The intestinal tissue homeostasis - the role of extracellular matrix remodeling in inflammatory bowel disease.

Introduction: Extracellular matrix (ECM) remodeling of the intestinal tissue is important in inflammatory bowel disease (IBD) due to the extensive mucosal remodeling. There are still gaps in our knowledge as to how ECM remodeling is related to intestinal epithelium homeostasis and healing of the intestinal mucosa.Areas covered: The aim of this review is to highlight the importance of the ECM in relation to the pathogenesis of IBD, while addressing basement membrane and interstitial matrix remodeling, and the processes of wound healing of the intestinal tissue in IBD.Expert opinion: In IBD, basement membrane remodeling may reflect the integrity of the intestinal epithelial-cell homeostasis. The interstitial matrix remodeling is associated with deep inflammation such as the transmural inflammation as seen in fistulas and intestinal fibrosis leading to fibrostenotic strictures, in patients with CD. The interplay between wound healing processes and ECM remodeling also affects the tissue homeostasis in IBD. The interstitial matrix, produced by fibroblasts, holds a very different biology as compared to the epithelial basement membrane in IBD. In combination with integration of wound healing, quantifying the interplay between damage and repair to these sub compartments may provide essential information in IBD patient profiling, mucosal healing and disease management.

Does severe bleeding in HHT patients respond to intravenous bevacizumab? Review of the literature and case series.

BACKGROUND: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder, with a wide variety of clinical manifestations due to the presence of multiple arteriovenous manifestations. Severe bleeding from the gastrointestinal (GI) tract and/or epistaxis presents a significant problem in a subgroup of patients and systemic bevacizumab, an angiogenesis inhibitor, has been suggested to benefit these patients. OBJECTIVE: To perform a review of the literature concerning the efficacy of systemic bevacizumab in treatment of bleeding from the nose or GI tract in patients with HHT, including patients from our own HHT-center. METHODS: A literature review was performed using the guideline "Preferred Reporting Items for systematic Reviews and MetaAnalysis statement" (PRISMA). RESULTS: After careful selection, we finally analysed the results of eight case series and 33 case reports. Among 195 patients 171 (88%) had reduced bleeding after bevacizumab. CONCLUSIONS: Based on the literature review and data from our own case series, systemic bevacizumab is very promising as treatment for HHT patients with severe epistaxis and/or GI-bleeding. However, care should be taken using bevacizumab, a potent angiogenesis inhibitor; long-term side effects have not been studied in this population. A randomized controlled study is warranted to support the results in HHT patients.

A randomized, double-blinded, placebo-controlled, parallel trial of vitamin D3 supplementation in adult patients with migraine.

BACKGROUND: Vitamin D levels have been linked to certain pain states, including migraine. This study investigated whether vitamin D supplementation would be beneficial for adult patients with migraine (ClinicalTrials.gov Identifier: NCT01695460). METHODS: A randomized, double-blinded, placebo-controlled parallel trial was conducted in migraine patients (36 women and 12 men, 18-65 years of age). A 4-week baseline period was conducted before randomization to 24 weeks of treatment. Participants were assigned to receive D3-Vitamin (n = 24, 18 women and 6 men, 100 µg/day D3-Vitamin) or placebo (n = 24, 18 women and 6 men). Migraine attacks and related symptoms were assessed by self-reported diaries. The response rate (i.e. experiencing a 50% or greater reduction in migraine frequency from baseline to week 24), change in migraine severity, and number of migraine days were recorded. Changes in migraine-related symptoms, HIT-6TM scores, and pain sensitivity tests (pressure pain threshold and temporal summation) were also evaluated. Serum levels of both 25 (OH)D and 1,25 (OH)2D were assessed from baseline to week 24. RESULTS: The number of headache days changed from 6.14 ± 3.60 in the treatment group and 5.72 ± 4.52 in the placebo group at baseline to 3.28 ± 3.24 and 4.93 ± 3.24 by the end of the trial, respectively. Migraine patients on D3-Vitamin demonstrated a significant decrease (p < .001) in migraine frequency from baseline to week 24 compared with placebo. However, migraine severity, pressure pain thresholds, or temporal summation did not show a significant change. 25(OH)D levels increased significantly for the D3-Vitamin group during the first 12 weeks of treatment. There was no significant change in 1,25(OH)2D. No side-effects were reported or noted. CONCLUSIONS: D3-Vitamin was superior to placebo in reducing migraine days in migraine patients. Larger studies are required to confirm that vitamin D3 might be one of the prophylactic options for adult patients with migraine.

T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression.

Background: Almost half of the patients with metastatic melanoma obtain only short-term or no benefit at all from checkpoint inhibitor (CPI) immunotherapy. In this study, we investigated whether the immune system of patients progressing following CPI treatment was able to generate functional tumor-specific immune responses. Materials and methods: Tumor-infiltrating lymphocytes (TILs) were isolated and expanded from metastatic melanoma lesions which progressed during or after anti-programmed cell death protein 1 (PD)-1 and anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) treatment. Tumor-specific immune responses were assessed with co-culture assays of TILs and autologous tumor cells. Results: TILs from 23 metastases of individual patients could be assessed for T cells recognition of autologous tumor cells. All metastases were progressive on or following anti-PD-1 (23/23, 100%), and the majority also after anti-CTLA-4 (17/23, 74%). Functional antitumor immune responses were detected in 19/23 patients (83%). Both CD8+ (in 18/23 patients, 78%) and CD4+ (in 16/23 patients, 70%) TILs were able to recognize autologous tumors. A large fraction of CD8+ TILs (median 23%, range 1.0%-84%) recognized tumor cells. This is similar to the cohorts of unselected patient populations with metastatic melanoma presented in previous studies. The localization of intratumoral immune infiltrates was heterogeneous among samples. In a phase I/II clinical trial, TILs were administered with lymphodepleting chemotherapy, pegIFNα2b and interleukin-2 to 12 patients with CPI-resistant melanoma. Out of 12 patients who previously failed CPI therapy, treatment with TILs resulted in two partial responses, of which one is ongoing. Conclusions: Tumor-reactive T cells appear to heavily infiltrate the tumor microenvironment of patients who failed previous CPI treatment. These patients can still respond to an infusion of unselected autologous TILs. Our results warrant further testing of novel immune re-activation strategies in melanoma patients who failed multiple CPI therapy.

Poor Outcomes of Complicated Pouch-Related Fistulas after Ileal Pouch-Anal Anastomosis Surgery.

BACKGROUND AND AIMS: Development of a pouch-related fistula tract is an uncommon but highly morbid complication to restorative proctocolectomy with ileal pouch-anal anastomosis. Pouch failure with permanent ileostomy is reported in 21%-30% of patients, yet the factors contributing to pouch excision remain poorly defined. The aim of this study was to determine the incidence and treatment results of complicated pouch-related fistula, as well as to evaluate factors involved in excision after pouch failure. MATERIAL AND METHODS: The study was conducted as a retrospective study. All patients with diagnosed pouch-related fistulas were registered with information related to fistula classification, treatments, and outcome. RESULTS AND CONCLUSION: The final analysis included 48 (10.7%) of the 447 total ileal pouch-anal anastomosis patients with complicated pouch-related fistulas. Pouch-vaginal fistulas, pouch-perianal fistulas, and other pouch-related fistulas were observed in 19 (63%), 29 (60%), and 10 (21%) patients, respectively, corresponding to an accumulated risk of 8%, 6%, and 2%, respectively. Time from ileal pouch-anal anastomosis surgery to fistula presentation was 24 (0.2-212) months. Overall pouch failure, defined as pouch excision or a diverting stoma, was seen in 34 (71%) patients, while pouch excision was seen in 23 (48%) of the patients. Patients who developed Crohn's disease had a significantly higher risk of pouch excision, as did patients with an early onset of the fistula after ileal pouch-anal anastomosis (P = 0.006 and P = 0.007, respectively). In conclusion, the present study demonstrated a high risk of pouch failure in patients with complicated pouch-related fistulas. Furthermore, it showed that Crohn's disease and the development of early onset fistulas are associated with pouch excision.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Short sleep duration and large variability in sleep duration are independently associated with dietary risk factors for obesity in Danish school children.

BACKGROUND: Lack of sleep and increased consumption of energy-dense foods and sugar-sweetened beverages (SSBs) have all been suggested as factors contributing to the increased prevalence of overweight and obesity. OBJECTIVE: To evaluate whether objectively measured sleep duration (average and day-to-day variability) as well as parent-reported sleep problems are independently associated with proposed dietary risk factors for overweight and obesity in 8-11-year-old children. DESIGN: In this cross-sectional study, data on sleep duration and day-to-day variability in sleep duration were measured in 676 Danish, apparently healthy children by an objective measure (actigraphy) for 8 nights, and the Children's Sleep Habits Questionnaire (CSHQ) was filled out by the parents. Diet was recorded using a web-based food record for 7 consecutive days. Fasting blood samples were obtained for measurements of plasma leptin and ghrelin levels. RESULTS: Sleep duration (h per night) was negatively associated with energy density (ED) of the diet (ß = -0.32 kJ g(-1)), added sugar (ß = -1.50 E%) and SSBs (ß = -1.07 E%) (all P ≤ 0.003). Furthermore, variability in sleep duration (10-min per night) was positively associated with SSBs (ß = 0.20 E%, P = 0.03), independent of sleep duration, and CSHQ score was positively associated with ED (ß = 0.16 kJ g(-1), P = 0.04). All of these associations were independent of potential confounders (age, sex, pubertal status, height, weight, screen time, moderate-to-vigorous physical activity and parental education and ethnicity). CONCLUSION: Our study suggests that short sleep duration, high sleep duration variability and experiencing sleep problems are all associated with a poor, obesity-promoting diet in children.

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study.

BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-α) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-α agents on post-operative outcomes 30 and 60 days after CD surgery in a nationwide Danish cohort. Outcomes were death, reoperation, anastomosis leakage, intra-abdominal abscess and bacteraemia. METHODS: We identified all patients having surgical procedures from 1 January 2000 to 31 December 2010 (n = 2293). Patients were classified according to use of anti-TNF-α agents within 12 weeks before surgery (exposed) or not (unexposed). Outcomes were obtained from nationwide registries and a bacteraemia registry. Sub-analyses were performed for bacteraemia and for impact of pre-operative timing of anti-TNF-α agents. RESULTS: Among surgical procedures for CD, 214 were exposed and 2079 were not. We found no increased relative risks of death or abscess drainage 30 or 60 days after follow-up. Among exposed, 7.5% had a reoperation within 30 days vs. 8.6% among unexposed, adjusted odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.52-1.63. Among exposed, 3.8% had an anastomosis leakage within 30 days after surgery vs. 2.8% among unexposed, adjusted OR = 1.33, 95% CI: 0.59-3.02. No further cases of anastomosis leakages appeared within 60 days. Sub-analyses indicated no increased risk of bacteraemia after 30 days and no increased risks when anti-TNF-α agents were given ≤14 days before surgery. CONCLUSION: We found no significantly increased relative risks of post-operative complications after use of anti-TNF-α agents either 12 weeks or ≤14 days before surgery for Crohn's disease.

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study.

BACKGROUND: It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC). AIM: In a nationwide Danish cohort of patients with UC, we aimed to examine the impact of pre-operative use of anti-TNF-α agents on post-operative adverse outcomes after colectomy for UC. Outcomes (within 30 and 60 days after surgery) were reoperation, anastomosis leakage, intra-abdominal abscess, bacteremia and death. METHODS: Based on the Danish National Patient Registry we identified all UC patients, aged ≥15 years, having their first surgery for UC in the period of 1 January 2003-31 December 2010 (n = 1226). Patients were classified according to use of anti-TNF-α agents within 12 weeks before surgery or not. Outcome data were obtained from Danish registries. Logistic regression analyses were used to estimate adjusted risks [with 95% confidence intervals (CI)] of post-operative outcomes among patients treated with anti-TNF-α agents, relative to those not treated. RESULTS: A total of 199 UC patients were exposed to anti-TNF-α agents within 12 weeks before colectomy, and 1027 were not. Among exposed, the adjusted odds ratio of reoperation and anastomosis leakage within 30 days after colectomy was 1.07 (95% CI: 0.71-1.59) and 0.52 (95% CI: 0.06-4.11) respectively. No deaths, cases of abscess drainage or bacteremia occurred among exposed within 30 days. Furthermore, no increased relative risks were found within 60 days after colectomy. CONCLUSIONS: Based on nationwide data on UC patients having colectomies, pre-operative use of anti-TNF-α agents did not increase the risk of post-operative complications.

Prediction of therapy in primary endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: It seems rational to perform endoscopic retrograde cholangiopancreatography (ERCP) if the probability of endoscopic therapy is high, but to carry out magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) first if this probability is moderate or low. The aim of the present study was to develop a model describing the probability of endoscopic therapy in patients without previous biliary imaging. PATIENTS AND METHODS: The development of the model was based on stepwise multiple logistic regression applied to 2470 prospectively registered first-time ERCP procedures. The model was evaluated by application to 442 prospectively registered first-time ERCP procedures entered in the database in the following 2 years. RESULTS: Predictors selected were: age, gender, p-amylase >/= 400 U/l, ln(s-bilirubin), ln(s-alkaline phosphatase), common bile duct (CBD) stone seen on transabdominal ultrasonography, gallbladder stone seen on transabdominal ultrasonography, interaction of dilated bile ducts seen on transabdominal ultrasonography with ln(s-bilirubin), and interaction between age and male gender. The area under the receiver operating characteristic (ROC) curve was 0.875 and there was good fit of the model. A test with a probability cutoff value of 80 % had a positive predictive value (PPV) of 92.8 %. Specificity was 87.1 % and, using this test, 52.4 % of patients would have been selected for primary ERCP. In the application cohort, the frequency of therapy was higher than in the development cohort. The area under the ROC curve was 78.7 %. When used in the evaluation cohort, with a cutoff probability of 80 %, the test had sensitivity 84.0 %, specificity 49.5 %, negative predictive value (NPV) 46.6 % and PPV 85.6 %. Of the patients, 76.7 % would have been selected for ERCP. This would have identified 85.5 % of individuals needing therapeutic ERCP without use first of MRCP or EUS. Test-positive cases constituted 90.3 % of stent insertions and 86.3 % of stone extractions. CONCLUSIONS: The model is useful for selection of patients for ERCP at our center.

Pharmacological monitoring of azathioprine therapy.

BACKGROUND: Studies on azathioprine (Aza) treatment in Crohn disease have indicated a positive correlation between clinical remission and a concentration in erythrocytes of the metabolites 6-thioguanine nucleotides (E-6-TGN) above 230 pmol/8 x 10(8) RBC. A concentration of the methylated Aza metabolites (E-6-MMP) above 5000 pmol/8 x 10(8) RBC has been correlated to hepatotoxicity. Thiopurine methyltransferase (TPMT) is responsible for the formation of methylated metabolites and lower E-TGN levels, and TPMT genotyping has been proposed as guidance for dosage. In a cross-sectional study we investigated relationships between the clinical outcome and Aza dose, the TPMT genotype and the Aza metabolite levels among patients with Crohn disease. METHODS: TPMT genotype (PCR assay), azathioprine metabolite levels (HPLC analysis) and xanthine oxidase (XO) activity were determined once in 71 randomly selected Crohn patients on an unaltered Aza dose for at least 3 months. RESULTS: None of the doses of Aza, TPMT genotype, E-6-TGN-, E-6-MMP levels or XO activity were significantly related to disease activity (H-B score), (P = 0.18, P = 0.69, P = 0.90, P = 0.54, P = 0.29, respectively). Leucopenia and/or hepatotoxicity were not demonstrated in any patient. Four patients had a heterozygous TPMT genotype (6.1%; 95% CI: 1.68%-14.80%). The 4 TPMT heterozygous patients had higher E-6-TGN levels than did the 67 remaining patients (P = 0.008). CONCLUSIONS: To explore the applicability of TPMT genotyping, E-6-TGN and E-6-MMP levels for therapeutic drug monitoring, large prospective studies with patient entry at the start of Aza therapy are needed. Until the results of such studies are available, the dose adjustments of Aza should be guided primarily by clinical response and blood counts; metabolite level measurements can only be applied to identify therapeutic non-compliance.

Incomplete remission with short-term prednisolone treatment in collagenous colitis: a randomized study.

BACKGROUND: Microscopic colitis is a disease of unknown aetiology characterized by chronic watery diarrhoea and diarrhoea can be eliminated by budesonide but frequently recurs when budesonide is stopped. We studied whether prednisolone could induce remission in patients with disabling, chronic diarrhoea due to microscopic colitis. METHODS: A double-blind, randomized (3:1) trial of oral prednisolone 50 mg daily or placebo for 2 weeks. Remission was defined as stool weight < or = 200 g/day or frequency < or = 2/day; effect was defined as > 50% reduction of either stool frequency or weight. Six centres screened 31 consecutive patients and included 11 with collagenous colitis and 1 with lymphocytic colitis. Median duration of diarrhoea was 9 months. Patients had a normal colonoscopy, and no evidence of coeliac disease, bile acid or lactose malabsorption. Patients with gastrointestinal infection, previous gastrointestinal surgery, abnormal biochemical screening or recent treatment with immunosuppressive agents were excluded. RESULTS: Stool weight (grams) declined in 7 of 9 patients given prednisolone and in 1 of 3 receiving placebo; changes in median weight were from 430 to 278 and from 825 to 489, respectively. Stool frequency (per day) declined from 6 to 3 and from 8 to 5. Remission was obtained in 2 and 0, and effect in 5 and 0, respectively (NS; Fisher exact test). CONCLUSIONS: Prednisolone 50 mg daily for 2 weeks induces incomplete remission in patients with chronic diarrhoea due to collagenous colitis.

Effects of topical ropivacaine on eicosanoids and neurotransmitters in the rectum of patients with distal ulcerative colitis.

BACKGROUND: Topical administration of lidocaine has been suggested to have beneficial clinical effects in patients with active ulcerative colitis, but the mechanism of action, if any, remains obscure. As local anaesthetics may exert anti-inflammatory actions through their inhibition of nervous reflexes, we have studied the local effects of a single rectal dose of ropivacaine gel on rectal concentrations of eicosanoids and neurotransmittors in patients with relapsing ulcerative colitis. METHODS: In a randomized, double-blind, placebo-controlled study, concentrations of leukotriene B4, thromboxane B2 and prostaglandin E2 in rectal dialysates and concentrations of substance P, neurokinin A, somatostatin, vasoactive intestinal polypeptide and calcitonin gene-related peptide in rectal biopsies from 19 patients with active, distally located, ulcerative colitis were measured before and after rectal administration of a 200-mg dose of ropivacaine- or placebo-gel by use of radioimmunoassays. For comparison with normal conditions, concentrations of neuropeptides were measured in another 19 patients with relapsing ulcerative colitis and 14 controls with non-inflamed colon. RESULTS: No significant changes in concentrations of eicosanoids or neuropeptides were observed after ropivacaine or placebo administration. Baseline concentrations of all neuropeptides, except somatostatin, were significantly lower in active ulcerative colitis than in controls with non-inflamed colon. CONCLUSIONS: These findings reveal no evidence of anti-inflammatory actions by ropivacaine in active ulcerative colitis and thus provide no rationale for topical treatment with local anaesthetics.

Collagen metabolites in the peripheral and splanchnic circulation of patients with Crohn disease.

BACKGROUND: Fragments of collagen arising during synthesis and breakdown have been suggested as markers of fibrous tissue remodelling in Crohn disease. We compared serum concentrations of the C-terminal propeptide of collagen I (PICP), the N-terminal propeptide of collagen III (PIIINP) and the C-terminal telopeptide of type I collagen (ICTP) in the splanchnic and systemic circulation in Crohn disease requiring segmental intestinal resection. METHOD: 15 consecutive patients undergoing surgery due to strictures or continuous inflammation. Male:female ratio was 6:9. Blood was drawn from a peripheral vein prior to surgery. Immediately before intestinal resection, additional samples were drawn from the antecubital vein and from a mesenteric vein draining the affected intestinal segment. PIIINP, PICP and ICTP were measured with radioimmunoassays. RESULTS: Pre-surgery S-ICTP (median 5.5 microg/L; range 3.2-17.2 microg/L) was significantly increased in peripheral blood compared with healthy controls (median 2.6 microg/L; range 0.6-5.7 microg/L), P < or = 0.05. By contrast, S-PICP (median 98 microg/L; range 62-137 microg/L) and S-PIIINP (median 2.5 microg/L; range 1.2-7.4 microg/L) were significantly lower than S-PICP (median 133 microg/L; range 66-284 microg/L) and S-PIIINP (median 3.4 microg/L; range 1.0-7.1 microg/L) in healthy controls, P < or = 0.05. During surgery. no difference in S-PICP and S-PIIINP was documented between peripheral blood and splanchnic blood. In contrast, S-ICTP was increased in splanchnic blood (median 6.2 microg/L; range 2.7-17.4) compared to peripheral blood (median 5.0 microg/L; range 3.1-13.4) (P=0.05). CONCLUSION: The present study provides further evidence that the altered intestinal collagen metabolism in Crohn disease is reflected in the local and systemic circulation.

[Cyclosporine treatment of patients with active ulcerative colitis refractory to high-dose glucocorticoid]. / Ciclosporinbehandling af patienter med aktiv colitis ulcerosa refraktaere over for højdosis-glukokortikoid.

In around 30-40% of patients with acute severe ulcerative colitis the disease is refractory to treatment with high-dose glucocorticoids. Adding intravenous cyclosporine to the therapy in these patients has shown encouraging short-term results. Case notes of twenty-three acutely ill patients, who received intravenous cyclosporine during the period 1992 to 1998 due to failure of high-dose glucocorticoid (n = 20) or due to medical complications (n = 3) which made surgery difficult, were reviewed. Eight patients had their first episode of ulcerative colitis whereas 15 had relapse or chronic active disease. Cyclosporine (4 mg/kg/dag) was added to glucocorticoid treatment after a median of 11 days. Clinical remission was achieved in 13 patients (57%) after a median of nine days, of these five subsequently underwent surgery. Ten did not obtain remission and went to surgery. Approximately a third of acutely ill ulcerative colitis patients refractory to standard treatment with high-dose glucocorticoids will benefit from intravenous cyclosporine in the longer term.