Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease.

BACKGROUND & AIMS: Bacteria might be involved in the development and persistence of inflammation in patients with Crohn's disease (CD), and antibiotics could be used in therapy. We performed a clinical phase 2 trial to determine whether a gastroresistant formulation of rifaximin (extended intestinal release [EIR]) induced remission in patients with moderately active CD. METHODS: We performed a multicenter, randomized, double-blind trial of the efficacy and safety of 400, 800, and 1200 mg rifaximin-EIR, given twice daily to 402 patients with moderately active CD for 12 weeks. Data from patients given rifaximin-EIR were compared with those from individuals given placebo, and collected during a 12-week follow-up period. The primary end point was remission (Crohn's Disease Activity Index <150) at the end of the treatment period. RESULTS: At the end of the 12-week treatment period, 62% of patients who received the 800-mg dosage of rifaximin-EIR (61 of 98) were in remission, compared with 43% of patients who received placebo (43 of 101) (P = .005). A difference was maintained throughout the 12-week follow-up period (45% [40 of 89] vs 29% [28 of 98]; P = .02). Remission was achieved by 54% (56 of 104) and 47% (47 of 99) of the patients given the 400-mg and 1200-mg dosages of rifaximin-EIR, respectively; these rates did not differ from those of placebo. Patients given the 400-mg and 800-mg dosages of rifaximin-EIR had low rates of withdrawal from the study because of adverse events; rates were significantly higher among patients given the 1200-mg dosage (16% [16 of 99]). CONCLUSIONS: Administration of 800 mg rifaximin-EIR twice daily for 12 weeks induced remission with few adverse events in patients with moderately active CD.

Clinical experiences derived from implementation of an easy to use concept for treatment of wound healing by secondary intention and guidance in selection of appropriate dressings.

The main objective of this case-cohort-type observational study conducted at different Surgical Departments of the Charité-Universitätsmedizin in Berlin was to evaluate the sequential use concept first described by Systagenix Wound Management in 2007. Fifty-two patients with different wound healing by secondary intention were treated for 7 weeks at the Charité-Universitätsmedizin in Berlin. A multidisciplinary team worked together to reach consensus in wound assessment; in classification of infection status according to the criteria described by European Wound Management Association (EWMA); in treatment protocol and on dressings to be used to 'cover' wounds. Before dressing application, all wounds were cleaned from debris. Following the sequential use concept, wounds classified as stages 2 and 3 were dressed with SILVERCEL(®) and TIELLE(®) or TIELLE PLUS(®) to 'clean' the wounds. After 2-3 weeks, treatment was changed to PROMOGRAN PRISMA(®) and TIELLE(®) to 'close and cover' wounds, thus providing optimal wound healing. Wounds classified as non infected were dressed with PROMOGRAN PRISMA(®) and TIELLE(®) during the complete treatment period. Patients were asked to evaluate the treatment using a simplified questionnaire developed at the Charité-Universitätsmedizin in Berlin. Wounds comprised 37 surgical procedures, 8 chronic mixed ulcer, 4 pressure sores, 1 diabetic foot ulcer, 1 venous leg ulcer, and 1 mixed arterial/venous ulcer. At baseline, 12 wounds were classified as stage 3, 38 wounds as stage 2 and 2 wounds as stage 1. After 7 weeks of treatment, all patients showed a positive clinical response to the sequential use treatment. Results of wound size showed a high significant progression of wound healing expressed with a profound reduction of wound area (P in all measurements <0·001, chi-square test) and improved granulation. This study summarises the clinical experiences derived from the evaluation of the sequential use concept in the daily clinical practice of wound treatment. On the basis of the wound healing results, patients' evaluation of treatment and the clinicians' and staff experiences, this concept was implemented at different Surgical Departments of the Charité-Universitätsmedizin in Berlin.

Time-gated fluorescence spectroscopy improves endoscopic detection of low-grade dysplasia in ulcerative colitis.

BACKGROUND: Dysplasia in ulcerative colitis is frequently missed with 4-quadrant biopsies. An experimental setup recording delayed fluorescence spectra simultaneously with white light endoscopy was recently developed. OBJECTIVE: We compared detection of invisible flat intraepithelial neoplasia with protoporphyrin IX fluorescence and standard 4-quadrant biopsies. DESIGN: Prospective, crossover design without randomization of the order of procedures. SETTING: Gastroenterology Department, Humboldt University, Charité, Berlin, Germany. PATIENTS: Forty-two patients with extensive ulcerative colitis of more than 10 years' duration were included. INTERVENTIONS: Colonoscopy with 4-quadrant biopsies and targeted biopsies of macroscopic lesions and time-gated fluorescence-guided colonoscopy were performed 2 weeks apart by 2 blinded endoscopists. Three independent pathologists examined the biopsy specimens. MAIN OUTCOME MEASUREMENTS: The primary outcome criterion was detection rate of invisible flat intraepithelial neoplasia. RESULTS: Invisible flat intraepithelial neoplasia was detected in 3 (7%) patients by white light 4-quadrant biopsies and in 10 (24%) patients by fluorescence-guided endoscopy (P = .02). The sensitivity and specificity for differentiating patients with and without dysplasia were 100% and 81%, respectively. Dysplastic and nondysplastic mucosa could be discriminated with a sensitivity and specificity of 73% and 81%, respectively. LIMITATIONS: The trial was not randomized. CONCLUSION: The detection rate of intraepithelial neoplasia in patients with ulcerative colitis can be improved by fluorescence-guided colonoscopy.

Hepatic 11beta-HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis.

CONTEXT: Nonalcoholic fatty liver disease represents the hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury. The pathophysiology that leads to NASH is not well understood. OBJECTIVE: We hypothesize that an altered cortisol metabolism in the liver may be a pathogenetic factor. DESIGN AND PATIENTS: 75 patients (28 men, 47 women) underwent liver biopsy for elevation in liver enzymes. Histological diagnosis identified normal liver in eight, fatty liver in 20, NASH grade 1 in 22, grade 2 in nine, grade 3 in three patients, and other forms of hepatitis or cirrhosis in 13 patients. We quantified hepatic 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) and hexose-6-phosphate-dehydrogenase (H6PDH) mRNA expression by real-time PCR. In addition, analysis of 24 h urinary excretion of cortisol metabolites using GCMS was performed and compared with healthy controls. RESULTS: 11beta-HSD1 mRNA expression correlated significantly (R2= 0.809; P < 0.001) with H6PDH mRNA expression, negatively with waist-to-hip ratio in women (R2= 0.394; P= 0.005), but not with urinary (THF + 5alpha-THF)/THE ratio, total cortisol metabolite excretion, age, BMI, degree of fatty liver or NASH stages. Total cortisol metabolite excretion was increased in patients with fatty liver or NASH compared with healthy controls. CONCLUSIONS: Our data suggest that expression of hepatic 11beta-HSD1 and H6PDH are closely interlinked. 11beta-HSD1 gene expression does not seem to be involved in the pathogenesis of fatty liver or NASH. However, those patients showed an increased 5alpha- and 5beta-reduction of cortisol leading to an increased cortisol turnover rate and an activation of the HPA axis.

Malnutrition and depression in the institutionalised elderly.

Malnutrition and depression are highly prevalent in the institutionalised elderly and can lead to unfavourable outcomes. The aim of the present study was to assess associations between nutritional status and depressive symptoms and to explore their impact on self-caring capacity and quality of life (QoL) in elderly nursing-home residents (NHR). We conducted a cross-sectional study with 114 NHR (eighty-six female) with a mean age of 84.6 (sd 9.1) years. Nutritional status was assessed with the Mini Nutritional Assessment (MNA). Depressive symptoms were rated with the Geriatric Depression Scale (GDS). Self-caring capacity was measured with the Barthel index (BI) and QoL was assessed with the short-form thirty-six-item (SF-36) questionnaire. Of the NHR, twenty-six (22.8 %) were malnourished according to the MNA and sixty-six (57.9 %) were at nutritional risk. Of the residents, seventy-five could be assessed with the GDS, whereof sixteen (21.3 %) had major and twenty-six (34.7 %) had minor depressive symptoms. GDS scores tended to be higher in patients with impaired nutritional status (5.4 (sd 3.6) in well-nourished subjects and 6.9 (sd 3.2) in residents with malnutrition or at risk of malnutrition). The MNA correlated significantly with the GDS (r - 0.313; P = 0.006) and the GDS emerged as the only independent risk factor for malnutrition in a multiple regression analysis, whereas age, sex, care level, number of prescriptions and self-caring capacity had no influence. The BI was not reduced in patients with a high GDS. QoL was affected in malnourished residents as well as in study participants with depressive symptoms. The results of the present study point towards an association between malnutrition and depressive symptoms. However, the relationship is complex and it remains unclear whether depression in NHR is the cause or consequence of impaired nutritional status. Further studies are needed to identify the direction of this relationship and to assess the effect of depression treatment on nutritional and functional status as well as on QoL.

Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease.

OBJECTIVE: Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease. METHODS: Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohn's disease [CD], 44 with ulcerative colitis [UC]), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index-matched healthy controls. Ninety-two patients were followed for 6 mo. RESULTS: Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased (P < 0.001) and retinol-binding protein-4 was increased (P < 0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin (r = -0.572, P < 0.001) and proved to be an independent protective factor for 6-mo maintenance of remission (P = 0.016). CONCLUSION: IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic-inflammatory response as a modulator in IBD.

No association of the CARD8 (TUCAN) c.30T>A (p.C10X) variant with Crohn's disease: a study in 3 independent European cohorts.

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.

An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole.

OBJECTIVE: The purpose of this study was to determine the efficacy of standard treatment with oral metronidazole in the eradication of the bacterial vaginosis biofilm. STUDY DESIGN: We conducted an interventional follow-up study in which 18 patients with bacterial vaginosis were treated with oral metronidazole during 1 week and subsequently had a single random follow-up assessment at 1-week intervals, up to 5 weeks, with 3 patients representing each point in time. Follow-up assessment included conventional scoring of the vaginal microflora and determination of bacterial biofilm characteristics on a vaginal biopsy through bacterial 16/23S recombinant DNA-based fluorescence in-situ hybridization. RESULTS: Although all patients recovered, we consistently observed the resurgence with treatment cessation of a dense and active bacterial biofilm on the vaginal mucosa, primarily consisting of Gardnerella vaginalis and Atopobium vaginae. CONCLUSION: A large reservoir of the core bacteria to bacterial vaginosis persists as a biofilm after metronidazole treatment.

Disease-related malnutrition but not underweight by BMI is reflected by disturbed electric tissue properties in the bioelectrical impedance vector analysis.

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.

Effects of food fortification on nutritional and functional status in frail elderly nursing home residents at risk of malnutrition.

OBJECTIVE: Malnutrition is a frequent problem in the elderly and is associated with an impaired functional status and higher morbidity and mortality. In this study we evaluated the effect of a 12-wk nutritional intervention with fortified food on nutritional and functional status in nursing home residents at risk of malnutrition. METHODS: Nutritional status was assessed with the Mini Nutritional Assessment. Body composition was measured with bioelectrical impedance analysis. Functional status was assessed with handgrip strength, peak flow, the Barthel Index, and the Physical Functioning component of the Short Form 36 questionnaire. The residents were assigned to a group receiving the standard food of the nursing home or a group with a protein- and energy-enriched diet and snacks. RESULTS: Sixty-five nursing home residents were included; 62 were at nutritional risk and 3 were severely malnourished according to the Mini Nutritional Assessment. Protein intake was significantly higher in the group on the enriched diet, whereas energy intake did not differ from the group on the standard diet. Both groups significantly improved most nutritional and body composition parameters during the intervention period. We did not observe convincing improvements in muscle function. Furthermore, the Barthel Index and the Physical Functioning component of the Short Form 36 questionnaire declined in all participants. CONCLUSION: Standard food in this nursing home provided sufficient energy and macronutrients. Provision of snacks was not effective in increasing energy intake. Although nutritional status improved, functional status did not increase as a consequence. Functional frailty in this study population seems to be influenced more by age-related morbidity and immobilization than by nutritional intake.

Malnutrition and impaired muscle strength in patients with Crohn's disease and ulcerative colitis in remission.

OBJECTIVE: This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. METHODS: Nutritional status (subjective global assessment [SGA], body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 +/- 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 +/- 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th-75th percentile). RESULTS: Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8-28.7, P = 0.021) and UC (22.6 kg, 21.0-28.0, P = 0.041) compared with controls (25.0 kg, 22.0-32.5). Handgrip strength correlated with BCM (r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0-41.1, P = 0.005) and UC (31.0 kg, 27.3-37.8, P = 0.001) compared with controls (36.0 kg, 31.0-52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. CONCLUSION: In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.

Azathioprine and mesalazine-induced effects on the mucosal flora in patients with IBD colitis.

BACKGROUND: The impact of azathioprine and 5-aminosalicylic acid (5-ASA) on the innate immunity and mucosal flora is unknown. The study investigated the influence of IBD treatment on the concentrations and spatial organization of mucosal bacteria using fluorescence in situ hybridization with 16s r-RNA targeting probes. METHODS: We prospectively investigated colonoscopic biopsies from five groups of 20 subjects each: patients with ulcerative or indeterminate colitis treated with azathioprine (group 1), azathioprine and 5-ASA (group 2), 5-ASA (group 3), untreated IBD (group 4), and healthy controls. RESULTS: The elevated numbers of leukocytes in mucus of IBD patients were reduced nearly to norm in patients treated with azathioprine alone. In contrast, 5-ASA therapy had no influence on mucus leukocyte migration and was associated with the lowest concentrations of mucosal bacteria of all IBD groups. The suppressed migration of leukocytes in azathioprine-treated patients was accompanied by a 28-fold higher concentration of mucosal bacteria when compared with the 5-ASA group or a 1000-fold increase when compared with healthy controls. The percent of the epithelial surface covered with adherent bacteria (P < 0.001) and the amenability of mucosal bacteria (P = 0.01) were also significantly increased in the azathioprine-treated group compared with all other IBD groups. The patients receiving both 5-ASA and azathioprine did not differ statistically from untreated IBD patients either in mucus leukocyte migration or in bacterial concentrations. CONCLUSIONS: Azathioprine and 5-ASA induce opposite effects on the mucus barrier. Concomitant therapy of 5-ASA and azathioprine mutually neutralizes the effects of both on the mucosal flora and the barrier function.

Viscosity gradient within the mucus layer determines the mucosal barrier function and the spatial organization of the intestinal microbiota.

BACKGROUND: Migration is an important virulence factor for intestinal bacteria. However, the role of bacterial mobility in the penetration of viscous mucus and their spatial organization within the colon is relatively unknown. METHODS: Movements of fecal bacteria were assessed in gels of varying agarose concentrations and were compared with patterns of bacterial distribution observed in colons from conventional and Enterobacter cloacae-monoassociated mice. Bacteria were visualized using fluorescence in situ hybridization. RESULTS: Long curly bacteria moved best in moderate viscosity gels, short rods and cocci preferred a low viscous environment, whereas high viscosity immobilized all bacterial groups. The spatial distribution of bacteria in the murine colon was also shape- and not taxonomy-dependent, indicating the existence of vertical (surface to lumen) and longitudinal (proximal to distal colon) viscosity gradients within the mucus layer. Our results suggest that mucus viscosity is low in goblet cells, at the crypt basis and close to the intestinal lumen, whereas sites adjacent to the columnar epithelium have a high mucus viscosity. The mucus viscosity increased progressively toward the distal colon, separating bacteria selectively in the proximal colon and completely in the distal colon. CONCLUSIONS: The site-specific regulation of mucus secretion and dehydration make the mucus layer firm and impenetrable for bacteria in regions close to the intestinal mucosa but loose and lubricating in regions adjacent to the luminal contents. Selective control of mucus secretion and dehydration may prove to be a key factor in the management of chronic diseases in which intestinal pathogens are involved.

Is bioelectrical impedance vector analysis of value in the elderly with malnutrition and impaired functionality?

OBJECTIVE: The calculation of body composition using bioelectrical impedance analysis is difficult in the elderly because most equations have been found to be inadequate, especially in the malnourished elderly. We therefore evaluated the use of bioelectrical impedance vector analysis in elderly nursing home residents. METHODS: One hundred twelve nursing home residents were included in the study (34 men, 78 women, age 85.1 y, age range 79.1-91.4 y). Nutritional status was determined by the Mini Nutritional Assessment (MNA), functional status was assessed by handgrip strength, knee extension strength, and Barthel's index, and bioelectrical impedance analysis was performed using Nutriguard M (Data Input, Darmstadt, Germany). RESULTS: Twenty-two nursing home residents were classified as well nourished (MNA I), 80 were considered to be at nutritional risk (MNA II), and 10 were classified as malnourished (MNA III). Handgrip strength, knee extension strength, and Barthel's index were lower in MNA II and MNA III than in MNA I. Phase angle also decreased significantly with the MNA (4.0, 3.8-4.7 degrees; 3.7, 3.3-4.3 degrees; and 2.9, 2.6-3.5 degrees). There was a significant displacement of the mean vector in MNA II and MNA III compared with MNA I. CONCLUSION: The bioelectrical impedance vector analysis resistance/reactance graph could represent a valuable tool to assess changes in body cell mass and hydration status in elderly nursing home residents.

Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding.

Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler's disease (hereditary hemorrhagic teleangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specific drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.

The c.1-260C>T promoter variant of CD14 but not the c.896A>G (p.D299G) variant of toll-like receptor 4 (TLR4) genes is associated with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest. METHODS: In this two-center, retrospective German and Hungarian cohort study, patients with Crohn's disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed. RESULTS: In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383). CONCLUSION: IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.

[Long-term follow-up of patients with suprasellar germinomas]. / Langzeitverlauf bei Patienten mit suprasellären Germinomen.

BACKGROUND: Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes. PATIENTS AND METHODS: The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas. RESULTS: Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case. CONCLUSION: Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Effects of creatine supplementation on nutritional status, muscle function and quality of life in patients with colorectal cancer--a double blind randomised controlled trial.

BACKGROUND & AIM: Nutritional status frequently deteriorates during chemotherapy in cancer. This is associated with a poor outcome. Since creatine supplementation has shown promising results in various diseases, we investigated the effects of creatine on nutritional status in patients with colorectal cancer undergoing chemotherapy. METHODS: Thirty patients with colorectal cancer undergoing chemotherapy were randomised to receive either creatine (n=16) or placebo (n=15) for 8 weeks. Body composition was determined with bioelectrical impedance analysis; muscle function by hand grip, hip flexion and knee extension strength and quality of life (QoL) was assessed by the QLQ30 questionnaire. RESULTS: Neither muscle function, body cell mass (BCM) nor QoL improved, but phase angle, a marker of BCM and cell integrity, increased significantly in the intervention patients (5.3+/-0.3 degrees to 5.4+/-0.2 degrees , P=0.030). Evaluating patients with different chemotherapy regimens, however, only intervention patients undergoing less aggressive chemotherapy were shown to benefit, increasing phase angle (5.11+/-0.22 degrees to 5.51+/-0.30 degrees , P=0.043) as well as BCM (27.22+/-2.85 to 29.60+/-3.54kg, P=0.043). CONCLUSION: Creatine failed to improve muscle mass or function and QoL in colorectal cancer patients but improved bioimpedance parameters that are predictive of poor outcome. Creatine might therefore be useful in patients with milder chemotherapy in order to maintain or increase BCM whereas patients undergoing aggressive chemotherapy however are not likely to benefit.

The German hospital malnutrition study.

BACKGROUND & AIMS: Malnutrition is frequently observed in chronic and severe diseases and associated with impaired outcome. In Germany general data on prevalence and impact of hospital malnutrition are missing. METHODS: Nutritional state was assessed by subjective global assessment (SGA) and by anthropometric measurements in 1,886 consecutively admitted patients in 13 hospitals (n=1,073, university hospitals; n=813, community or teaching hospitals). Risk factors for malnutrition and the impact of nutritional status on length of hospital stay were analyzed. RESULTS: Malnutrition was diagnosed in 27.4% of patients according to SGA. A low arm muscle area and arm fat area were observed in 11.3% and 17.1%, respectively. Forty-three % of patients 70 years old were malnourished compared to only 7.8% of patients <30 years. The highest prevalence of malnutrition was observed in geriatric (56.2%), oncology (37.6%), and gastroenterology (32.6%) departments. Multivariate analysis revealed three independent risk factors: higher age, polypharmacy, and malignant disease (all P<0.01). Malnutrition was associated with an 43% increase of hospital stay (P<0.001). CONCLUSIONS: In German hospitals every fourth patient is malnourished. Malnutrition is associated with increased length of hospital stay. Higher age, malignant disease and major comorbidity were found to be the main contributors to malnutrition. Adequate nutritional support should be initiated in order to optimize the clinical outcome of these patients.

Conventional therapy for Crohn's disease.

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.