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Hereditary hemochromatosis (HHC) represents an autosomal recessive disease in which increased iron absorption causes iron overload and irreversible tissue damage. The recently detected association between two point mutations in the HFE gene on chromosome 6p and HHC has made it possible to screen for the disease before the onset of irreversible tissue damage. Conventional genetic testing is based on restriction fragment-length polymorphisms (RFLP) using two endonuclease recognition sites in codon 63 or 282, respectively. In this study, we have adapted single-strand conformation polymorphism analysis for capillary electrophoresis (SSCP-CE) to detect homozygote or heterozygote point mutations. Two HFE gene fragments spanning codons 63 and 282 were amplified by a duplex PCR using genomic DNA from peripheral blood or from tissue sections of paraffin-embedded liver biopsies as template. Thereby, rapid genotyping of both HFE mutations was achieved with a single PCR, omitting the need of further analysis by restriction digest. Eighty-five patients with liver disease and/or suspected iron overload were genotyped using SSCP-CE, and all results were verified by conventional RFLP analysis. In summary, SSCP-CE proved to be a reliable, cost-effective, sensitive and rapid method for genotyping HFE mutations. This method will further facilitate high-throughput genetic screening using capillary array electrophoretic devices.

Zusammenfassung  Die akute Pankreatitis nimmt in bis zu 20% der Fälle einen schweren Verlauf und ist dann mit einer hohen Mortalität von bis zu 40% behaftet. Eine wesentliche Komplikation stellt dabei die Infektion der (peri)pankreatischen Nekrosen dar. Therapeutisches Ziel ist es, den Infektfokus zu entfernen. Während chirurgische Methoden hierfür bislang den Goldstandard darstellen, gewinnen minimal-invasive, interventionelle Methoden immer mehr an Bedeutung. Diese Übersicht soll die verschiedenen interventionellen Therapieverfahren, insbesondere die perkutane, CT-gesteuerte Drainagenanlage und die perkutane Nekrosektomie vorstellen. Therapiealternativen, ebenso wie Limitierungen und Risiken für diese neuen Therapieverfahren werden erläutert. Des Weiteren soll eine Zusammenfassung über die derzeit publizierten Untersuchungen zu diesem Thema einen Überblick verschaffen. [ABSTRACT FROM AUTHOR]

Summary   We report the first interhospital transfer applying pumpless extracorporal lung assist (PECLA) in a severe case of pulmonary failure of a young man. The patient, a 25-yr-old man, developed respiratory failure due to legionnaires’ disease. The treatment regime included appropriate antibiotic treatment, mechanical ventilation and, finally, the transport of the patient after PECLA installation from the ICU of a county hospital to the medical ICU of a university hospital. The initiation of PECLA resulted in dramatic improvement within the next 6 days. The patient could be successfully weaned from PECLA after 12 days and from mechanical ventilation after another 5 days. In conclusion, pumpless extracorporal lung assist improved oxygenation and hemodynamic performance in this case of severe respiratory failure, so that the patient could be transported to a center for maximal intensive care treatment. [ABSTRACT FROM AUTHOR]

Summary   Infection with Varicella zoster virus (VZV) usually occurs in children up to 15 years with mild symptoms. We present a case of a 22-year old man with a fatal varicella zoster infection. He developed fulminant hepatitis with acute liver failure and an acute respiratory distress syndrom (ARDS). In this article the general aspects of VZV infection are discussed. Treatment options and previous publications are reviewed. [ABSTRACT FROM AUTHOR]

Zusammenfassung Diese Übersicht bildet den Abschluss der Serie über die Interaktion von Gastrointestinaltrakt und Intensivmedizin. Es werden 10 typische Störungen von Organen des Verdauungstraktes bei kritisch Kranken behandelt: stressbedingte Mukosaläsionen, Schockpankreas, Cholestase bei Sepsis, Schockleber, Gallenblasensludge und akalkulöse Cholezystitis, bakterielle Translokation, Pseudoobstruktion, Ileuskrankheit, nichtokklusive mesenteriale Ischämie und Clostridium difficile Infektion. Aufbauend auf einer kurzen Zusammenfassung der Pathophysiologie werden jeweils die wichtigsten Aspekte von Diagnostik und Therapie zusammengefasst. Es ergibt sich, dass noch wesentlicher Forschungsbedarf besteht. [ABSTRACT FROM AUTHOR]

Summary Infectious diseases are a common problem in the intensive care unit. 33–53% of critically ill patients receive antibiotics while being treated in the ICU. The indication for the use of antimicrobial agents is based not only on the patient’s clinical course but also on symptoms such as fever, leucocytosis, or the presence of elevated acute phase proteins. The identification of a pathogen is often a helpful adjunct in making a decision. Thus, the question arises whether it is useful to establish microbiological surveillance cultures as routine procedure in intensive care units. This article will present information on the rational use of urine, fecal and blood cultures as well as diagnostic measures of respiratory infections. In addition the relevance of screening for multiresistant pathogens is discussed in this update A summary of available data demonstrates that prompt identification and therapy of an infection in critical ill patients is necessary to establish appropriate therapy, and early proof of the causative pathogen improves outcome. Nevertheless, it has not been shown yet that routine microbiological survillance is advantageous except for single indications. There is no firm evidence for the general proof of principle of this expensive procedure. [ABSTRACT FROM AUTHOR]

Summary Subsets of acute mesenteric circulation disorders comprise mesenteric artery embolism and thrombosis, mesenterial vein thrombosis and non-occlusive mesenteric ischemia. Clinical presentation is often characterized by a discrepancy between severe subjective pain and relatively unspectacular findings on physical examination; all forms still carry an appallingly high mortalitiy rate. The most important point for better survival rates is early and, if indicated, invasive and aggressive diagnosis and treatment. Unfortunately, there are no non-invasive diagnostic tests of sufficient sensitivity and specificity so far, and mesenterial angiography (or abdominal CT, if mesenterial venous thrombosis is supected) remains the gold standard of diagnosis. With the introduction of new techniques (multidetector row CT), computed tomography may play a more important role in the future. In the obstructive forms of arterial mesenteric ischemia, the main therapeutic step after stabilization of the circulation remains an early laparotomy with embolectomy or revascularization and, if appropriate, resection of infarcted bowel. In patients with nonocclusive mesenteric ischemia, counteraction of mesenteric vasoconstriction is the main therapeutic principle. This review describes the different forms of acute mesenteric circulation disorders and gives an overview of the currently established and recommended forms of diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Summary Acute pancreatitis is divided into a mild, edematous and a severe, necrotizing form. The later is associated with an elevated mortality. The etiology of pancreatitis is often biliary or alcoholic. Diagnosis is based on clinical examination, determination of serum lipase activity, and supported by abdominal ultrasound or computer tomography. Initial aims are establishment of diagnosis, clarification of etiology and assessment of prognosis. Clinical examination, scores and computer tomography are used to estimate the patient’s prognosis. Interleukins and acute-phase proteins represent promising new tools. Basic management strategies include fluid administration, treatment of pain and early enteral feeding. The usefulness of prophylactic application of antibiotics in case of pancreatic necrosis is under investigation at present. If systemic complications occur, treatment at an intensive care unit is warranted. As yet, surgery is indicated in case of infected necrosis or occurrence of local complications. Recent data suggest that percutaneous drainage may become a reasonable alternative. [ABSTRACT FROM AUTHOR]

Summary Up to now, strategies for the verification of the correct localization of gastric tubes have not been internationally standardized. In Germany, most units rely on the auscultation method, whereas in the United States a radiological control after tube placement is considered mandatory. In this pilot study, the feasibility of a simple sonographic method for the correct localization of a gastric tube in intensive care units is evaluated. In 60 gastric tube insertions (with 50 patients being on artificial ventilation) performed on a medical intensive care unit, the correct placement of the tube was controlled by 1) auscultation, 2) pH measurement of the aspirate, and 3) sonography. In sonography, correct placement of the tip of the tube in the stomach was ascertained by detecting a 50 ml air jet applied with a syringe via the gastric tube. Results of ultrasound and the other control methods were compared to radiological control of the tube. In 43 patients (72%), the correct placement of the gastric tube was documented by ultrasound, compared to only 23% of patients in which a pH value of less than 4 allowed the proof of correct localization. In 2/20 patients without a detectable air jet on sonography, the gastric tube was located in the esophagus. We conclude that ?bedside? sonography is a fast and easy to perform method for the ascertainment of the correct positioning of a gastric tube and may in most cases be able to replace radiology for this indication. [ABSTRACT FROM AUTHOR]

summary during the past three years, new insight has been gained into the pathogenesis of sepsis, and after years of frustrating failures, this progress has eventually been translated into new therapies. we are now able to recommend, based on large and carefully designed studies, at least some strategies that may improve the outcome of the puzzling syndrome of severe sepsis. more effective treatment strategies for sepsis have been developed in the areas of supportive therapy with early, goal-oriented therapy including volume resuscitation, catecholamine therapy and transfusion, in endocrinology by substitution of hydrocortisone in septic shock patients and strict blood glucose control, by administering appropriate antibiotic therapy, and by ventilation with low tidal volumes and higher peep. finally, human recombinant activated protein c, which reverses disseminated intravascular coagulation and also exerts several other effects on endothelial cells, has proved to reduce mortality in patients with severe sepsis. subsequently, it has been licensed in the us in 2001 and in 2002 also in europe for adjuvant therapy, in addition to standard therapy, in patients with severe sepsis and a high risk for death. based on newly discovered pathophysiological concepts, several other compounds for adjuvant therapy of sepsis are in various stages of preclinical or clinical development. today, a patient who suffers from severe sepsis should receive conventional and supportive therapy optimized according to the findings of recent studies in this field, and he should also be evaluated for adjuvant sepsis therapy. zusammenfassung in den vergangenen ca. drei jahren sind im verständnis der pathophysiologie und in der therapie der sepsis erhebliche fortschritte erzielt worden. nach jahren der frustration und stagnation in diesem gebiet können aus den jüngst veröffentlichten studien nun für den kliniker bessere leitlinien zur behandlung der patienten mit diesem schweren krankheitsbild abgeleitet werden. diese fortschritte betreffen den bereich der supportiven therapie mit differenzierter und vor allem rascher volumensubstitution und transfusion, die endokrinologie mit substitution des stresshormones cortisol durch hydrocortison und strenge blutzucker-einstellung, die optimierte kalkulierte antibiotika-therapie und die protektive beatmung. schließlich wurde durch die modulation der disseminierten intravasalen gerinnung und anderer physiologischer imbalancen bei der sepsis durch die behandlung mit aktiviertem protein c erstmals ein erfolg mit einer adjuvanten sepsis-therapie erzielt. rekombinantes humanes aktiviertes protein c ist seit ende 2001 in den usa und seit ende 2002 auch in europa für die behandlung der schweren sepsis zusätzlich zur standardtherapie zugelassen. eine reihe von weiteren substanzen und verfahren zur adjuvanten sepsis-therapie, die unterschiedliche, pathophysiologisch begründete ansätze verfolgen, sind in unterschiedlichen phasen der vorklinischen und klinischen entwicklung. um heutzutage einen patienten mit schwerer sepsis optimal zu behandeln, sollte sichergestellt sein, dass dessen konventionelle und supportive therapie nach aktuellen gesichtspunkten optimiert wurde und individuell überprüft werden, ob dieser patient ein kandidat für eine adjuvante sepsis-therapie ist. [ABSTRACT FROM AUTHOR]

Objectives. We have characterized the expression and the function of the chemokine receptor CCR7 on fibroblast-like synoviocytes (FLS) of patients with RA and OA and on dermal fibroblasts. Methods. FLS were obtained after enzymatic digestion of synovial tissue (ST) of patients with RA and OA undergoing knee replacement surgery and taken into culture for chemokine receptor analysis by RT–PCR, flow cytometry and functional tests. Immunofluorescence for CCR7, fibroblast and T-cell markers was performed on ST of RA and OA patients. To study the response of FLS to CCR7 ligands and other chemokines, migration assays were performed in modified Boyden chambers. After stimulation of FLS with CCR7 ligands, the secretion of VEGF was evaluated by ELISA and Luminex. Results. CCR7 is expressed on FLS of patients with RA and OA, but not on dermal fibroblasts. FLS migrated in response to the CCR7 ligands, CCL19 and CCL21. Stimulation of FLS with CCL19 resulted in a significantly increased secretion of VEGF of RA- and OA-FLS. Conclusion. Apart from the migration of FLS in response to CCL19 and CCL21, it was shown that activation of the CCR7 receptor on FLS results in an enhanced VEGF secretion. A considerable expression of CCR7 ligands in proximity to perivascular infiltrates has previously been described in inflamed synovial tissue of RA patients. Stimulation of FLS via CCR7 could thereby contribute to angiogenesis in the synovial tissue. [ABSTRACT FROM AUTHOR]

Intestinal epithelial cells (IEC) form the largest surface of the human body and are of pivotal importance to digest and absorb nutrients. Furthermore these cells play a critical role shielding the organism against microorganisms and toxins present in the intestinal lumen. It is therefore not surprising that a large group of researchers take great interest in the study of these cells. However, to date it is a challenge to purify viable primary human intestinal epithelial cells and it has been even more fastidious to maintain IEC in culture ex-vivo as IEC undergo apoptosis within hours due to loss of cell anchorage ('anoikis') following the isolation process. Over recent years the authors aimed to continuously improve the isolation technique for primary IEC, allowing a simple, effective and rapid isolation of highly purified non-apoptotic human IEC. In this study the newly improved method is presented and applied to establish ex-vivo cultures of highly purified, fully viable primary IEC displaying important functional properties, making these cells amenable for ex-vivo research on primary human intestinal epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries., Methods: Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded., Results: In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications., Conclusions: Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: There is no consensus on the best way to integrate biomarkers into inflammatory bowel disease (IBD) research and clinical practice. The International Organization for the Study of Inflammatory Bowel Disease aimed to outline biomarker definitions, categories, and operating properties required for their use in registration trials and clinical practice. Using fecal calprotectin as an example, we provide a framework for biomarker development and validation in patients with IBD., Methods: We reviewed international society guidelines, regulatory agency guidance documents, and standardized reporting guidelines for biomarkers, in combination with publications on fecal calprotectin levels in patients with IBD. We assessed the validity of fecal calprotectin to serve as a surrogate biomarker of IBD activity and outlined a framework for further validation and development of biomarkers., Results: No endpoints have been fully validated as surrogates of risk of disease complications; mucosal healing is the most valid endpoint used to determine risk of disease complications. Fecal level of calprotectin has not been validated as a biomarker for IBD activity because of lack of technical and clinical reliability, assessment of performance when used as a replacement for endoscopy, and assessment of responsiveness to changes in disease states. The level of fecal calprotectin can be used only as a prognostic factor for disease recurrence in patients in remission after medical or surgical treatment., Conclusions: We reviewed guidelines, regulatory documents, and publications to identify properties required for the development of biomarkers of IBD activity and areas in need of clarification from regulatory agencies and societies. We propose a path forward for research of biomarkers for IBD., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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.

Background and Aims: To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD]., Methods: Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician's Global Assessment., Results: Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns., Conclusions: Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD., (© European Crohn’s and Colitis Organistion (ECCO) 2016.)

Background & Aims: There is a need for a scoring system that provides a comprehensive assessment of structural bowel damage, including stricturing lesions, penetrating lesions, and surgical resection, for measuring disease progression. We developed the Lémann Index and assessed its ability to measure cumulative structural bowel damage in patients with Crohn's disease (CD)., Methods: We performed a prospective, multicenter, international, cross-sectional study of patients with CD evaluated at 24 centers in 15 countries. Inclusions were stratified based on CD location and duration. All patients underwent clinical examination and abdominal magnetic resonance imaging analyses. Upper endoscopy, colonoscopy, and pelvic magnetic resonance imaging analyses were performed according to suspected disease locations. The digestive tract was divided into 4 organs and subsequently into segments. For each segment, investigators collected information on previous operations, predefined strictures, and/or penetrating lesions of maximal severity (grades 1-3), and then provided damage evaluations ranging from 0.0 (no lesion) to 10.0 (complete resection). Overall level of organ damage was calculated from the average of segmental damage. Investigators provided a global damage evaluation (from 0.0 to 10.0) using calculated organ damage evaluations. Predicted organ indexes and Lémann Index were constructed using a multiple linear mixed model, showing the best fit with investigator organ and global damage evaluations, respectively. An internal cross-validation was performed using bootstrap methods., Results: Data from 138 patients (24, 115, 92, and 59 with upper tract, small bowel, colon/rectum, and anus CD location, respectively) were analyzed. According to validation, the unbiased correlation coefficients between predicted indexes and investigator damage evaluations were 0.85, 0.98, 0.90, 0.82 for upper tract, small bowel, colon/rectum, anus, respectively, and 0.84 overall., Conclusions: In a cross-sectional study, we assessed the ability of the Lémann Index to measure cumulative structural bowel damage in patients with CD. Provided further successful validation and good sensitivity to change, the index should be used to evaluate progression of CD and efficacy of treatment., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© 2014 S. Karger AG, Basel.)

More than one-third of patients with IBD are affected by extraintestinal manifestations or extraintestinal complications beyond the intestinal manifestation of the disease. The most common manifestations include arthropathies, mucocutaneous and ophthalmological manifestations, as well as conditions affecting the hepatobiliary system, both in Crohn's disease and ulcerative colitis. However, less frequent manifestations, such as pulmonary or neurological manifestations, should also be considered in patients with IBD. Several extraintestinal manifestations follow the course of the underlying intestinal activity, whereas others are independent from the intestinal inflammation. Extraintestinal complications such as iron-deficiency anaemia and osteoporosis are consequences of the intestinal disease or of disease-specific treatment. As extraintestinal manifestations and complications strongly influence quality of life, and to avoid severe complications, adequate treatment is mandatory in affected patients. We provide a comprehensive overview of different extraintestinal manifestations and complications, including their management, in patients with IBD.

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.

Background: Nerve fibers can exert trophic/anti-trophic effects on epithelial cells. Substance P (SP) is a pro-proliferative neuropeptide, whereas sympathetic noradrenaline is anti-proliferative at high concentrations., Methods: Density of noradrenergic and sensory nerve fibers and presence of nerve repellent factors specific for noradrenergic (semaphorin 3F) and sensory nerve fibers (semaphorin 3A) were investigated in colorectal adenomas., Key Results: The pedunculus was innervated by noradrenergic fibers, whereas the mucosa was sparsely innervated. The control submucosa compared with control mucosa demonstrated increased density of noradrenergic fibers. Control tissue was much better innervated than the polyp. This was accompanied by strong expression of semaphorin 3F in epithelial cells. Density of sensory SP+ nerve fibers was higher in control colon mucosa compared with polyp mucosa, and SP+ cell clusters and semaphorin 3A-positive cells appeared in the intercrypt space in polyps, but not in control tissue., Conclusions & Inferences: This study demonstrated a marked loss of noradrenergic and sensory nerve fibers in polyp mucosa, which was associated with a strong increase of semaphorin 3F and 3A. Up-regulation of the sympathetic repellent semaphorin 3F in the polyps possibly triggers sympathetic repulsion and polyp growth due to the loss of anti-proliferative noradrenaline and presence of SP from local SP+ cells., (© 2011 Blackwell Publishing Ltd.)

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., (© 2011 John Wiley & Sons A/S.)

A number of immunosuppressants are used in the treatment of IBD. They have different modes of action but most of them affect different cell types and all are able to increase the number of infections, in particular opportunistic infections. Some may also lead to an increased number of malignomas. This is of particular importance in a disease such as Crohn's disease, which seems to be at least in part due to an immune deficiency. Data with regard to the differences of the effects of immunosuppressant combinations versus monotherapy are rare. Combinations with steroids, particularly, seem to pose a problem; however, an increased risk most probably also exists for other combinations. Therefore, in order to downregulate inflammation, we should use combined immunosuppression only if really necessary and only for short periods of time. The ultimate goal of the restitution of epithelial integrity and the maintenance of the mucosal barrier will better be achieved by other approaches., (Copyright © 2012 S. Karger AG, Basel.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background & Aims: Intestinal bacterial overgrowth and increased permeability are features of non alcoholic steatohepatitis (NASH). Bacterial endotoxin has been shown to promote NASH progression. Application of dextran sulfate sodium (DSS) is a colitis model in mice characterized by damage of the intestinal barrier. This study was designed to investigate if application of DSS aggravates experimental NASH., Methods: Male C57bl/6 mice were allocated into four experimental groups receiving either (I) standard chow (SC), (II) a high fat (HF) diet, (III) SC+DSS (1% in the drinking water), and (IV) HF+DSS for 12 weeks., Results: DSS treatment caused inflammation and proinflammatory gene expression (IL-1β, IL-17, TNF) in the colon. Expression of colonic antimicrobial peptide Cramp was significantly induced in SC+DSS mice, whereas expression was blocked in the HF+DSS group. Endotoxin levels were elevated in SC+DSS and HF mice but further augmented in the HF+DSS group. In line with this, increased hepatic TLR4 and TLR9 mRNA levels were detected in HF+DSS mice. The histological analysis revealed hepatic steatosis in both HF groups. Hepatic inflammation was more severe in HF+DSS mice, reflected by histology and analysis of proinflammatory gene expression (TNF and MCP-1). HF+DSS mice showed increased hepatic fibrosis by sirius red staining, hepatic collagen I expression, and α-SMA positive cells accompanied by higher p47(phox), TIMP-1, TGF-β, Pai-1, and α-SMA mRNA expression., Conclusions: Induction of an intestinal inflammation in experimental NASH promotes LPS translocation, hepatic inflammation, and fibrogenesis probably due to inhibition of intestinal antimicrobial peptides. These findings underscore the pathophysiological role of the gut-liver axis in the progression of NASH., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2010. Published by Elsevier B.V.)

Background: Bolus impaction in the esophagus is a common indication for emergency endoscopy. The aim of this study was to determine the most common causes of esophageal bolus impaction., Methods: In this retrospective study, data of 54 patients (41 male, 13 female) with bolus impaction in the esophagus were analyzed. Type and localization of the bolus and the endoscopic extraction tool used were evaluated. In 48 of 54 patients (89%), biopsy samples were taken of the esophagus for histological examination., Results: Mean age of the patients was 53 ± 20 years. Fourteen of 54 patients (26%) had experienced bolus impaction previously. Meat bolus (n = 35, 65%) was the most common cause of esophageal obstruction. In most cases, boluses were found in either the distal (n = 31) or the proximal (n = 18) esophagus. In 22 patients (41%), the bolus was pushed into the stomach by the endoscope. In most other cases the bolus, including foreign bodies, could be removed with the 5-arm polyp grasper or alligator forceps. Main causes of bolus impaction were eosinophilic esophagitis (n = 10) or reflux disease with or without peptic stenosis (n = 10), respectively., Conclusion: Bolus impaction is frequently correlated with eosinophilic esophagitis and reflux esophagitis; therefore, diagnostic workup should include esophageal biopsy sampling.

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

Aims/hypothesis: Obesity and insulin resistance are characterized by a chronic and low grade state of inflammation and the pro-inflammatory response of monocytes is affected in type 2 diabetes mellitus (T2D). We aimed to investigate whether LPS-induced monocytic cytokine and chemokine release depends on serum lipoprotein parameters in T2D patients., Methods: Primary human monocytes were isolated from 29 patients with known T2D and from 20 healthy volunteers. Anthropometric and disease-related parameters such as age, gender, BMI, WHR, diabetes duration, diabetes complications, and diabetes control (HbA1c) were documented. Monocytes were stimulated for 18 h with LPS (1 μg/ml). Unstimulated monocytes served as control. The supernatant concentrations of CCL2, CCL3, CCL4, CCL5, MIF and resistin were measured by ELISA., Results: LPS-stimulation significantly (p<0.001) increased CCL chemokine and resistin concentrations in healthy controls and in patients with T2D, whereas MIF release was not affected in both groups. LPS-induced CCL2 and resistin concentrations were significantly higher in T2D patients when compared to healthy controls. In T2D patients, LPS-induced CCL3 concentration was higher in males when compared to females (p=0.039) and supernatant resistin concentration upon stimulation with LPS showed a significant and positive correlation with age (r=0.6; p=0.001). LPS-induced CCL2 concentration was significantly and positively correlated with serum triglyceride concentration (r=0.4; p=0.009) in T2D patients. Furthermore, LPS-induced CCL4 concentration was significantly and positively correlated with total (r=0.4; p=0.035) and LDL cholesterol (r=0.4; p=0.033) concentration., Conclusions: LPS responsiveness of monocytes is altered in T2D and is affected by the respective serum lipoprotein metabolism., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objectives: 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., Methods: 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)., Results: 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, P<0.001, sensitivity: 93.3%, specificity: 81.8%, likelihood ratio: 5.1, post-test probability: 93%) by using a cutoff value of 1.8 ng/ml., Conclusions: 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.

Different approaches of engineering cartilage to treat defects in the articulating surfaces of the joints have been designed, which mainly use mesenchymal stem cells or autologous chondrocytes for in situ transplantation. However, these cells are poorly characterized with respect to viability, degree of differentiation and morphology or production of extracellular matrix. At present, one of the key approaches to generate chondrocytes is the stimulation of stem cells with transforming growth factor (TGF) β1. To characterize the molecular alterations occurring during the cellular transformation induced by TGF-β1 exposure, the differentiation process of bone marrow-derived stem cells into chondrocytes was investigated using an in vitro chondrogenesis model and the RNA arbitrarily primed PCR (RAP-PCR) fingerprinting technique. Distinct genes were found to be differentially regulated during chondrocyte development beginning on day 1: collagen type I, non-muscle myosin MYH9, followed by manganese superoxide dismutase and sodium-potassium ATPase on day 7. The results suggest that using RAP-PCR for differential display fingerprinting is a useful tool to investigate the differentiation process of bone marrow-derived stem cells following TGF-β1-stimulation.

Background and Aims: Sclerosing cholangitis in critically ill patients (SC-CIP) with sepsis and acute respiratory distress syndrome (ARDS) is a cholestatic liver disease with a rapid progression to liver cirrhosis and hepatic failure. Data on outcome of these patients after liver transplantation (LT) are sparse., Patients and Methods: Eleven patients (46 ± 12 years; mean labMELD-score: 27 ± 7) with SC-CIP underwent LT. Six patients had severe polytrauma with multiple bone fractures, sepsis and ARDS. Five non-traumatic patients acquired SC-CIP during long-term intensive-care-unit stays due to sepsis and ARDS. Time to diagnosis, the microbiologic results and the survival rates after LT were evaluated., Results: SC-CIP was diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) within 3 ± 1 months after manifestation of cholestasis and histologically confirmed in explanted livers. The predominant microorganisms isolated in bile were: Enterococcus and Candida albicans. Mean follow-up after LT was 28 ± 20 months. One female patient (non-traumatic) died due to sepsis 26 days after LT. All other patients left the hospital alive, but two (non-traumatic) patients died from sepsis, and one (traumatic) patient died in a hemorrhagic shock, thereafter. Seven of 11 patients (5 with polytrauma) are still alive and have a good quality of life. The survival of the SC-CIP patients after LT was comparable with that of patients transplanted due to alcoholic liver cirrhosis., Conclusion: SC-CIP develops rapidly within several months. Enterococcus and C. albicans were the main isolated microorganisms in the bile. Sepsis was the main cause of death after LT. Overall, SC-CIP is a good indication for LT in selected patients.

Background: Fistulae or leakages of anastomotic junctions of the gastrointestinal tract used to be an indication for surgery. However, patients often are severely ill and endoscopic therapeutic options have been suggested to avoid surgical intervention., Purpose: This is a retrospective analysis of fibrin glue application in the treatment of gastrointestinal fistulae or anastomotic leakages., Aim: The aim of this study was to investigate the value of fibrin glue in the treatment of gastrointestinal fistulae and leakages., Methods: From September 1996 to November 2002, 52 patients with gastrointestinal fistulae or insufficiencies have been treated endoscopically including the use of fibrin glue (Tissucol Duo S®, Baxter, Unterschleissheim, Germany). Clinical data comprising concomitant therapies and results were analysed by chart review., Results: Twenty-six lesions were located in the oesophagus or gastroesophageal junction, 4 in the stomach, 7 in the small intestine, 13 colorectal and 2 in the pancreas. The duration of treatment ranged from 12 to 1,765 days. Two to 81 ml fibrin glue (median 8.5) was used in 1-40 sessions (median 4). All patients received antibiotics; additional endoscopic options were frequently applied. Endoscopic therapy cured 55.7% patients (n = 29); 36.5% (n = 19) were cured with fibrin glue as sole endoscopic option. In 23.1% (n = 12), surgical intervention became necessary. Patients without major infectious complications tended to have a higher cure rate without surgery (87.5% vs. 50%). Eleven patients died (21.1%)., Conclusion: Endoscopic therapy is a valuable option in the treatment of fistulae and anastomotic insufficiencies of the gastrointestinal tract. It usually is applied repeatedly. Fibrin glue is a mainstay of this procedure. Major infectious complications seem to define a subgroup of patients with poorer outcome.

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., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The case of a patient with neurofibromatosis type 1 with chronic abdominal pain and iron deficiency anemia is described. Diagnostic procedures including esophagogastroduodenoscopy and ileocolonoscopy did not disclose a definitive cause. CT scan and MRI revealed multiple intraluminal tumors in the small bowel, especially in the ileum. These findings were verified by double balloon enteroscopy. Endoscopic resection was not performed due to size and number of the polyps, and the patient was sent for diagnostic laparotomy. A conglomerate tumor of the ileum was resected. Histopathological analysis revealed 13 inflammatory polyps and 2 gastrointestinal stroma tumors.

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., (Copyright © 2010 S. Karger AG, Basel.)

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., (Copyright © 2011 S. Karger AG, Basel.)

Background: Recently we found that migration of colonic lamina propria fibroblasts in Crohn's disease patients (CD-CLPF) from inflamed mucosa is significantly reduced as compared to control-CLPF. The behavior of CD-CLPFs isolated from fistulae and strictures was now investigated in detail., Methods: Initially migration assays for all CLPF cultures (CD-CLPF, fibrosis-CLPF, and fistula-CLPF) were performed in the modified 48-well Boyden chamber. Subsequently, for a migration assay more resembling the in vivo situation a 3D matrix model was developed. After seeding of cells into the 3D matrix the CLPF layer was wounded by an ERBIUM:YAG laser leading to circular cell rupture without effect on the extracellular matrix., Results: In the modified Boyden chamber migration of fistula-CLPF was significantly reduced compared to CD-CLPF. This was correlated with a decrease in FAK-protein expression, whereas in migrating fibrosis-CLPF an increase in FAK-protein expression, -autophosphorylation and migratory potential was found. This was confirmed in the 3D matrix wounding assay: Fistula-CLPF migrated less than CD-CLPF, whereas fibrosis-CLPF migrated significantly more in the 3D matrix wounding assay. Between 1 to 36 hours incubation time fibrosis-CLPF always displayed increased migration ability as compared to CD-CLPF. In contrast, fistula-CLPF migratory potential was always below that of CD-CLPF., Conclusions: Myofibroblasts isolated from inflamed, fibrostenotic, or fistulized CD mucosa differ in their migratory potential both in the modified Boyden chamber as well as in a 3D matrix model. These different migratory behaviors could be an explanation for impaired or excess wound healing and subsequently for fistula and fibrosis formation., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Objective: To estimate risk factors associated with long-term outcome (i.e., 1-year survival) in patients with Staphylococcus aureus bacteremia (SAB)., Methods and Materials: This was a retrospective study in which the microbiological laboratory data records of patients admitted to the University Hospital of Regensburg between January 2004 and June 2005 were examined to identify those patients with blood cultures positive for S. aureus. Corresponding clinical records for all patients were reviewed using a standardized questionnaire. Of the 119 patients identified with SAB, 80 were available for the >1-year follow-up., Results: Crude 1-year mortality was 47.5; 30- and 90-day mortality was 28.8 and 37.5%, respectively. In-hospital mortality was 28.8%. There were no significant differences in 1-year survival in terms of age, gender, antibiotic resistance, and mode of acquisition (nosocomial vs. community-acquired). A significantly better survival was observed with an identifiable focus present, if the chosen empiric antibiotic therapy was adequate or if the body mass index of the patient was >24., Conclusion: In summary, in this patient cohort, considerable additional mortality due to SAB beyond 30 or 90 days was present. Our results suggest that long-term survival data should be taken into account in outcome studies involving patients with S. aureus bacteremia.

Introduction: We report the first case of a patient who underwent simultaneous kidney and pancreas transplantation and who then suffered from repeated episodes of severe gastrointestinal bleeding over a period of seven years. Locating the site of gastrointestinal bleeding is a challenging task. This case illustrates that detection of an arterio-enteric fistula can be very difficult, especially in technically-challenging situations such as cases of severe intra-abdominal adhesions. It is important to consider the possibility of arterio-enteric fistulas in cases of intermittent bleeding episodes, especially in transplant patients., Case Presentation: A 40-year-old Caucasian man received a combined pancreas-kidney transplantation as a result of complications from diabetes mellitus type I. Thereafter, he suffered from intermittent clinically-relevant episodes of gastrointestinal bleeding. Repeat endoscopic, surgical, scintigraphic, and angiographic investigations during his episodes of acute bleeding could not locate the bleeding site. He finally died in hemorrhagic shock due to arterio-enteric bleeding at the kidney graft site, which was diagnosed post-mortem., Conclusions: In accordance with the literature, we suggest considering the removal of any rejected transplant organs in situations where arterio-enteric fistulas seem likely but cannot be excluded by repeat conventional or computed tomography-angiographic methods. Arterio-enteric fistulas may intermittently bleed over many years.

Proteins secreted by adipocytes (adipokines) play an important role in the pathophysiology of type 2 diabetes mellitus and the associated chronic and low-grade state of inflammation. It was the aim to characterize the antiinflammatory potential of the new adipocytokine, C1q/TNF-related protein-3 (CTRP-3), which shows structural homologies to the pleiotropic adipocytokine adiponectin. mRNA and protein expression of CTRP-3 was analyzed by RT-PCR and Western blot. Recombinant CTRP-3 and small interfering RNA-based strategies were used to investigate the effect of CTRP-3 on toll-like receptor (TLR) ligand, lipopolysaccharide (LPS)-, and lauric acid-induced chemokine release of monocytes and adipocytes. Together with complex ELISA-based techniques, a designed TLR4/myeloid differentiation protein-2 fusion molecule shown to bind LPS was used to prove the ability of CTRP-3 to act as endogenous LPS antagonist. CTRP-3 is synthesized in monocytes and adipocytes. The recombinant protein dose-dependently inhibits the release of chemokines in monocytes and adipocytes that were induced by lauric acid, LPS, and other TLR ligands in vitro and ex vivo. CTRP-3 inhibits monocyte chemoattractant protein-1 release in adipocytes, whereas small interfering RNA-mediated knockdown of CTRP-3 up-regulates monocyte chemoattractant protein-1 release, reduces lipid droplet size, and decreases intracellular triglyceride concentration in adipocytes, causing a dedifferentiation into a more proinflammatory and immature phenotype. By using a designed TLR4/MD-2 fusion molecule, it is shown by different techniques that CTRP-3 specifically and effectively inhibits the binding of LPS to its receptor, TLR4/MD-2. CTRP-3 inhibits three basic and common proinflammatory pathways involved in obesity and type 2 diabetes mellitus (adipo-inflammation) by acting as an endogenous LPS antagonist of the adipose tissue.