| 1. |
- Bouma, Gerd, et al.
(författare)
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Microscopic Colitis
- 2015
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Ingår i: Digestive Diseases. - : Karger. - 0257-2753 .- 1421-9875. ; 33:2, s. 208-214
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Tidskriftsartikel (refereegranskat)abstract
- Microscopic colitis (MC) is the common denominator for lymphocytic and collagenous colitis (CC). It is now recognized as a relatively frequent cause of diarrhea that equals the prevalence of inflammatory bowel disease. Patients are typically middle-aged women, but disease may occur at every age. Patients with MC report watery, non-bloody diarrhea in the absence of endoscopic and radiologic abnormalities. Lymphocytic colitis is characterized by an increased number of intraepithelial lymphocytes, and CC by a thickened subepithelial collagen band, whereas in both an increased mononuclear infiltration of the lamina propria is found. The pathogenesis of MC is largely unknown, but may relate to autoimmunity, adverse reactions to drugs or (bacterial) toxins, and abnormal collagen metabolism in the case of CC. Budesonide is so far the only drug that has proven efficacy in randomized controlled trials both for the induction and maintenance of remission. Patients who are nonresponsive, dependent or who experience side effects on budesonide may benefit from thiopurine or anti-TNF treatment, but these options are still experimental. The long-term prognosis of MC is good; it does not appear to predispose to malignancies and can in some cases be self-limiting. Further research and randomized clinical trials are required to expand our understanding of the natural course and the pathogenesis of MC.
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| 2. |
- Daferera, Niki, et al.
(författare)
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Fecal stream diversion and mucosal cytokine levels in collagenous colitis : A case report
- 2015
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Ingår i: World Journal of Gastroenterology. - Pleasanton, USA : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 21:19, s. 6065-6071
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Tidskriftsartikel (refereegranskat)abstract
- In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1β, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-γ, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.
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| 3. |
- Daferera, Niki, et al.
(författare)
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Single-centre experience with anti-tumour necrosis factor treatment in budesonide-refractory microscopic colitis patients
- 2019
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Ingår i: United European Gastroenterology journal. - : SAGE PUBLICATIONS INC. - 2050-6406 .- 2050-6414. ; 7:9, s. 1234-1240
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Tidskriftsartikel (refereegranskat)abstract
- Background: Microscopic colitis is an inflammatory bowel disease that causes chronic, watery diarrhoea. Microscopic colitis is usually effectively treated with budesonide, but some patients are refractory. Data on alternative treatments are sparse. Aims: The purpose of this study was to retrospectively evaluate outcome of microscopic colitis patients receiving anti-tumour necrosis factor therapy at our centre. Methods:Treatment results, including side effects, for all microscopic colitis patients receiving anti-tumour necrosis factor therapy were registered at week 12 and at end of follow-up. Clinical remission was defined as a mean of Results: The study cohort comprised 18 patients; mean age at diagnosis was 47 years (range 19-77). Ten and eight patients, respectively, received adalimumab and infliximab as first-line anti-tumour necrosis factor; seven patients received second-line anti-tumour necrosis factor due to non-response, loss of response or side effects. At week 12, 9/18 patients had achieved remission, 6/18 were responders and 3/18 were non-responders. Of the nine remission patients, 3/18 (16%) had long-lasting clinical remission post-induction therapy alone. Five patients (28%) (one first-line, four second-line anti-tumour necrosis factor) were in remission and one patient (6%) responded to maintenance treatment; follow-up was mean 22 (range 4-60) months. Six patients (33%) had minor, reversible side effects. Conclusions: Over half of budesonide-refractory microscopic colitis patients can achieve clinical remission or response on anti-tumour necrosis factor agents. Prospective studies are mandatory to evaluate the efficacy and safety of anti-tumour necrosis factor treatments in budesonide-refractory microscopic colitis.
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| 4. |
- Falessi, Davide, et al.
(författare)
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Empirical software engineering experts on the use of students and professionals in experiments
- 2018
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Ingår i: Empirical Software Engineering. - : Springer New York LLC. - 1382-3256 .- 1573-7616. ; 23:1, s. 452-489
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Tidskriftsartikel (refereegranskat)abstract
- [Context] Controlled experiments are an important empirical method to generate and validate theories. Many software engineering experiments are conducted with students. It is often claimed that the use of students as participants in experiments comes at the cost of low external validity while using professionals does not. [Objective] We believe a deeper understanding is needed on the external validity of software engineering experiments conducted with students or with professionals. We aim to gain insight about the pros and cons of using students and professionals in experiments. [Method] We performed an unconventional, focus group approach and a follow-up survey. First, during a session at ISERN 2014, 65 empirical researchers, including the seven authors, argued and discussed the use of students in experiments with an open mind. Afterwards, we revisited the topic and elicited experts’ opinions to foster discussions. Then we derived 14 statements and asked the ISERN attendees excluding the authors, to provide their level of agreement with the statements. Finally, we analyzed the researchers’ opinions and used the findings to further discuss the statements. [Results] Our survey results showed that, in general, the respondents disagreed with us about the drawbacks of professionals. We, on the contrary, strongly believe that no population (students, professionals, or others) can be deemed better than another in absolute terms. [Conclusion] Using students as participants remains a valid simplification of reality needed in laboratory contexts. It is an effective way to advance software engineering theories and technologies but, like any other aspect of study settings, should be carefully considered during the design, execution, interpretation, and reporting of an experiment. The key is to understand which developer population portion is being represented by the participants in an experiment. Thus, a proposal for describing experimental participants is put forward.
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| 5. |
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| 6. |
- Langner, Cord, et al.
(författare)
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Histology of Microscopic Colitis - Review with Practical Approach for Pathologists
- 2015
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Ingår i: Histopathology. - : Wiley-Blackwell. - 0309-0167 .- 1365-2559. ; 66:5, s. 613-626
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Forskningsöversikt (refereegranskat)abstract
- Microscopic colitis has emerged as a major cause of chronic watery non-bloody diarrhoea, particularly in elderly females. The term is used as an umbrella term to categorize a subgroup of colitides with distinct clinicopathologic phenotypes and no significant endoscopic abnormalities: Lymphocytic colitis is defined by an increased number of surface intraepithelial lymphocytes, collagenous colitis by a thickened collagen band underneath the surface epithelium. There is increased inflammation in the lamina propria, but only little or no crypt architectural distortion. Incomplete and variant forms showing less characteristic features have been reported under different names. Differential diagnosis mainly includes resolving infectious colitis and changes related to the intake of drugs such as non-steroidal anti-inflammatory drugs. Substantial clinical and histological overlap between lymphocytic and collagenous colitis has been described, raising the suspicion that the conditions are two histological manifestations of the same entity, possibly representing different manifestations during the disease course or different stages of disease development. In this review we provide a practical approach for pathologists with focus on diagnostic criteria and differential diagnosis, discuss recent insights into the pathogenesis of disease and the relation to classical chronic inflammatory bowel disease, i.e. Crohn's disease and ulcerative colitis.
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| 7. |
- Larsson, Johanna K, et al.
(författare)
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Cancer Risk in Collagenous Colitis
- 2019
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 8:11
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Tidskriftsartikel (refereegranskat)abstract
- Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 +/- 11 and 66 +/- 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).
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| 8. |
- Mansouri, Larry, et al.
(författare)
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Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. 2666-2670
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Tidskriftsartikel (refereegranskat)abstract
- We recently reported a truncating deletion in the NFKBIE gene, which encodes IκBϵ, a negative feedback regulator of NF-κB, in clinically aggressive chronic lymphocytic leukemia (CLL). Preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, hence we screened a large patient cohort (n=1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal-zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary CNS lymphoma (3-4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases, 22.7%) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases, 27.3%). NFKBIE-deleted PMBL patients were more often therapy-refractory (P=.022) and displayed inferior outcome compared to wildtype patients (5-year survival: 59% vs. 78%; P=.034); however they appeared to benefit from radiotherapy (P=.022) and rituximab-containing regimens (P=.074). NFKBIEaberrations remained an independent factor in multivariate analysis (P=.003), also when restricting to immunochemotherapy-treated patients (P=.008). Whole-exome sequencing and gene expression-profiling verified the importance of NF-κB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.
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| 9. |
- Miehlke, Stephan, et al.
(författare)
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Efficacy and Safety of Budesonide, vs Mesalazine or Placebo, as Induction Therapy for Lymphocytic Colitis
- 2018
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Ingår i: Gastroenterology. - : W B SAUNDERS CO-ELSEVIER INC. - 0016-5085 .- 1528-0012. ; 155:6, s. 1795-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND amp; AIMS: Lymphocytic colitis is a common cause of chronic, nonbloody diarrhea. However, the effects of treatment are unclear and randomized placebo-controlled trials were requested in a Cochrane review. We performed a randomized, placebo-controlled, multicenter study to evaluate budesonide and mesalazine as induction therapy for lymphocytic colitis. METHODS: Patients with active lymphocytic colitis were randomly assigned to groups given budesonide 9 mg once daily (Budenofalk granules), mesalazine 3 g once daily (Salofalk granules), or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as amp;lt;= 21 stools (including amp;lt;= 6 watery stools), in the 7 days before week 8. RESULTS: The final analysis included 57 patients (19 per group). Most patients were female (72%) and the mean age was 59 years. The proportion of patients in clinical remission at week 8 was significantly higher in the budesonide group than in the placebo group (intention-to-treat analysis, 79% vs 42%; P=.01). The difference in proportions of patients in clinical remission at week 8 between the mesalazine (63%) and placebo groups was not significant (P=.09). The proportion of patients with histologic remission at week 8 was significantly higher in the budesonide group (68%) vs the mesalazine (26%; P=.02) or placebo (21%; P=.008) groups. The incidence of adverse events was 47.4% in the budesonide group, 68.4% in the mesalazine group, and 42.1% in the placebo group. CONCLUSIONS: In a randomized multicenter study, we found oral budesonide 9 mg once daily to be effective and safe for induction of clinical and histologic remission in patients with lymphocytic colitis, compared with placebo. Oral mesalazine 3 g once daily was not significantly better than placebo. ClinicalTrials.gov no: NCT01209208.
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| 10. |
- Miehlke, Stephan, et al.
(författare)
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Microscopic colitis: pathophysiology and clinical management
- 2019
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Ingår i: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 4:4, s. 305-314
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Forskningsöversikt (refereegranskat)abstract
- Microscopic colitis is a chronic inflammatory disease of the colon that frequently causes chronic watery diarrhoea that might be accompanied by abdominal pain, nocturnal diarrhoea, urgency, and faecal incontinence. These symptoms lead to poor quality of life and increased health-care costs. Diagnosis relies on histological examination of multiple biopsy samples from the colonic mucosa, which often show no or only few abnormalities on endoscopy. Two major histological subtypes can be distinguished-collagenous colitis and lymphocytic colitis-but incomplete and variant forms with fewer characteristic features have been reported. Here we summarise the latest evidence on epidemiology, pathogenesis, and risk factors, and discuss established and novel therapeutic options for clinical remission. Finally, we propose an updated treatment algorithm. Further prospective studies are needed to clarify the natural history of microscopic colitis, supported by validated criteria for the assessment of disease activity.
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