Galectin 4 is a biomarker for early recurrence and death after surgical resection for pancreatic ductal adenocarcinoma

Background: Galectins are a group of carbohydrate-binding proteins that are involved in neoplastic development and progression. In a previous mass spectrometry-based study, we identified galectin 4 as a down-regulated protein in short-term survivors of pancreatic cancer. This study was performed to validate the prognostic value of galectin 4 in a larger cohort of pancreatic cancer patients undergoing surgical resection.

Methods: Galectin 4 expression was evaluated by tissue microarrays and immunohistochemistry in 140 patients with surgically resected pancreatic cancer. Kaplan-Meier and Cox proportional hazards modeling were used to explore the association between galectin 4 and survival.

Results: Galectin 4 staining expression was positive in 111 cases (79.3%). The expression of galectin 4 was significantly associated with tumor size (p?=?.008) and differentiation (p?=?.001). Galectin 4 expression was significantly correlated with disease recurrence within 1 year of surgery (adjusted HR 0.485, p?=?.027). There was also a significant association between galectin 4 and overall survival at 1 year (adjusted HR 0.482, p?=?.047) and at 3 years (adjusted HR 0.550, p?=?.025).

Conclusion: Galectin 4 expression is a novel biomarker for early recurrence and mortality after surgical resection for pancreatic cancer.     

Multidonor FMT capsules improve symptoms and decrease fecal calprotectin in ulcerative colitis patients while treated – an open-label pilot study

Background: Growing evidence indicates that gut dysbiosis is a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) appears to be promising in inducing UC remission, but there are no reports regarding administration using capsules.

Methods: Seven patients with active UC, aged 27–50 years, were treated with 25 multidonor FMT capsules daily for 50 days as a supplement to their standard treatment in an open-label pilot study. The primary objective was to follow symptoms through the Simple Clinical Colitis Activity Index (SCCAI). Secondary objectives were to follow changes in fecal calprotectin and microbial diversity through fecal samples and quality of life through the Inflammatory Bowel Disease Questionnaire (IBDQ). Participants were followed through regular visits for six months.

Results: From a median of 6 at baseline, the SCCAI of all participants decreased, with median decreases of 5 (p?=?.001) and 6 (p?=?.001) after 4 and 8 weeks, respectively. Three of the seven patients had flare-up/relapse of symptoms after the active treatment period. The median F-calprotectin of ≥1800?mg/kg at baseline decreased significantly during the treatment period, but increased again in the follow-up period. The median IBDQ improved at all visits compared to baseline. The fecal microbiota α-diversity did not increase in the study period compared to baseline. All participants completed the treatment and no serious adverse events were reported.

Conclusion: Fifty days of daily multidonor FMT capsules temporarily improved symptoms and health-related life quality and decreased F-calprotectin in patients with active UC.     

Long-term evolution of direct healthcare costs for inflammatory bowel diseases: a population-based study (2006–2015)

Introduction: We explored the long-term evolution of direct healthcare costs for inflammatory bowel diseases (IBD) using a population-level database in a country with an escalating burden of IBD.

Methods: We searched the database of the Korean National Health Insurance Claims, which covers more than 97% of the South Korean population. An IBD diagnosis was defined as the combination of a billing code for Crohn’s disease (CD: K50.xx) or ulcerative colitis (UC: K51.xx) and at least one claim for IBD-specific drugs. Between 2006 and 2015, a total of 59,447 patients (CD: 17,677; UC: 41,770) were included.

Results: The total and mean cost per capita increased significantly over time. In the last year of the study (2015), the cost for anti-tumor necrosis factor (TNF) therapy accounted for 68.8% (CD) and 48.8% (UC) of the total cost. Age at diagnosis (<20 years vs. ≥30 years) and anti-TNF use were independent predictors of increased total IBD cost. Anti-TNF therapy was the strongest predictor of high-cost outliers (designated as the top 20 percentile of the total costs) for IBD (OR: 160.4; 95% CI: 89.0–289.2). The mean cost among patients with newly diagnosed CD increased significantly over the 8-year follow-up period (p?=?.03), while costs associated with UC remained stable. Only medication costs increased significantly during the follow-up period for CD.

Conclusions: Over the past 10 years, the increased usage of anti-TNF agents has been the key driver of IBD-related healthcare costs. Long-term cost-cutting strategies for patients with CD are warranted.     

Does postoperative adjuvant transarterial chemoembolization benefit for all patients with hepatocellular carcinoma combined with microvascular invasion: a meta-analysis

Purpose: To evaluate the clinical efficacy of postoperative adjuvant transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) patients combined with microvascular invasion (MVI).

Patients and methods: Eligible studies were searched by PubMed, MedLine, Embase, the Cochrane Library, Web of Science, from 1st January 2000 to 31st December 2018, comparing the overall survival (OS) rates and disease-free survival (DFS) rates between postoperative adjuvant TACE and operation only for HCC patients with MVI. Hazard ratio (HR) with 95% confidence interval (CI) was used to determine the effect size.

Results: Eight studies were enrolled in this meta-analysis, including 774 patients in the postoperative adjuvant TACE group and 856 patients in the operation only group. The pooled HR for the OS and DFS rates were significantly different between the postoperative adjuvant TACE group and the operation only group (HR 0.57, 95%CI 0.48?～?0.68, p?<?.00001; HR 0.66, 95%CI 0.58?～?0.74, p?<?.00001; respectively). However, in the subgroup analysis stratified by proportion of multiple-nodules, no significant differences were observed in the pooled HR for the OS/DFS rates between the postoperative adjuvant TACE group and the operation only group (HR 0.83, 95%CI 0.60?～?1.13, p?=?.23; HR 0.76, 95%CI 0.41?～?1.40, p?=?.37; respectively).

Conclusions: Postoperative adjuvant TACE will benefit patients with HCC and MVI, but not for multiple-HCC with MVI. However, more high-quality studies are warranted to validate the conclusion.     

Biochemical response to ursodeoxycholic acid among PBC patients: a nationwide population-based study

Objective: To assess the proportion of PBC patients with a biochemical response to ursodeoxycholic acid (UDCA) in a population-based cohort and the association of biochemical response with outcomes.

Methods: All patients diagnosed with PBC in Iceland from 1991–2015 were identified. Patients taking UDCA for an adequate period of time were analyzed for treatment response according to the Barcelona, Paris I, Paris II and Toronto criteria and outcomes.

Results: Overall 182 females and 40 males were diagnosed with PBC and 135 patients were treated with UDCA. Overall 99 (73%) patients had adequate data on UDCA treatment and results of liver tests to assess biochemical response according to the Barcelona criteria, 95 (70%) according to the Toronto criterion and 85 (63%) according to the Paris I and II criteria. In all 74% (n?=?63), 67% (n?=?64), 54% (n?=?53) and 46% (n?=?39) responded to treatment according to the Paris I, Toronto, Barcelona and Paris II criteria. Among nonresponders according to the Paris I, Toronto, Paris II and Barcelona criteria, 50%, 39%, 33% and 30% developed cirrhosis versus 10%, 6%, 5% and 11% of responders, HR 5.36 (p?=?.002), 6.61 (p?=?.002), 10.94 (p?=?.003) and 2.21(p?=?.11), respectively. Age-adjusted mortality was significantly lower among responders according to the Paris I and Paris II criteria, HR 0.33 (p?=?.02) and 0.31 (p?=?.02), respectively.

Conclusion: Development of cirrhosis and higher mortality was significantly associated with a lack of biochemical response to UDCA. Frequent development of cirrhosis and increased mortality in nonresponders underlines the need for a more effective therapy than UDCA for this sizeable subgroup of patients.     

Evaluation of fatigue in inflammatory bowel disease - a useful tool in daily practice

Background: Fatigue is a common symptom reported in inflammatory bowel disease (IBD) patients. It can be severe and modify the self-perception of disease.

Objective: To evaluate the contribution of clinical and demographic factors to the level of fatigue in IBD patients.

Methods: Patients consecutively observed in an outpatient IBD clinic during a 9-month period were studied. Demographic and clinical data were collected. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). A FACIT-F score <30 was considered as severe fatigue.

Results: One hundred and five patients were evaluated. Of them, 57.1% had Crohn´s Disease (CD) and 42.9% had Ulcerative Colitis. Also 85.0% and 77.8% were in clinical remission, respectively. The mean FACIT-F score was 39.63?±?9.67. Severe fatigue was observed in 17.1% of patients. Female gender and active CD were significantly associated with a severe level of fatigue (p?=?.05 and p?=?.04). There was no significant correlation between the level of fatigue (severe vs. non-severe) and type of IBD, hemoglobin, C-reactive protein, ferritin levels or previous surgeries. Patients under biological therapy had a significantly higher level of fatigue and a higher rate of previous hospitalizations (p?=?.02).

Conclusions: Fatigue level is a simple and useful tool to evaluate the disease’s impact in patients’ life, and it should, therefore, be included in clinical practice. Biological therapy was associated to higher levels of fatigue. Future studies should evaluate the impact of therapy on the level of fatigue.     

Indirect comparison of vedolizumab and adalimumab for biologic-naive patients with ulcerative colitis

Aim: Indirect comparison of efficacy and safety of vedolizumab with adalimumab in biologic-naïve patients with moderate to severe ulcerative colitis (UC).

Methods: Vedolizumab is a gut-selective medication for moderate to severe UC. Since no comparative trials are available for direct comparison of vedolizumab vs adalimumab in UC, a systematic review of literature databases was conducted to identify randomized, placebo-controlled trials of the two drugs in patients with moderate to severe UC after failure of conventional treatment. Studies were screened for eligibility by two reviewers based on predefined inclusion criteria. Bucher’s adjusted indirect comparison was used to compare vedolizumab and adalimumab indirectly through placebo as common comparator.

Results: One vedolizumab study (GEMINI 1) and three adalimumab studies (ULTRA 1, ULTRA 2 and M10-447) met the eligibility criteria. Baseline characteristics of the included populations were similar in biologic-naïve UC patients across study arms. Although no statistically significant differences between treatments were found for induction efficacy endpoints, there was a trend toward a benefit of vedolizumab over adalimumab. There were also no significant differences between treatments for any maintenance efficacy endpoints, with no clear trend favoring either agent. Vedolizumab exhibited statistically superior maintenance safety compared with adalimumab, with significant reductions in risks of adverse events (relative risk 0.67 [95% confidence interval 0.57–0.80]; p?<?.0001), serious adverse events (0.20 [0.09–0.42]; p?<?.0001) and adverse events leading to discontinuation (0.14 [0.05–0.43]; p?=?.0006).

Conclusion: This analysis indicates that vedolizumab has comparable efficacy to adalimumab with improved safety in biologic-naïve patients with moderate to severe UC.     

Surgery combined with post-operative trancatheter arterial chemoembolization improves survival of intermediate hepatocellular carcinoma

Aim: To investigate the efficacy of surgery combined with post-operative trancatheter arterial chemoembolization (TACE) for intermediate hepatocellular carcinoma (HCC).

Methods: A total of 102 patients were divided into two groups: Radical liver resection only (LR group, 52 patients) and radical liver resection combined with post-operative TACE (combined group, 50 patients). Survival analysis was performed using the Kaplan–Meier method. Univariate and multivariate analysis were performed using Cox proportional analysis to detect prognostic factors of survival outcomes.

Results: The 1-, 3- and 5-year survival rate in the LR group were significantly lower compared with those in combined group (p?=?.019). The 1-, 3- and 5-year progression-free survival rate in the LR group were also lower than those in the combined group (p?=?.048). Multivariate analysis detected that tumor number (multiple vs single), tumor distribution (both lobes vs semi-liver), treatment strategy (surgery?+?TACE vs surgery) were independent factors for OS (HR values were 2.307, 3.155 and 0.526, respectively) and PFS (HR values were 1.938, 3.425 and 0.633, respectively; p?<?.05).

Conclusion: In conclusion, surgery combined with post-operative TACE may improve survival outcomes for patients with intermediate HCC. Tumor number, tumor distribution and treatment strategy (surgery?+?TACE) were significantly associated with the prognosis of patients with intermediate HCC.     

Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn’s disease patients

Objectives: Anti-TNF agents are effective to treat perianal Crohn’s disease (CD). Evidence suggests that Crohn’s disease patients with perianal fistulas need higher infliximab (IFX) serum concentrations compared to patients without perianal CD to achieve complete disease control. Our aim was to compare anti-TNF serum concentrations between patients with actively draining and closed perianal fistulas.

Methods: A retrospective survey was performed in CD patients with perianal disease treated with IFX or adalimumab (ADL). Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging.

Results: We identified 66?CD patients with a history of perianal fistulas treated with IFX (n?=?47) and ADL (n?=?19). Median IFX serum trough concentrations ([interquartile range]) were higher in patients with closed fistulas (n?=?32) compared to patients with actively draining fistulas (n?=?15): 6.0?µg/ml [5.4–6.9] versus 2.3?µg/ml [1.1–4.0], respectively (p?<?.001)). A similar difference was seen in patients treated with ADL: median serum concentrations were 7.4?µg/ml [6.5–10.8] in 13 patients with closed fistulas versus 4.8?µg/ml [1.7–6.2] in 6 patients with producing fistulas (p?=?.003). Serum concentrations of ≥5.0?µg/ml for IFX (area under the curve of 0.92; 95% CI: 0.82–1.00)) and 5.9?µg/ml for ADL (area under the curve of 0.89; 95% CI 0.71–1.00) were associated with fistula closure.

Conclusion: Cut-off serum concentrations ≥5.0?µg/ml for IFX and ≥5.9?µg/ml for ADL were associated with perianal fistula closure. Hence, patients with producing perianal fistulas may benefit from anti-TNF dose intensification to achieve fistula closure.     

Efficacy of preoperative colonoscopic tattooing with indocyanine green on lymph node harvest and factors associated with inadequate lymph node harvest in colorectal cancer

Objective: Adequate lymph node harvest (LNH) in colorectal cancer is closely related to survival. This study aimed to evaluate the effect of preoperative colonoscopic tattooing (PCT) with indocyanine green (ICG) on adequate LNH in colorectal cancer.

Materials and methods: A total of 1079 patients who underwent surgical resection for colorectal cancer were divided into two groups: a tattooing group and a non-tattooing group. The patients were retrospectively analyzed for the number and adequacy of LNH according to tumor locations and stages. Univariate and multivariate analysis for factors associated with adequate LNH were done.

Results: There was no significant difference between the two groups in the number and adequacy of LNH according to tumor locations. However, T1 colorectal cancer in the tattooing group had significantly higher adequate LNH (91.6% vs 82.1%, OR 2.370, p?=?.048) and T1 and N0 rectal cancer in the tattooing group also had higher adequate LNH although there was no statistical significance (100% vs 82.4%, OR 12.088, p?=?.095; 96.9% vs 84.8%, OR 5.570, p?=?.099) when compared to the non-tattooing group. Male sex and T1 stage were significantly associated with inadequate LNH in multivariate analysis (OR 0.556 (95% CI 0.340–0.909), p?=?.019; OR 0.555 (95% CI 0.339–0.910), p?=?.019, respectively).

Conclusion: PCT with ICG did not improve adequate LNH in colorectal cancer but effectively improved adequate LNH in early colorectal cancer. Male sex and early cancer were risk factors for inadequate LNH in colorectal cancer, so PCT is needed for adequate LNH in these patients.     

Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study

Background: Seronegative celiac disease (CD) poses a diagnostic challenge.

Aims: Characterize and identify differences between seronegative and seropositive CD.

Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980–2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression.

Results: Of 315?CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p?=?.016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p???.001) and Marsh I lesion (34.6% vs. 3.7%, p???.001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD.

Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.     

Urban–rural environmental exposure during childhood and subsequent risk of inflammatory bowel disease: a meta-analysis

Background: The relationship between living conditions in urban and rural areas during childhood and subsequent inflammatory bowel disease (IBD) remains controversial.

Aim: To explore the association between environmental exposures early in life and the subsequent risk of IBD.

Methods: Literature searches were conducted in the following databases: PubMed, EMBASE, and Conference Proceedings Citation Index. Studies were analyzed separately using rate ratios (RRs) or odds ratios (ORs) with 95% confidence intervals.

Results: The search strategy identified 15 studies. Of these, 9 studies explored the association between urban exposure during childhood and ulcerative colitis (UC), and 12 and 4 studies explored this relationship with Crohn’s disease (CD) and IBD, respectively. A meta-analysis showed that the pooled ORs estimated for the case–control studies of UC, CD, and IBD were 1.16 (0.83, 1.61), 1.45 (1.45, 1.85), and 1.34 (1.11, 1.62), respectively. The pooled RR estimated for the cohort studies of CD and IBD was 1.48 (1.17, 1.87). The stratified analysis and meta-regression showed significant relationships between CD and living conditions in case–control studies published during 2010–2017 and in non-European countries (P < 0.05).

Conclusions: Living conditions during childhood are positively associated with the subsequent development of IBD. Urban living environment is more common among those with CD than UC.     

Real world data on effectiveness,safety and therapeutic drug monitoring of vedolizumab in patients with inflammatory bowel disease. A single center cohort

Background and aims: The efficacy of vedolizumab (VDZ) has been demonstrated in clinical trials. The aim of this report is to evaluate the long-term effectiveness and safety of VDZ in a real-world cohort and to explore possible associations between concentration measurements of VDZ and treatment effectiveness.

Methods: This is a prospective clinical follow-up including all adult patients with ulcerative colitis (UC) and Crohn’s disease (CD) treated with VDZ from October 2014 until September 2017 at a single center in Norway. The patients were followed for at least 14 weeks or until termination of treatment. Clinical and biochemical activity were obtained at every infusion throughout follow-up. Plasma measurements of VDZ (p-VDZ) were performed before every infusion during maintenance therapy.

Results: In total, 71 patients received VDZ. Improvement of CRP and hemoglobin was observed in CD but not in UC, whereas Partial Mayo Score improved in UC while no change in Harvey Bradshaw Index was revealed in CD. Furthermore, CRP at baseline was negatively correlated with p-VDZ at week 14 in CD but not in UC patients.

Conclusion: Improvement of biochemical markers of inflammation was observed in CD while clinical activity scores improved in UC patients. For CD, baseline CRP was correlated with lower concentrations of p-VDZ at week 14.     

Low fecal calprotectin predicts clinical remission in Crohn's disease patients: the simple answer to a challenging question

Background and aim: Fecal calprotectin (FC) is a noninvasive marker of intestinal inflammation. Predicting relapses in Crohn’s disease (CD) patients can allow earlier changes in therapy. The aim of this study was to evaluate the role of FC in predicting relapse in CD patients in clinical remission within six months follow-up.

Methods: Patients with CD who were in clinical remission at least ≥3 months were included in this study. The first FC sample during the remission period was evaluated and was used as the baseline value. Relapse was defined as an unexpected escalation in therapy, hospitalization or need for surgery for active CD. The accuracy and optimal cutoff FC values for predicting clinical relapse at six months were assessed by the area under the ROC curve (AUC).

Results: One hundred and forty-four patients were evaluated, with mean age of 38.4 years. Of these, 13 (9%) had a relapse during the follow-up period. The mean FC value was significantly lower for non-relapsers (203.2?μg/g) than for relapsers (871.3?μg/g), p?<?.001. The AUC for predicting relapse by using FC values was 0.924. The optimal cutoff FC value to predict relapse was 327?μg/g; with values of sensitivity, specificity, negative predictive value and positive predictive value were 92.3%, 82.4%, 99.1% and 34.3%, respectively.

Conclusions: FC is more useful in predicting remission maintenance than relapse in patients with CD in clinical remission. Values of FC ≤327?μg/g can exclude relapse at least at six months follow-up period.     

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

Acute pancreatitis in elderly patients: a single-center retrospective evaluation of clinical outcomes

Introduction: Acute pancreatitis (AP) incidence in the elderly population has increased in the last years. However, the role of age as influencing factor on the AP clinical course is still debated.

Methods: We reviewed clinical records of consecutive patients admitted with diagnosis of AP. Patients were divided in elderly (≥65 years) and non-elderly (<65 years). Primary endpoint was comparison of overall mortality. Secondary endpoint included ICU admission, in-hospital length of stay (LOS) and surgical procedures.

Results: We enrolled 352 elderly and 532 non-elderly patients. A higher mortality rate (7.4% vs 1.9%; p?<?.001), ICU admission rate (18.9% vs 6.3%; p?<?.001) and prolonged length of hospital stay (9 (6–14) vs 7 (5–11.7) days; p?=?.01) were registered in the ≥65 years group. Multivariate analysis identified age (OR: 3.5; 95% CI:1.645–7.555; p?=?.001), a higher Ranson score at admission (OR: 5.52; 95% CI:1.11–27.41; p<.001) and necrotic pancreatitis (OR: 8.6; 95% CI:2.46–30.27; p?=?.001) as independent predictors of mortality. Conversely age and necrotic pancreatitis were independent risk factors for higher LOS and ICU admission.

Conclusions: Patients with AP and age ≥65 years have a higher mortality, ICU admission and prolonged LOS. Early recognition and prompt treatment are key elements to improve outcomes in this population.     

Impact of sclerosing dacryoadenitis/sialadenitis on relapse during steroid therapy in patients with type 1 autoimmune pancreatitis

Objectives: Steroids are the first-line drugs for induction of remission in patients with type 1 autoimmune pancreatitis (AIP), and the usefulness of steroid maintenance therapy to prevent relapse has recently been reported. However, even during steroid therapy, a relatively large percentage of patients relapse and the predictive factors for relapse have not yet been elucidated. The aim of this study was to clarify the predictive factors for relapse of AIP patients during steroid therapy.

Materials and methods: The medical records of 76 patients with type 1 AIP with continued steroid therapy after induction of remission were analyzed retrospectively. The relapse rate during steroid therapy was evaluated, and the risk factors for relapse were investigated by univariate and multivariate analysis of clinical factors.

Results: Relapse occurred in 28.9% (22/76) of the patients. The cumulative relapse rates were 10.5% at 1 year, 25.0% at 3 years, 34.9% at 5 years, and 43.0% at 10 years. In multivariate analysis, presence of sclerosing dacryoadenitis/sialadenitis at the time of initial diagnosis of AIP was an independent risk factor for relapse (HR 3.475, p?=?.009). The cumulative relapse rates of patients with sclerosing dacryoadenitis/sialadenitis reached 21.4% at 1 year, 56.0% at 3 years, and 78.0% at 5 years.

Conclusions: Sclerosing dacryoadenitis/sialadenitis was a predictive factor for relapse in type 1 AIP during steroid therapy; in such cases, strict follow-up is necessary with relapse in mind.     

Roseburia intestinalis inhibits oncostatin M and maintains tight junction integrity in a murine model of acute experimental colitis

Objective: Levels of oncostatin M (OSM) and the composition of gut microbiota predict responses to anti-TNF agents used for IBD therapy. Here, the aim was to investigate the effects of Roseburia intestinalis, a gut microbiota, on OSM and on intestinal barrier in colitis.

Methods: In the murine model of 3% dextran sulfate sodium (DSS)-induced colitis, we tested disease activity index (DAI), colon length, histological score and expression of tight junction (TJ) proteins (ZO-1, occludin and claudin-1), OSM, TNF-α and TLR5. In addition, a cellular model was used to examine the role of R. intestinalis during secretion of OSM by lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) and TLR5 knockout (TLR5 KO) mice. Furthermore, we evaluated the impact of OSM on expressions of TJ proteins by Caco-2 cells.

Results: R. intestinalis in DSS-induced colitis decreased DAI score (p?<?.001), colon length shortening (6.46?±?0.36?cm vs 5.65 ± 0.47 cm, p?=?.022), histological score (2.667?±?1.15 vs 5.33 ± 1.14, p?=?.018) and increased expression of TJ proteins (p?<?.05). In addition, R. intestinalis reduced expression of OSM (p?<?.05) and TNF-α (p?<?.05), while increasing expression of TLR5 (p?<?.05). Furthermore, R. intestinalis reduced secretion of OSM (p?<?.05) by LPS-induced BMDMs isolated from WT and TLR5 KO mice. Moreover, OSM downregulated expression of TJ proteins (p?<?.05) by Caco-2 cells in a concentration-dependent manner.

Conclusions: These results indicate that R. intestinalis attenuates inflammation in IBD by decreasing secretion of OSM and by promoting intestinal barrier function. Taken together, the data provide insight into the role of the gut microbiota in patients with IBD who are resistant to anti-TNF therapy.