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Summary Purpose The nomenclature in clinical nutrition differs locally, among (para)medical disciplines, and both nationally and internationally. The inconsistencies hamper public, professional and scientific discussions. A working group of the German Society of Nutritional Medicine (DGEM) was established to work out definitions for the relevant terms used in nutritional support within Germany. Methods Terms were searched in (inter)national hard print technical literature (medical dictionaries, text books, (inter)national guidelines and online (PubMed, Embase, CINAHL, Google Scholar, general internet). (Inter)nationally agreed definitions published by Clinical Nutrition Societies were preferred to other reports. Results The terms were organised into four categories totaling 53 definitions: 1. Fields and structure: medical nutrition, clinical nutrition, nutrition steering committee, nutritional care, care catering, dietetics (dietary advice), obesity as part of clinical nutrition (obesity team), nutritional support (nutrition support team, malnutrition screening, nutritional support therapy), functional nutrition, nutritional assessment, nutrition therapy plan, nutritional therapy, 2. Nutritional conditions: disease-related malnutrition (starvation induced malnutrition, chronic disease-related malnutrition, acute disease-related malnutrition), cachexia, sarcopenia, specific nutrient deficiencies, refeeding syndrome, 3. Forms of nutrition: diet (regular diet, therapeutic diet, fortified food), artificial nutritional support (oral nutritional supplementation, enteral nutrition, parenteral nutrition) 4. Products: oral nutritional supplements and enteral formulas (whole protein formula, peptide-based formula, free amino acid formula, standard formula), parenteral solutions (total nutrient admixtures, multi-chamber systems, multiple bottle systems). Conclusion A comprehensive list of definitions for terms in nutritional support has been established for the first time and is made available to the international community for further development and discussions.

Summary Background & aims The selection of appropriate outcome variables in clinical nutrition is particularly challenging, since nutrition is an adjunct therapy in most cases. Therefore, its effect may be confounded with the primary therapy, and classic biomedical outcomes may not reflect the effect of the nutritional intervention. This paper scrutinizes different alternatives to the biomedical perspective. Results Five different outcome models are proposed and analyzed for their suitability in clinical nutrition studies: biomedical, patient-centered/-reported, health economic, decision-making, and integration of classical and patient-reported endpoints. Most published studies in the field of clinical nutrition make use of biomedical endpoints, but the growing importance of patient-centered/-reported and health economic outcomes is recognized. We recommend avoiding to focus solely on biomedical endpoints in clinical nutrition studies. The availability and value of a broader set of outcome-models should be acknowledged. Conclusion Patient-centered/-reported, health economic or combined endpoints are particularly useful to assess the effect of nutritional therapies, especially when applied in conjunction with a primary therapy. The proposed outcome models can also contribute to refine clinical nutrition guidelines in assessing the clinical relevance of the study results.

The Society for Sarcopenia, Cachexia, and Wasting Disease convened an expert panel to develop nutritional recommendations for prevention and management of sarcopenia. Exercise (both resistance and aerobic) in combination with adequate protein and energy intake is the key component of the prevention and management of sarcopenia. Adequate protein supplementation alone only slows loss of muscle mass. Adequate protein intake (leucine-enriched balanced amino acids and possibly creatine) may enhance muscle strength. Low 25(OH) vitamin D levels require vitamin D replacement.

Inflammatory bowel disease (IBD) is frequently associated with malnutrition. Up to 75% of patients with an active phase of IBD suffer from weight loss and hypoalbuminemia. Anaemia and vitamin deficiencies (specifically vitamin D and vitamin B12) as well as trace element deficiencies are also described. Malnutrition with loss of muscle mass and body fat is more frequent in Crohn’s disease than in ulcerative colitis and is usually restricted to the active phase. In quiescent disease malnutrition is uncommon and restricted to patients with short bowel, high output fistulas or a severe stenosis reducing food intake. The aetiology of malnutrition is partly due to anorexia because of food associated symptoms, e.g. pain, and partly due to increased intestinal losses (albumin and blood). An increased energy expenditure in the active phase may only play a smaller role in the development of malnutrition.

Background Cardiopulmonary bypass (CPB) impairs intestinal barrier function and induces systemic inflammation after cardiac surgery. The objective of this study was to evaluate the effect of profound haemodilution (haematocrit 19–21%) during normothermic CPB on gastrointestinal permeability and cytokine release in comparison with a standard haemodilution (haematocrit 24–26%). Methods This was a prospective, controlled, randomized pilot trial of 60 patients without gastrointestinal disease undergoing normothermic CPB (35.5–36°C) for coronary artery bypass graft surgery. Gastrointestinal permeability was measured by the triple-sugar technique (sucrose, lactulose, and mannitol excretion in urine) before and after CPB. Interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNFα) were quantified using enzyme-linked immunosorbent assays. Results Data from 59 patients (19–21% haematocrit, n =28; 24–26% haematocrit, n =31) were analysed. Data on gastrointestinal permeability were available for 47 patients (19–21% haematocrit, n =23; 24–26% haematocrit, n =24), blood samples for cytokine analysis from 59 patients. Mannitol excretion was normal before and after surgery without significant differences between the groups (after operation: 5.4% vs 2.9%, P =0.193). Lactulose and sucrose excretion was within a normal range before surgery and increased afterwards without differences between the groups. IL-6, IL-10, and TNFα were elevated after surgery, but there was no difference between the groups [IL-6 ( P =0.78), IL-10 ( P =0.74), and TNFα ( P =0.67)]. Conclusions Profound haemodilution during normothermic CPB brought about significant changes neither in intestinal permeability nor in cytokine release. It may be concluded that a haematocrit of 19–21% during normothermic CPB does not impair intestinal barrier function and cytokine response in patients without gastrointestinal comorbidity.

Background and aims A recent study reported that a nonsynonymous SNP rs2241880 (c.898A>G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A>G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands. Methods In total, we included 910 European IBD patients and compared the ATG16L1 c.898A>G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n =310; ulcerative colitis [UC] n =179), Hungary (CD n =147; UC n =117), and the Netherlands (CD n =157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics. Results We found a highly significant association of c.898A>G to CD. The association was significant ( p =0.0005) for the total CD cohort but also for the individual populations from Germany ( p =0.02) and Netherlands ( p =0.02) whereas in the Hungarian CD patients a clear trend was observed ( p =0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A>G and UC. No statistical interactions were observed between ATG16L1 c.898A>G and C ARD15 variants. Furthermore no association to a CD subphenotype was detected. Conclusions We confirm that ATG16L1 variant c898A>G confers a risk variant for CD but is not associated with a distinct CD phenotype.

Objectives We evaluated morphology and function of the gut in patients with chronic heart failure (CHF). Background Intestinal translocation of bacterial endotoxin may contribute to the inflammatory state observed in patients with CHF. The morphology and function of the gut may be abnormal. Methods We studied 22 patients with CHF (age 67 2 years, left ventricular ejection fraction [LVEF] 31 1%, New York Heart Association functional class 2.3 0.1, peak VO2 15.0 1.0 ml/kg/min) and 22 control subjects (62 1 years, LVEF 68 2%, peak VO2 24.7 1.3 ml/kg/min). Bowel wall thickness was assessed by transcutaneous sonography, small intestinal permeability by the lactulose-mannitol test, passive carrier-mediated transport by D-xylose test, large intestinal permeability by sucralose test (5- and 26-h urine collection, high-performance liquid chromatography), and mucosal bacterial biofilm by fluorescence in situ hybridization in biopsies taken during sigmoidoscopy. Results Chronic heart failure patients, compared with control patients, showed increased bowel wall thickness in the terminal ileum (1.48 0.16 mm vs. 1.04 0.08 mm), ascending colon (2.32 0.18 mm vs. 1.31 0.14 mm), transverse colon (2.19 0.20 vs. 1.27 0.08 mm), descending colon (2.59 0.18 mm vs. 1.43 0.13 mm), and sigmoid (2.97 0.27 mm vs. 1.64 0.14 mm) (all p 0.01). Chronic heart failure patients had a 35% increase of small intestinal permeability (lactulose/mannitol ratio: 0.023 0.001 vs. 0.017 0.001, p 0.006), a 210% increase of large intestinal permeability (sucralose excretion: 0.62 0.17% vs. 0.20 0.06%, p 0.03), and a 29% decrease of D-xylose absorption, indicating bowel ischemia (26.7 3.0% vs. 37.4 1.4%, p 0.003). Higher concentrations of adherent bacteria were found within mucus of CHF patients compared with control subjects (p 0.007). Conclusions Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition. (J Am Coll Cardiol 2007;50:1561‐9) © 2007 by the American College of Cardiology Foundation

BACKGROUND: A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease. AIM: To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour. METHODS: We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics. RESULTS: The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes. CONCLUSIONS: The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.

Aim: To study the role of mucus in the spatial separation of intestinal bacteria from mucosa. Patients and methods: Mucus barrier characteristics were evaluated using histological material obtained by biopsy from purged colon, colon prepared with enema and material from untreated appendices fixed with non-aqueous Carnoy solution. Bacteria were evaluated using fluorescence in situ hybridization, with bacterial 16S RNA probes and related to the periodic acid Schiff alcian blue stain. Biopsies from controls (n = 20), patients with self-limiting colitis (SLC; n = 20), ulcerative colitis (n = 20) and 60 randomly selected appendices were investigated. Results: The mucosal surface beneath the mucus layer was free of bacteria in ⩾80% of the normal appendices and biopsies from controls. The thickness of the mucus layer and its spread decreased with increasing severity of the inflammation; the epithelial surface showed bacterial adherence, epithelial tissue defects and deep mucosal infiltration with bacteria and leucocytes. Bacteria and leucocytes were found within mucus in all biopsy specimens from patients with ulcerative colitis, SLC, and acute appendicitis. The concentration of bacteria within mucus was inversely correlated to the numbers of leucocytes. Conclusions: The large bowel mucus layer effectively prevents contact between the highly concentrated luminal bacteria and the epithelial cells in all parts of the normal colon. Colonic inflammation is always accompanied by breaks in the mucus barrier. Although the inflammatory response gradually reduces the number of bacteria in mucus and faeces, the inflammation itself is not capable of preventing bacterial migration, adherence to and invasion of the mucosa.

We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.

Normothermic, nonpulsatile cardiopulmonary bypass (CPB) impairs systemic and splanchnic oxygen transport and increases gastrointestinal permeability. It is an important therapeutic goal to avoid splanchnic dysoxia during CPB. Small-dose prostacyclin therapy improves splanchnic oxygen transport and microcirculation in septic patients. In this study, we sought to determine if during cardiac surgery, the prostacyclin analog epoprostenol improves the balance of systemic and splanchnic oxygen transport. Eighteen patients undergoing cardiac valve replacement were randomized to receive either epoprostenol (3 ng x kg(-1) x min(-1)) or placebo during, and for 1 hour after, surgery. Systemic and splanchnic oxygen delivery, consumption, and extraction and arterial, mixed venous, and hepato-venous lactate concentrations were measured before, during, and after CPB. Gastrointestinal permeability was measured 1 day before and 1 day after surgery using the triple sugar permeability test. During CPB, the epoprostenol group had decreased systemic oxygen consumption and splanchnic oxygen extraction (P = 0.024). These effects were not present 1 hour after the end of epoprostenol infusion. The study was not adequately powered to determine whether epoprostenol altered the trend towards increased lactate metabolism and increased postoperative gastrointestinal permeability, nor could we demonstrate any differences between groups in clinically relevant end-points. In conclusion, these findings suggest that during normothermic CPB, small-dose epoprostenol therapy may reduce systemic oxygen consumption and splanchnic oxygen extraction.

Summary Background : Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease. Aims : To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease. Methods : We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters. Results : In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01). Conclusions : Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.

Background & Aims: In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC. Methods: In patients with histologically confirmed cholangiocarcinoma, endoscopic or percutaneous double stenting was performed. Patients fulfilling inclusion criteria were randomized to group A (stenting and subsequent PDT) and group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm; light dose, 180 J/cm 2 ). Further treatments were performed in cases of residual tumor in the bile duct. The primary outcome parameter was survival time. Secondary outcome parameters were cholestasis and quality of life. Results: PDT resulted in prolongation of survival (group A: n=20, median 493 days; group B: n=19, median 98 days; P Conclusions: PDT, given in addition to best supportive care, improves survival in patients with NCC. The study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.

Background & Aims: Microorganisms that directly interact with the intestinal mucosa are obscured by fecal flora and poorly characterized. Methods: We investigated the mucosal flora of washed colonoscopic biopsies of 305 patients with bowel inflammation and 40 controls. The microbial cultures were validated by quantitative polymerase chain reaction with subsequent cloning and sequencing, fluorescence in-situ hybridization, and electron microscopy. Results: We found high concentrations of mucosal bacteria in patients with bowel inflammation, but not in controls. The concentrations of mucosal bacteria increased progressively with the severity of disease, both in inflamed and non-inflamed colon. In patients with >10,000 cfu/μL, a thick bacterial band was attached to the intact mucosa without signs of translocation. Patients with inflammatory bowel disease (IBD) and concentrations of mucosal bacteria >50,000 cfu/μL had characteristic inclusions of multiple polymorphic bacteria within solitary enterocytes located next to the lamina propria, without or having no contact with the fecal stream. The identified bacteria were of fecal origin. Conclusions: Our findings suggest that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response. We hypothesize that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD. GASTROENTEROLOGY 2002;122:44-54

It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross‐sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12‐h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low‐grade inflammation defined by high‐sensitivity C‐reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P =0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low‐grade inflammation or presence of noninsulin‐dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low‐grade inflammation alone (P =0.043) or type 2 diabetes alone (P =0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low‐grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier., Until now, it has not been clear if the small intestinal mucosal barrier deteriorates with age per se. We investigated the pooled data of 215 nonsmoking healthy adults, 84 of whom were aged between 60 and 82 years and found similar intestinal permeability results in all age classes. However, in participants with low‐grade inflammation coupled with type 2 diabetes the small intestinal integrity was compromised.

Lipatrophic diabetes, also referred to as familial partial lipodystrophy, is a rare disease that is metabolically characterized by hypertriglyceridemia and insulin resistance. Affected patients typically present with regional loss of body fat and muscular hypertrophic appearance. Variable symptoms may comprise pancreatitis and/or eruptive xanthomas due to severe hypertriglyceridemia, acanthosis nigricans, polycystic ovaria, and carpal tunnel syndrome. Mutations within the LMNA gene on chromosome 1q21.2 were recently reported to result in the phenotype of familial partial lipodystrophy. The genetic trait is autosomal dominant. We identified a family with partial lipodystrophy carrying the R482W (Arg482Trp) missense mutation within LMNA. Here we present the lipoprotein characteristics in this family in detail. Clinically, the loss of sc fat and muscular hypertrophy especially of the lower extremities started as early as in childhood. Acanthosis and severe hypertriglyceridemia developed later in life, followed by diabetes. The characterization of the lipoprotein subfractions revealed that affected children present with hyperlipidemia. The presence and severity of hyperlipidemia seem to be influenced by age, apolipoprotein E genotype, and the coexistence of diabetes mellitus. In conclusion, dyslipemia is an early and prominent feature in the presented lipodystrophic family carrying the R482W mutation within LMNA.

ISIS-2302, an antisense oligonucleotide directed against intercellular adhesion molecule 1, was effective in steroid refractory Crohn's disease in a pilot trial. The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn's disease (CACD).A dose-interval, multicenter, placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD (Crohn's Disease Activity Index [CDAI], 200-400). The primary endpoint was steroid-free remission (CDAI150) at week 14.Only 2 of 60 (3.3%) ISIS-2302-treated and no placebo patients reached the primary endpoint. Steroid-free remission at week 26 (secondary endpoint) was reached in 8 of 60 (13.3%) active treatment and 1 of 15 (6.7%) placebo patients. A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose10 mg/day at weeks 14 and 26 (48.3% vs. 33.3% and 55.0% vs. 40.0%, respectively, and a glucocorticoid dose of 0 mg [prednisone equivalent] at week 26 [23.3% vs. 6.7%, respectively]). Treatment with ISIS-2302 was safe. The most common side effects were injection site reactions in the active treatment group (23% in ISIS-2302-treated patients vs. none in placebo patients). No statistically significant differences in the frequency of side effects were detected between dose groups.The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint. Positive trends were observed in some of the secondary endpoints.

BACKGROUND—Hyperammonaemia is a pathogenetic factor for hepatic encephalopathy that may be augmented after a transjugular intrahepatic portosystemic shunt (TIPS). Experimental data suggest that hyperammonaemia may be caused to a large extent by metabolism of small intestinal enterocytes rather than colonic bacteria. AIMS—To evaluate if ammonia release and glutamine metabolism by small intestinal mucosa contribute to hyperammonaemia in vivo in patients with liver cirrhosis. METHODS—Using TIPS to examine mesenteric venous blood, we measured mesenteric venous-arterial concentration differences in ammonia and glutamine in patients with liver cirrhosis before, during, and after enteral (n=8) or parenteral (n=8) isonitrogenous infusion of a glutamine containing amino acid solution. RESULTS—During enteral nutrient infusion, ammonia release increased rapidly compared with the post-absorptive state (65 (58-73) v 107 (95-119) µmol/l after 15 min; mean (95% confidence interval)) in contrast with parenteral infusion (50 (41-59) v 62 (47-77) µmol/l). This resulted in a higher portal ammonia load (29 (21-36) v 14 (8-21) mmol/l/240 minutes) and a higher degree of systemic hyperammonaemia (14 (11-17) v 9 (6-12) mmol/l/240 minutes) during enteral than parenteral infusion. The mesenteric venous-arterial concentration difference in glutamine changed from net uptake to release at the end of the enteral infusion period (−100 (−58 to −141) v 31 (−47-110) µmol/l) with no change during parenteral nutrition. CONCLUSIONS—These data suggest that small intestinal metabolism contributes to post-feeding hyperammonaemia in patients with cirrhosis. When artificial nutrition is required, parenteral nutrition may be superior to enteral nutrition in patients with portosystemic shunting because of the lower degree of systemic hyperammonaemia. Keywords: hepatic encephalopathy; intestinal metabolism; ammonia; glutamine; enteral nutrition; parenteral nutrition

Abnormalities in lung function are frequent findings in patients with terminal stage chronic liver disease. While spirometric parameters improve early after liver transplantation, a reduction in diffusion capacity has been reported up to 15 months after transplantation. It is unknown to what extent this disturbance in gas exchange occurs among long term survivors after liver transplantation. We assessed lung function in terms of spirometry, and gas exchange as well as pulmonary morphology by high resolution computed tomography (HRCT) in 40 patients 38 months (median, range 20–147 months) after liver transplantation. The prevalence of restrictive or obstructive changes was not different from predicted values. For the whole group of long-term survivors the carbon monoxide transfer coefficient (KCO) was reduced to 71.3 + 12.0 % predicted (P < 0.05). HRCT revealed interstitial changes in only 2/40 (5.0 %), emphysematous bullae in 2/40 (5.0 %) and pleural thickening in 9/40 (22,5 %). Diffusion abnormalities are prevalent in the majority of patients after liver transplantation, whereas spirometric abnormalities are absent also in the long term. The high prevalence of impaired gas exchange and the absence of interstitial lesions imply that changes in pulmonary blood vessels are the most likely cause.

Background & Aims: Successful treatment in nonresectable Bismuth type III and IV cholangiocarcinoma is seldom achieved. The aim of this study was to evaluate the effect of photodynamic therapy on cholestasis, quality of life, and survival in these patients. Methods: Nine patients with advanced nonresectable cholangiocarcinomas Bismuth type III and IV, who showed no sufficient drainage (bilirubin decrease Results: After photodynamic therapy, bilirubin serum levels declined from 318 ± 72 to 103 ± 35 μmol/L ( P = 0.0039) with no significant increase during the two monthly follow-ups. Quality of life indices improved dramatically and remained stable (e.g., Karnofsky index from 32.2% ± 8.13% to 68.9% ± 6.1%; P = 0.0078). Thirty-day mortality was 0%, and median survival time was 439 days. Conclusions: This study provides clear evidence that photodynamic therapy is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas Bismuth type III and IV. Compared with published data, survival time seems to be prolonged. GASTROENTEROLOGY 1998;114:536-542

The effect of normothermic (36.2 degrees C +/- 0.6 degree C) nonpulsatile cardiopulmonary bypass (CPB) on splanchnic (hepatic) blood flow (SBF), splanchnic oxygen transport (DO2spl) and oxygen consumption (VO2spl), splanchnic lactate uptake and gastric mucosal pH (pHi, gastric tonometry) was studied in 12 adults (New York Heart Association class II, ejection fractionor = 0.4) undergoing coronary artery surgery. SBF was estimated with the constant-infusion indocyanine green (ICG) technique using a hepatic venous catheter. DO2spl, VO2spl, and splanchnic lactate uptake were calculated using the Fick principle after the induction of anesthesia, during aortic cross-clamping, after CPB, and 2 and 7 h after admission to the intensive care unit (ICU). SBF, DO2spl, and VO2spl did not decrease during CPB but increased after ICU admission, whereas pHi decreased 7 h after ICU admission. Initial ICG extraction was 0.78, which decreased to 0.54 during aortic clamping and remained low thereafter. The increased arterial blood lactate concentrations were not associated with a decreased splanchnic lactate uptake. We conclude that normothermic CPB is not associated with deterioration in the global intestinal oxygen supply. The increase of blood lactate levels and the decrease in ICG extraction, as well as in pHi, are consistent with a systemic inflammatory response to CPB.This study demonstrated that normothermic cardiopulmonary bypass (at flows2.4 L.min-1.m-2) was not associated with deterioration in global intestinal oxygen delivery, which suggests that increased blood lactate concentrations and decreased gastric mucosal pH and indocyanine green extraction are manifestations of a systemic inflammatory response to cardiopulmonary bypass.

Malnutrition is a prominent feature in liver cirrhosis, with deleterious impact on clinical outcome. The objective of this study is to investigate whether malnutrition is associated with increased gastrointestinal permeability in liver cirrhosis reflected by altered urinary excretion of non-metabolizable sugar probes. Patients with advanced liver cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was determined according to the Subjective Global Assessment. Intestinal permeability was assessed by measuring the urinary excretion of orally administered, non-metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker for intestinal permeability and reflects non-carrier-mediated transcellular and paracellular transport of the small intestine during the first 5 h. Sucrose recovery in urine within the first 5 h reflects gastroduodenal permeability; sucralose recovery in urine 5–26 h after consumption reflects colonic permeability. Sixty-four patients (56.7±10.8 years; 33% female) were included in the study. Twenty-one patients were considered well nourished according to the Subjective Global Assessment, 23 moderately nourished and 20 patients severely malnourished; 74% had alcoholic liver disease and 67% had cirrhosis stage Child C. Gastroduodenal and colonic permeability was significantly increased in patients with liver cirrhosis compared with 63 healthy controls (0.23±0.22 and 1.37±1.42% vs 0.14±0.10 and 0.41±0.72% in controls), but not different between well and malnourished subjects. Small intestinal permeability (lactulose/mannitol ratio) was increased in all patients (0.069±0.055%) and further increased in malnourished patients (0.048±0.031% vs 0.084±0.061%, P=0.004) due to decreased mannitol recovery only. Gastric, small intestinal and even colonic permeability was altogether increased in liver cirrhosis, and malnutrition was associated with further increased small intestinal permeability indicative of villous atrophy.

International audience; Background: Nutritional intervention with oral nutritional supplements (ONS) has been shown to increase quality of life in malnourished patients. We investigated whether post-hospital supplementation with ONS is cost-effective according to international benchmarks in malnourished patients. Methods: 114 malnourished patients (50.6±16.1 years, 63 female) with benign gastrointestinal disease were included and randomised to receive either ONS for three months and dietary counselling at discharge (intervention, n= 60) or only dietary counselling at discharge (control group, n=54). Nutritional status was assessed with Subjective Global Assessment. Intervention patients documented daily intake of ONS, quality of life was assessed with SF-36 Health Survey and SF-36 values were transformed into health-status utilities. Quality-adjusted life years (QALYs) were calculated by adopting the area-under-the-curve method. We used 2 different pricing scenarios for ONS (minimum price: 2.30€ and maximum: 2.93€/tetra pack). The incremental cost-effectiveness ratio (ICER) of supplementation with ONS was calculated for both price scenarios. All analyses were corrected for age and gender. Results: Intervention patients consumed 2.4±0.8 ONS per day. Intervention and control patients did not differ in their health-status utilities at baseline (0.594±0.017 vs. 0.619±0.018), but after three months the health-status utilities were significantly higher in intervention patients than control patients (0.731±0.015 vs. 0.671±0.016, p=0.028). Intervention was associated with significantly higher costs (ICER: €9,497 and €12,099 /additional QALY, respectively) but deemed cost-effective according to international thresholds (

Contains fulltext : 81167.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Chronic pancreatitis (CP) and pancreatic adenocarcinoma (pCA) are associated with risk factors such as alcohol intake and tobacco smoking. Microsomal epoxide hydrolase (EPHX1) is a phase II detoxifying enzyme capable of tobacco-borne toxicant inactivation. We studied the role of the EPHX1 c.337T>C (p.Y113H) variant, whichleads to altered enzyme activity, in pancreatic diseases. METHODS: We genotyped 2391 patients by melting curve analysis. We enrolled 367 patients with pCA, 341 patients with alcoholic CP (aCP), 431 patients with idiopathic CP or hereditary pancreatitis, 192 patients with acute pancreatitis, and 679 controls of German descent. We replicated data in 77 patients with aCP and 304 controls from The Netherlands. RESULTS: In German patients with aCP, Y113 was more common than in controls (allele frequencies, 0.73 vs 0.68; risk ratio, 1.21 [95% confidence interval, 1.05-1.39]). However, we could not confirm this association in the Dutch population (allele frequencies, 0.62 vs 0.68, P=not significant). In total, Y113 frequency was 0.71 in aCP and 0.68 in controls (P = not significant). Allele frequencies did not differ in the other disease groups (acute pancreatitis, 0.69; idiopathic CP or hereditary pancreatitis, 0.68; pCA, 0.68; and control, 0.68). CONCLUSIONS: The EPHX1 Y113H variant is not associated with pancreatic diseases indicating that EPHX1 does not play a significant role in the initiation of pancreatic inflammation or cancer.

The calculation of body composition using bioelectrical impedance analysis in sick and hospitalized patients is hampered due to altered hydration state. We wanted to investigate how disease-related malnutrition assessed by the Subjective Global Assessment (SGA) is reflected in the bioelectrical impedance vector analysis. Patients with benign gastrointestinal disease (n 242) were entered in the study. Nutritional status was assessed by SGA. Arm muscle and fat area were estimated by anthropometry, muscle function was determined by hand grip strength. Whole body impedance measurements were made at 50 kHz. Ninety-eight patients were considered well nourished (SGA A), ninety-four were classified moderately malnourished (SGA B) and fifty patients were classified severely malnourished (SGA C) according to the SGA. The mean vector was significantly displaced between SGA C and SGA A and B, showing comparable resistance with a significantly reduced reactance, indicating comparable hydration but loss of dielectrical mass of soft tissues. This distinctive vector migration was not seen when studying the patients grouped according to BMI. In conclusion, disease-related malnutrition as assessed by the SGA is associated with a distinctive bioelectrical vector migration, implying that abnormal tissue structure and not reduced body mass only occurs in disease-related malnutrition. These disturbances are not seen in underweight according to BMI. Bioelectrical impedance vector analysis appears to be an attractive tool to identify disease-related malnutrition and to monitor nutritional intervention.

Contains fulltext : 71092.pdf (Publisher’s version ) (Closed access) BACKGROUND: A recent study reported that the c.30T>A (p.Cys10Ter; rs2043211) variant, in the CARD8 (TUCAN) gene, is associated with Crohn's disease (CD). The aim of this study was to analyze the frequency of p.C10X in 3 independent European (IBD) cohorts from Germany, Hungary, and the Netherlands. METHODS: We included a European IBD cohort of 921 patients and compared the p.C10X genotype frequency to 832 healthy controls. The 3 study populations analyzed were: (1) Germany [CD, n = 317; ulcerative colitis (UC), n = 180], (2) Hungary (CD, n = 149; UC, n = 119), and (3) the Netherlands (CD, n = 156). Subtyping analysis was performed in respect to NOD2 variants (p.Arg702Trp, p.Gly908Arg, c.3020insC) and to clinical characteristics. Ethnically matched controls were included (German, n = 413; Hungarian, n = 202; Dutch, n = 217). RESULTS: We observed no significant difference in p.C10X genotype frequency in either patients with CD or patients with UC compared with controls in all 3 cohorts. Conversely to the initial association study, we found a trend toward lower frequencies of the suggestive risk wild type in CD from the Netherlands compared with controls (P = 0.14). We found neither evidence for genetic interactions between p.C10X and NOD2 nor the C10X variant to be associated with a CD or UC phenotype. CONCLUSIONS: Analyzing 3 independent European IBD cohorts, we found no evidence that the C10X variant in CARD8 confers susceptibility for CD.

Background: Chronic heart failure (CHF) is a state of chronic inflammation. High serum levels of TNF alpha and the presence of cardiac cachexia are known to predict poor survival in CHF. Abnormal balance of pro- and anti-inflammatory circulating cytokine mRNA gene expression is thought to contribute to cachexia in humans, but has never been studied in CHF patients. Methods and Results: We studied 7 patients with cardiac cachexia (age 70±4 years, LVEF 28±2%, peak VO2 12.7±1.6 mL/kg/min, all >6% weight loss in previous 6–24 months), 19 noncachectic CHF patients (age 68±2 years, LVEF 31±2%, peak VO2 14.7±1.1 mL/kg/min) and 17 control subjects of similar age and gender (peak VO2 25.1±1.7 mL/kg/min, LVEF 71±2%). The mRNA gene expression of circulating mononuclear blood cells for pro-inflammatory mediators that have been implicated in the wasting process of ageing (TNF, STAT-1, STAT-3, SOCS-1 and SOCS-3) as well as anti-inflammatory cytokines (IL-10, tumor growth factor (TGF) beta were investigated by real time polymerase chain reaction. Values for the house keeping gene and genes of interest were calculated from double determinations within 40 cycles. We found higher TNF expression in cachectic compared to noncachectic CHF patients (log mean −0.5±0.17 vs. −1.2±0.12, p=0.002, ANOVA-p=0.0071) and control subjects (log mean −1.2±0.1, p=0.006). In contrast, there was no change in IL-10 gene expression in cachectic patients compared to noncachectic patients and controls (log mean −2.6±0.2 vs. −3.0±0.09 vs. −2.9±0.1, all p>0.13). Consequently TNF/IL-10 expression ratio was highest in cachectic patients (308±138 vs. 132±55 in noncachectic CHF patients vs. 101±37 in controls, p0.17). Similarly, no differences were found for gene expression of TGF beta (p>0.15). Conclusion: The balance between the pro-inflammatory cytokine TNF and the anti-inflammatory cytokine IL-10 on the level of mRNA expression of circulating mononuclear cells is significantly disturbed. Proinflammatory cytokine imbalance in cardiac cachexia may be important for the pathophysiology of body wasting and may represent the activated immune reflex.

Crohn's disease (CD) is a multifactorial disorder of unknown cause. Outstanding progress regarding the pathophysiology of CD has led to the development of innovative therapeutic concepts. Numerous controlled trials have been performed in CD over the last years. However, many drugs have not been approved by regulatory authorities due to lack of efficacy or severe side effects. Therefore, well-known drugs, including 5-ASA, systemic or topical corticosteroids, and immunosuppressants such as azathioprine, are still the mainstay of CD therapy. Importantly, biologicals such as infliximab have shown to be efficacious in problematic settings such as fistulizing or steroid-dependent CD. This review is intended to give practical guidelines to clinicians for the conventional treatment of CD. We concentrated on the results of randomized, placebo-controlled trials and meta-analyses, when available, that provide the highest degree of evidence. We provide evidence-based treatment algorithms whenever possible. However, many clinical situations have not been answered by controlled clinical trials and it is important to fill these gaps through expert opinions. We hope that this review offers a useful tool for clinicians in the challenging treatment of CD.

Studies in animal models of inflammatory bowel disease (IBD) suggest that supplementation of total parenteral nutrition with glutamine (gln), a conditionally essential amino acid in catabolic conditions, increases gln plasma concentrations, reduces intestinal damage, improves nitrogen balance and may improve the course of the disease. However, human data supporting this assumption are missing.A total of 24 consecutive patients with an acute exacerbation of IBD (19 Crohn's disease; five ulcerative colitis) and scheduled for total parenteral nutrition (TPN) (7 days) were randomised. Parallel to a standardised anti-inflammatory therapy, the patients received either a TPN with 1.5 g/kg body weight of a standard amino acid or an isonitrogenic, isocaloric TPN with 1.2 g/kg body weight of a standard amino acid and 0.3 g/kg L-alanine-L-glutamine. Primary end points were gln plasma concentrations and intestinal permeability assessed by urinary lactulose and D-xylose ratio.Gln plasma levels did not differ significantly in either group throughout the study. Intestinal permeability did not change within 7 days either with or without gln supplementation (Delta-lactulose/xylose ratio: 0.01+/-0.05 (gln+) vs 0.02+/-0.1 (gln-)). The observed changes in inflammatory and nutritional parameters, and also disease activity, length of TPN and hospital stay, were independent of glutamine substitution. Five (41%) patients in the gln+ group and three (25%) patients in the gln- group needed surgical intervention.Although limited by the sample size, these results do not support the hypothesis that glutamine substitution has an obvious biochemical or clinical benefit in patients with active IBD scheduled for total parenteral nutrition.

Background The proteolysis-inducing factor (PIF) was identified as a tumour product in various gastrointestinal cancers. A previous study in pancreatic cancer patients suggested PIF expression as a tumour marker, which is not related to tumour size. We hypothesized that PIF could be a useful marker to exclude benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass. Methods Urine of patients with a pancreatic mass of uncertain malignancy was investigated for PIF expression by Western blot. Sufficient urine protein for analysis was available in 59 patients. The diagnosis was established by histology in 54 patients and by follow up in five patients with chronic pancreatitis. In addition, serum CA19-9 was measured. Results The sensitivity (specifity) for the detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9 and PIF, respectively. The sensitivity (specifity) for the distinction of pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19-9 and PIF, respectively. Conclusion Evaluation of PIF in urine is of no diagnostic value in patients with a pancreatic mass of unknown malignancy.

AIM: To analyse the impact of NOD2/CARD15 mutations on the clinical course of Crohn’s disease patients from an eastern European country (Hungary). METHODS: We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 1007finsC) in 148 patients with Crohn’s disease, 128 patients with ulcerative colitis and 208 controls recruited from the University of Szeged, Hungary. In patients with Crohn’s disease, the prevalence of NOD2/CARD15 mutations was correlated to the demographical and clinical parameters. RESULTS: In total, 32.4% of Crohn’s disease patients carried at least one mutant allele within NOD2/CARD15 compared to 13.2% of patients with ulcerative colitis (P = 0.0002) and to 11.5% of controls (P

Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in copper overload in various tissues and cells. The aim was to assess both the phenotype in Brazilian WD patients and the corresponding ATP7B genotype. Sixty subjects belonging to 46 pedigrees diagnosed as WD were included in this study. Direct sequencing of all 21 exons within ATP7B and their flanking introns was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained. We identified twenty-five mutations, twelve of them reported for the first time. The c.3402delC mutation had the highest allelic frequency (30.8%), followed by the c.2123T>C (p.L708P) (16.7%). Exons 8 and 15 were the site of 62.5% of the mutations. The common European mutation c.3207C>A (p.H1069Q) was not present at all. Phenotype varied greatly among individuals with the same ATP7B genotype. Our data confirm the heterogeneity of ATP7B genotype in Brazilian WD patients. The mutational spectrum is compatible with the Brazilian history of Mediterranean immigration; however, new mutations, and different frequencies and phenotype associated with the previously known mutations characterize this population. Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD.

Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.

Accessible online at: www.karger.com/ddi Nutritional therapy, once a cornerstone of medical treatment, has lost its attractivity in favor of drug treatment, molecular genetic interventions or other high-tech therapies. As a consequence, data about nutritional status or dietary habits are missing in many patient charts. This development reflects the opinion of many doctors that nutrition does not greatly affect the course of diseases, and that nutritional intervention is laborious but much less effective than other forms of therapy. In view of this trend, it seems interesting to analyze the importance of nutrition in different dieseases. Of course, it is well accepted that nutrition is an important factor for the therapy and prognosis in several diseases, such as diabetes mellitus, hyperlipidemia, obesity or hemochromatosis. However, the most basic nutritional disturbance – malnutrition – is frequently ignored since it is considered as a complication of the disease process, with little bearing on the prognosis and little possibility for therapeutic intervention. However, an analysis of the literature reveals that malnutrition is an independent risk factor in many disease processes and that treatment of malnutrition can indeed improve the patients’ prognosis. Such an analysis has to address several questions, mainly the prevalence and diagnosis of malnutrition and its impact on the patients’ prognosis. It should set the stage for the papers in this issue of Digestive Diseases, which deals with nutritional questions.

Cushing's syndrome (CS) is associated with low fat-free mass, but it is unclear whether hypercortisolism causes a loss of whole body protein. Body composition was studied prospectively in 15 patients with untreated CS (n = 14 pituitary adenoma; n = 1 adrenal adenoma), in 15 nonobese healthy controls, and in 15 weight-matched obese controls by 3 different methods: total body potassium counting (TBP), bioelectrical impedance analysis (BIA), and anthropometry. In 6 patients, body composition was studied before and within 6 months after pituitary surgery. In CS patients and weight-matched controls, body weight and total body fat were significantly higher than in nonobese controls. In CS patients, TBP was 18.4% lower than predicted, whereas in weight-matched controls TBP was 7.1% higher than predicted. As compared with nonobese and weight-matched controls, in CS patients TBP indicated a significant loss of body cell mass (BCM) of -20.2 and -21.1%, respectively. A significantly reduced arm muscle area of -21.3% compared with weight-matched controls also indicated a loss of whole body protein. In CS, however, BIA overestimated BCM when compared with TBP by +18% and agreement between BIA and TBP in the individual patient was poor (limits of agreement plus minus 27.6%), indicating the invalidity of standard BIA equations in this population. Measurements performed before and 6 months after successful pituitary surgery demonstrated a significant loss of body weight (-11%) and body fat (-33%), but BCM and muscle mass remained on a constant low level. In conclusion, this study shows that, in patients with CS, a significantly reduced BCM indicates a true protein loss. The second interesting finding is that in the early recovery after successful treatment of hypercortisolism patients lose body fat without gaining BCM or muscle mass.

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.

WILLIAM J. SANDBORN,*,‡ BRIAN G. FEAGAN,§ STEPHEN B. HANAUER,*,‡ HERBERT LOCHS,* ROBERT LOFBERG,* ROBERT MODIGLIANI,*,\ DANIEL H. PRESENT,*,‡ PAUL RUTGEERTS,* JURGEN SCHOLMERICH,* EDUARD F. STANGE,* and LLOYD R. SUTHERLAND* *The Clinical Trials Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD), ‡The Clinical Alliance of the Crohn’s and Colitis Foundation of America, the §Clinical Network of the Crohn’s and Colitis Foundation of Canada, and the \Groupe d’Etude Therapeutique des Affections Inflammatoires Digestives. See Appendix I for institutional affiliations for each author and for the complete membership of the IOIBD Clinical Trials Task Force

Background & Aims: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. Methods: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. Results: Cumulative relapse rates (±SE) after 18 months were 24.5% ± 3.6% and 31.4% ± 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively ( P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% ± 5.6% vs. 39.7% ± 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease ( P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). Conclusions: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease. GASTROENTEROLOGY 2000;118:264-273

Sorbitol intake should be considered in patients with bowel problems, chronic diarrhoea, and weight loss

Background & Aims: Although multiple studies have focused on Helicobacter pylori , little is known about the mucosa-associated flora of the colon. The aim of this study was to detect bacteria directly in colonic mucosa from patients screened for colorectal cancer. Methods: Bacteria were quantified with the polymerase chain reaction and identified by comparative sequence analysis in colonoscopic biopsy specimens from 31 asymptomatic and 34 symptomatic controls with normal colonoscopic findings, 29 patients with colonic adenoma, and 31 patients with colorectal carcinoma. In 41 patients, intra- and extracellular location of bacteria was confirmed with the gentamicin protection assay. Results: No bacteria were detected in biopsy specimens from 97% of asymptomatic and 69% of symptomatic controls. In contrast, bacterial concentrations of 10 3 –10 5 colony-forming units per microliter were detected in biopsy specimens from both malignant and macroscopically normal tissue in 90% and 93% of patients with adenoma and carcinoma, respectively. E. coli and coli -like bacteria were shown to colonize the colonic mucosa in 82% of these patients. The gentamicin protection assay indicated that E. coli was partially intracellular in 87% of patients with adenoma and carcinoma and in none of the controls. Conclusions: The colonic mucosa of patients with colorectal carcinoma but not normal colonic mucosa is colonized by intracellular E. coli . GASTROENTEROLOGY 1998;115:281-286

Partial enteral nutrition is unlikely to suppress inflammation and so treat active Crohn’s disease Enteral nutrition is an effective therapy for active Crohn’s disease (CD) although less effective than steroids. This has been shown in a number of original studies and meta-analyses.1,2 Enteral nutrition leads to remission in approximately 60% of patients within 4–6 weeks. Unfortunately, enteral nutrition has never been compared with placebo or other medical therapies such as mesalamine or topical steroids. With the lack of such studies demonstrating that enteral nutrition is superior to placebo, the question has been raised if enteral nutrition has any therapeutic effect at all. However, remission rates with enteral nutrition range from 53% to 80%, which is higher than remission rates of placebo groups in most studies, which range from 18% to 40%. Therefore, a direct anti-inflammatory effect of enteral nutrition in active CD is generally accepted. The therapeutic efficacy of enteral nutrition in active CD is also suggested by results of recent studies demonstrating mucosal healing as well as a reduction in proinflammatory cytokines3,4 by enteral nutrition. The effect of enteral nutrition appears to be similar if the diet is drunk or applied via a tube and is also comparable with the effect of parenteral nutrition. Specific compositions of enteral diets—elemental diets or diets containing specific components—have no advantage over standard polymeric diets.1,5–7 In adults, enteral nutrition is rarely used as the sole therapy for active CD in clinical practice. This is partly due to its inferiority compared with steroids and partly to the inconvenience of enteral nutrition, resulting in low patient compliance—specifically if the mostly unpalatable diets are drunk. This appears to be different in children, who accept enteral nutrition much better, with compliance rates …

Introduction. Results from clinical trials often employ the odds ratio or relative risk to compare the proportion of subjects responding to experimental treatment to the proportion responding to control treatment. These measures have the advantage of using a single index to summarize the study results, but neither measure provides information that is intuitively meaningful to clinicians, and both can vary in different ways depending on the response to control treatment. Methods. We calculated the odds ratio and relative risk for responses to control treatment varying from 5% to 75% with a fixed difference of 20% between experimental and control responses. We then compared these values to those for two measures of effect size: number-needed-to-treat (NNT; N Engl J Med 1988; 318:1728-1733) and Probabilistic Index (Statist Med 2006; 25:591-602). Results. The Figure illustrates that with a fixed difference between responses to control and experimental treatment, as the response to control treatment increases, the odds ratio decreases to a plateau and then increases, whereas the relative risk decreases progressively. Since NNT and Probabilistic Index depend only on the difference between response to control and experimental treatment, values for these measures do not change with changing response to control treatment. That is, for a 20% difference between control and experimental responses, the NNT of 5 gives the number of experimental subjects needed to obtain one more success than treating the same number of control subjects. The Probabilistic Index for these same data is 0.6, and gives the probability that a randomly selected experimental subject has an outcome preferable to that from a randomly selected control subject. Conclusion. The NNT and Probabilistic Index depend only on the difference between responses to control and experimental treatment and can help clinicians assess the potential clinical significance of different values of the odds ratio and relative risk.