Probiotic Treatment of Ulcerative Colitis with Trichuris suis ova: A Randomized, Double-blinded, Placebo-controlled Clinical Trial (the PROCTO Trial).

BACKGROUND AND AIMS: To demonstrate that administration of 7500 Trichuris suis ova every second week over 24 weeks would reduce the intestinal inflammation in moderate ulcerative colitis. METHODS: A single-centre, randomized, double-blinded, placebo-controlled, phase 2b clinical trial of 7500 Trichuris suis ova every two weeks for 24 weeks compared to placebo in moderate activity of ulcerative colitis (Mayo score 6-10) were performed. Primary outcome: Clinical remission. Secondary outcomes: Clinical response at 24 weeks, complete corticosteroid-free clinical remission, endoscopic remission, symptomatic remission at 12 and 24 weeks and partial Mayo score over time. RESULTS: 119 patients were randomized to Trichuris suis ova (n=60) and placebo (n=59). At week 24, clinical remission was achieved in 30% of Trichuris suis ova-treated vs. 34% of placebo-treated (RR=0.89; CI:0.52-1.50; p=0.80, ITT). No difference was found in clinical response in any of the clinical response subgroups. However, in patients who did not need treatment with corticosteroids during the trial, a temporary effect of TSO was seen in the analysis of symptomatic remission of week 12 (p=0.01), and the partial Mayo score at week 14 and week 18 (p<0.05 and p=0.02). CONCLUSIONS: Compared to placebo, Trichuris suis ova was not superior in achieving clinical remission at week 24 in ulcerative colitis or in achieving clinical Mayo score reduction, complete corticosteroid-free clinical remission or endoscopic remission. However, Trichuris suis ova treatment induced symptomatic temporary remission at week 12.

The Use and Efficacy of Biological Therapies for Inflammatory Bowel Disease in a Danish Tertiary Centre 2010-2020.

Background: Patients with inflammatory bowel disease (IBD) who receive biologicals frequently experience lack or loss of response. Our aim was to describe the use and efficacy of biological therapy in a tertiary IBD center. Methods: We included all bio-naive IBD patients who initiated biological therapy between 2010 and 2020 at our centre. Their medical records were reviewed. Results: The population consisted of 327 Crohn's disease (CD) patients, 291 ulcerative colitis (UC) patients, and 3 patients with IBD unclassified (IBDU). The median follow-up was 3 years (interquartile range = 2-5) after initiating therapy. The annual number of patients initiating biological therapy rose from 29 (2010) to 85 (2019). Most patients (457, 73.6%) received 1 biological drug; 164 (26.4%) patients received 2 or more biologicals. Primary lack of response was observed in 36.4% (106/291) and 17.4% (57/327) of UC and CD patients; loss of response was observed in 27.1% (79/291) and 31.5% (103/327) of UC and CD patients, respectively. The 5-year surgery rates were 26.6% and 20.4% in UC and CD patients, respectively. Multivariate Cox regression showed that treatment with thiopurine reduced the likelihood of needing to switch biological therapy, requiring surgery or corticosteroids in UC patients (HR: 0.745, 95% CI: 0.559-0.993), but not in CD patients (HR: 0.996, 95% CI: 0.736-1.349). Conclusions: The annual number of IBD patients initiated on biological therapy increased considerably between 2010 and 2020. One-quarter of these patients required surgery after 5 years. Our findings suggest a beneficial effect of concurrent thiopurines for UC patients receiving biologicals, but this was not found for CD patients. This effect in UC patients was not observed when we included patients initiating thiopurines up to 6 months after the introduction of biological therapy.

Adalimumab in the treatment of chronic pouchitis. A randomized double-blind, placebo-controlled trial.

BACKGROUND: Pouchitis is a complication of ileal pouch-anal anastomosis and occurs in up to 50% of patients 10 years after IPAA with 10% developing refractory pouchitis. OBJECTIVE: To evaluate the effect of a TNF-α inhibitor (Adalimumab) in the treatment of refractory pouchitis. MATERIALS AND METHODS: A multicenter, randomized double-blind, placebo-controlled trial includes patients with refractory pouchitis for more than 4 weeks despite antibiotic treatment. Patients were randomized to Adalimumab or placebo for 12 weeks. Primary outcome was reduction in clinical pouchitis disease activity index (PDAI) of ≥2 at any time. Secondary endpoints were remission of pouchitis, endoscopic and histologic effect and quality of life. RESULTS: Thirteen patients were included; six patients received active treatment and seven patients received placebo. Nine patients (5/4, Adalimumab/placebo) completed the 12-week program. Reduction in clinical PDAI ≥ 2 was achieved in three patients in each group (50%/43%, Adalimumab/placebo, p > .5). Total PDAI improved in six patients treated with Adalimumab and two patients on placebo (100%/29%, p = .13). There were no differences in secondary endpoints between the groups. CONCLUSIONS: In this randomized controlled trial of treatment with Adalimumab in patients with refractory pouchitis, we were not able to identify any clinical benefit in the primary or secondary endpoints.

Challenges and obstacles in the transition process through the eyes of the gastroenterologist.

BACKGROUND: Adult and pediatric care have different views and ways of handling the patients and the parents, which may result in insufficient coordination and communication of transfer. The young patient, the parents, the pediatric, and the adult provider constitute four central actors in transition and transfer, and they have different roles, approaches, and needs. Our aim was to clarify the challenges and background for each actor. MATERIALS AND METHODS: Statements from semistructured interviews of adult gastroenterologists and nurses were analyzed and interpreted by social scientific principles. The interviews were conducted individually, and each interview was completed within 30 min. The interviews were taped, transcribed, and sent to the interviewees for approval. RESULTS: The analysis of the statements included a description of the motives, perspectives, and approaches of the interviewees as well as an exploration and interpretation of the underlying meaning, patterns, and models. The main points of the article are illustrated through excerpts from the interviews and concluded in the recommendations. CONCLUSION: (I) Pediatricians and adult gastroenterologist need to rethink their view on patients aged 15-20 years and understand that they are different from other patients and do have different demands. (II) Transfer should be considered a three-part process: (a) transition at the pediatric department, (b) a coordinated transfer, and (c) a consolidation phase after transfer. (III) Adolescent patients need proper education and empowerment during transition. (IV) Parents need to be timely prepared including an adjustment and redefinition of their roles.

Disease-Specific Enteric Microbiome Dysbiosis in Inflammatory Bowel Disease.

Inflammatory Bowel disease (IBD) is traditionally divided into Crohn's disease (CD) and ulcerative colitis (UC). UC is a relapsing non-transmural inflammatory disease that is restricted to the colon and is characterized by flare-ups of bloody diarrhea. CD is a chronic, segmental localized granulomatous disease that can affect any part of the entire gastrointestinal tract. Ileo-anal pouch is a procedure restoring functionality of the rectum after a colectomy. IBD is a multifactorial disease and flares of IBD are probably triggered by changes in the intestinal microbiota followed by an abnormal immune response. In this study, we aim to analyze the intestinal bacterial diversity in IBD patients during various stages of disease compared with healthy controls. Permission for human experiments and recruitment of participants was obtained from the Ethic Committee for Copenhagen County hospitals (Permission no. KA-03019, Permission no. KA-20060159). Stools from 26 healthy controls, 42 CD, 38 UC and 18 pouch patients were collected. Stool DNA extraction was performed using Qiagen, DNA mini stool kit Denmark. DGGE-PCR amplifying the V2-V3 region of 16S-rDNA gene of the bacteria was amplified by universal primers HDA1 and HDA2. Analysis of DGGE was performed blinded using BioNumerics version 7.5. After normalization, a DGGE gel band matching was performed. The similarities between profiles were calculated with a ranked Pearson correlation coefficient based on the band matching results using band intensities. Simpson's index of diversity and Pielou's species evenness were calculated. Based on the Shannon Diversity Index, UC patients had lower species diversity and bacterial evenness in comparison to healthy persons, p < 0.05. However, only CD and disease pouch patients had lower species diversity compared to those with inactive disease and healthy controls. Well-functioning pouch patients had decreased species evenness in comparison to diseased pouch patients and control group. During the active disease stage in CD and pouch, the patients have a low bacterial diversity in their gut when compared to the inactive stage. In UC patients, a generally low diversity was observed at all stages of the disease compared to healthy controls.

S100A8/A9 (Calprotectin), Interleukin-6, and C-Reactive Protein in Obesity and Diabetes before and after Roux-en-Y Gastric Bypass Surgery.

BACKGROUND: In obesity, which is a major contributor to insulin resistance and diabetes, the circulating level of S100A8/A9 (calprotectin) is elevated and declines after Roux-en-Y gastric bypass surgery (RYGB). However, studies on S100A8/A9 and the pathophysiological mechanisms in insulin resistance and diabetes are few and contradictory. METHODS: We studied 48 subjects who underwent RYGB, comprising a non-diabetic control group and two diabetic groups in whom diabetes either regressed or persisted, 6-12 months post-surgically. S100A8/A9, interleukin 6 (IL-6) as well as other inflammatory and diabetes-related markers were measured pre- and post-surgically. RESULTS: Significant and similar decreases of BMI were found in all groups. S100A8/A9 and IL-6 decreased significantly in the group with diabetes remission and in the control group, but not in the group with persistent diabetes. The relative changes in S100A8/A9 and IL-6 correlated significantly (r = 0.905, p = 0.005) only in the group with persistent diabetes. In contrast, leukocyte count and C-reactive protein correlated significantly to S100A8/A9 only in the control group. CONCLUSION: Our study is suggestive of S100A8/A9 and IL-6 being related to a persistent diabetes status post-surgically and of different pathophysiological mechanisms being involved in the post-surgical changes in the three groups, despite similar decreases in BMI.

Extraintestinal pathogenic Escherichia coli are associated with intestinal inflammation in patients with ulcerative colitis.

E. coli of the phylogenetic group B2 harbouring Extra intestinal Pathogenic Escherichia coli (ExPEC) genes are frequently seen as colonizers of the intestine in patients with active ulcerative colitis (UC). In this study, we describe the influence of E. coli Nissle (EcN) B2 as add-on treatment to conventional therapies in patients with active UC. For this study one hundred active UC patients were randomized to ciprofloxacin or placebo for 1 week followed by EcN or placebo for 7 weeks. Stool samples were collected at weeks 0, 1, 8, 12, where E. coli were characterized and fecal calprotectin was measured. We showed that in the active UC patient group receiving Placebo/EcN, fewer patients reached remission, in comparison to the patient group receiving Placebo/placebo (p < 0.05). Active UC patients initially colonized with E. coli B2 had increased fecal calprotectin values and Colitis Activity Index scores in comparison to patients colonized with E. coli A and D (p < 0.05*). In conclusion, treatment of UC patients with E. coli Nissle (B2) does not promote clinical remission and active UC patients colonized with E. coli B2 have an increased intestinal inflammation.

Fecal Calprotectin Predicts Relapse and Histological Mucosal Healing in Ulcerative Colitis.

BACKGROUND: Mucosal healing in ulcerative colitis leads to a decreased need for medication and decreased risk of disease relapse and colectomy. Histological healing seems to improve the disease prognosis even further. An assessment of both endoscopic and histological mucosal healing requires endoscopy, and the need for a reliable noninvasive biomarker to predict disease relapse is obvious. METHODS: Seventy patients were included and followed up for 12 months. Inclusion criteria were a total Mayo score ≤1 and a Mayo endoscopic score = 0. The patients underwent sigmoidoscopy with rectal biopsies. Fecal calprotectin (FC) was measured 2 to 3 days before the sigmoidoscopy. The tissue samples were evaluated for neutrophilic inflammation. We aimed at testing the predictive performance of FC and histological inflammatory activity on disease relapse. RESULTS: A baseline FC level of more than 321 mg/kg predicted disease relapse at both the 6- and 12-month follow-ups. Histological inflammatory activity, C-reactive protein, or length of remission was not predictive of relapse. Of note, 11.8% of all patients had histological inflammatory activity despite endoscopic remission and were found to have a higher level of FC (236.5 versus 56 mg/kg, P = 0.02). A receiver operating characteristic analysis estimated a cutoff level of ≤40.5 mg/kg for FC (area under the curve, 0.755 and confidence interval 95%, 0.5895-0.9208) for predicting a histological inflammatory activity score of 0. CONCLUSIONS: FC measurements can be used to identify patients with increased risk of relapse after 6 and 12 months and to predict histological mucosal healing. Regular measurement of FC may alter disease monitoring and improve prognosis, and may decrease the need for endoscopy.

Effect of paracentesis on metabolic activity in patients with advanced cirrhosis and ascites.

OBJECTIVE: Patients with decompensated cirrhosis often suffer from malnutrition. To enable appropriate nutritional supplementation a correct estimation of resting energy expenditure (REE) is needed. It is, however, unclear whether the volume of ascites should be included or not in the calculations of the REE. MATERIAL AND METHODS: In 19 patients with cirrhosis and ascites, measurements of REE by indirect calorimetry were performed before paracentesis, after paracentesis, and four weeks after paracentesis. Moreover, handgrip strength (HGS), dual X-ray absorptiometry (DXA), and biochemistry were assessed. RESULTS: Calculated and measured REE differed more than 10% in 63% of the patients at baseline. By including the weight of ascites in the calculation of REE, the REE was overestimated by 283 (-602-1381) kJ/day (p = 0.69). By subtracting the weight of ascites in the calculation of REE, it was underestimated by -379 (-1915 - 219) kJ/day, (p = 0.06). Patients in whom measured REE decreased after paracentesis had higher middle arterial pressure (MAP) (p = 0.02) and p-sodium (p = 0.02) at baseline. Low HGS (M: <30 kg; W < 20 kg) was evident in 68% of the patients. T-scores revealed osteopenia and osteoporosis in 58% and 16%, respectively. Reduced vitamin D levels (<50 nmol/l) were found in 68%. CONCLUSIONS: The presence of ascites seems to increase REE, why we suggest that when REE is calculated, the weight of ascites should be included. Indirect calorimetry is, however, preferable for REE estimation. More than two-third of patients with ascites suffer from muscle weakness and/or osteopenia.

Level of Fecal Calprotectin Correlates With Endoscopic and Histologic Inflammation and Identifies Patients With Mucosal Healing in Ulcerative Colitis.

BACKGROUND & AIMS: In patients with ulcerative colitis (UC), mucosal healing is an important goal of treatment. However, mucosal healing is difficult to determine on the basis of clinical evaluation alone, and endoscopy is uncomfortable and can cause complications. Fecal calprotectin (FC) is a marker of inflammation, and its levels have been associated with disease activity. We investigated the association between level of FC and mucosal healing and clinical disease activity in patients with UC. METHODS: We performed an observational cross-sectional study of 120 patients with active or inactive UC who underwent sigmoidoscopy at Copenhagen University Hospital Hvidovre from September 2012 through 2014. Endoscopic inflammation was evaluated by using the Mayo Endoscopic Score (MES) and Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and histologic inflammatory activity by a slightly modified Harpaz Index, which measures acute inflammation. The Partial Mayo Score was used to measure the clinical disease activity. RESULTS: A cutoff level of FC of 192 mg/kg identified patients with endoscopic evidence of mucosal healing, which was based on the MES and UCEIS, with positive predictive values of 0.71 and 0.65, respectively; negative predictive values were 0.90 and 0.93, respectively. A cutoff level of 171 mg/kg identified patients with histologic evidence of mucosal healing, with positive predictive value of 0.75 and negative predictive value of 0.90. Levels of FC increased significantly with increases in endoscopic and histologic disease activity. There was high concordance between MES and UCEIS as well as between MES or UCEIS and histologic inflammatory activity. The histologic activity index had an interobserver variation of 4.35%. CONCLUSIONS: Level of FC identifies patients with UC who have endoscopic and histologic features of mucosal healing and correlates with endoscopic and histologic inflammatory activity. The UCEIS seems to be as accurate as the MES in identifying patients with mucosal healing and as easy to use. The histologic activity index had a high concordance with recognized endoscopic score systems.

The Impact of Endoscopic Inflammation and Mucosal Healing on Health-related Quality of Life in Ulcerative Colitis Patients.

BACKGROUND: Health-related quality of life [HRQoL] is impaired in ulcerative colitis and is correlated to clinical disease activity. The recent shift towards more objective treatment goals like mucosal healing generates a need for evaluating the association between endoscopic disease activity, mucosal healing and HRQoL. METHODS: In this cross-sectional study, patients with either active or inactive ulcerative colitis underwent sigmoidoscopy. Clinical disease activity was assessed by the Simple Clinical Colitis Activity Index [SCCAI], endoscopic inflammation by the Mayo Endoscopic Subscore [MES], and HRQoL by the Short Inflammatory Bowel Disease Questionnaire [SIBDQ] and Short Health Scale [SHS]. RESULTS: A total of 110 patients, 71% with active disease, had a median SCCAI score of 3 and a median MES score of 1. Patients in clinical remission had a mean SIBDQ of 60 and SHS of 6. HRQoL decreased significantly with increasing clinical (SIBDQ [χ(2) = 61.8, p < 0.0001] and SHS [χ(2) = 63.4, p < 0.0001]) and endoscopic disease activity (SIBDQ [χ(2) = 33.1, p < 0.0001] and SHS [χ(2) = 40.3, p < 0.0001]). Mucosal healing was associated with a higher HRQoL than active inflammation (59/46, p < 0.0001 [SIBDQ] and 7/20, p < 0.0001 [SHS]). Decreased HRQoL was observed with more extensive disease. Linear regression revealed strong association between SIBDQ and SHS. CONCLUSIONS: Not only clinical disease activity but also endoscopic inflammation and disease extent were associated with decreased HRQoL. Patients with mucosal healing had significant higher HRQoL, emphasising the importance of this treatment goal. Both SHS and SIBDQ are easy to use and to implement, and were strongly correlated.

Nutrition impact symptoms, handgrip strength and nutritional risk in hospitalized patients with gastroenterological and liver diseases.

OBJECTIVE: Malnutrition is common among patients with diseases of the liver and gastrointestinal tract. Nutritional intake may be negatively affected by nutrition impact symptoms (NIS). Therefore, the aims were to assess: 1) the prevalence of NIS in this group of patients and 2) the relationship between NIS and nutritional status as well as nutritional risk. MATERIAL AND METHODS: We performed a cross-sectional study among patients with liver disease, inflammatory bowel disease, cancer or pancreatitis. Nutritional risk was assessed by the NRS-2002. Nutritional status was assessed by body mass index (BMI) and handgrip strength (HGS), which were both measured within 5 days after admission. NIS were assessed by the Eating Symptoms Questionnaire (ESQ) and the Disease-Related Appetite Questionnaire (DRAQ). RESULTS: In total, 126 patients were included (women 39%) with a mean BMI of 24 ± 5 kg/m(2). The prevalence of low HGS was 38%, and the prevalence of those at nutritional risk was 58%. The number of NIS reported by 50% of the patients were 4 or more in the ESQ and 5 or more in the DRAQ. Patients who were both at nutritional risk and had a low HGS more frequently reported difficulties swallowing, poor appetite, feeling full after having one-fourth of the meal and food tasting bad. CONCLUSIONS: NIS that preclude food intake are very frequent among patients with diseases of the liver and gastrointestinal tract. Specific NIS are associated with low HGS, weight loss and being at nutritional risk.

[Faecal calprotectin is a useful biomarker for intestinal inflammation].

Faecal calprotectin is a biomarker for inflammation in the intestinal mucosa. Faecal calprotectin has the ability to detect inflammatory causes of gastrointestinal symptoms and to distinguish these from irritable bowel syndrome. The test is very sensitive but not specific to any particular gastrointestinal disease. In inflammatory bowel disease, faecal calprotectin correlates with symptoms, biochemical markers and the endoscopic findings. It can be used to monitor disease activity, treatment response and mucosal healing as well as predict relapse. We propose an algorithm for the use of faecal calprotectin in patients with unspecific abdominal complaints.

Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis: a double-blind randomized placebo controlled clinical trial.

BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The probiotic bacterium Escherichia coli Nissle 1917 (EcN) has been used to maintain and induce clinical remission in UC. Our aim was to test the effect of Ciprofloxacin and/or orally administered EcN as add-on to conventional therapies in patients with active UC. PATIENTS AND METHODS: Our single center double-blinded randomized placebo controlled study included patients with a Colitis Activity Index (CAI) score of at least 6. Patients were randomized to Ciprofloxacin or placebo for 1week followed by EcN or placebo for 7weeks. All 4 treatments were given as add-on treatments. RESULTS: One hundred subjects with active UC were recruited. In the per-protocol analysis we, surprisingly, found that in the group receiving placebo/EcN fewer patients, 54%, reached remission compared to the group receiving placebo/placebo, 89%, p<0.05. Among patients treated with Cipro/placebo and Cipro/EcN, 78% and 66% reached remission, respectively. Furthermore, the group receiving placebo/EcN had the largest number of withdrawals, 11 of 25 (44%), compared to 15 of 75 (20%) in any of the other groups, p<0.05. Indication of lack of mucosal healing was found in the group treated with placebo/Nissle, since only 4 (29%) of the 14 patients, who completed the study, reported no blood in stools at week 12 (p<0.02), compared to 63%, 67% and 65% in groups treated with Cipro/Nissle, Cipro/placebo and placebo/placebo, respectively. CONCLUSIONS: Our data suggest that there is no benefit in the use of E. coli Nissle as an add-on treatment to conventional therapies for active ulcerative colitis. Furthermore, treatment with E. coli Nissle without a previous antibiotic cure resulted in fewer patients reaching clinical remission.

The correlation between fecal calprotectin, simple clinical colitis activity index and biochemical markers in ulcerative colitis during high-dose steroid treatment.

OBJECTIVE: Monitoring active ulcerative colitis (UC) is essential for making correct and timely treatment decisions. The current monitoring is based on symptom scores and biochemical markers, among which the role of fecal calprotectin (FC) is debated. The aims were to assess the development in FC during steroid treatment and to compare FC with symptom scores and biochemical markers. MATERIAL AND METHODS: A prospective observational study, including 16 patients with active UC requiring high-dose steroid treatment. FC, C-reactive protein (CRP), leukocytes, hemoglobin, albumin, and simple clinical colitis activity index (SCCAI) were assessed before the initiation of treatment, as well as on days 2, 6, 13, and 27. The one-year follow-up data were retrospectively obtained. RESULTS: All patients had significant decreasing levels of FC (-1014 mg/kg, p = 0.0061), CRP (-10 mmol/l, p = 0.0313), and SCCAI (-3, p = 0.0002) during the first 4 days. After 27 days, the FC had decreased to 216 mg/kg (p = 0.002). A significant correlation between the changes in CRP and SCCAI was found (r(s) = 0.65, p = 0.03) but not between FC and CRP or SCCAI. Overall, significant correlations between absolute levels of FC, CRP, and SCCAI were found. Levels of FC on day 0 and day 4 were not predictive of sustained clinical remission at 1-year follow up. CONCLUSIONS: FC, CRP, and SCCAI seem to be reliable markers of treatment response during steroid treatment. High initial levels of FC and a subsequent rapid reduction during steroid treatment were identified. FC levels were not found to be predictive of disease prognosis after one year.

Nutritional intake and status in persons with alcohol dependency: data from an outpatient treatment programme.

PURPOSE: Malnutrition increases the risk of developing alcohol-related complications. The aim of this study was to describe nutrient intake, nutritional status and nutrition-related complications in a Danish population of outpatients with alcohol dependency. METHODS: This was a cross-sectional study with a 6-month follow-up enrolling persons with alcohol dependency (n = 80) admitted to a hospital-based outpatient clinic. Body mass index, the waist-to-hip ratio and handgrip strength (HGS) were measured, a 7-day food diary was collected, and biochemical testing was conducted. Dual-energy X-ray absorptiometry was performed to determine body composition and bone mineral density (BMD). RESULTS: In total, 64% of the patients with alcohol dependency had vitamin D insufficiency (25-OH-vit D <50 nmol/l). Compared with surveys of the general population, the patients with alcohol dependency had lower energy intake (p = 0.008), s-zinc levels (p < 0.001), s-magnesium levels (p = 0.02), Z-scores for BMD (lumbar spine, p = 0.03; total hip, p = 0.009) and HGS (p < 0.001). Osteopenia was observed in 52% of individuals, and overt osteoporosis was noted in 7%. Comparing baseline data with data from the follow-up (n = 30), we found a decrease in s-CRP (p = 0.002) and s-alanine amino transferase (p = 0.01) levels and an increase in s-parathyroid hormone levels (p = 0.02). CONCLUSIONS: Patients with alcohol dependency have an altered nutritional status and risk of complications, as evidenced by osteopenia/osteoporosis and reduced muscle strength. Treatment at an outpatient clinic improved the variables related to liver function, but no change was observed in nutritional status over time. These findings suggest that specific screening and targeted treatment regimens for nutritional deficits could be beneficial.

Biologic therapy in inflammatory bowel disease.

In luminal Crohn's disease with moderate to severe inflammatory activity, infliximab and adalimumab can be used in the case of treatment failure with conventional therapies, such as systemic steroids and immunosuppressive therapy or if this treatment is not tolerated. Further treatment strategy depends on the primary response to induction therapy. Effect of maintenance therapy should be evaluated clinically and paraclinically at least every 26-52 weeks, and maybe supplemented by endoscopy or MRI scan. Decision of treatment discontinuation is based on disease manifestation, treatment response and paraclinical parameters. In fistulising Crohn's disease, treatment with infliximab or adalimumab can be initiated in simple fistula with rectal inflammation or complex fistula when the initial treatment has insufficient effect. Further treatment strategy depends on the primary response to induction therapy. Maintenance therapy is often necessary in complex fistulas. Treatment efficacy and possible discontinuation of treatment is evaluated at least every 26-52 weeks - if possibly with diagnostic imaging. In acute severe ulcerative colitis, treatment with infliximab can be used in patients with partial response after 3-5 days of treatment with a high-dose systemic steroid and when surgical treatment is not preferred or required. Further treatment strategy depends on the response to the first drug administration and colectomy should always be considered as an option. Effect of subsequent initiated maintenance therapy should be evaluated at least every 26-52 weeks on the basis of symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. In chronic active ulcerative colitis, infliximab and adalimumab can be used in the case of treatment with immunosuppressive therapy fails and if surgery is not preferred. Further treatment strategy depends on the response to induction therapy. Treatment efficacy is assessed by symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. Effect of maintenance therapy should be evaluated at least every 26-52 weeks. During treatment with biologic drugs focus should be on possible complications, such as infections, infusion or injection reactions and dermatological side effects. An overview of levels of evidence and recommendations is presented.

Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment.

These national clinical guidelines outlining the screening, prophylaxis and critical information required prior to initiating anti-TNF-alpha treatment have been approved by the Danish Society for Gastroenterology. Anti-TNF-alpha therapy is widely used in gastroenterology (for inflammatory bowel disease), rheumatology (for rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies) and dermatology (for psoriasis). With this background, the Danish Society for Gastroenterology established a group of experts to assess evidence for actions recommended before treatment with anti-TNF-alpha agents. Screening should take place for both active tuberculosis and latent tuberculosis. Screening must evaluate the risk of hepatitis B exposure/infection and that of other viral infections such as human immunodeficiency virus (HIV) and varicella zoster virus (VZV). The assessment should include a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X-rays and laboratory tests, including an interferon gamma release assay, a hepatitis B test, an HIV test and, when prior VZV infection is uncertain, a VZV antibody test. Prophylaxis: Isoniazid should be administered in cases of suspected latent TB infection. Antiviral treatment is recommended in HBsAg-positive patients at the start of anti-TNF-alpha treatment. Before anti-TNF-alpha therapy, vaccination with 23-valent pneumococcal vaccine is recommended, and HBV vaccination may be considered in seronegative patients. Annual vaccination against seasonal influenza is recommended. Human papilloma virus vaccination should be administered in accordance with the guidelines of the National Board of Health of Denmark. In patients without a prior VZV infection, VZV vaccination may be considered. Information for patients: Anti-TNF-alpha treatment results in a generally increased risk of infection and latent tuberculosis flare-up. Women are advised to comply with the national guidelines for screening for cervical cancer, and their HPV immunisation status should be clarified. An increased risk of lymphoma with biological therapy in combination with thiopurines should be mentioned. Patients are advised to seek medical advice in case of herpes zoster infection.