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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.

A recent randomized study of whipworm Trichuris suis ova (TSO) in ileal Crohn’s disease failed to demonstrate a clinical benefit compared to placebo after 12 weeks. Nonetheless, it has recently been shown that the spontaneous small intestinal inflammatory changes in Nod2-/- (Nucleotide-binding oligomerization domain 2) mice could be substantially ameliorated when these mice were colonized by Trichuris muris. Those and complementary epidemiologic findings in humans lead to the hypothesis that helminths may be advantageous only in patients carrying defective NOD2 variants. Thus, 207 participants of the TSO trial were retrospectively genotyped for six functional NOD2 genetic variants to evaluate whether the treatment outcome differed in patients carrying NOD2 variants. We observed no significant association of the NOD2 variants or their haplotypes with clinical outcome after TSO treatment.

During the last 20 years, treatment paradigms as well as drugs used for IBD have changed significantly. However, there are still many unmet needs and a significant number of patients needing better therapy. It is obvious from this situation that many attempts have been made to implement new drugs and treatment algorithms including biologicals, new formulations of old drugs and ‘fancy molecules or approaches'. For about 10 years, the application of Trichuris suis ova has been promoted and used in quite a number of patients. Two early studies suggested positive effects in ulcerative colitis as well as in Crohn's disease. These studies were based on experimental data in animal models as well as in vitro experiments. However, two large randomized controlled trials were not able to provide significant clinical effects in active Crohn's disease as compared to placebo, although a biological reaction (eosinophilia) was found. Another approach is the use of locally released phosphatidylcholine in ulcerative colitis. This approach is based on decreased phosphatidylcholine concentrations in the colonic mucus in patients, and showed positive effects in a number of monocentric trials in steroid-refractory and chronic active ulcerative colitis. A dose-finding study gave a positive signal in the highest-dose group and this approach is being tested further in controlled trials. Many other ‘fancy molecules' including cannabis, vitamin D, thalidomide, hyaluronic acid, lidocaine, clonidine, chondroitin sulfate, naltrexone and melatonin have been tested in patients with claims of success. For most of those, however, controlled data in appropriate studies are lacking. Many more substances have been used in animal models and are probably applied in individual patients. Results of preliminary studies on some of the molecules mentioned are presented.

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.

Chronic psychosocial stress is a risk factor for many affective and somatic disorders, including inflammatory bowel diseases. In support chronic subordinate colony housing (CSC, 19 days), an established mouse model of chronic psychosocial stress, causes the development of spontaneous colitis. However, the mechanisms underlying the development of such stress-induced colitis are poorly understood. Assessing several functional levels of the colon during the initial stress phase, we show a pronounced adrenal hormone-mediated local immune suppression, paralleled by impaired intestinal barrier functions, resulting in enhanced bacterial load in stool and colonic tissue. Moreover, prolonged treatment with broad-spectrum antibiotics revealed the causal role of these early maladaptations in the development of stress-induced colitis. Together, we demonstrate that translocation of commensal bacteria is crucial in the initiation of stress-induced colonic inflammation. However, aggravation by the immune-modulatory effects of fluctuating levels of adrenal hormones is required to develop this into a full-blown colitis.

BCL-2 modifying factor (BMF) is a sentinel considered to register damage at the cytoskeleton and to convey a death signal to B-cell lymphoma 2. B-cell lymphoma 2 is neutralized by BMF and thereby facilitates cytochrome C release from mitochondria. We investigated the role of BMF for intestinal epithelial cell (IEC) homeostasis. Acute colitis was induced in Bmf-deficient mice (Bmf(-/-)) with dextran sulfate sodium. Colonic crypt length in Bmf(-/-) mice was significantly increased as compared with WT mice. Dextran sulfate sodium induced less signs of colitis in Bmf(-/-) mice, as weight loss was reduced compared with the WT. Primary human IEC exhibited increased BMF in the extrusion zone. Quantitative PCR showed a significant up-regulation of BMF expression after initiation of anoikis in primary human IEC. BMF was found on mitochondria during anoikis, as demonstrated by Western blot analysis. RNAi mediated knockdown of BMF reduced the number of apoptotic cells and led to reduced caspase 3 activity. A significant increase in phospho-AKT was determined after RNAi treatment. BMF knockdown supports survival of IEC. BMF is induced in human IEC by the loss of cell attachment and is likely to play an important role in the regulation of IEC survival.

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 Oligodeoxynucleotides (ODNs) containing unmethylated cytosine–guanosine (CpG) sequence motifs constitute the immunostimulatory components of bacterial DNA which potently activate innate immunity. Administration of CpG-ODNs before the onset of experimental colitis prevents intestinal inflammation by induction of colitis-suppressing T cells. Aims To identify the interplay between innate and adaptive immune cells finally leading to protective CpG-ODN effects in intestinal inflammation. Methods Total splenic cells or purified selected cell types (CD4 + CD62L + T cells alone or with B cells or dendritic cells (DCs)) from BALB/c mice were (co)-incubated in vitro with CpG-ODN for 5 days and CD4 + CD62L + cells were injected intraperitoneally into C.B.-17 SCID (severe combined immunodeficiency) mice. Splenic CD4 + CD62L + T cells were isolated from transgenic donor mice in which CD11c + DCs were depleted by diphtheria toxin administration during CpG-ODN treatment and injected into C57BL/6 Rag2 −/− recipients. Intestinal inflammation was evaluated by histological scoring and cytokine secretion of mesenteric lymph node cells. Results CpG-ODN treatment of total splenic cells but not of purified CD4 + CD62L + cells reduced the colitogenic potential of transferred T cells. While CpG-ODN stimulation of co-cultured CD4 + CD62L + and B-cells did not alter the colitogenic potential of T cells, co-incubation of CpG-ODN-stimulated DCs and CD4 + CD62L + cells reduced the colitogenic potential of the T cell population. Depletion of CD11c + DCs during CpG-ODN administration in vivo abolished the protective CpG-ODN effects. Conclusions CpG-ODN-dependent protective effects in experimental colitis act indirectly on CD4 + CD62L + T cells. While the involvement of B cells could be excluded, CD11c + DCs were identified as key mediators of CpG-ODN-induced protection in experimental colitis.

The understanding of the role of adipose tissue has changed from a lipid storage organ to an endocrine and immunologically active organ. Here, we summarize the evidence for an important role of adipose tissue in innate immunity. The review focuses on the expression and function of Toll-like receptors (TLRs) in adipocytes and on the role of adipose tissue macrophages. The dual activation of TLR4 in adipocytes by lipopolysaccharide and fatty acids represents a molecular gate that connects innate immunity with metabolism. Dichotomic molecules derived from ancient precursor molecules control metabolism and immune function. Visceral adipose tissue is infiltrated by macrophages in obesity, and there is local crosstalk between these two types of cells, leading to an inflammatory transformation of adipose tissue.

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.

Introduction Monitoring of physiologic parameters in critically ill patients is currently performed by threshold alarm systems with high sensitivity but low specificity. As a consequence, a multitude of alarms are generated, leading to an impaired clinical value of these alarms due to reduced alertness of the intensive care unit (ICU) staff. To evaluate a new alarm procedure, we currently generate a database of physiologic data and clinical alarm annotations. Methods Data collection is taking place at a 12-bed medical ICU. Patients with monitoring of at least heart rate, invasive arterial blood pressure, and oxygen saturation are included in the study. Numerical physiologic data at 1-second intervals, monitor alarms, and alarm settings are extracted from the surveillance network. Bedside video recordings are performed with network surveillance cameras. Results Based on the extracted data and the video recordings, alarms are clinically annotated by an experienced physician. The alarms are categorized according to their technical validity and clinical relevance by a taxonomy system that can be broadly applicable. Preliminary results showed that only 17% of the alarms were classified as relevant, and 44% were technically false. Discussion The presented system for collecting real-time bedside monitoring data in conjunction with video-assisted annotations of clinically relevant events is the first allowing the assessment of 24-hour periods and reduces the bias usually created by bedside observers in comparable studies. It constitutes the basis for the development and evaluation of “smart” alarm algorithms, which may help to reduce the number of alarms at the ICU, thereby improving patient safety.

New knowledge regarding the etiopathophysiology of inflammatory bowel diseases (IBD) may provide new approaches for treatment. The most convincing concept at the moment is a defective mucosal barrier due to inappropriate recognition of the luminal flora or to a defective defense against those bacteria. These concepts indicate that the paradigm of immune suppression may not be the optimal concept. Therefore variable approaches to improve the barrier function or to modulate luminal components have to be studied in the future. This includes probiotics, bile acid receptor agonists, Toll-like receptor agonists and many other as yet hypothetical ideas. We still have much to learn about the concepts mentioned in order to achieve the goals of treatment, i.e. avoiding structural damage and complications.

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

The family of Toll-like receptors (TLRs) plays a pivotal role in host defense against pathogens. However, overstimulation of these receptors may lead to uncontrolled general inflammation and eventually to systemic organ dysfunction or failure. With the intent to control overwhelming inflammation during gram-negative bacterial sepsis, we constructed soluble fusion proteins of the lipopolysaccharide (LPS)-receptor complex to modulate TLR signaling in multiple ways. The extracellular domain of mouse TLR4 and mouse myeloid differentiation factor 2 (MD-2) fusions (LPS-Trap) were linked to human immunoglobulin G Fc domains (LPS-Trap-Fc). In addition to the ability to bind LPS or gram-negative bacteria and to inhibit interleukin-6 secretion of monocytic cells after LPS treatment, LPS-Trap-Fc was able to opsonize fluorescentEscherichia coliparticles. This led to enhancement of phagocytosis by monocytic cells which was strictly dependent on the presence of the Fc region. Moreover, only LPS-Trap-Fc- and not LPS-Trap-coated bacteria were sensitized to complement killing. Therefore, LPS-Trap-Fc not only neutralizes LPS but also, after binding to bacteria, enhances phagocytosis and complement-mediated killing and could thus act as a multifunctional agent to fight gram-negative bacteria in vivo.

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.

Accumulating evidence indicates that bacteria and bacterial products promote hepatic fibrogenesis. The activation of hepatic stellate cells (HSC) plays a central role in hepatic fibrosis. Here, we demonstrate that HSC express toll-like receptor 9 (TLR9), a pattern recognition receptor that is activated by CpG motifs present specifically in bacterial DNA. Upon CpG stimulation human as well as murine HSC isolated from wild-type (TLR9+/+) mice express increased levels of the profibrogenic chemokine monocyte chemotactic protein 1 (MCP-1). In contrast, HSC isolated from TLR9 deficient (TLR9-/-) mice lacked CpG motif induced MCP-1 expression indicating the functionality of TLR9 in HSC. Bile duct ligation revealed significantly lower hepatic MCP-1 and collagen expression and less hepatic fibrosis in TLR9-/- compared to TLR9+/+ mice. In addition, the expression of hepatic alpha-smooth-muscle actin, a known marker for HSC activation, was reduced in TLR9-/- mice indicating that bacterial DNA induces the activation of HSC and therefore promotes hepatic fibrosis.

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.

Aim: Bacterial translocation (BT) to mesenteric lymph nodes (MLN) in cirrhosis has been linked to impaired host defence. Phagocytosis by polymorphonuclear leucocytes (PMNLs) is the primary event in the killing of bacteria but has not been investigated in relation to the presence of BT. Methods: Mesenteric lymph nodes were harvested sterile and assessed for BT by culture techniques. Study groups included ascitic cirrhotic rats (LC), healthy controls (Con) as well as portal-vein-ligated (PVL) rats 2 days (acute PVL with and without norfloxacin) or 3 weeks after surgery (chronic PVL). PMNLs were isolated from systemic blood and the capacity to phagocytose opsonized Escherichia coli was evaluated by FACS analysis. Results: No BT was observed in Con and chronic PVL animals but 11/20 LC (55%) and six out of six acute PVL (100%) presented with BT. In the presence of BT, PMNL from PVL as well as LC rats showed significantly increased phagocytic activity as compared with controls. In contrast, PMNL from animals without BT, whether PVL or LC, exhibited phagocytic activity similar to those from control rats. The number of PMNLs involved in the phagocytic process was significantly increased only in portal-hypertensive rats with but not without BT as compared with controls. Norfloxacin did prevent BT in acute PVL animals, thereby correcting the increase in phagocytic capacity in PMNL. Conclusions: Cirrhosis per se is not associated with alterations of the phagocytic capacity of PMNL. The occurrence of BT, however, increases the phagocytic capacity of PMNL, being observed likewise in prehepatic portal hypertension, indicating an in vivo‘priming’ of PMNL by BT independent of cirrhosis.

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.