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International audience; Background: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD.Methods: Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale.Results: In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn's disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth.Conclusions: STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers.

Some but not all epidemiological studies suggest that helminth infection in childhood protects against development of inflammatory bowel disease (IBD) in later years. In animal models of IBD, helminths have shown protective effects and changed bacterial flora in the gut. Based on these concepts, small trials and series have been published showing some positive effects of Trichuris suis ova in ulcerative colitis and Crohn's disease. Currently, large randomized placebo-controlled trials are under way. Results remain to be awaited in order to clarify a possible role of T. suis ova in the treatment of IBD.

Crohn's disease is a heterogeneous entity. Previous attempts of classification have been based primarily on anatomic location and behavior of disease. However, no uniform definition of patient subgroups has yet achieved broad acceptance. The aim of this international Working Party was to develop a simple classification of Crohn's disease based on objective variables. Eight outcome-related variables relevant to Crohn's disease were identified and stepwise evaluated in 413 consecutive cases, a database survey, and by clinical considerations. Allocation of variables was conducted with well-defined Crohn's disease populations from Europe and North America. Cross-table analyses were performed by chi-square testing. Three variables were finally elected: Age at Diagnosis [below 40 years (A1), equal to or above 40 years (A2)], Location [terminal ileum (L1), colon (L2), ileocolon (L3), upper gastrointestinal (L4)], and Behavior [nonstricturing nonpenetrating (B1), stricturing (B2), penetrating (B3)]. The allocation of patients to these 24 subgroups proved feasible and resulted in specific disease clusters. Cross-table analyses revealed associations between Age at Diagnosis and Location, and between Behavior and Location (all p < 0.001). The Vienna classification of Crohn's disease provides distinct definitions to categorize Crohn's patients into 24 subgroups. Operational guidelines should be used for the characterization of patients in clinical trials as well as for correlation of particular phenotypes with putative biologic markers or environmental factors.

Connective tissue growth factor (CTGF) is induced in liver fibrosis and enhances the activity of transforming growth factor β (TGFβ). Recently we have shown that the hepatoprotective adipokine adiponectin downregulates CTGF in primary human hepatocytes (PHH). In the current study, the mechanisms mediating suppression of CTGF by adiponectin and the well described downstream effector of adiponectin receptor 2 (AdipoR2), peroxisome proliferator activated receptor α (PPARα), were analyzed in more detail. Adiponectin downregulated CTGF mRNA and protein in primary human hepatocytes (PHH) and suppression was blocked by a PPARα antagonist indicating that AdipoR2 is involved. The PPARα agonists fenofibrate and WY14643 also reduced CTGF protein in these cells. Adiponectin further impaired TGFβ-mediated upregulation of CTGF. Phosphorylation of the TGFβ downstream effectors SMAD2 and –3 was reduced in PHH incubated with adiponectin or PPARα agonists suggesting that early steps in TGFβ signal transduction are impaired. CTGF and TGFβ mRNA levels were increased in human non-fibrotic non-alcoholic steatohepatitis (NASH), and here AdipoR2 expression was significantly reduced. Current data show that CTGF and TGFβ are already induced in non-fibrotic NASH and this may be partly explained by low adiponectin bioactivity which interferes with TGFβ signaling by reducing phosphorylation of SMAD2/3 and by downregulating CTGF.

Fatty liver is commonly detected in obesity and has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of liver diseases. Transforming growth factor beta (TGFβ) and activin A, both members of the TGFβ superfamiliy, are central regulators in liver fibrosis and regeneration, and the effect of hepatocyte lipid accumulation on the release of these proteins was studied. Primary human hepatocytes (PHH) were incubated with palmitic acid or oleic acid to increase lipid storage. Whereas activin A and its natural inhibitor follistatin were not affected, TGFβ was 2-fold increased. The hepatoprotective adipokine adiponectin dose-dependently induced activin A while lowering follistatin but did not alter TGFβ. Activin A was markedly reduced in hepatocyte cell lines compared to PHH and was not induced upon adiponectin incubation demonstrating significant differences of primary and transformed cells. In free fatty acid (FFA)-incubated PHH adiponectin-mediated induction of activin A was impaired. Inhibition of TGFβ receptors ALK4/5 and blockage of SMAD3 phosphorylation rescued activin A synthesis in FFA and in TGFβ incubated cells suggesting that FFA inhibit adiponectin activity by inducing TGFβ. To evaluate whether serum levels of activin A and its antagonist are altered in patients with hepatic steatosis, both proteins were measured in the serum of patients with sonographically diagnosed fatty liver and age- and BMI-matched controls. Systemic adiponectin was significantly reduced in patients with fatty liver but activin A and follistatin were not altered. In summary the current data demonstrate that lipid accumulation in hepatocytes induces TGFβ which impairs adiponectin bioactivity, and thereby may contribute to liver injury.

Background: Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study. Methods: We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres. Results: Ten patients presented with culture-positive SBP, 19 with culture-negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non-neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P=0.036], culture-positive SBP (OR 6.0; P=0.012) and bacterascites (OR 6.0; P=0.050) were more often carriers of NOD2 variants than patients with sterile non-neutrocytic ascites. The mutations 1007fs and G908R were associated with culture-positive SBP (P≤0.005) and R702W with bacterascites (P=0.014). There was no significant association of NOD2 variants with culture-negative SBP (OR 1.6; P=0.493). In logistic regression, previous SBP, a higher model for end-stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P=0.386). In patients without hepatocellular carcinoma at study entry (N=148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P=0.045). Conclusion: NOD2 variants increase the risk for culture-positive SBP and bacterascites in cirrhosis and may affect survival.

Adipocytes of peripancreatic and intrapancreatic adipose tissue secret adipocytokines such as leptin, adiponectin, and resistin. For resistin, a role as an early predictor of peripancreatic necrosis and clinical severity in acute pancreatitis has been reported. It was the aim of this study to investigate whether the adipocytokine visfatin is able to serve as an early marker predicting peripancreatic necrosis and clinical severity.A total of 50 patients (20 females and 30 males) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and APACHE-II (Acute Physiology and Chronic Health Evaluation II) score. Pancreatic and peripancreatic necrosis were quantified by the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Visfatin was measured at admission and daily for 10 days by enzyme-linked immunosorbent assay (ELISA).Visfatin values were significantly and positively correlated with clinical severity (APACHE-II score and Ranson score) and with clinical end points such as death and need for interventions. Admission visfatin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver operator characteristics that admission visfatin concentration provides a positive predictive value of 93.3% in predicting the extent of peripancreatic necrosis (area under the curve (AUC): 0.89, P0.001, sensitivity: 93.3%, specificity: 81.8%, likelihood ratio: 5.1, post-test probability: 93%) by using a cutoff value of 1.8 ng/ml.Admission visfatin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Visfatin may have potential for clinical use as a new and diagnostic serum marker.

Systemic concentrations of interleukin-6 (IL-6) are elevated in patients with liver cirrhosis, and impaired hepatic uptake of IL-6 was suggested to contribute to higher levels in these patients. To test this hypothesis IL-6 was measured in portal venous serum (PVS), hepatic venous serum (HVS) and systemic venous serum (SVS) of 41 patients with liver cirrhosis and four patients with normal liver function. IL-6 was higher in PVS than HVS of all blood donors and about 43% of portal vein derived IL-6 was extracted by the healthy liver, and 6.3% by the cirrhotic liver demonstrating markedly impaired removal of IL-6 by the latter. Whereas in patients with CHILD-PUGH stage A IL-6 in HVS was almost 25% lower than in PVS, in patients with CHILD-PUGH stage C IL-6 was similarly abundant in the two blood compartments. Ascites is a common complication in cirrhotic patients and was associated with higher IL-6 levels in all blood compartments without significant differences in hepatic excretion. Hepatic venous pressure gradient did not correlate with the degree of hepatic IL-6 removal excluding hepatic shunting as the principal cause of impaired IL-6 uptake. Furthermore, patients with alcoholic liver cirrhosis had higher IL-6 in all blood compartments than patients with cryptogenic liver cirrhosis. Aetiology of liver cirrhosis did not affect hepatic removal rate indicating higher IL-6 synthesis in patients with alcoholic liver cirrhosis. In summary, the current data provide evidence that impaired hepatic removal of IL-6 is explained by hepatic shunting and liver dysfunction in patients with liver cirrhosis partly explaining higher systemic levels.

Introduction: Many reports, mainly from the US and Canada but also a recent report from a center in Europe, have documented the increasing impact of Clostridium difficile infections in patients with inflammatory bowel disease (IBD) during the last years. To determine the prevalence of C. difficile infections in hospitalized IBD patients in a tertiary referral center in Germany, we conducted this retrospective analysis. Methods: Data of all IBD in-patients treated due to an acute flare of their IBD at the Department of Internal Medicine I of the University of Regensburg between January 1, 2001, and June 30, 2008, were analyzed. In patients with a concomitant diagnosis of C. difficile infection, further variables such as IBD-related treatment at the time of infection or outcome were examined. Results: In total, 995 in-patients with IBD were treated in this hospital [638 patients with Crohn’s disease (CD), 357 with ulcerative colitis (UC)] during the study period. Of these, 279 patients with CD and 242 patients with UC were admitted with an acute flare and suffering from diarrhea and abdominal pain. Only 10 of those were diagnosed as having a concomitant infection with C. difficile. Six patients were female and the median age was 49 years (range: 15–80). Six patients with C. difficile infections suffered from UC and 4 patients from CD, all with previous colonic involvement. Eight patients used immunosuppressive therapies; only 2 patients were treated with antibiotics before infection. Conclusion: In contrast to recent reports from other countries, only a low percentage of hospitalized patients with acute flares of their IBD were identified as having an underlying C. difficile infection in this German tertiary referral center. However, in IBD patients with an acute flare, a concomitant C. difficile infection should be excluded, especially in patients with immunosuppressive treatment and colonic involvement of their disease. Further research is needed to evaluate if regions with different risks of C. difficile infections exist and to find out more about potential reasons for this observation.

OBJECTIVES: Peripancreatic necrosis determines clinical severity in acute pancreatitis. Early markers predicting peripancreatic necrosis and clinical severity are lacking. Because adipocytes of peripancreatic adipose tissue secret highly active adipocytokines, the aim of the study was to investigate whether adipocytokines are able to serve as early markers predicting peripancreatic necrosis and clinical severity. METHODS: A total of 50 patients (20 women, 30 men) with acute pancreatitis were included in this noninterventional, prospective, and monocentric cohort study on diagnostic accuracy. Clinical severity was classified by the Ranson score and the APACHE (Acute Physiology And Chronic Health Evaluation) II score. Pancreatic and peripancreatic necrosis were quantified by using the computed tomography-based Balthazar score, the Schroeder score, and the pancreatic necrosis score. Adiponectin, leptin, and resistin were measured at admission and daily for at least 10 days by enzyme-linked immunosorbent assay. RESULTS: In contrast to admission C-reactive protein values, admission resistin values were significantly correlated with clinical severity and even with clinical end points such as death and need for interventions. Admission resistin levels were significantly elevated in patients with higher pancreatic and extrapancreatic necrosis scores. It was shown by receiver-operator characteristics that admission resistin concentration provides a positive predictive value of 89% in predicting the extent of peripancreatic necrosis (area under the curve, 0.8; P=0.002; sensitivity, 80%; specificity, 70%) by using a cutoff value of 11.9 ng/ml. CONCLUSIONS: Admission resistin concentration serves as an early predictive marker of peripancreatic necrosis and clinical severity in acute pancreatitis. Resistin may have potential for clinical use as a new and diagnostic serum marker.

Background/Aims: Some suggest MRI to be superior to ultrasound in Crohn’s disease. We analyzed how often MR enterography (MRE) following a routine ultrasound leads to a change in therapeutic decision. Material and Methods: We retrospectively evaluated 47 patients with Crohn’s disease undergoing routine ultrasound examination. Actual medical history, complete blood count, C-reactive protein (CRP), and sonographic findings were assessed independently by two specialists who retrospectively provided a therapeutic proposal. Additionally, all patients received MRE. Thereafter, the specialists had to provide a new therapeutic concept regarding all the available information. Results: Evaluation of the rectum was not successful by ultrasound, but MRE gave good results. Only 1 of 7 abscesses was identified sonographically. Three of the abscesses missed at sonography were localized in the perirectal/perianal region. MRE detected more inflamed bowel segments, but ultrasound assessment of anatomically fixed bowel parts showed good recognition by MRE. With increasing CRP values, we found more positive results of ultrasound and MRE. Therapeutic change was suggested in only 18 patients. Conclusions: Ultrasound should be performed by an experienced examiner, and a proctological examination should be added. MRE is justified in cases of discrepancy between clinical findings and the results of diagnostic ultrasound and, moreover, if Crohn’s lesions are suspected at sites proximal to the terminal or neoterminal ileum., OA-Komponente aus Allianzlizenz

BACKGROUND:: Chemerin is an adipokine that stimulates chemotaxis of cells of the innate immune system. Inflammatory bowel disease (IBD) is linked to an impaired immune response and, therefore, we hypothesized that systemic chemerin may be altered in IBD patients. METHODS:: Serum was collected from patients with Crohn's disease (CD, 230 patients), ulcerative colitis (UC, 80 patients), and healthy controls (HC, 80 probands). Chemerin and adiponectin, which has already been measured in the serum of similar cohorts by others, were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS:: Chemerin was elevated in IBD compared to HC and was higher in male CD than UC patients. Female and male CD patients had lower adiponectin levels compared to UC, and adiponectin was lower in female CD patients compared to female HC. Adiponectin tended to be higher in female and male UC patients compared to HC and this difference became significant in the whole study group. Correlations with disease activity were only found in males. Here, chemerin was higher in CD patients on remission but was reduced in UC with nonactive disease. Adiponectin was higher in UC with inactive disease. Treatment with corticosteroids was linked to elevated adiponectin in male CD patients and higher chemerin in female UC patients. Unlike adiponectin, which was elevated in female serum in all cohorts, chemerin was only higher in female UC patients. CONCLUSIONS:: These findings further indicate potential regulatory functions of adipokines in intestinal inflammation that are partly gender-dependent and that may even be associated with the distinct immunopathogenesis of UC and CD. (Inflamm Bowel Dis 2009;).

Background The adipokine chemerin modulates the function of innate immune cells and may link obesity and inflammation, and therefore, a possible relation of chemerin to inflammatory proteins in obesity and type 2 diabetes (T2D) was analysed. As visceral fat contributes to systemic inflammation, chemerin was measured in portal venous (PVS), hepatic venous (HVS) and systemic venous (SVS) blood of patients with liver cirrhosis. Patients and methods Systemic chemerin was determined by ELISA in the serum of normal-weight, overweight and T2D males, in the serum of T2D patients of both sexes, and in PVS, HVS and SVS of patients with liver cirrhosis. Results Circulating chemerin was similar in T2D and obese individuals but was significantly elevated in both cohorts compared to normal-weight individuals. Chemerin positively correlated with leptin, resistin and C-reactive protein (CRP). In T2D, chemerin was similar in male and female patients and increased in patients with elevated CRP. Chemerin was similar in PVS and SVS, indicating that visceral fat is not a major site of chemerin synthesis. Higher levels of chemerin in HVS demonstrate that chemerin is also released by the liver. Conclusions Visceral fat is not a major site of chemerin release, and elevated systemic levels of chemerin in obesity and T2D seem to be associated with inflammation rather than body mass index.

Adipocytes synthesize galectin-3 whose deficiency protects from inflammation associated with metabolic diseases. We aimed to study circulating galectin-3 in obesity and type 2 diabetes (T2D).Galectin-3 was measured by ELISA in the serum of male normal-weight and overweight controls and T2D patients and in T2D patients of both sexes. Because visceral fat contributes to systemic inflammation, galectin-3 was analyzed in paired samples of human and rodent sc and visceral adipose tissue. Visceral adipose tissue adipokines are released to the portal vein, and galectin-3 was analyzed in portal, hepatic, and systemic venous serum (PVS, HVS, and SVS, respectively) of patients with liver cirrhosis and in patients who underwent surgery for nonhepatic diseases. The effect of metformin on adipocyte galectin-3 was analyzed by immunoblot.Circulating galectin-3 was similarly elevated in T2D and obesity compared with normal-weight individuals and revealed a body mass index-dependent positive correlation with leptin, resistin, IL-6, and age. In T2D patients, galectin-3 was increased in serum of patients with elevated C-reactive protein and negatively correlated with glycated hemoglobin. Metformin treatment was associated with lower systemic galectin-3. Reduced galectin-3 in metformin-incubated human adipocytes indicated that low galectin-3 may be a direct effect of this drug. Galectin-3 was higher in PVS compared with HVS and SVS, suggesting that the splanchnic region is a major site of galectin-3 synthesis. Low galectin-3 in HVS compared with PVS demonstrated hepatic removal.Systemic galectin-3 is elevated in obesity and negatively correlates with glycated hemoglobin in T2D patients, pointing to a modifying function of galectin-3 in human metabolic diseases.

Objective IA injections of SIJs with corticosteroids are often performed in patients suffering from low back pain due to active sacroiliitis. However, SIJ injections are technically demanding, and therefore the clinical outcome of ultrasound-guided corticosteroid SIJ injections was analysed in relation to the accuracy of the injection. Methods Ultrasound-guided injections were performed with 40 mg triamcinolone and 0.78 mg gadolinium in 20 SIJ of 14 consecutive patients suffering from active sacroiliitis. Immediately following SIJ injection, MRI scanning was initiated to verify the correct placement of the drug. Clinical outcome of the intervention was determined using a numerical pain rating scale (NRS) at Days 1 and 28. Results Despite ultrasound guidance, only 8 injections (40%) were exactly positioned into the SIJ space, whereas the other 12 injections (60%) missed the SIJ. However, there were no significant differences observed in the clinical outcome between the IA-injected group and the peri-articular-injected group. There was similar pain relief observed in both groups 24 h and 28 days following the intervention [IA injection group: mean NRS-baseline: 6.8 (range 4-9), NRS-24 h: 4.3 (range 1-7) and NRS-day 28: 3.5 (range 1-5); peri-articular injection group: mean NRS-baseline: 7.0 (range 5-10), NRS-24 h: 4.1 (range 1-10) and NRS-day 28: 4.5 (range 1-8)]. Conclusion These results demonstrate that IA SIJ injections remain technically challenging despite ultrasound guidance. However, peri-articular deposition of triamcinolone appears sufficient for pain and symptom control in patients suffering from active sacroiliitis.

Die Kliniken stehen im Spannungsfeld zwischen einer qualitativ hochwertigen Patientenversorgung einerseits und optimierter Ressourcennutzung andererseits. Vor diesem Hintergrund wurde an der Schnittstelle zwischen ambulanter und stationarer Behandlung eine zentrale Patientenaufnahme (ZPA) in einer internistisch-rheumatologischen Fachklinik eingerichtet. Alle uber eine zentrale Terminvergabe einbestellten Patienten wurden initial in der ZPA von einem Facharzt behandelt. Unter Berucksichtigung eines mit dem Medizinischen Dienst der Krankenversicherung in Bayern (MDK-Bayern) konsentierten Aufnahmeprotokolls wurde die stationare Behandlung bereits in der ZPA eingeleitet oder eine vorstationare Behandlung durchgefuhrt. Die Auswirkungen dieser Masnahmen wurden uber einen Zeitraum von 30 Monaten im Hinblick auf die vorstationare und stationare Patientenversorgung sowie die Belegungszahlen analysiert. Uber einen Zeitraum von 30 Monaten nach Einrichtung der ZPA konnten insgesamt 10% der Patienten vorstationar behandelt werden, wahrend 90% der eingewiesenen Patienten stationar aufgenommen wurden. Trotzdem konnten die Belegungszahlen zwischen dem 1. und 2. Jahr nach Einfuhrung der ZPA um 20,7% gesteigert werden, wobei insbesondere ein Anstieg der spezialisierten facharztlichen Einweisungen zu verzeichnen war. Durch die Einfuhrung der ZPA wurde die primare Fehlbelegung im untersuchten Zeitraum vollstandig vermieden. Die notwendigen Umstrukturierungen und der erforderliche Mehraufwand bei der Etablierung einer ZPA werden durch eine optimierte, effizientere sowie sektorubergreifende Patientenversorgung wettgemacht, die zu einer groseren Zufriedenheit bei den betreuten Patienten, zuweisenden Arzten und auch Klinikmitarbeitern fuhrt.

Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, we implanted healthy human cartilage together with RASFs subcutaneously into severe combined immunodeficient (SCID) mice. At the contralateral flank, we implanted healthy cartilage without cells. RASFs showed an active movement to the naive cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a marked destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.

Congress of the German Society of Internal Medicine 2009: Evaluation of the Poster Exhibition Background and Purpose: The presentation of scientific posters gives young scientists the opportunity to present their data in the setting of a medical congress. In preparation of the organization of the 116th Congress of the German Society of Internal Medicine (DGIM) 2010, the authors evaluated the poster

Ein 17-jahriger Patient wurde aufgrund eines impaktierten Nahrungsbolus von den Kollegen der Hals-Nasen-Ohren-Klinik in der internistischen Notaufnahme vorgestellt. Die HNO-arztliche Untersuchung zeigte deutliche Speichelseen in beiden Recessus piriformes, die radiologische Untersuchung des Osophagus ergab einen 1,6 cm messenden Fremdkorper im Bereich des osophagogastralen Ubergangs mit einem proximalen Kontrastmittelspiegel. In der klinischen Untersuchung und der Laborchemie fanden sich keinerlei Auffalligkeiten. Es folgte die Durchfuhrung einer Notfallosophagogastroskopie. Hier zeigte sich der in der Breischluckuntersuchung nachgewiesene Fremdkoper im Bereich des gastroosophagealen Ubergangs. Der als Nahrungsbolus identifizierte Fremdkorper wurde mittels Gastroskop vorsichtig in den Magen vorgeschoben. Im Magen befanden sich weitere Nahrungsreste, so dass die Untersuchung bei Aspirationsgefahr abgebrochen wurde. In einer am Folgetag elektiv durchgefuhrten Gastroskopie wurden aus dem Osophagus Stufenbiopsien bei klinischem V.a. eosinophile Osophagitis (EO) entnommen. Die histologische Aufarbeitung ergab eine deutliche Eosinophilie (> 15 Eosinophile/HPF bei 400facher Vergroserung) und reaktive Veranderungen im distalen Osophagus. Somit wurde die Diagnose einer EO gestellt. Eine Therapie mit Fluticason fuhrte zu einer deutlichen Symptombesserung, erneute Bolusimpaktionen traten im Verlauf nicht mehr auf.

A 57-year-old woman presented with obscure gastrointestinal bleeding. Double balloon enteroscopy, angiography, and surgery including intraoperative enteroscopy failed to identify the bleeding site. Multidetector computed tomography (CT) depicted active bleeding of a small bowel segment. The bleeding segment was localized by CT-guided percutaneous needle insertion and subsequently removed surgically.

Liver cirrhosis is the main risk factor for the development of hepatocellular carcinoma (HCC). Activated hepatic stellate cells (HSC) are the effector cells of hepatic fibrosis and also infiltrate the HCC stroma where they might play a critical role in HCC progression. Here we aimed to analyze the effects of activated HSC on the proliferation and growth of HCC cell lines in vitro and in vivo. Conditioned media (CM) collected from HSC significantly induced proliferation and migration of HCC cells cultured in monolayers. In a 3-dimensional spheroid coculture system, HSC promoted HCC growth and diminished the extent of central necrosis. In accordance, in vivo simultaneous implantation of HSC and HCC cells into nude mice promoted tumor growth and invasiveness, and inhibited necrosis formation. As potential mechanism of the tumorigenic effects of HSC we identified activation of NFkappaB and extracellular-regulated kinase (ERK) in HCC cells, two signaling cascades that play a crucial role in HCC progression. In summary, our data indicate that stromal HSC promotes HCC progression and suggest the HSC-HCC interaction as an interesting tumor differentiation-independent target for therapy of this highly aggressive cancer.

We report the case of a 45-year-old male who was admitted to the intensive care unit with impaired consciousness and acute renal failure after liver transplantation because of cirrhosis of the liver due to hepatitis C and a complex course of disease after transplantation including recurrence of cirrhosis.

Fehler und ihre Folgen spielen in der Medizin eine immer grosere Rolle. Gerade in der Intensivmedizin zeigt sich die Anfalligkeit fur Fehler im Vergleich zu anderen medizinischen Bereichen deutlich erhoht. Das Fehlerspektrum imponiert vielfaltig, eine Rolle spielen dabei Informationsverluste. Vor diesem Hintergrund fuhrten wir ein Qualitatsmanagementprojekt mit dem Ziel der Evaluation der arztlichen Ubergabe auf der Intensivstation durch. Wir analysierten die Ubergabe einer internistischen 12 Betten Intensivstation an einem Universitatsklinikum. Die Auswertung erfolgte anhand einer Fragebogenaktion der Assistenzarzte sowie einer Videodokumentation zunachst wahrend eines Dreischichtsystems mit 3 arztlichen Ubergaben pro 24 Stunden. Die Analyse wurde nach Umstellung auf ein Zweischichtsystem mit 2 Ubergaben pro 24 Stunden ein Jahr spater wiederholt. 60 Minuten wurden als zeitlicher Rahmen fur ausreichend erachtet. Die Ubergabe sollte im Patientenzimmer bzw. je nach zu ubergebender Information vor diesem stattfinden und die Pflege sollte beteiligt sein. Wesentliche Informationsverluste wurden nicht bemerkt. Als eher nachrangig wurden bei der Informationsubermittlung die Ubergabe von sozialem Kontext und die Nachvollziehbarkeit von Anderungen erachtet. Storungen der Ubergabe wurden haufig beobachtet. Eine Kombination mit Visiten erschien nicht sinnvoll. Die Ubergabe folgte keinem definiertem Konzept. Wesentliche Informationsverluste konnten dennoch nicht beobachtet werden. Weitere Untersuchungen zur Optimierung des Ablaufs der arztlichen Ubergabe sind wunschenswert.

Eine 28-jahrige Patientin wurde bei lateraler Schenkelhalsspontanfraktur ohne adaquates Trauma ins Krankenhaus eingewiesen. Die durchgefuhrte Knochendichtemessung zeigte eine Osteoporose ohne erkennbare Ursache oder eindeutige Risikofaktoren. Die endokrinologische Abklarung erbrachte die Diagnose eines Hyperkortisolismus. Schlieslich konnte ein Morbus Cushing diagnostiziert werden, und es erfolgte eine transsphenoidale Hypophysenresektion. Die Patientin erhielt eine Osteoporosetherapie mit Vitamin-D- und Calciumsubstitution sowie Bisphosphonaten. Die glukokortikoidinduzierte Osteoporose ist eine der haufigsten sekundaren Osteoporoseformen. Falle mit okkultem endogenen Cushing-Syndrom und manifester Osteoporose als einzige Manifestation der Erkrankung sind beschrieben, wenn auch sehr selten. Daher sollte bei Osteoporose unklarer Ursache ein Hyperkortisolismus ausgeschlossen werden.

Adiponectin was discovered in 1995 by Phillip Scherer’s research group and described as a novel serum protein similar to C1q, being produced exclusively in adipocytes.1 Adiponectin represents an anti-inflammatory, anti-diabetic and anti-fibrotic adipokine that is highly abundant in human plasma. Adiponectin is induced during adipocyte differentiation and secreted from mature adipocytes into the blood stream where it circulates as homo-trimeric, hexameric, nonameric and higher molecular weight isoforms. Mutations in the gene encoding adiponectin result in an impaired multimer formation and cause lower levels of high-molecular weight isoforms in the plasma as well as a reduced abundance of all isoforms due to a disturbed secretion from the adipocyte.2 There are two receptors for adiponectin, AdipoR1 and AdipoR2, which are expressed in a wide variety of organs and cell types. The full-length and the truncated globular isoforms of adiponectin exhibit different receptor binding activities. Processes leading to a cleavage of the full-length protein and the exact mode of receptor interaction of different isoforms are only poorly understood. Adiponectin represents the only adipokine that is downregulated in obesity. Adiponectin exerts pleiotropic effects in several organs and its role in metabolism3 and in inflammation,4–7 in general, are reviewed elsewhere. Obesity can be regarded as a chronic and low-grade state of inflammation8 and the interpretation of the role of the adipose tissue has developed from a simple energy store to a highly active endocrine,9 inflammatory5 and immunological4 organ. In the context of obesity, the adipose tissue undergoes an inflammatory transformation10 and becomes infiltrated by significant amounts of macrophages.8 11 Since adiponectin is secreted by intra-abdominal adipose tissue and acts on monocytes in an anti-inflammatory way, it seems reasonable to review the role of adiponectin with respect to inflammatory gastrointestinal diseases, especially to those …

Ethylenglykol ist eine per se nicht toxische Substanz, die im menschlichen Organismus in hoch-toxische Metabolite umgewandelt wird. Die akute Intoxikation ist durch eine schwere metabolische Azidose, Vigilanzstorung, respiratorische Insuffizienz und Nierenversagen gekennzeichnet. Bereits die Aufnahme einer geringen Menge Ethylenglykol kann unbehandelt zum Tod fuhren. Fruhzeitige Diagnosestellung und Therapiebeginn konnen deshalb lebensrettend sein. Wir berichten uber einen 47-jahrigen Patienten, der seine Ethylenglykolvergiftung dank fruhzeitiger intensivmedizinischer Behandlung uberlebte.

Although often recommended, it is unclear whether fasting enhances the imaging quality of abdominal sonography examinations. The aim of this study was to produce experimental evidence of the effect of fasting on the imaging quality of abdominal organs.Formally consenting medical inpatients who underwent elective abdominal sonography examinations at a university medical center were randomized to either a fasting or a non-fasting preparation. Blinded examiners evaluated the imaging quality of 11 anatomical regions. The primary end-point was the proportion of completely evaluable patients for each region. In secondary analyses, values of an imaging index reflecting the mean imaging quality of all regions (range 0-1) were compared. RESULTS. Of 280 screened patients, 102 (36%) met the exclusion criteria and 35 (13%) declined participation. Of the 143 randomized patients, 130 (91%) were included in the primary analyses (66 fasting, 64 non-fasting). The proportion of completely evaluable patients did not differ significantly for any of the 11 regions, but a large nominal difference occurred for the gallbladder (45/66 (73%) fasting versus 34/64 (56%) non-fasting patients, p=0.051). The median (range) imaging index was 0.57 (0.14-0.95) for fasting and 0.43 (0.00-1.00) for non-fasting subjects (p =0.078). A significant (p=0.002) difference favoring fasting was detected in the post-hoc subgroup analyses for male patients.For examinations of the gallbladder and for male patients, fasting might improve the sonographic imaging quality to some extent. Overall, no significant improvement in the imaging quality of abdominal organs was reached with a fasting preparation.

Eine Muskelschwache mit oder ohne Erhohung des Kreatinkinase-(CK-)Werts ist eine von Patienten haufig vorgetragene Beschwerdesymptomatik, die eine differentialdiagnostische Herausforderung darstellt. Sowohl infektiose, neurologische, iatrogene, genetische als auch endokrinologische und rheumatologische Ursachen mussen in Betracht gezogen werden. Eine 66-jahrige Patientin mit bekanntem systemischem Lupus erythematodes (SLE) wurde mit stark erhohter CK (1 618 U/l), ausgepragter Muskelschwache und Muskelschmerzen unter dem Verdacht auf eine Myositis im Rahmen der Grunderkrankung stationar aufgenommen. Als Ursache der Symptomatik konnte ein akuter Schub des SLE diagnostisch ausgeschlossen werden. Stattdessen fand sich eine manifeste Hypothyreose im Rahmen einer Hashimoto-Thyreoiditis. Unter einer Substitution mit L-Thyroxin kam es zu einer vollstandigen Ruckbildung der Beschwerden und der CK-Erhohung. Auch wenn Muskelbeschwerden mit CK-Erhohung bei SLE-Patienten auf eine Myositis im Rahmen der Grunderkrankung hinweisen, muss eine sorgfaltige differentialdiagnostische Evaluation erfolgen, die bei der vorgestellten Patientin eine Hypothyreose als Ursache der Symptomatik ergab.

The biguanide metformin is an oral antihyperglycemic drug for the treatment of type 2 diabetes mellitus. Further, a moderate improvement of dyslipidemia by metformin was reported, and therefore, the effect of metformin on the release of apolipoprotein B (ApoB) and ApoE in primary human hepatocytes was determined. Metformin at 0.5 and 1 mM reduced hepatic ApoB secretion but ApoE was not altered. Metformin is well known to stimulate the AMP kinase that subsequently reduces hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB. However, HNF4-alpha was only diminished by 1 mM metformin and ApoB mRNA was not suppressed indicating that this pathway may not explain reduced ApoB release. Lower abundance of lysophosphatidylcholine (lysoPC) may also diminish ApoB secretion. Therefore, electrospray ionization tandem mass spectrometry was applied to measure cellular lipids. PC, lysoPC (produced by hydrolysis of PC), phosphatidylserine and sphingomyelin (derived from PC) were lower in metformin-treated hepatocytes whereas phosphatidylethanolamine, an alternative precursor of PC, was not affected. In addition, ABCB4, the canalicular membrane flippase essential for biliary PC secretion, was diminished. Supplementation with lysoPC led to a selective elevation of endogenous lysoPC and rescued ApoB secretion in metformin-treated cells. Therefore, it is concluded that metformin reduces lysoPC in human hepatocytes and this may secondarily lead to a therapeutically beneficial lower release of ApoB.

Background Environmental factors are likely to be involved in the pathogenesis of inflammatory bowel disease (IBD), as the incidence of both Crohn's disease (CD) and ulcerative colitis (UC) increased with improved living standards in Europe after World War II. On the basis of earlier reports suggesting that hygienic standards may also play a role in the pathogenesis of IBD, we investigated the influence of hepatitis A seroprevalence as an indicator for poorer hygienic conditions and worm infestations in IBD. Methods Hepatitis A seroprevalence was examined in patients with UC and CD. Patients with minor endocrinological disorders served as controls. All patients were questioned about immunizations, parasitic infections (worms), contact with animals, living on a farm, and ever traveling abroad. Patients were excluded for active hepatitis A immunization or recent passive immunization. Results are presented as Mantel-Haenszel odds ratios with 95% confidence interval, adjusted for age group. Results The sample included 307 patients (73 CD, 48 UC, and 186 controls). Hepatitis A seroprevalence was strongly associated with age older than 50 years. Age adjusted Mantel-Haenszel odds ratios were 0.25 (0.09-0.71) for UC and 0.75 (0.38-1.46) for CD versus controls. For parasitic infections, the odds ratios were 1.15 (0.52-2.53) for UC and 0.34 (0.13-0.89) for CD. Conclusion We were able to demonstrate a negative association of hepatitis A infection with UC only. In contrast, a novel finding was a strong protective effect of worm infestations for the occurrence of CD, but not UC.

Prophylaxis of gastrointestinal bleeding is attempted in widely varying situations. In NSAID-induced peptic ulcer, the advantage of selective cyclooxygenase 2 inhibitors with regard to gastrointestinal damage has yet to be translated into an advantage in overall morbidity. Strategies for primary and secondary prevention of variceal bleeding have been established. Therapy tailored to hepatic venous pressure gradient has the potential to achieve clinical relevance. Several methods have been developed to prevent postpolypectomy bleeding, but their optimal risk-tailored application has yet to be demonstrated. Although octreotide treatment seems to be beneficial in reducing the blood loss from angiodysplasias, controlled studies to determine its optimal use are awaited. Stress-ulcer prophylaxis is commonly applied in critically ill patients. Although data indicate that H 2 -receptor antagonists and omeprazole are effective in preventing clinically significant bleeding, evidence for an advantage with respect to length of hospital or intensive-care-unit stay, as well as mortality, is still lacking. Since there is misuse of acid-suppressing drugs on regular wards, in-house guidelines may offer the potential for saving costs and reducing inappropriate prescription.

Vascular disorders of the liver except portal hypertension are rare. They can be visualised via ultrasound, as demonstrated by two cases of cavernous transformation of the portal vein, one case of Osler's disease of the liver, and one case of Budd-Chiari's syndrome. The cavernous transformation and the occlusion of the hepatic veins can be diagnosed by ultrasound, while Osler's disease cannot be differentiated with certainty from other disorders.

Two patients with complicated acute pancreatitis are demonstrated. Sonographic factors are compared to laboratory and clinical findings. Ultrasound can add relevant information for classification and thereby supply an indication for surgery in patients with acute pancreatitis. This is especially true since laboratory classification of the grade of the disease is as yet not generally accepted.

Objective Some patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) improve rapidly from anti–tumor necrosis factor (anti-TNF) therapy. No sensitive markers are available that might predict outcome of anti-TNF therapy. We undertook this study to investigate the predictive value of hypothalamic–pituitary–adrenal (HPA) axis hormones for clinical improvement during anti-TNF therapy. Methods An observational study in 23 RA patients was followed by a validation study in 38 RA patients. The patients receiving anti-TNF antibodies had no glucocorticoid treatment, and we measured baseline serum levels of adrenocorticotropic hormone (ACTH) and cortisol. Improvement during anti-TNF antibody treatment was judged by the Disease Activity Score in 28 joints (DAS28), and serum levels of cortisol were measured at followup. Results The observational study demonstrated that improvement in the DAS28 correlated negatively with baseline serum levels of cortisol (R = −0.520, P = 0.011) and the cortisol:ACTH ratio (R = −0.700, P = 0.0002). In the longitudinal part of the study at followup, those patients with good improvement and initially low serum levels of cortisol demonstrated an increase of serum cortisol, in contrast to patients with little or no improvement. Findings in the observational study were supported by those in the validation study in a group of RA patients with less inflammation (correlation of improvement in the DAS28 with cortisol:ACTH ratio: R = –0.320, P = 0.025). Conclusion This is the first study in a human chronic inflammatory disease to demonstrate that inflammation-induced TNF interferes with HPA axis integrity, which is linked to the disease outcome. These findings position the HPA axis centrally in the vicious circle of perpetuation of chronic inflammation.

Stress-induced gastrointestinal bleeding is associated with increased morbidity and mortality in critically ill patients. Within the past few decades, the incidence of stress-induced gastrointestinal bleeding has decreased. Prophylaxis of stress-induced gastrointestinal bleeding, which is aimed at preventing morbidity and mortality, has to be achieved with as few adverse effects as possible. Data indicate that not all critically ill patients need prophylaxis for stress-induced gastrointestinal bleeding. The main risk factors associated with clinically important hemorrhage are mechanical ventilation for48 h, and coagulopathy (thrombocyte count50/nl, partial thromboplastin time (PTT)2 times the upper limit of the normal range, international normalized ratio (INR)1.5). Ranitidine is more effective than sucralfate for the prevention of clinically important bleeding. Immediate-release omeprazole is as effective as cimetidine, and is more efficient at increasing the intragastric pH. As yet, however, there is no firm evidence that any of the drugs used for prophylaxis of stress-induced gastrointestinal bleeding in critically ill patients decrease mortality or the length of hospital stay. When to stop prophylaxis is decided on clinical grounds rather than on the basis of data from clinical studies.

Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells in liver fibrogenesis. The excessive synthesis of ECM proteins deteriorates hepatic architecture and results in liver fibrosis and cirrhosis. This study investigated the role of bone morphogenetic protein 7 (BMP7) as a member of the transforming growth factor (TGF)-beta superfamily in chronic liver disease. Plasma levels of BMP7 were significantly elevated in patients with chronic liver disease compared with healthy controls. Immunohistochemistry of cirrhotic human liver demonstrated upregulated BMP7 protein expression in hepatocytes as compared with normal human liver. Because gene expression for all putative BMP7 receptors was induced during the culture activation process of primary human HSCs, we studied the effects of BMP7 on hTERT immortalized human HSCs in vitro. BMP7, as expressed and secreted after infection with adenoviruses encoding BMP7 (AdBMP7), increased proliferation of HSCs. The mRNA and protein expression of type I collagen and fibronectin was increased in BMP7-stimulated HSCs. Elevated systemic and hepatic levels of BMP7 in patients with chronic liver disease may contribute to progression of liver fibrogenesis in vivo.

This Review discusses the ways in which obesity in general and adipose tissue in particular might contribute to breast cancer. It details how the balance of adipokines such as leptin and adiponectin might affect tumorigenesis, and the contribution of peritumoral adipose tissue to a cancer-promoting microenvironment. A vast number of epidemiological studies suggest an important, but still controversial, role for obesity and adipose tissue mass in breast cancer risk and an association with tumor phenotype. The main conclusions from these studies raise the possibility that the adipose tissue can act as an effector organ that influences both cancer risk and tumor behavior. Here we also review heterotypic mechanisms in breast-cancer tumorigenesis; these mechanisms involve soluble secreted factors from peritumoral cells, extracellular-matrix components and interactions between stromal cells and tumor cells that create a specific and local peritumoral microenvironment. As a special focus, we discuss the increasing evidence for a role of peritumoral adipose tissue and secreted adipokines (such as adiponectin and leptin) in breast cancer; furthermore, the cellular and molecular basis of the peritumoral 'desmoplastic' tissue reaction observed in breast cancer is reviewed in detail.

Die Sepsis stellt trotz diverser Fortschritte der Therapie weiterhin eine grose medizinische Herausforderung dar. Die meisten Daten zur Sepsis stammen aus Studien zur Erforschung neuer Sepsismedikamente bzw. aus internationalen Kollektiven. Ziel dieser Arbeit war die Beschreibung unselektionierter Patienten mit schwerer Sepsis an einem deutschen Universitatsklinikum in Bezug auf Erreger, Mortalitat und Risikofaktoren. Von Mai 1999 bis Dezember 2002 wurden alle Patienten internistischer und chirurgischer Intensivstationen mit neu aufgetretener schwerer Sepsis und zumindest einem Organversagen in die prospektive Beobachtungsstudie „Unicenter Sepsis Survey Regensburg“ aufgenommen. 182 Patienten wurden eingeschlossen. Das mediane Alter der Patienten lag bei 58 Jahren, der mittlere SAPS-II-Wert bei 42 und die 14-Tage- bzw. 30-Tage-Mortalitat bei 25% bzw. 34%. 48% der Patienten entwickelten aufgrund einer internistischen Erkrankung, 33% nach chirurgischen Notfalleingriffen und 19% nach geplanten chirurgischen Eingriffen eine Sepsis. Chirurgische Notfallpatienten hatten hohere SAPS-II-Werte und eine schlechtere Prognose. 35% aller Patienten entwickelten ein akutes Nierenversagen. 85% der Patienten erhielten eine Therapie mit Vasopressoren, 90% mussten mechanisch beatmet werden. 105 Patienten (58%) hatten eine wahrscheinliche, 70 Patienten (38%) eine gesicherte fokale Infektion, bei sieben Patienten (4%) erwies sich abschliesend in der retrospektiven Analyse eine infektiose Genese als nicht wahrscheinlich. Die Charakteristika dieser unselektionierten Patienten mit schwerer Sepsis stimmen bezuglich Mortalitat, Erkankungsschwere und Erregerspektrum gut mit den Populationen neuerer Sepsisstudien uberein.

Acute and chronic critical conditions are associated with reduced serum levels of free triiodothyronine (FT(3)), free thyroxine FT(4), and thyrotropin, known as nonthyroidal illness syndrome (NTIS). It is still controversial whether these changes reflect a protective mechanism or a maladaptive process during prolonged illness. However, larger studies to determine the prevalence of the NTIS and its association with outcome in medical intensive care units (ICUs) are missing. Complete thyroid hormone levels from 247 of 743 patients admitted to our ICU between October 2002 and February 2004 were retrospectively evaluated. From these patients, Acute Physiology and Chronic Health II scores, ICU mortality, length of stay, mechanical ventilation, and concomitant medication were recorded. Ninety-seven patients (44.1%) had low FT(3) levels indicating an NTIS, either with normal (23.6%) or reduced (20.5%) serum thyrotropin levels. Of 97 patients with NTIS, 24 (23.3%) also showed reduced serum FT(4) levels. The NTIS was significantly associated with Acute Physiology and Chronic Health II scores, mortality, length of stay, and mechanical ventilation. In a multivariate Cox regression analysis, the combination of low FT(3) and low FT(4) was an independent risk factor for survival. Nonthyroidal illness syndrome is frequent at a medical ICU. A reduction of FT(4) together with FT(3) is associated with an increase in mortality and might reflect a maladaptive process, thereby worsening the disease.

Aufgrund der schlechten Prognose des Pankreaskarzinoms waren wahrend der letzten Jahre Vorlauferlasionen des invasiven Karzinoms Ziel vieler Studien. Als Vorlaufer des duktalen Pankreaskarzinoms wurden intraepitheliale Neoplasien (PanIN) beschrieben, welche in unterschiedliche Stadien – PanIN-1A, -1B, -2 und -3 – unterteilt werden. Ergebnisse molekulargenetischer Untersuchungen unterstutzen die Vorstellung eines Progressionsmodells, welches die Entstehung des invasiven Karzinoms aus Lasionen mit niedrigeren Neoplasiegraden postuliert. Der entscheidende Schritt in der Karzinogenese scheint dabei durch das Auftreten einer PanIN-3-Lasion gekennzeichnet zu sein. Ebenso wie die PanIN konnen bei den intraduktalen papillar-muzinosen Neoplasien (IPMN) verschiedene Stadien von benignen bis hin zu malignen Lasionen unterschieden werden. Bei invasivem Wachstum der IPMN konnen diese Neoplasien u. a. einem duktalen Adenokarzinom, aber auch einem prognostisch deutlich gunstigeren Kolloidkarzinom entsprechen. In dieser Ubersicht werden die beiden Vorlauferlasionen naher charakterisiert sowie die molekulargenetischen Veranderungen der Neoplasien dargestellt.

Low circulating levels of high molecular weight adiponectin (HMW-Apm) have been linked to dyslipidaemia and systemic HMW-Apm negatively correlates with very low density lipoprotein (VLDL), apolipoprotein B (ApoB), and ApoE and is positively associated with ApoA-I. Therefore, it was investigated whether HMW-Apm alters the hepatic synthesis of ApoB, ApoE, and ApoA-I or the activity of the hepatic ATP-binding cassette transporter A1 (ABCA1), as the main determinant of plasma HDL. HMW-Apm reduces hepatic ApoB and ApoE release whereas ABCA1 protein, activity and ApoA-I were not altered. Global gene expression analysis revealed that hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB are downregulated by HMW-Apm and this was confirmed at the mRNA and protein level. Therefore it is concluded that HMW-adiponectin may ameliorate dyslipidaemia by reducing the hepatic release of ApoB and ApoE, whereas ABCA1 function and ApoA-I secretion are not influenced.

Fibronectin (FN) is an essential factor for the induction of migration of primary colonic lamina propria fibroblasts (CLPF). The FN isoform ED-A is an important inducer of migration. Recently, we have shown that CLPF isolated from inflamed Crohn's disease (CD) mucosa migrated significantly less than control CLPF. We, therefore, investigated changes in FN or integrin expression that could be relevant for CLPF migration.mRNA of control-CLPF and CLPF isolated from fibrotic mucosa of CD patients was subtractively hybridized. Expression of FN, ED-A, and ED-B in frozen sections from intestinal mucosa was determined by immunohistochemistry. The mRNA expression of the FN isoforms in control, CD, and fibrosis biopsies was quantified by real-time polymerase chain reaction (PCR). Integrin alpha5beta1 protein and mRNA expression was analyzed by fluorescence activated cell sorting (FACS) and PCR, respectively.Subtractive hybridization indicated differential regulation of FN isoform expression in CD. The immunohistochemical analysis of FN protein revealed a reduction of FN isoforms in inflamed CD mucosa compared to control mucosa. In CD fistulae, the ED-A and ED-B isoforms were virtually absent. In fibrotic mucosa, both proteins were increased. Real-time PCR showed a decrease of FN and ED-A expression during mucosal inflammation in CD in contrast to UC and a significant increase of FN and isoforms in CD fibrosis. No difference was found for protein and mRNA of integrin alpha5beta1 in control, CD, and fibrosis CLPF by FACS and PCR.Downregulated expression of migration-inducing FN-isoforms in contrast to unchanged FN receptor expression may contribute to the observed alterations of CD CLPF migration.

Since adipocytes express specific receptors for pituitary hormones and hypothalamic releasing factors, adipose tissue has to be regarded as a fast-acting endocrine gland under the control of the brain. Expanding on this suggestion, the existence and clinical impact of a hypothalamic-pituitary-adipose axis is reviewed. The term 'adipotropins' is introduced in order to describe pituitary and hypothalamic hormones or releasing factors that directly target adipocytes by their specific receptors.

Leitlinien, Behandlungspfade und klinische Algorithmen sind heutzutage beliebte Instrumente zur Qualitatssicherung und Okonomisierung von arztlicher Arbeit. Diese Begriffe werden allerdings haufig nur unscharf voneinander abgegrenzt. Leider verkomplizieren medizinische Standards oft den Verfahrensablauf und erleichtern die Entscheidungsfindung im klinischen Alltag kaum. In unserer Klinik werden praktikable standardisierte Vorgehensweisen in Form strukturierter Textdokumente verfasst. Diese sollen einerseits als unmittelbare Entscheidungshilfe fur den Arzt am Krankenbett und andererseits als arztlich vorgegebener Grundriss fur die Ausarbeitung betriebsorganisatorisch ausgerichteter Behandlungspfade auf interdisziplinarer Ebene dienen. Am Beispiel der Abklarung bei Verdacht auf Tuberkulose werden Gliederung und Inhalt dieses an unserer Klinik etablierten Textdokuments dargestellt.

Eine 63-jahrige Patientin stellte sich mit Verdacht auf Reaktivierung einer Lymphknotentuberkulose (LK-Tbc) in der Klinik der Autoren vor. Eine im Vorjahr diagnostizierte LK-Tbc war erfolgreich behandelt worden. Klinisch zeigten sich akut eine Verschlechterung des Allgemeinzustands, zervikale Lymphknoten-(LK-)Schwellungen, Nachtschweis, Dyspnoe und eine oberflachliche Inflammation der rechten Brust. Computertomographie von Hals, Thorax und Abdomen mit Kontrastmittel: ausgedehnte LK-Vergroserung zervikal, axillar, mediastinal und retroperitoneal. Multiple intrapulmonale nodulare Lasionen mit einem Durchmesser bis zu 6 mm. Ausgepragter Pleuraerguss rechts. Unter der Annahme einer Reaktivierung der vorbekannten LK-Tbc wurde die Patientin initial mit einer erweiterten antituberkulosen Therapie behandelt. Nach klinischer Progredienz erfolgte eine erneute LK-Biopsie aus der linken Axilla, welche nunmehr den Nachweis eines Morbus Hodgkin vom Mischtyp mit teils histiozytar nekrotisierender, teils tuberkuloider Begleitreaktion ohne Nachweis saurefester Stabchen erbrachte. Die daraufhin eingeleitete Chemotherapie nach dem ABVD-Schema fuhrte zu einer raschen Verbesserung der klinischen Beschwerdesymptomatik. Sowohl bei dem Verdacht als auch bei gesicherter Diagnose einer LK-Tbc sollte differentialdiagnostisch ein Lymphom ausgeschlossen werden. Dieser Abwagung kommt insofern eine besondere Bedeutung zu, als der Morbus Hodgkin charakteristischerweise mit einem T-Zell-Defekt assoziiert ist, welcher zu einer Tbc pradestiniert.

In den letzten Jahren wurden zahlreiche Studien zur Wirkung von Biologika bei chronisch entzundlichen Darmerkrankungen durchgefuhrt. Mit Ausnahme von Infliximab und anderen Tumornekrosefaktor-Antikorpern hat sich bisher keines der Prinzipien als hinreichend erfolgreich erwiesen, um in die Praxis uberfuhrt zu werden. Der Integrin-Antikorper Natalizumab zum Beispiel ist wegen Nebenwirkungsproblemen sogar vom Markt genommen worden. Bei Betrachtung der Studien zeigt sich, dass haufig die falschen Patienten eingeschlossen wurden, gelegentlich auch ubersehen wurde, dass die Hemmung eines einzelnen Mediators aus einem redundanten Netzwerk nicht wirklich erfolgversprechend ist. Somit ist festzuhalten, dass Infliximab unser therapeutisches Arsenal bereichert hat, zumal es auch bei der Colitis ulcerosa bei etlichen Patienten wirksam ist, dass aber ein wirklicher Durchbruch in der Therapie durch die Biologika bislang nicht erfolgt ist. During the last years numerous studies on the effects of biologics in chronic inflammatory bowel disease have been performed. With the exception of infliximab and some other tumor necrosis factor antibodies none of the principles has been sufficiently successful to be included in the routine armamentarium. The integrin antibody natalizumab has been retracted from the market due to serious side effects. When looking at the studies it becomes obvious that often wrong patients have been included into the trials and sometimes it has been overlooked that the inhibition of a signal mediator out of a redundant network is not really promising. Thus, we can conclude that infliximab has enriched our therapeutic arsenal, in particular since it also works in ulcerative colitis in a number of patients. However, the real breakthrough in the therapy has not yet been achieved by biologics.

INTRODUCTION: We have examined the association of bone mineral density of patients with inflammatory bowel disease with a polymorphism in the gene encoding the vitamin D receptor. The thymine/cytosine (T/C) polymorphism in the first of two start codons can be defined by a restriction fragment length polymorphism using the restriction endonuclease FokI. Vitamin D receptor alleles containing the polymorphism have been denoted by f and alleles lacking the site by F. METHODS: We report on an association analysis of a basic population of 244 caucasian patients with Crohn's disease. We have genotyped the FokI polymorphism of the VDR in these patients and associated the genotype with the bone mineral density of the lumbar spine and the femoral neck. RESULTS: In the cohort 42% of the patients were scored FF homozygous, 43.7% Ff heterozygous, and 14.3% ff homozygous. 14.4% of the FF patients, 18.8% of the Ff patients, and 9.7% of the ff patients had osteoporosis of the lumbar spine and 21.25% of the FF patients, 25.3% of the Ff patients, and 18.5% of the ff patients had osteoporosis of the femoral neck. In this cohort no association between the genotype and the bone mineral density in the group as a whole nor when separated according to sex or age was found. CONCLUSIONS: In summary in our cohort no association of the FokI polymorphism and the BMD of the lumbar spine and femoral neck in patients with inflammatory bowel disease was found.

The competence network chronic inflammatory bowel disease (KN-CED) is one of 17 networks of competence initiated by the German Federal Ministry of Education and Research (BMBF). These networks are concerned with disease patterns which are characterized by their high frequency, high mortality rate or which present a large expense factor. The project-executing organization is the German Center for Air and Space Travel (DLR e. V.). The central structure of organization is the Telematic Platform for medical Networks (TMF e. V.). Aim of the KN-CED is to investigate, in their complexity, the incurable chronic diseases ulcerative colitis and Crohn's disease, particularly with regard to the causes of disease, the establishment of new therapy standards as well as patient care. To achieve this goal, the competence network is integrated into both national and international research associations and is also backed by the national self-help group DCCV and the pharmaceutical industry. Principal items of the competence network are the core facilities and their main focus on molecular genetics, animal and cell models and serum markers. Having stored the data of more than 4,000 patients so far, the central database of the competence network is one of the largest databases worldwide with regard to inflammatory bowel disease (IBD). The successful cooperation within the network is reflected in numerous publications. Thus, two of the three known genes of Crohn's disease were identified. Also with the participation of the competence network national guidelines for the diagnosis and therapy of IBD were generated.Furthermore, the competence network operates study centers where significant therapeutic developments in the field of biotechnological drugs are taking place. The analysis of existing structures of care as well as the development of standards of organization for patients with IBD top the research within the competence network and emphasize the claim to find comprehensive answers to the questions connected with IBD.

Objective: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated. Methods: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available. Results: SF values were significantly increased in men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF. Conclusions: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.