnosed in cooperation with a gastroenterologist who is performing endoscopy and possibly ultrasound. Uncomplicated relapses can nevertheless be successfully treated at the office of a family physician - mostly with steroids. Steroids are not appropriate for long-term treatment though. In those cases an early treatment with immunosuppressants in collaboration with a gastroenterologist is required. Cooperation with several different sub specialists is necessary when surgery is required as well as for the treatment of fistula, psychosomatic aspects and extraintestinal manifestations.

T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription.

T helper type 1 (Th1) development is facilitated by interrelated changes in key intracellular factors, particularly signal transducer and activator of transcription (STAT)4, T-bet, and GATA-3. Here we show that CD4+ cells from T-bet-/- mice are skewed toward Th2 differentiation by high endogenous GATA-3 levels but exhibit virtually normal Th1 differentiation provided that GATA-3 levels are regulated at an early stage by anti-interleukin (IL)-4 blockade of IL-4 receptor (R) signaling. In addition, under these conditions, Th1 cells from T-bet-/- mice manifest IFNG promotor accessibility as detected by histone acetylation and deoxyribonuclease I hypersensitivity. In related studies, we show that the negative effect of GATA-3 on Th1 differentiation in T-bet-/- cells arises from its ability to suppress STAT4 levels, because if this is prevented by a STAT4-expressing retrovirus, normal Th1 differentiation is observed. Finally, we show that retroviral T-bet expression in developing and established Th2 cells leads to down-regulation of GATA-3 levels. These findings lead to a model of T cell differentiation that holds that naive T cells tend toward Th2 differentiation through induction of GATA-3 and subsequent down-regulation of STAT4/IL-12Rbeta2 chain unless GATA-3 levels or function is regulated by T-bet. Thus, the principal function of T-bet in developing Th1 cells is to negatively regulate GATA-3 rather than to positively regulate the IFNG gene.

Pancreatic panniculitis in an 88-year-old man with neuroendocrine carcinoma.

Pancreatic panniculitis is a rare complication that occurs in 0.3-3% of patients with pancreatic diseases. Most of the cases reported to date were associated with adenocarcinoma and acute or chronic pancreatitis. We here present an 88-year-old man who was admitted to our institution with a nonfunctional neuroendocrine carcinoma of the pancreas. He subsequently developed pancreatic panniculitis and arthritis. Treatment with octreotide did not have an effect neither on progression of the carcinoma nor on development of new skin lesions. Two months after the diagnosis of pancreatic panniculitis had been made, the patient died from progressing carcinoma. A review of the literature shows that there is no congruent hypothesis for the pathogenesis of pancreatic panniculitis. Vascular damage seems to induce lipolysis by pancreatic enzymes. This eventually leads to fat necrosis. The diversity of disorders that can go along with pancreatic panniculitis suggests an unspecific damage of pancreatic tissue as a first step in the chain of events.