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Severe obesity (BMI ≥60 kg/mIn this proof-of-concept study, prospective data from patients treated with RWR (intervention group 1, n = 26) were mathematically matched with retrospective biometric data of 26 patients with severe obesity (historic control group 2) who underwent standard 6-month bridging with IB. A rating scale was developed to identify patients needing urgent fast-track bridging.Rapid weight loss was observed in all patients on the RWR therapy. All achieved operability after a mean RWR bridging duration of 20.7 ± 6.9 days. Baseline weight was 236.3 ± 35.8 kg in group 1 compared with 230.1 ± 32.7 kg in group 2. Mean body weight loss during RWR was 27.5 ± 14.1 kg, compared with 20.9 ± 10.5 kg in group 2 (P = 0.0629).Pre-operative bridging using liraglutide in combination with a leucine-rich amino acid infusion and hypocaloric diet was effective in all cases of acutely life-threatening severe obesity, achieving technical operability within only ca. 2-4 weeks. This therapy has potential as a life-saving rescue therapy for multimorbid patients with severe obesity who were previously untreatable. This study is registered at ClinicalTrials.gov (identifier: NCT02616003).

Both laparoscopic Roux-en-Y gastric bypass (RYGB) and duodenojejunal bypass liner (DJBL) have been shown to induce weight loss and dramatically ameliorate type 2 diabetes mellitus (T2DM). Since DJBL implantation causes nutrients to pass through the duodenum without contact with the digestive juices and the duodenal mucosa, its mechanisms have been suggested to mimic those of RYGB. This study aimed to compare the outcomes of these two bariatric procedures in terms of glycemic control and BMI in patients with obesity and T2DM.A retrospective observational cohort propensity score-weighted comparison of laparoscopic Roux-en-Y gastric bypass (RYGB) vs duodenojejunal bypass liner (DJBL) was conducted in patients with obesity and T2DM undergoing either procedure from 05/2014 to 12/2017. Propensity scores were weighted for body weight, body mass index (BMI), and glycated hemoglobin A1c (HbA1c). The primary outcome was comparative improvement of HbA1c. Secondary comparative effectiveness outcomes were decrease of body weight and BMI.Forty-six patients were included: 21 (10 male, 11 female; mean age 50.6 ± 11.7 years) underwent RYGB, while DJBL was implanted in 25 (10 male, 15 female; 52.5 ± 9.5 years). After twelve months, mean ΔBMI was 11.54 ± 4.47 kg/mRYGB and DJBL seem to be associated with similar remission rates of hyperglycemia after one year. However, RYGB induces more significant weight loss than DJBL.

Background In the absence of a feasible noninvasive gold standard, iron deficiency (ID) anemia (IDA) is best measured using multiple indicators. However, the choice of an appropriate single iron biomarker for ID screening continues to be debated. Low hemoglobin density (LHD%) from Coulter counters has been suggested as a useful tool to detect ID. This study investigated the reliability of LHD% for the assessment of iron status in patients with inflammatory bowel disease (IBD) and IDA, anemia of chronic disease (ACD) or mixed anemia (MIX). Methods The study population consisted of 143 patients with IBD (aged 39.03±12.53 years, 61.5% female). Blood count, transferrin saturation, serum ferritin, and C-reactive protein were determined by routine assays. Patients with anemia were divided into 3 groups: IDA, ACD and MIX, according to specific criteria. Receiver operator characteristic (ROC) curves were constructed. Results ROC analysis for LHD% in the detection of ID yielded a cutoff value of 3.8%. In anemic patients, LHD% values did not differ statistically significantly between groups (IDA, ACD, MIX) and no significant difference in LHD% values was observed between patients with IDA and ID. Conclusions These results demonstrate that LHD% is a reliable biomarker for the detection of iron deficiency in patients with IBD and anemia, regardless of whether inflammation is present. Our findings indicate that LHD% can provide added value in diagnosing iron deficiency.

Iron deficiency is the primary cause of anaemia worldwide and is particularly common among children and adolescents. Intravenous (IV) iron therapy is recommended for paediatric patients with certain comorbidities or if oral iron treatment has been unsuccessful. IV ferric carboxymaltose (FCM) has recently been approved by the US Food and Drug Administration for use in children aged > 1 year. This narrative review provides an overview of the available publications on the efficacy and safety of IV FCM in children and adolescents. A literature search using PubMed and Embase yielded 153 publications; 33 contained clinical data or reports on clinical experience relating to IV FCM in subjects Conclusion: The available publications indicate that IV FCM, a nanomedicine with a unique and distinctive therapeutic profile, is an effective and generally well-tolerated treatment for iron deficiency or iron deficiency anaemia in children and adolescents. Despite the wealth of retrospective evidence, prospective, randomised controlled trials in the paediatric setting are still necessary. What is Known:• Iron deficiency and iron deficiency anaemia are usually managed using oral iron therapy, but intravenous iron therapy is recommended for certain paediatric patients.• Intravenous ferric carboxymaltose (FCM) has recently been approved in the US for use in children aged > 1 year. What is New:• Despite evidence that FCM is effective and generally well tolerated in children and adolescents, so far, only retrospective studies, non-randomised uncontrolled prospective studies, or case reports have been published in full.• There is a strong need for prospective, randomised controlled trials on FCM in the paediatric setting.

BACKGROUND AND AIMS: Physical activity is beneficial in several chronic disorders including Crohn′s disease, but the preferred type of exercise is unknown. Our study aimed to examine and compare the safety, feasibility and potential beneficial effects of individual moderate endurance and moderate muscle training in patients with Crohn’s disease. METHODS: Quiescent or mildly active (Crohn’s disease activity index

Background: Biotin, a water-soluble B vitamin, has demonstrable anti-inflammatory properties. A biotin-deficient diet induced a colitis-like phenotype in mice, alleviable by biotin substitution. Mice with dextran sulfate sodium (DSS)-induced colitis showed biotin deficiency and diminished levels of sodium-dependent multivitamin transporter, a protein involved in biotin absorption. Biotin substitution induced remission by reducing activation of NF-κB, a transcription factor involved in intestinal permeability and inflammatory bowel disease (IBD). We investigated for the first time a possible clinical role of biotin status in IBD. Methods: In a comparative, retrospective, cross-sectional study, serum samples of 138 patients with IBD (67 female; 72 Crohn’s disease (CD), 66 ulcerative colitis (UC)) aged 18–65 years and with a mean age (±SD) of 42.5 ± 14.3 years as well as 80 healthy blood donors (40 female; 40.0 ± 10.0 years; range 20–60 years) were analyzed. Inflammation was defined as hsCRP ≥5 mg/L, and to determine biotin status, serum 3-hydroxyisovaleryl carnitine (3HIVc) levels were measured by LC-MS/MS. Results: A total of 138 patients with IBD (67f; 72CD/66 UC; 42.5 ± 14.3 years) were enrolled: 83/138 had inflammation. Mean serum 3HIVc levels were significantly higher in IBD patients but unaffected by inflammation. Biotin deficiency (95th percentile of controls: >30 nmol/L 3HIVc) was significantly more common in IBD patients versus controls. Conclusion: High serum 3HIVc levels and biotin deficiency were associated with IBD but not inflammatory activity or disease type. Our findings suggest biotin may play a role as cause or effect in IBD pathogenesis. Routine assessment and supplementation of biotin may ameliorate IBD and support intestinal integrity.

Searching digitized detector signals for piled-up delayed components with distinct energy and delay time signatures is a smart method to provide common NaI(Tl) detectors with additional neutron detection capabilities at no extra cost. This technique nicely complements the idea of neutron detection by analyzing events with high energy depositions above the range of common gamma-ray energies. In combination, both approaches can provide half of the neutron sensitivity offered by a commercial 6Li co-doped NaI(Tl) (NaIL™) scintillator of the same size, at the price of higher and load-dependent background contributions. Delayed-coincidence techniques are most suitable for neutron monitoring or long-term measurements, where the statistics of the acquired delay-time distributions allows separate fitting of the effect and background contributions. In this case, the thermal neutron flux can be quantified in parallel to gamma-ray spectroscopy at overall detector loads exceeding 10 kcps.

Introduction: Obesity is a major global health problem associated with comorbidities such as diabetes, cardiovascular disease, and cancer. Bariatric surgery is recognized to be the most effective weight loss intervention, but it is highly invasive and costly and can have serious side effects. Intragastric balloon (IGB) placement by endoscopy and hypocaloric diets are among a number of techniques that have been used in patients unsuitable for, or unwilling to undergo, obesity surgery. In this study, we compared the efficacy, safety, and cost-effectiveness of the hypocaloric OPTIFAST program (OPT) with endoscopic IGB placement for weight loss. Methods: In this retrospective observational cohort propensity score-weighted comparison (performed May 2014 to December 2020), participants with a BMI of 30–55 kg/m2, aged 18–70 years, were randomized to OPT or IGB for 26 weeks, followed by a weight maintenance phase. Patients were matched according to age, gender, and BMI. The study outcomes were percentage excess body weight lost, total body weight lost (TBWL), and percentage TBWL (%TBWL). Results: A total of 148 participants (75% of those randomized; 74 OPT, 74 IGB) made up the ITT population. Mean age was 44.1 ± 10.4 years, and the patients were predominantly female (77%). Baseline BMI was 44.1 ± 10.4 kg/m2. At 26 weeks, %TBWL in the OPT group was 19.6 ± 6.8% versus 11.9 ± 6.7% for IGB (p < 0.001). At 52 weeks, %TBWL for OPT was 18.2 ± 9.0% versus 12.0 ± 6.6% for IGB (p < 0.001). The OPT cohort also experienced significantly fewer adverse events compared with the IGB group. Conclusion: IGB placement and OPT induce clinically meaningful weight loss. However, OPT appears to induce clinically superior weight loss and has economic advantages through lower rates of complications and adverse events.

Iron deficiency (ID) is a common manifestation of inflammatory bowel disease (IBD), arising primarily due to chronic inflammation and/or blood loss. There is no gold standard for ID diagnosis, which is often complicated by concomitant inflammation. Zinc protoporphyrin (ZnPP) correlates with parameters of iron homeostasis and has been identified as a promising marker for ID, irrespective of inflammation. We investigated the diagnostic performance of ZnPP in ID, iron deficiency anemia, anemia of chronic disease and mixed anemia in a cross-sectional study in 130 patients with IBD. Different parameters were compared by receiver operator characteristic (ROC) analysis as detectors of iron-restricted erythropoiesis (IRE). IRE was detected in 91 patients (70.0%), fifty-nine (64.8%) had absolute ID and 23 (25.4%) functional ID. When inflammation was present, ZnPP was a more reliable sole biomarker of IRE than MCV, transferrin saturation (TSAT) or ferritin (AUC, 0.855 vs. 0.763, 0.834% and 0.772, respectively). The specificity of TSAT was significantly lower than ZnPP when inflammation was present (38% vs. 71%, respectively). We conclude that ZnPP is a reliable biomarker of functional ID in patients with IBD and more dependable than ferritin or TSAT, which are influenced by chronic inflammation. We propose that ZnPP may also have utility in patients with other chronic diseases.

Background and Aims: KRP203 is a potent oral agonist of the sphingosine-1-phosphate receptor subtype 1 that induces the sequestration of peripheral lymphocytes, thereby potentially reducing the number of activated lymphocytes circulating to the gastrointestinal tract. Methods: We conducted a multicentre, double-blind, placebo-controlled, parallel-group, proof-of-concept study to evaluate the efficacy, safety, and tolerability of KRP203 in patients with moderately active 5-aminosalicylate-refractory ulcerative colitis (UC). Patients were randomly assigned to receive 1.2 mg KRP203 or placebo daily for 8 weeks. Primary efficacy variable was clinical remission, defined as partial Mayo Score 0–1 and modified Baron Score 0–1 with rectal bleeding subscore 0. Results: KRP203 was safe and well tolerated overall. The most common adverse events (AEs) were gastrointestinal disorders and headache. Importantly, no KRP203-related cardiac AEs were reported. Total peripheral lymphocytes and selectively affected lymphocyte subtypes decreased, causing marked decreases in naive and central memory CD4+ and CD8+ T cells, and also in B cells. Clinical remission occurred in 2/14 (14%) patients under KRP203, compared with 0/8 (0%) under placebo. Conclusions: Overall, KRP203 was safe and well tolerated by patients with UC. Importantly, no cardiac AEs were reported. Although KRP203 did not meet the minimum clinically relevant threshold for efficacy, the results may suggest that KRP203 treatment is superior to placebo. However, in this small study population, the difference was insignificant. Based on these data, studies with an improved design and a larger population should be considered.

The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise questions regarding the unclarified heterogeneity of pathological mechanisms promoting disease progression. While biomarkers for the differentiation of Crohn’s disease (CD) versus ulcerative colitis (UC) have been suggested, specific markers for a CD subclassification in ileal CD versus colonic CD are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterize potential biomarkers by focusing on the downstream enzymes and metabolites of kynurenine metabolism. Using immunohistochemical stainings, we analyzed and compared the mucosal tryptophan immune metabolism in bioptic samples from patients with active inflammation due to UC or CD versus healthy controls. Localization-specific quantification of immune cell infiltration, tryptophan-metabolizing enzyme expression and mucosal tryptophan downstream metabolite levels was performed. We found generally increased immune cell infiltrates in the tissue of all patients with IBD. However, in patients with CD, significant differences were found between regulatory T cell and neutrophil granulocyte infiltration in the ileum compared with the colon. Furthermore, we observed decreased kynurenine levels as well as strong kynureninase (KYNU) expression specifically in patients with ileal CD. Correspondingly, significantly elevated levels of the kynurenine metabolite 3-hydroxyanthranilic acid were detected in the ileal CD samples. Highlighting the heterogeneity of the different phenotypes of CD, we identified KYNU as a potential mucosal biomarker allowing the localization-specific differentiation of ileal CD versus colonic CD.

Evidence gained from recent studies has generated increasing interest in the role of vitamin D in extraskeletal functions such as inflammation and immunoregulation. Although vitamin D deficiency has been implicated in the pathophysiology of inflammatory diseases including inflammatory bowel disease (IBD), evidence as to whether vitamin D supplementation may cure or prevent chronic disease is inconsistent. Since 25OH-vitamin D (25OHD) has been suggested to be an acute-phase protein, its utility as a vitamin D status marker is therefore questionable. In this study, possible interactions of vitamin D and inflammation were studied in 188 patients with IBD, with high-sensitivity C-reactive protein (hsCRP) levels ≥ 5 mg/dL and/or fecal calprotectin ≥ 250 µg/g defined as biochemical evidence of inflammatory activity. Levels of 25OHD and vitamin D-binding protein (VDBP) were determined by ELISA, and 1,25-dihydroxyvitamin D (1,25OHD) and dihydroxycholecalciferol (24,25OHD) by LC-MS/MS. Free and bioavailable vitamin D levels were calculated with the validated formula of Bikle. Serum 1,25OH2D and vitamin D binding protein (VDBP) levels were shown to differ between the inflammatory and noninflammatory groups: patients with inflammatory disease activity had significantly higher serum concentrations of 1,25OH2D (35.0 (16.4−67.3) vs. 18.5 (1.2−51.0) pg/mL, p < 0.001) and VDBP (351.2 (252.2−530.6) vs. 330.8 (183.5−560.3) mg/dL, p < 0.05) than patients without active inflammation. Serum 24,25OH2D levels were negatively correlated with erythrocyte sedimentation rate (ESR) (−0.155, p = 0.049) while concentrations of serum 1,25OH2D correlated positively with hsCRP (0.157, p = 0.036). Correlations with serum VDBP levels were found for ESR (0.150, p = 0.049), transferrin (0.160, p = 0.037) and hsCRP (0.261, p < 0.001). Levels of serum free and bioavailable 25OHD showed a negative correlation with ESR (−0.165, p = 0.031, −0.205, p < 0.001, respectively) and hsCRP (−0.164, p = 0.032, −0.208, p < 0.001 respectively), and a moderate negative correlation with fecal calprotectin (−0.377, p = 0.028, −0.409, p < 0.016, respectively). Serum total 25OHD concentration was the only vitamin D parameter found to have no specific correlation with any of the inflammatory markers. According to these results, the traditional parameter, total 25OHD, still appears to be the best marker of vitamin D status in patients with inflammatory bowel disease regardless of the presence of inflammation.

Medical therapies have developed to the point where an overwhelming majority of patients with mild to moderate symptoms of GERD can be quite successfully treated by this therapeutic option. Along with diet, important lifestyle components can be used to treat GERD symptoms.

Background Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure. Methods We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated. Discussion This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment. Trial registration 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).

Introduction Iron deficiency and iron deficiency anaemia are common complications in inflammatory bowel disease [IBD] patients. Anaemia in IBD is attributable to chronic blood loss and/or impaired iron intake and absorption. International guidelines recommend intravenous iron supplementation in IBD patients, since oral supplements are frequently poorly tolerated and can exacerbate inflammation. Intravenous ferric carboxymaltose [FCM; Ferinject® 50 mg ferric iron[III]/mL suspension] was approved in Europe in 2007 for correction of iron deficiency, and can be administered in single 15-min infusions of up to 1000 mg. Methods A prospective non-interventional post-marketing study was performed in 101 centres in Germany to assess the efficacy, tolerability, and convenience of Ferinject® in clinical practice in a large cohort of IBD patients. Primary endpoints were haemoglobin [Hb] normalisation or increase ≥2 g/dL [responders], and normalisation of serum ferritin [s-ferritin] and transferrin saturation. Adverse events [AEs], clinical signs/symptoms, and disease activity indices were also analysed. Results In all, 224 subjects (127 Crohn's disease [CD]; 97 ulcerative colitis [UC]) were treated. Mean total iron dose was 1139 mg [range: 100 mg-4800 mg], with 76.7% of doses between 500 mg and 2000 mg; 63.3% of patients responded, and no adverse drug reactions or drug-attributed serious adverse events [SAEs] or deaths occurred. Mean increases of Hb [10.0 to 12.3 g/dL], ferritin [52 μg/L to 103 μg/L], transferrin saturation [TSAT, 15% to 25%], and s-iron [6.1 to 12.4 μmol/L] were significant [p = 0.0001]. Clinical scores and quality of life improved due to the amelioration of anaemia symptoms. Conclusions Ferinject®-therapy was proven to be effective and safe in a large cohort of patients with IBD-associated anaemia in routine practice. Rapid, high-dose application is convenient for physicians and reduces patients' time lost from work.

Introduction Adjuvant radiation therapy (aRT) after radical prostatectomy (RP) is associated with impaired urinary continence recovery as compared to surveillance. Less is known regarding the effect of salvage radiation therapy (sRT) dose intensification on continence outcomes. Materials and methods Urinary continence recovery was investigated within a multicentre randomized trial in biochemically recurrent prostate cancer patients who received either 64 Gy (32 fractions) or 70 Gy (35 fractions) sRT. Incontinence was assessed using Common Toxicity Criteria for Adverse Events v4.0 at baseline, at the end of sRT and 3 months afterward. Quality of life (QoL) was assessed with the EORTC QoL questionnaires C30 and PR25 at baseline and 3 months after completion of sRT. A total of 344 patients were evaluable. Results At baseline 233 (68%) of patients were fully continent and 14% in both arms became incontinent three months after treatment. Of the remaining 111 (32%) patients being incontinent at baseline, continence recovery was achieved 3 months after sRT by 44% vs. 41% with 64 vs. 70 Gy, respectively (p = 0.8). This analysis is limited by its short follow-up. Conclusions Dose intensification of sRT had no impact on early urinary continence recovery or prevalence of de novo incontinence.

Jürgen Stein,1,2 Jennifer Scarlet Haas,3 Siew Hwa Ong,4 Kathrin Borchert,3 Thomas Hardt,5 Elmira Lechat,4 Kerry Nip,5 Douglas Foerster,4 Sebastian Braun,3 Daniel C Baumgart6 1Interdisciplinary Crohn Colitis Center Rhein-Main, Frankfurt/Main, Germany; 2Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Teaching Hospital of the J.W. Goethe University, Frankfurt/Main, Germany; 3Xcenda GmbH, Hannover, Germany; 4Vifor Pharma Ltd., Glattbrugg, Switzerland; 5Vifor Pharma Deutschland GmbH, Munich, Germany; 6Division of Gastroenterology, University of Alberta, Edmonton, AB, Canada Background: Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. Aim: This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. Methods: IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. Results: In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48%) and ID/A-related hospitalizations (5% vs 14%) than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were calculated to be €367. While higher expenditure for medication (€1,876) was observed in the intravenous iron group, the inpatient setting achieved most cost savings (€1,887). Conclusion: IBD patients receiving intravenous iron were less frequently hospitalized and incurred lower total health care costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains. Keywords: inflammatory bowel disease, iron-deficiency anemia, claims data, iron treatment, health care cost, Germany

Patients with inflammatory conditions such as inflammatory bowel disease (IBD), chronic heart failure (CHF), and chronic kidney disease (CKD) have high rates of iron deficiency with adverse clinical consequences. Under normal circumstances, serum ferritin levels are a sensitive marker for iron status but ferritin is an acute-phase reactant that becomes elevated in response to inflammation, complicating the diagnosis. Proinflammatory cytokines also trigger an increase in hepcidin, which restricts uptake of dietary iron and promotes sequestration of iron by ferritin within storage sites. Patients with inflammatory conditions may thus have restricted availability of iron for erythropoiesis and other cell functions due to increased hepcidin expression, despite normal or high levels of serum ferritin. The standard threshold for iron deficiency (μg/L) therefore does not apply and transferrin saturation (TSAT), a marker of iron availability, should also be assessed. A serum ferritin threshold of μg/L or TSAT < 20% can be considered diagnostic for iron deficiency in CHF, CKD, and IBD. If serum ferritin is 100–300 μg/L, TSAT < 20% is required to confirm iron deficiency. Routine surveillance of serum ferritin and TSAT in these at-risk groups is advisable so that iron deficiency can be detected and managed.

Dear Editor,We read with interest the analysis of Pollock and Biggar [1] concerning the comparative safety of ferric derisomaltose/iron isomaltoside 1000 (FDI), ferric carboxymaltose (FCM), and iro...

ZusammenfassungDie Zöliakie ist eine der weltweit häufigsten Erkrankungen mit einer geschätzten Prävalenz von etwa 0,5 – 1 %. Die Erkrankung entsteht als Folge einer Kombination von Umweltfaktoren (Glutenproteine von Weizen, Roggen oder Gerste) und genetischen Faktoren (hauptsächlich humane Leukozytenantigene HLA-DQ2 oder -DQ8). Aktuell stellt eine strikte glutenfreie Diät (GFD) die einzige Therapiemöglichkeit dar. Allerdings ist die Einhaltung dieser Diät schwierig, nicht zuletzt deshalb, weil Gluten in vielen Fertignahrungsmitteln enthalten ist. Folglich kann die konsequente Vermeidung von Gluten tiefe Einschnitte sowohl in der Nahrungsauswahl als auch im Sozialleben zur Folge haben. Zudem führt die GFD auch bei völlig adhärenten Patienten nicht in jedem Fall zu einer klinischen und histologischen Normalisierung. Deshalb ist das Interesse an (adjunktiven) nicht-diätischen Therapieansätzen für die Zöliakie groß. Ziel dieser Arbeit ist es, basierend auf pathophysiologischen Konzepten zur Zöliakie neueste pharmakologische Therapieansätze vorzustellen und zu diskutieren.

Anemia is a common extraintestinal manifestation in patients with inflammatory bowel disease, impacting disease prognosis, morbidity, hospitalization rates and time lost from work. While iron deficiency anemia and anemia of chronic inflammation predominate, combinations of hematimetric and biochemical markers facilitate the diagnosis and targeted therapy of other etiologies according to their underlying pathophysiological causes. Intravenous iron replacement is currently recommended in IBD patients with moderate to severe anemia or intolerance to oral iron. Areas covered: This review examines the impact, pathophysiology and diagnostics of iron deficiency and anemia, compares the characteristics and safety profiles of available oral and intravenous iron preparations, and highlights issues which require consideration in decision making for therapy administration and monitoring. Expert opinion: Modern intravenous iron formulations have been shown to be safe and effective in IBD patients, allowing rapid anemia correction and repletion of iron stores. While traditional oral iron preparations are associated with increased inflammation, negative effects on the microbiome, and poor tolerance and compliance, first clinical trial data indicate that newer oral compounds such as ferric maltol and sucrosomial iron offer improved tolerability and may thus offer a viable alternative for the future.

SummaryBackground Iron deficiency anaemia (IDA) is a common complication of inflammatory bowel disease (IBD) associated with reduced quality of life and increased hospitalisation rates. While the best way of treating IDA in IBD patients is not clearly established, current European guidelines recommend intravenous iron therapy in IBD patients with severe anaemia or intolerance to oral iron compounds. Aim To compare the efficacy and tolerability of different intravenous iron formulations used to treat IDA in IBD patients in a systematic review and Bayesian network meta-analysis (NMA), PROSPERO registration number: 42016046565. Methods In June 2016, we systematically searched for studies analysing efficacy and safety of intravenous iron for IDA therapy in IBD. Primary outcome was therapy response, defined as Hb normalisation or increase ≥2 g/dL. Results Five randomised, controlled trials (n = 1143 patients) were included in a network meta-analysis. Only ferric carboxymaltose was significantly more effective than oral iron [OR=1.9, 95% CrI: (1.1;3.2)]. Rank probabilities showed ferric carboxymaltose to be most effective, followed by iron sucrose, iron isomaltose and oral iron. Pooled data from the systematic review (n = 1746 patients) revealed adverse event rates of 12.0%, 15.3%, 12.0%, 17.0% for ferric carboxymaltose, iron sucrose, iron dextran and iron isomaltose respectively. One drug-related serious adverse event (SAE) each was reported for ferric carboxymaltose and iron isomaltoside, and one possibly drug-related SAE for iron sucrose. Conclusions Ferric carboxymaltose was the most effective intravenous iron formulation, followed by iron sucrose. In addition, ferric carboxymaltose tended to be better tolerated. Thus, nanocolloidal IV iron products exhibit differing therapeutic and safety characteristics and are not interchangeable.

Background ECCO guidelines acknowledge the limitations of oral iron for iron deficiency anaemia in IBD and recommend first-line IV iron in patients with active disease. Ferric carboxymaltose (FCM) is approved for iron deficiency when oral iron is ineffective/inappropriate. FCM has shown benefit in RCTs, and as with other IV irons, is known to cause a transient decrease in serum phosphate (PO4), which in most cases is asymptomatic. The aim of this pooled analysis was to characterise the frequency, duration, risk factors, and clinical signs of hypophosphataemia (HP) across 45 interventional trials with FCM. Methods 15,080 subjects were included (FCM n = 8,245; controls n = 6,835). 12,683 had post-baseline serum PO4 measurements (FCM n = 6,879), which were pooled by time-point, clinical characteristics, dose, and iron parameters. Serum PO4 thresholds were: 2.5– Results 2,760 FCM subjects (40.1%) with normal PO4 at baseline developed HP (PO4 Conclusion HP is recognised as a common adverse drug reaction with FCM as with several other IV iron preparations. This analysis shows that the transient decreases in PO4 levels were more frequent in patients receiving multiple and/or large doses of FCM but were not associated with an increased rate of potential signs/symptoms of HP.

Background The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise question regarding the unclarified heterogeneity of disease pathomechanisms. While biomarkers for the differentiation of Crohn’s disease (CD) vs. ulcerative colitis (UC) have been suggested, specific markers for a subclassification of CD phenotypes are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterise potential biomarkers focusing on the downstream metabolites of kynurenine metabolism. The widely varying therapeutic response of patients with inflammatory bowel disease (IBD) continues to raise question regarding the unclarified heterogeneity of disease pathomechanisms. While biomarkers for the differentiation of Crohn’s disease (CD) vs. ulcerative colitis (UC) have been suggested, specific markers for a subclassification of CD phenotypes are still rare. Since an altered signature of the tryptophan metabolism is associated with chronic inflammatory disease, we sought to characterise potential biomarkers focusing on the downstream metabolites of kynurenine metabolism. Methods Using immunohistochemical staining, we analysed and compared the mucosal tryptophan immune metabolism in biotic samples from patients with UC (n = 11), CD (n = 11) and healthy control (n = 12). Localisation-specific quantification of immune cell infiltration, tryptophan-metabolizing enzyme expression and mucosal tryptophan downstream metabolite levels was performed. Results As expected, we found generally increased immune cell infiltrates in the tissue of all patients with IBD. However, in patients with CD, significant differences were found between regulatory T-cell markers in the ileum compared with the colon. In line with this finding, we identified kynureninase as a modulator of immunosuppressive kynurenine levels specifically in the ileum of patients with CD. Correspondingly, significantly elevated levels of the kynurenine metabolite 3-hydroxyanthranilic acid were detected in CD ileum samples. Conclusion Highlighting the heterogeneity of the different phenotypes of CD, we identified 3-hydroxyanthranilic acid as a potential mucosal biomarker allowing the localisation-specific differentiation of ileum or colon inflammation in patients with CD. Moreover, we characterised the kynurenine-degrading enzyme kynureninase as a modulator of immunosuppression and chronic inflammation with potential therapeutic relevance.

Synthese und Exkretion von Gallenflussigkeit (Cholerese) ins Lumen der Gallenkapillaren (Canaliculi) stellen fundamentale Funktionen des Hepatozyten dar und dienen letztlich der Elimination endogener (Bilirubin, Gallensauren, Cholesterin) und exogener (Medikamente) Substanzen. Der Gallefluss (ca. 500 ml/Tag) beruht auf energieabhangigen, aktiven Transportprozessen von Ionen, die uber die Generierung eines osmotischen Gradienten zwischen Kanalikuluslumen und dem Hepatozyten zu einem sekundaren osmotischen Wasserfluss fuhren. Als Cholestase wird eine mehr oder weniger ausgepragte Reduktion des Galleflusses bezeichnet.

Background and AimsAnaemia is common in patients with inflammatory bowel disease [IBD], its two main aetiologies being iron deficiency anaemia [IDA] and anaemia of chronic inflammation [ACI]. Impaired intestinal iron absorption due to inflammatory cytokines is thought to play a role in ACI. We undertook for the first time a controlled prospective study investigating effects of differing underlying diseases, disease locations, and types of iron deficiency or anaemia on oral iron absorption in adult IBD patients with and without inflammation.MethodsThis study was a comparative, single-centred open clinical trial in adults with IBD [n = 73] and healthy controls [n = 22]. Baseline parameters included blood count, iron status [ferritin, transferrin, transferrin saturation, soluble transferrin receptor, hepcidin, serum iron], high-sensitivity C-reactive protein [hsCRP] and interleukin-6. Iron absorption was tested using one oral, enteric-coated capsule containing 567.7 mg iron[II]-glycine-sulphate complex. Serum iron was determined 60/90/120/180/240 min after ingestion.ResultsIron absorption capacity was shown to be influenced by inflammation and anaemia or iron deficiency [ID] type but not by underlying disease type or localisation. The ACI group showed a significantly lower iron absorption capacity than all others. Whereas hsCRP levels [-0.387, p < 0.001], IL-6 [-0.331, p = 0.006], ferritin [-0.531, p < 0.001], and serum hepcidin [-0.353, p = 0.003] correlated negatively with serum iron change at 2 h, transferrin showed a positive correlation at the same time point [0.379, p < 0.001].ConclusionsUnderlying disease type and localisation appear to have little effect on iron absorption capacity, whereas lack of response to oral iron correlates well with serum markers of inflammation. Iron absorption capacity is thus significantly reduced in the presence of inflammation.

Background and Aims: The IL-12/23 inhibitor ustekinumab (UST) opened up new treatment options for patients with Crohn’s disease (CD). Due to the recent approval, real-world German data on long-term efficacy and safety are lacking. This study aimed to assess the clinical course of CD patients under UST therapy and to identify potential predictive markers. Methods: Patients with CD receiving UST treatment in three hospitals and two outpatient centers were included and retrospectively analyzed. Rates for short- and long-term remission and response were analyzed with the help of clinical (Harvey–Bradshaw Index (HBI)) and biochemical (C-reactive protein (CRP), Fecal calprotectin (fCal)) parameters for disease activity. Results: Data from 180 patients were evaluated. One-hundred-and-six patients had a follow-up of at least eight weeks and were included. 96.2% of the patients were pre-exposed to anti- TNFα agents and 34.4% to both anti-TNFα and anti-integrin antibodies. The median follow-up was 49.1 weeks (95% CI 42.03-56.25). At week 8, 51 patients (54.8%) showed response to UST, and 24 (24.7%) were in remission. At week 48, 48 (51.6%) responded to UST, and 25 patients (26.9%) were in remission. Steroid-free response and remission at week eight was achieved by 30.1% and 19.3% of patients, respectively. At week 48, 37.6% showed steroid-free response to UST, and 20.4% of the initial patient population was in steroid-free remission. Conclusion: Our study confirms short- and long-term UST effectiveness and tolerability in a cohort of multi-treatment-exposed patients.

The endoscopically implanted duodenal-jejunal bypass liner (DJBL) is an impermeable fluoropolymer device which prevents food making contact with the proximal intestine, thus inducing weight loss and improvement of type 2 diabetes mellitus (T2DM). However, weight and HbA1c levels generally increase post explantation. This study investigated the safety and feasibility of early DJBL reimplantation in five patients with obesity whose glucose levels had relapsed post explantation, examining the effect of reimplantation on weight loss, BMI and T2DM management. All DJBL implantation and explantation procedures were performed without complications. Despite reduction of T2DM medications, reduction in body weight and HbA1c levels resumed after reimplantation. In conclusion, early reimplantation of DJBL appears feasible, safe and effective.

BACKGROUND: In patients with inflammatory bowel disease (IBD), iron deficiency anemia (IDA) is a frequent complication. Causes include intestinal bleeding, reduced iron intake and impaired duodenal iron absorption due to chronic inflammation and concomitant medications (eg. 5-ASA, PPI). Reduced absorptive capacity and low therapy adherence often render oral iron therapies ineffective. Intravenous (IV) iron substitution has been shown to be more effective in IBD patients with IDA and international guidelines recommend IV iron therapy. Variances in core size, composition and shell density cause variations in the efficacy and tolerability of IV iron products. AIMS: We aimed to compare response rates and safety of ferric carboxymaltose (FCM), ferumoxytol (FOX), iron sucrose/saccharate (IS), iron isomaltoside (ISM) and iron dextran (IDX) in IBD patients with IDA by adding recent data to our 2016 network metaanalysis (NMA) and systematic review. METHODS: Using the same methodology, PUBMED, SCOPUS, Web of Science and Cochrane databases were searched in 8/2018 for articles published since 7/2016. Primary outcome was hematopoietic response (% of patients) defined as Hb normalization or increase ≥2g/dL. Secondary outcome was AE rate (safety population). RESULTS: We identified 151 studies including 4 prospective observational studies (2 FCM, 2 ISM), making 18 studies in total. No studies on FOX were eligible and no RCTs eligible for the NMA (4 studies) were found. In total, the updated systematic review included 7 studies (n= 798) for FCM, 2 studies (n=78) for IDX, 8 studies (n=508) for IS, and 3 studies (n=423) for ISM (infusion/bolus). Overall response rates were: FCM 599/798(78%); IDX 33/78(42%); IS 344/508(68%); ISM 265/423(63%). All IV iron products were reported to be well tolerated. Overall rates of AEs and SAEs were 66/836(7.9%), 1/836(0.1%) for FCM; 10/83(12%), 0/83 for IDX; 72/471(15.3%), 1/471(0.2%) for IS; 54/424(12.7%), 5/424(1.2%) for ISM. FCM was significantly more effective than oral iron (OR=1.9, 95% CrI [1.1;3.2]). IS and ISM showed better response rates than oral iron (insignificant). For the node-splitting analysis of the Bayesian NMA, p

Anemia is a common extraintestinal manifestation in IBD patients and considerably impacts disease prognosis, hospitalization rates and time lost from work. While iron deficiency anemia is predominant, combinations of hematimetric and biochemical markers enable detection and targeted therapy of other etiologies including vitamin B12/folic acid deficiencies, hemolysis, myelosuppression and pharmacotherapies. Areas covered: Current literature was searched for articles focusing on etiology, diagnostics and therapy of anemia in IBD. In the light of their own experience, the authors describe the physiology of anemia in IBD and present current evidence endorsing diagnostic and therapeutic options, focusing particularly on non-iron-related etiologies. Expert commentary: Anemia in IBD is polyetiological, reaching far beyond iron deficiency anemia. While clinicians need to be aware of the increasing pallet of diagnostic tools and therapeutic options, detailed studies are needed to develop more convenient test procedures, long-term treatment and monitoring strategies, and unified guidelines for daily practice.

Die Verknappung der fossilen Ressourcen erfordert die Suche nach alternativen Edukten fur die Produktion von wichtigen Grundchemikalien. Diethylsuccinat auf Basis von biobasierter Bernsteinsaure kann als erneuerbare Alternative zu fossilen Rohstoffen fur die Herstellung von γ-Butyrolacton, 1,4-Butandiol und Tetrahydrofuran eingesetzt werden. Kommerziell erhaltliche ZnO-freie Kupferkatalysatoren in einem Festbettreaktor zeigen eine vielversprechende Selektivitat zu C4-Produkten, wobei 1,4-Butandiol an sauren Katalysatorbestandteilen wie Aluminium- und Zirconiumoxid zu Tetrahydrofuran dehydratisiert wird. The shortage of fossil resources necessitates the search for alternative sources for the production of important bulk chemicals. Diethyl succinate derived from biobased succinic acid can be used as a renewable alternative to fossil resources for the production of γ-butyrolactone, 1,4-butanediol and tetrahydrofuran. Commercially available ZnO-free copper catalysts in a fixed-bed reactor show promising selectivity to C4 products, but 1,4-butanediol dehydration to tetrahydrofuran occurs over acidic sites, like alumina and zirconia.

Die Genese der nichtalkoholischen Fettleber­erkrankung (NAFLD) ist ein multifaktorielles Geschehen, an dem neben einem dysfunk­tionalen Fettgewebe die De-novo-Lipogenese aus Kohlenhydraten einen entschei­den­den Anteil hat. Die NAFLD ist ein Risikofaktor fur Typ-2-Diabetes, kardiovaskulare Erkankungen und chronische Nieren­erkrankungen.

Die Erhohung der korperlichen Aktivitat und Ernahrungstherapie, v. a. die Kohlenhydratreduktion, sind die entscheidenden Bausteine in der Behandlung der nichtalkoholischen Fettleber. Eine Studie an Patienten mit hohem NAFLD-Risiko zeigt, dass durch Leberfasten mit Hepafast® Gewicht und Bauchumfang reduziert und Blutfettwerte sowie leber- und diabetesspezifische Parameter signifikant verbessert wurden.