ResearchPad - inflammatory-bowel-disease https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Epidemiology, mortality and prevalence of colorectal cancer in ulcerative colitis patients between 2010-2016 in Hungary – a population-based study]]> https://www.researchpad.co/article/elastic_article_14610 The incidence and prevalence of ulcerative colitis (UC) varies geographically. The risk of colorectal cancer (CRC) and possibly some other malignancies is increased among patients with UC. It is still debated if patients with UC are at a greater risk of dying compared with the general population. Our aim was to describe the epidemiology and mortality of the Hungarian UC population from 2010 to 2016 and to analyze the associated malignancies with a special focus on CRC.MethodsThis is an observational, descriptive, epidemiological study based on the National Health Insurance Fund social security databases from 2010 to 2016. All adult patients who had at least two events in outpatient care or at least two medication prescriptions, or at least one inpatient event with UC diagnosis were analyzed. Malignancies and CRC were defined using ICD-10 codes. We also evaluated the survival of patients suffering from UC compared with the general population using a 3 to 1 matched random sample (age, gender, geography) from the full population of Hungary.ResultsWe found the annual prevalence of UC 0.24–0.34%. The incidence in 2015 was 21.7/100 000 inhabitants. Annual mortality rate was 0.019–0.023%. In this subpopulation, CRC was the most common cancer, followed by non-melanotic skin and prostate cancer. 8.5% of the UC incident subpopulation was diagnosed with CRC. 470 (33%) of the CRC patients died during the course of the study (25% of all deaths were due to CRC), the median survival was 9.6 years. UC patients had significantly worse survival than their matched controls (HR = 1.65, 95% CI: 1.56–1.75).SummaryThis is the first population-based study from Eastern Europe to estimate the different malignancies and mortality data amongst Hungarian ulcerative colitis patients. Our results revealed a significantly worse survival of patients suffering from UC compared to the general population. ]]> <![CDATA[Harnessing helminth-driven immunoregulation in the search for novel therapeutic modalities]]> https://www.researchpad.co/article/elastic_article_14550 Parasitic helminths have coevolved with humans over millennia, intricately refining and developing an array of mechanisms to suppress or skew the host’s immune system, thereby promoting their long-term survival. Some helminths, such as hookworms, cause little to no overt pathology when present in modest numbers and may even confer benefits to their human host. To exploit this evolutionary phenomenon, clinical trials of human helminth infection have been established and assessed for safety and efficacy for a range of immune dysfunction diseases and have yielded mixed outcomes. Studies of live helminth therapy in mice and larger animals have convincingly shown that helminths and their excretory/secretory products possess anti-inflammatory drug-like properties and represent an untapped pharmacopeia. These anti-inflammatory moieties include extracellular vesicles, proteins, glycans, post-translational modifications, and various metabolites. Although the concept of helminth-inspired therapies holds promise, it also presents a challenge to the drug development community, which is generally unfamiliar with foreign biologics that do not behave like antibodies. Identification and characterization of helminth molecules and vesicles and the molecular pathways they target in the host present a unique opportunity to develop tailored drugs inspired by nature that are efficacious, safe, and have minimal immunogenicity. Even so, much work remains to mine and assess this out-of-the-box therapeutic modality. Industry-based organizations need to consider long-haul investments aimed at unraveling and exploiting unique and differentiated mechanisms of action as opposed to toe-dipping entries with an eye on rapid and profitable turnarounds.

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<![CDATA[Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study]]> https://www.researchpad.co/article/elastic_article_10120 COVID-19 has rapidly become a major health emergency worldwide. Patients with IBD are at increased risk of infection, especially when they have active disease and are taking immunosuppressive therapy. The characteristics and outcomes of COVID-19 in patients with IBD remain unclear.DesignThis Italian prospective observational cohort study enrolled consecutive patients with an established IBD diagnosis and confirmed COVID-19. Data regarding age, sex, IBD (type, treatments and clinical activity), other comorbidities (Charlson Comorbidity Index (CCI)), signs and symptoms of COVID-19 and therapies were compared with COVID-19 outcomes (pneumonia, hospitalisation, respiratory therapy and death).ResultsBetween 11 and 29 March 2020, 79 patients with IBD with COVID-19 were enrolled at 24 IBD referral units. Thirty-six patients had COVID-19-related pneumonia (46%), 22 (28%) were hospitalised, 7 (9%) required non-mechanical ventilation, 9 (11%) required continuous positive airway pressure therapy, 2 (3%) had endotracheal intubation and 6 (8%) died. Four patients (6%) were diagnosed with COVID-19 while they were being hospitalised for a severe flare of IBD. Age over 65 years (p=0.03), UC diagnosis (p=0.03), IBD activity (p=0.003) and a CCI score >1 (p=0.04) were significantly associated with COVID-19 pneumonia, whereas concomitant IBD treatments were not. Age over 65 years (p=0.002), active IBD (p=0.02) and higher CCI score were significantly associated with COVID-19-related death.ConclusionsActive IBD, old age and comorbidities were associated with a negative COVID-19 outcome, whereas IBD treatments were not. Preventing acute IBD flares may avoid fatal COVID-19 in patients with IBD. Further research is needed. ]]> <![CDATA[Clinical role, optimal timing and frequency of serum infliximab and anti-infliximab antibody level measurements in patients with inflammatory bowel disease]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc1f4

Background

Serum infliximab (IFX) and antibody-to-infliximab (ATI) levels are objective parameters, that may have a great role in the therapeutic decisions during maintenance biological therapy.

Research design and methods

48 inflammatory bowel disease patients receiving maintenance IFX therapy were prospectively enrolled and divided into adequate (complete remission N = 20) and inadequate responder (partial response, loss of response, dose escalation; N = 28) groups. Blood samples were collected just before (trough level, TL) and two (W2aTL) and six weeks (W6aTL) after the administration of IFX.

Results

Single measurement of ATI titer was insufficient for predicting therapeutic response due to transient expression of ATI, however, using the three points’ measurements, significant difference has been detected between the adequate and inadequate responder group (5.0% vs 35.7%; p = 0.016). The mean value of TL was significantly higher in the adequate responder group (3.11±1.64 vs.1.19±1.11; p<0.001) without further difference on the second and sixth week. Sensitivity and specificity for predicting the therapeutic response were 85.0% and 71.4% based on the cut-off value of TL 2.0 μg/ml.

Conclusion

Simultaneous measurement of serum IFX level prior to administration of regular IFX infusion and ATI titers significantly increase the diagnostic accuracy for the therapeutic decision in patients uncertainly responding to the therapy. The measurement of W2aTL and W6aTL levels did not result in further improvement in the prediction of therapeutic response.

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<![CDATA[Outcomes of inflammatory bowel disease in patients with eosinophil-predominant colonic inflammation]]> https://www.researchpad.co/article/N647728ff-a24d-42cc-8a35-fa461dfc8f4a

Background

Inflammatory bowel disease (IBD) is characterised by acute intestinal mucosal inflammation with chronic inflammatory features. Various degrees of mucosal eosinophilia are present along with the typical acute (neutrophil-predominant) inflammation. The effect of intestinal eosinophils on IBD outcomes remains unclear.

Methods

This is a retrospective study. Archived intestinal mucosal biopsy specimens of treatment-naïve IBD patients were examined by two pathologists. The number of eosinophils per high-power field was counted, and the mucosal inflammation was classified according to the eosinophilic inflammatory patterns. Clinical outcomes during the follow-up period were recorded.

Results

142 treatment-naïve IBD patients were included. Mean age was 39 years. 83% of patients had ulcerative colitis, and median follow-up was 3 years. 41% of patients had disease flare(s) and 24% required hospitalisation. Eosinophil count was not associated with risk of disease flare or hospitalisation. Patients with neutrophil-predominant inflammation (>70% neutrophils) had greater risk of disease flare(s): 27(55%) versus 24(36%) and 7(28%) in patients with mixed and eosinophil-predominant inflammation, respectively (p=0.04). Overall, patients with neutrophil-predominant inflammation were more likely to have a disease flare; HR: 2.49, 95% CI (1.0 to 5.6). Hospitalisation rate was higher in patients with neutrophil-predominant inflammation: 17(35%) compared to 17(19%) in patients with eosinophil-rich inflammation (p=0.04). Kaplan–Meier analysis showed higher flare-free survival in patients with eosinophil-predominant inflammation compared to mixed and neutrophil-predominant inflammation.

Conclusion

IBD patients with eosinophil-predominant inflammation phenotype might have reduced risk of disease flares and hospitalisation. Larger prospective studies to assess IBD outcomes in this subpopulation are warranted.

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<![CDATA[Inflammation-Associated Microsatellite Alterations Caused by MSH3 Dysfunction Are Prevalent in Ulcerative Colitis and Increase With Neoplastic Advancement]]> https://www.researchpad.co/article/N9f17b958-898b-4d7b-b831-9ee3ce8e4533

OBJECTIVES:

Inflammation-associated microsatellite alterations (also known as elevated microsatellite alterations at selected tetranucleotide repeats [EMAST]) result from IL-6–induced nuclear-to-cytosolic displacement of the DNA mismatch repair (MMR) protein MSH3, allowing frameshifts of dinucleotide or longer microsatellites within DNA. MSH3 also engages homologous recombination to repair double-strand breaks (DSBs), making MSH3 deficiency contributory to both EMAST and DSBs. EMAST is observed in cancers, but given its genesis by cytokines, it may be present in non-neoplastic inflammatory conditions. We examined ulcerative colitis (UC), a preneoplastic condition from prolonged inflammatory duration.

METHODS:

We assessed 70 UC colons without neoplasia, 5 UC specimens with dysplasia, 14 UC-derived colorectal cancers (CRCs), and 19 early-stage sporadic CRCs for microsatellite instability (MSI) via multiplexed polymerase chain reaction capable of simultaneous detection of MSI-H, MSI-L, and EMAST. We evaluated UC specimens for MSH3 expression via immunohistochemistry.

RESULTS:

UC, UC with dysplasia, and UC-derived CRCs demonstrated dinucleotide or longer microsatellite frameshifts, with UC showing coincident reduction of nuclear MSH3 expression. No UC specimen, with or without neoplasia, demonstrated mononucleotide frameshifts. EMAST frequency was higher in UC-derived CRCs than UC (71.4% vs 31.4%, P = 0.0045) and higher than early-stage sporadic CRCs (66.7% vs 26.3%, P = 0.0426). EMAST frequency was higher with UC duration >8 years compared with ≤8 years (40% vs 16%, P = 0.0459).

DISCUSSION:

Inflammation-associated microsatellite alterations/EMAST are prevalent in UC and signify genomic mutations in the absence of neoplasia. Duration of disease and advancement to neoplasia increases frequency of EMAST. MSH3 dysfunction is a potential contributory pathway toward neoplasia in UC that could be targeted by therapeutic intervention.

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<![CDATA[Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study]]> https://www.researchpad.co/article/N5bd7bce9-81b8-4185-b0d5-7229dd140c8d

Objectives

To better understand the real-world impact of biologic therapy in persons with Crohn’s disease (CD) and ulcerative colitis (UC), we evaluated the effect of marketplace introduction of infliximab on the population rates of hospitalisations and surgeries and public payer drug costs.

Design

We used health administrative data to study adult persons with CD and UC living in Ontario, Canada between 1995 and 2012. We used an interrupted time series design with segmented regression analysis to evaluate the impact of infliximab introduction on the rates of IBD-related hospitalisations, intestinal resections and public payer drug costs over 10 years among patients with CD and 5 years among patients with UC, allowing for a 1-year transition.

Results

Relative to what would have been expected in the absence of infliximab, marketplace introduction of infliximab did not produce significant declines in the rates of CD-related hospitalisations (OR at the last observation quarter 1.06, 95% CI 0.811 to 1.39) or intestinal resections (OR 1.10, 95% CI 0.810 to 1.50), or in the rates of UC-related hospitalisations (OR 1.22, 95% CI 1.07 to 1.39) or colectomies (OR 0.933, 95% CI 0.54 to 1.61). The findings were similar among infliximab users, except that hospitalisation rates declined substantially among UC patients following marketplace introduction of infliximab (OR 0.515, 95% CI 0.342 to 0.777). There was a threefold rise over expected trends in public payer drug cost among patients with CD following infliximab introduction (OR 2.98,95% CI 2.29 to 3.86), suggesting robust market penetration in this group, but no significant change among patients with UC (OR 1.06, 95% CI 0.955 to 1.18).

Conclusions

Marketplace introduction of infliximab has not yielded anticipated reductions in the population rates of IBD-related hospitalisations or intestinal resections, despite robust market penetration among patients with CD. Misguided use of infliximab in CD patients and underuse of infliximab in UC patients may largely explain our study findings.

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<![CDATA[Cytomegalovirus colitis in inflammatory bowel disease and after haematopoietic stem cell transplantation: diagnostic accuracy, predictors, risk factors and disease outcome]]> https://www.researchpad.co/article/5ca10febd5eed0c48456c406

Background

Concurrent cytomegalovirus (CMV) colitis in inflammatory bowel disease (IBD) and after haematopoietic stem cell transplantation (HSCT) is an important clinical entity associated with high rates of morbidity and mortality.

Methods

A retrospective study of 47 patients with IBD and 61 HSCT patients was performed regarding the evaluation of diagnostic accuracy of applied methods, predictors, risk factors for CMV disease manifestation, the proportion of patients with antiviral treatment and disease outcome.

Results

The sensitivity of quantitative PCR (qPCR) with a cut-off value of >250 copies/mg for CMV colitis in patients with IBD and HSCT patients was 79% and 92%, respectively. Predictors for CMV colitis in the IBD cohort were anaemia and the presence of endoscopic ulcers. Glucocorticoids, calcineurin inhibitors and >2 concurrent lines of treatment with immunosuppressive drugs could be identified as risk factors for CMV colitis in the IBD cohort with an OR of 7.1 (95% CI 1.7 to 29.9), 21.3 (95% CI 2.4 to 188.7) and 13.4 (95% CI 3.2 to 56.1), respectively. Predictors and risk factors for CMV gastroenteritis in the HSCT cohort was the presence of endoscopic ulcers (OR 18.6, 95% CI 3.3 to 103.7) and >2 concurrent lines of treatment with immunosuppressive drugs. Antiviral therapy was administered in 70% of patients with IBD and 77% of HSCT patients with CMV disease. 71% of antiviral-treated patients with IBD showed an improvement of their disease activity and 14% underwent colectomy. The mortality rate of HSCT patients was 21% irrespective of their CMV status.

Conclusions

In addition to the implementation of histological methods, qPCR may be performed in patients with suspected high-risk IBD and HSCT patients for CMV colitis. Independent validations of these results in further prospective studies are needed.

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<![CDATA[Body image dissatisfaction in patients with inflammatory bowel disease: a systematic review]]> https://www.researchpad.co/article/5ca10fe9d5eed0c48456c3cc

Background and aims

Little is known about the relationship between inflammatory bowel disease (IBD) and body image. The aim of this systematic review was to summarise the evidence on body image dissatisfaction in patients with IBD across four areas: (1) body image tools, (2) prevalence, (3) factors associated with body image dissatisfaction in IBD and (4) association between IBD and quality of life.

Methods

Two reviewers screened, selected, quality assessed and extracted data from studies in duplicate. EMBASE, MEDLINE, PsycINFO and Cochrane CENTRAL were searched to April 2018. Study design–specific critical appraisal tools were used to assess risk of bias. Narrative analysis was undertaken due to heterogeneity.

Results

Fifty-seven studies using a body image tool were included; 31 for prevalence and 16 and 8 for associated factors and association with quality of life, respectively. Studies reported mainly mean or median scores. Evidence suggested female gender, age, fatigue, disease activity and steroid use were associated with increased body image dissatisfaction, which was also associated with decreased quality of life.

Conclusion

This is the first systematic review on body image in patients with IBD. The evidence suggests that body image dissatisfaction can negatively impact patients, and certain factors are associated with increased body image dissatisfaction. Greater body image dissatisfaction was also associated with poorer quality of life. However, the methodological and reporting quality of studies was in some cases poor with considerable heterogeneity. Future IBD research should incorporate measurement of body image dissatisfaction using validated tools.

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<![CDATA[Pretreatment neutrophil-to-lymphocyte ratio predicts clinical relapse of ulcerative colitis after tacrolimus induction]]> https://www.researchpad.co/article/5c8acc85d5eed0c48498f939

Objectives

Although tacrolimus is useful as an induction therapy in patients with ulcerative colitis (UC), information regarding the long-term outcome after tacrolimus therapy is insufficient. The aim of this study was to evaluate the clinical significance of the pretreatment neutrophil-to-lymphocyte ratio (NLR) as a prognostic factor in patients with UC receiving tacrolimus, to aid treatment selection.

Materials and methods

Patients with moderate-to-severe active UC who received oral tacrolimus induction therapy and subsequent immunomodulatory maintenance therapy at our hospital between 2009 and 2017 and who showed clinical response at week 12, were retrospectively enrolled. Cox regression analysis was conducted to study the prognostic role of the pretreatment NLR. The combined impact of the NLR and other known prognostic factors was investigated with multivariate regression.

Results

Among 45 patients included in this study, 21 patients experienced relapse during a median follow-up period of 16.6 months. Multivariate Cox regression analysis identified the pretreatment NLR (hazard ratio [HR]: 0.82, 95% confidence interval [CI]: 0.72–0.94, P < 0.01) and the use of immunomodulators at the start of tacrolimus treatment (HR: 0.18, 95% CI: 0.05–0.66, P = 0.01) as independent predictors of clinical relapse.

Conclusions

The pretreatment NLR is an independent prognostic factor in patients with UC treated with tacrolimus.

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<![CDATA[Combination of colonoscopy and magnetic resonance enterography is more useful for clinical decision making than colonoscopy alone in patients with complicated Crohn's disease]]> https://www.researchpad.co/article/5c76fe3fd5eed0c484e5b78a

Background/aims

The small bowel is affected in more than half of patients with Crohn’s disease (CD) at the time of diagnosis, and small bowel involvement has a negative impact on the long-term outcome. Many patients reportedly have active lesions in the small intestine even in patients in clinical remission. This study was performed to compare findings of magnetic resonance enterography (MRE) and ileocolonoscopy.

Methods

A single-center retrospective study was conducted in 50 patients (60 imaging series) with CD, for whom MRE was additionally performed during the bowel preparation for subsequent ileocolonoscopy. Endoscopic remission was defined as a Simple Endoscopic Score for CD (SES-CD) of <5. MRE remission was defined as a Magnetic Resonance Index of Activity (MaRIA) score of <50. The time to treatment escalation was assessed by the log-rank test.

Results

Importantly, 7 of 29 patients (24.1%) with endoscopic remission had a MaRIA score of ≥50. Both SES-CD and MaRIA correlated with the need for treatment escalation (P = 0.025, P = 0.009, respectively). MRE predicted the need for treatment escalation even in patients with endoscopic remission. Although no correlation was present between SES-CD and MaRIA score in patients with structuring/penetrating disease, or insufficient ileal insertion (<10cm), a high MaRIA score still correlated with the need for treatment escalation in stricturing or penetrating disease (P = 0.0306).

Conclusions

The MaRIA score predicts the need for treatment escalation even in patients with endoscopic remission, indicating that addition of MRE to conventional ileocolonoscopy alone can be a useful, noninvasive tool for monitoring CD especially in stricturing or penetrating disease.

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<![CDATA[Genetic polymorphisms in tumour necrosis factor receptors (TNFRSF1A/1B) illustrate differential treatment response to TNFα inhibitors in patients with Crohn’s disease]]> https://www.researchpad.co/article/5c8ad952d5eed0c4849a0d2c

Background

Monoclonal antibodies inhibiting tumour necrosis factor-α (TNFα) signalling pathway (anti-TNFα) have been widely used in Crohn’s disease (CD). However, treatment response varies among patients with CD and the clinical outcome is dependent on single nucleotide polymorphisms (SNP) in TNFα receptor superfamily 1A and 1B (TNFRSF1A/1B).

Methods

We tested nine SNPs in TNFα, TNFRSF1A and TNFRSF1B by TaqMan genotyping from peripheral blood samples of 104 subjects. Additionally, we quantified the effects of these SNPs on their corresponding gene expression by RT-PCR and susceptibility to Mycobacterium avium subsp paratuberculosis (MAP) infection by IS900 nested PCR.

Results

Four SNPs (TNFα:rs1800629, TNFRSF1A:rs767455, TNFRSF1B:rs1061624 and TNFRSF1B:rs3397) were over-represented significantly (p<0.05) among patients with CD compared with healthy controls. The TNFRSF1A:rs767455 GG genotype was found in 15/54 patients with CD (28%), while it was only found in 2/50 healthy controls (4%) (OR 9.2, 95% CI 1.98 to 42.83). The TNFRSF1B:rs3397 TT genotype was found in 15/54 patients with CD (28%) compared with (4/50) healthy controls (8%) (OR 4.4, 95% CI 1.36 to 14.14). Furthermore, the SNPs TNFRSF1A:rs767455 and TNFRSF1B:rs3397 were associated with downregulating their corresponding genes significantly (p<0.05). MAP infection was predominantly found among patients with CD in comparison to healthy controls (57% vs 8%, respectively), which was also dependent on the SNPs TNFRSF1A:rs767455 and TNFRSF1B:rs3397. Our SNP haplotype analysis of TNFRSF1A:rs767455 and TNFRSF1B:rs3397 indicates that the G–T haplotype is significantly distributed among patients with CD (46%) and MAP infection susceptibility is also associated with this specific haplotype (31%).

Conclusion

The SNPs TNFRSF1A:rs767455 and TNFRSF1B:rs3397, which are known to affect anti-TNFα clinical outcome in CD, were associated with lower corresponding gene expression and higher MAP infection susceptibility.

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<![CDATA[SLC39A8 missense variant is associated with Crohn's disease but does not have a major impact on gut microbiome composition in healthy subjects]]> https://www.researchpad.co/article/5c5ca2e0d5eed0c48441ec3e

Background

Gene-microbiome interactions are important in aetiology and pathogenesis of inflammatory bowel disease, a chronic inflammatory disorder of the gastrointestinal tract consisting of Crohn’s disease and ulcerative colitis. Scarce studies on gene-microbiome interactions show very little overlap in their results. Therefore, it is of utmost importance that gene-microbiome studies are repeated. We aimed to replicate the association between the SLC39A8 [Thr]391 risk allele and gut microbiome composition in patients with inflammatory bowel disease and healthy controls.

Methods

We collected faecal samples, peripheral blood and extensive phenotype data from 291 patients with inflammatory bowel disease and 476 healthy controls. Carrier status information was obtained from whole exome sequencing data, generated using the Illumina HiSeq. The gut microbiome composition was determined by tag-sequencing the 16S rRNA gene. Associations between carrier status and disease were tested using the Wilcoxon-Mann-Whitney test. Associations between carriers and gut microbiome composition were determined using principal coordinate analyses, variance explained, alpha diversity and additive general linear models in inflammatory bowel disease, healthy controls and all groups combined.

Results

Crohn’s disease patients were more often carriers of the missense variant (21/171, 12.3%) than controls (30/476, 6.3%) (OR = 2.1, P = 0.01). We could not identify associations between carrier status and overall gut microbiome composition and microbial richness in all tested groups after correcting for potential confounding factors. We did identify 37 different operational taxonomical units to be associated with carrier status among the tested groups. Two of these 37 were identified before in the discovery study.

Conclusions

We could confirm the genetic association of the SLC39A8 [Thr]391 risk allele with Crohn’s disease but we could only limited replicate the association in gut microbiome composition. Independent replication of gene-microbiome studies is warranted to identify true biological mechanisms.

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<![CDATA[Occurrence of skin manifestations in patients of the Swiss Inflammatory Bowel Disease Cohort Study]]> https://www.researchpad.co/article/5c64490dd5eed0c484c2f500

Background/Aims

Extraintestinal cutaneous manifestations of IBD represent a severe disease complication and an early and accurate treatment might positively influence the disease course. Using the patient collective of the Swiss IBD Cohort Study (SIBDCS), we analysed epidemiological as well as clinical factors being associated with the onset of pyoderma gangrenosum, erythema nodosum and aphthous ulcers in IBD patients.

Methods

We included 3266 SIBDCs patients, 1840 with Crohn’s disease (CD) and 1426 with ulcerative colitis (UC) or IBD unclassified (IBDU) and analysed the association of cutaneous manifestations with age, age at diagnosis time, type of disease, gender, family history, HLA-allotype, smoking, intestinal disease activity, therapy and other extraintestinal manifestations (EIM).

Results

354 CD patients and 136 UC/IBDU patients presented with skin manifestations at any time during their disease course. In both, CD and UC, female gender and younger age at IBD diagnosis were significantly associated with extraintestinal skin manifestations. For CD, we also detected a positive family history as associated factor. As an indicator of more intensive intestinal disease activity, patients with cutaneous manifestations of IBD needed more frequently therapy with antibiotics, steroids, immunomodulators and anti-TNF. Multivariate analysis revealed female gender, younger age at diagnosis and presence of other extraintestinal manifestations as factors being associated with skin EIM in IBD patients and anti-TNF as well as immunomodulatory treatment in CD patients.

Conclusion

Our results suggest that young females with a positive family history of IBD might be at increased risk for the onset of skin manifestations and require a careful screening for such complications.

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<![CDATA[Strain specific maturation of Dendritic cells and production of IL-1β controls CD40-driven colitis]]> https://www.researchpad.co/article/5c605a19d5eed0c4847cc98f

Intestinal integrity is maintained by balanced numbers of CD103+ Dendritic cells (DCs), which generate peripherally induced regulatory T cells (iTregs). We have developed a mouse model where DC-specific constitutive CD40 signals caused a strong reduction of CD103+ DCs in the lamina propria (LP) and intestinal lymph nodes (LN). As a consequence, also iTregs were strongly reduced and transgenic mice on the C57Bl/6-background (B6) developed fatal colitis. Here we describe that transgenic mice on a pure Balb/c-background (B/c) do not show any pathologies, while transgenic C57Bl/6 x Balb/c (F1) mice develop weak colon inflammation, without fatal colitis. This graded pathology correlated with the effects of CD40-signalling on DCs in each background, with striking loss of CD103+ DCs in B6, but reduced in F1 and diminished in B/c background. We further show direct correlation of CD103+ DC-numbers with numbers of iTregs, the frequencies of which behave correspondingly. Striking effects on B6-DCs reflected robust loss of surface MHCII, known to be crucial for iTreg induction. Furthermore, elevated levels of IL-23 together with IL-1, found only in B6 mice, support generation of intestinal IFN-γ+IL-17+ Th17 cells and IFN-γ+ Th1 cells, responsible for onset of disease. Together, this demonstrates a novel aspect of colitis-control, depending on genetic background. Moreover, strain-specific environmental sensing might alter the CD103+ DC/iTreg-axis to tip intestinal homeostatic balance to pathology.

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<![CDATA[Beyond opinion classification: Extracting facts, opinions and experiences from health forums]]> https://www.researchpad.co/article/5c3fa56ad5eed0c484ca4115

Introduction

Surveys indicate that patients, particularly those suffering from chronic conditions, strongly benefit from the information found in social networks and online forums. One challenge in accessing online health information is to differentiate between factual and more subjective information. In this work, we evaluate the feasibility of exploiting lexical, syntactic, semantic, network-based and emotional properties of texts to automatically classify patient-generated contents into three types: “experiences”, “facts” and “opinions”, using machine learning algorithms. In this context, our goal is to develop automatic methods that will make online health information more easily accessible and useful for patients, professionals and researchers.

Material and methods

We work with a set of 3000 posts to online health forums in breast cancer, morbus crohn and different allergies. Each sentence in a post is manually labeled as “experience”, “fact” or “opinion”. Using this data, we train a support vector machine algorithm to perform classification. The results are evaluated in a 10-fold cross validation procedure.

Results

Overall, we find that it is possible to predict the type of information contained in a forum post with a very high accuracy (over 80 percent) using simple text representations such as word embeddings and bags of words. We also analyze more complex features such as those based on the network properties, the polarity of words and the verbal tense of the sentences and show that, when combined with the previous ones, they can boost the results.

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<![CDATA[Risk interval analysis of emergency room visits following colonoscopy in patients with inflammatory bowel disease]]> https://www.researchpad.co/article/5c3fa587d5eed0c484ca5700

Background and aims

Prior studies suggest that colonoscopy may exacerbate inflammatory bowel disease (IBD) symptoms. Thus, our study aimed to determine risk of emergency room (ER) visits associated with colonoscopy among IBD patients and evaluate potential modifiers of this risk.

Methods

The study population included IBD patients in the Multi-Payer Claims Database who were >20 years old and had a colonoscopy from 2007–2010. We used a self-controlled risk interval design and mixed-effects Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI) comparing the incidence of ER visits in the 1–4 weeks following colonoscopy (risk interval) to the incidence of ER visits in the 7–10 weeks after colonoscopy (control interval). We also conducted stratified analyses by patient characteristics, bowel preparation type, and medication.

Results

There were 212,205 IBD patients with at least 1 colonoscopy from 2007–2010, and 3,699 had an ER visit during the risk and/or control interval. The risk of an ER visit was higher in the 4-week risk interval following colonoscopy compared to the control interval (RR = 1.24; 95% CI: 1.17–1.32). The effect was strongest in those <41 years old (RR = 1.60; 95% CI: 1.21–2.11), in women (RR = 1.32; 95% CI: 1.21–1.44), and in those with sodium phosphate bowel preparation (RR = 2.09; 95% CI: 1.02–4.29). Patients using immunomodulators had no increased risk of ER visits (RR = 0.75; 95% CI: 0.35–1.59).

Conclusions

Our results suggest that there is an increased risk of ER visits following colonoscopy among IBD patients, but that immunomodulators and mild bowel preparation agents may mitigate this risk.

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<![CDATA[Quantitative comparison of the neutralizing capacity, immunogenicity and cross-reactivity of anti-TNF-α biologicals and an Infliximab-biosimilar]]> https://www.researchpad.co/article/5c1966ebd5eed0c484b53548

Introduction

TNF-α-neutralizing antibodies, such as infliximab (IFX) and adalimumab (ADA), are effective in the treatment of inflammatory bowel diseases (IBD), but they are expensive and become ineffective when patients develop anti-IFX or anti-ADA antibodies (ATI and ATA, respectively). Second-generation anti-TNF-α antibodies, such as Golimumab, Etanercept, Certolizumab-pegol and IFX biosimilars, may solve these issues.

Aim

To determine the neutralizing capacity of first- and second generation anti-TNF-α antibodies and to determine whether ATI show cross-reactivity with the IFX biosimilar CT-P13 (Inflectra).

Methods

TNF-α neutralization was measured using a quantitative TNF-α sensor assay consisting of HeLa 8D8 cells that express the Green Fluorescence Protein (GFP) under control of a NF-кB response element. All available anti-TNF-α drugs and the IFX biosimilar CT-P13 (Inflectra) were tested for their TNF-α-neutralizing capacity. In addition, patient sera with ATI were tested for their potential to block the activity of IFX, IFX (F)ab2-fragment, biosimilar CT-P13 (Inflectra) and ADA.

Results

TNF-α strongly induced GFP expression in Hela 8D8 cells. Higher concentrations of first-generation anti-TNF-α drugs were required to neutralize TNF-α compared to the second-generation anti-TNF-α drugs. Serum of IBD patients with proven ATI blocked TNF-α-neutralizing properties of IFX biosimilar CT-P13 (Inflectra), whereas such sera did not block the effect of ADA.

Conclusion

The second-generation anti-TNF-α drugs show increased TNF-α-neutralizing potential compared to first-generation variants. ATI show cross-reactivity toward IFX biosimilar CT-P13 (Inflectra), consequently patients with ATI are unlikely to benefit from treatment with this IFX biosimilar.

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<![CDATA[Colonic levels of vasoactive intestinal peptide decrease during infection and exogenous VIP protects epithelial mitochondria against the negative effects of IFNγ and TNFα induced during Citrobacter rodentium infection]]> https://www.researchpad.co/article/5bb3df3140307c54ff8ce8ee

Citrobacter rodentium infection is a model for infection with attaching and effacing pathogens, such as enteropathogenic Escherichia coli. The vasoactive intestinal peptide (VIP) has emerged as an anti-inflammatory agent, documented to inhibit Th1 immune responses and successfully treat animal models of inflammation. VIP is also a mucus secretagogue. Here, we found that colonic levels of VIP decrease during murine C. rodentium infection with a similar time dependency as measurements reflecting mitochondrial function and epithelial integrity. The decrease in VIP appears mainly driven by changes in the cytokine environment, as no changes in VIP levels were detected in infected mice lacking interferon gamma (IFNγ). VIP supplementation alleviated the reduction of activity and levels of mitochondrial respiratory complexes I and IV, mitochondrial phosphorylation capacity, transmembrane potential and ATP generation caused by IFNγ, TNFα and C. rodentium infection, in an in vitro mucosal surface. Similarly, VIP treatment regimens that included the day 5–10 post infection period alleviated decreases in enzyme complexes I and IV, phosphorylation capacity, mitochondrial transmembrane potential and ATP generation as well as increased apoptosis levels during murine infection with C. rodentium. However, VIP treatment failed to alleviate colitis, although there was a tendency to decreased pathogen density in contact with the epithelium and in the spleen. Both in vivo and in vitro, NO generation increased during C. rodentium infection, which was alleviated by VIP. Thus, therapeutic VIP administration to restore the decreased levels during infection had beneficial effects on epithelial cells and their mitochondria, but not on the overall infection outcome.

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<![CDATA[Development of Drug-Induced Inverse Psoriasis in a Patient with Crohnʼs Disease]]> https://www.researchpad.co/article/5b5b2c4a463d7e186098e4a9

Crohn’s disease is difficult to manage and often requires multiple medications. While these drugs vastly improve quality of life, physicians must monitor for adverse events. We report a case of a flare of inverse psoriasis after 15 months of treatment with ustekinumab. This is the third reported case of a flare of drug-induced psoriasis with ustekinumab, and it is the first reported case with an inverse presentation; however, the clinical picture is confounded by concomitant use of hydroxychloroquine. Inverse psoriasis is a rare variant of drug-induced psoriasis of which physicians must be cognizant while treating patients with Crohn’s disease.

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