Soluble CD40 ligand,interleukin (IL)-6, and hemostatic parameters in metabolic syndrome patients with and without overt ischemic heart disease

Background and aimSoluble CD40 ligand (sCD40L, also known as CD154) is a marker for platelet activation which could increase coagulation and inflammation. In this case-control study, we aimed to assess the levels of plasma sCD40L, IL-6, and some hemostatic parameters in patients with metabolic syndrome (MetS) whether or not associated with overt ischemic heart disease (IHD).Subjects and methodsWe measured plasma sCD40L (an index of platelet activation), interleukin (IL)-6 (a proinflammatory cytokine), and some hemostatic parameters (tissue factor [TF], thrombin–antithrombin [TAT] and D-dimer) in 47 patients with metabolic syndrome (21 with and 26 without overt IHD) versus 25 comparable healthy control subjects.ResultsSignificantly higher levels of sCD40L, IL-6, and thrombotic markers (TF, D-dimer and TAT) were found in patients with metabolic syndrome compared to healthy controls. The levels of IL-6 and sCD40 were highest in patients with overt IHD. Strong positive correlations existed between sCD40L and IL-6 (r = 0.67, p = 0.003), TF (r = 0.59, p = 0.008), and platelets count (r = 0.64, p = 0.005).ConclusionHigher levels of sCD40L, IL-6, and thrombotic markers exist in MetS patients, particularly those with IHD. The strong positive correlations between sCD40L and IL-6, TF, and platelets count support a link between the CD40–CD40L system and the underlying inflammatory and hypercoagulable state in MetS patients.     

Serum anti-Müllerian hormone levels are lower in reproductive-age women with Crohn's disease compared to healthy control women

Background and aimCrohn’s disease (CD) decreases fertility both directly, by inducing inflammation in the fallopian tubes and ovaries, and indirectly, through the surgical interventions and tubal adhesions associated with disease treatment. Anti-müllerian hormone (AMH) is a reliable indicator of ovarian reserve in women. We aimed to compare serum AMH levels between reproductive-age women with CD and healthy controls.MethodsSerum AMH levels were measured by ELISA in 35 women with CD and 35 age-matched healthy women controls.ResultsCD patients and controls were similar in terms of age, height, weight and BMI. Mean CD duration was 60 months. CRP, ESR and leukocyte counts were significantly higher in CD patients compared to the controls (p < 0.001, p = 0.004 and p = 0.04, respectively). AMH levels in CD patients (1.02 ± 0.72) were significantly lower compared to the controls (1.89 ± 1.80) (p = 0.009). Serum AMH levels in CD patients with active disease (0.33 ± 0.25) were significantly lower compared to CD patients who were in remission (1.53 ± 0.49) (p = 0.001). Serum AMH levels were similar in CD patients with a disease duration of less than 5 years (17 patients) and CD patients with a disease duration of greater than 5 years (18 patients) (p = 0.8). In CD patients, a negative correlation between CDAI and serum AMH levels was found (r = -0.718, p < 0.001). Serum AMH levels were similar in CD patients who had (6 patients) and had not undergone (29 patients) surgical treatment (p = 0.2).ConclusionSerum AMH levels of reproductive-age women with CD were significantly lower compared to the controls. CDAI and AMH are inversely correlated.     

Platelet activation and thrombus formation relates to the presence of myocardial inflammation in patients with cardiomyopathy

BackgroundPatients with cardiomyopathy show a significantly increased risk for thromboembolic events due to a hypercoagulable state and platelet dysfunction. The pathophysiologic mechanism underlying the increasing platelet activity in patients with cardiomyopathy remains unclear. We performed a clinical study to elucidate the link between myocardial tissue alterations and platelet activation in patients with cardiomyopathy.MethodsA total of 30 patients with suspected cardiomyopathy and 10 healthy control patients were included in our study. Hemodynamic parameters were measured by catheterization and echocardiography. Endomyocardial biopsies were taken to determine myocardial inflammation. Flow cytometry was performed to examine the platelet activation by quantification of p-selectin and thrombospondin expression on platelets.ResultsThe p-selectin (8.46 ± 3.67 AU) and thrombospondin (26.56 ± 23.21 AU) expression was significantly correlated with the amount of CD3+ T cells (p-selectin: r = 0.573, p < 0.05; thrombospondin: r = 0.488, p < 0.05) and the endothelial/interstitial activation (p-selectin: r = 0.521, p < 0.05; thrombospondin: r = 0.39, p < 0.05). This was found to be independent of hemodynamic parameters, age, and gender. The platelet activation of patients (n = 3) with echocardiographically documented ventricular thrombi was significantly increased (p-selectin: 12.57 ± 5.5 AU vs. 8.1 ± 3.2 AU, p < 0.05) and this was associated with elevated myocardial inflammation scores.ConclusionMyocardial inflammation is associated with a significant increase in platelet activation and ventricular thrombus formation independently of the hemodynamic conditions.     

The usefulness of factor XIII levels in Crohn's disease

Background and AimsThe assessment of inflammatory activity in Crohn's disease (CD) is challenging, and no specific laboratory marker is currently available. Several studies have reported decreased serum factor XIII levels in CD patients as a function of disease activity. We aimed to determine whether the factor XIII level could be a marker for the evolution of CD.MethodsIn this prospective, single-centre trial, 129 patients were included and categorised into two groups: functional bowel disorders (FBDs, n = 42) and CD (n = 86). The CD group was divided into two subgroups depending on disease activity, as defined by the Crohn's Disease Activity Index score: active disease (CDa, n = 41) and disease remission (CDb, n = 45). The factor XIII levels were evaluated for each patient. Serial factor XIII levels were evaluated in the patients within the CDa subgroup.ResultsThe factor XIII levels were significantly different between the FBD (117.69%) and CD (101.89%) groups (p = 0.009) but there was no significant difference between the CDa and CDb subgroups (99.04% vs 104.65%, p > 0.05), and the levels did not vary during follow-up for the patients in the CDa subgroup. By multivariate analysis, factor XIII levels did not correlate with the time course of disease evolution, CRP, serum fibrin levels, platelet count, disease distribution within the bowel, or the presence of a fistulising form of CD.ConclusionsOur results confirm that factor XIII levels are decreased in CD patients but cannot be recommended as a marker for the disease activity.     

Does Azathioprine induce endoscopic and histologic healing in pediatric inflammatory bowel disease? A prospective,observational study

BackgroundThe new concept of disease remission for pediatric inflammatory bowel diseases (IBD) implies the achievement of mucosal healing.AimsWe aimed to evaluate endoscopic and histologic healing in children with Ulcerative Colitis (UC) and Crohn’s disease (CD) in clinical remission after 52 weeks of Azathioprine.MethodsFrom December 2012 to July 2015 we prospectively enrolled IBD children starting Azathioprine. Enrolled patients in clinical remission underwent colonoscopy after 52 weeks. Macroscopic assessment was described with Mayo score and the simplified endoscopic score for UC and CD, respectively. For microscopic assessment, an average histology score was used. Data on inflammatory markers and fecal calprotectin were also collected.ResultsFourty-seven patients were included in the analysis. Endoscopic healing was detected in 20/26 (76.9%) UC children and 10/21 (47.6%) CD patients. Median Mayo score and simplified endoscopic score were significantly decreased at week 52 (p < 0.001; p = 0.005). Median average histology score was not significantly different at week 52 in both diseases. Fecal calprotectin was directly correlated with simplified endoscopic score (T0: r = 0.4, p = 0.05; T52: r = 0.5, p = 0.01), but not with Mayo score. No correlation was found between endoscopic and histologic scores.ConclusionsIBD children under Azathioprine reach endoscopic healing, but not histological remission.     

Microscopic colitis patients have increased proportions of Ki67+ proliferating and CD45RO+ active/memory CD8+ and CD4+8+ mucosal T cells

BackgroundCollagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC.MethodsLamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n = 7), LC (n = 6), as well as LC or CC patients in histopathological remission, (LC-HR) (n = 6) and CC-HR (n = 4) and non-inflamed controls (n = 10) were phenotypically characterized by four-color flow cytometry.ResultsThe proportions of CD8⁺ IELs were increased in CC and LC (p < 0.01) compared to controls. Increased proportions of CD45RO⁺CD8⁺ IELs and LPLs were observed in LC and even more in CC patients (p < 0.01). Both CC (p < 0.05) and LC patients had elevated proportions of CD4⁺8⁺ IELs and LPLs compared to controls. The proportions of CD45RO⁺ cells were increased in CD4⁺8⁺ IELs and LPLs (p < 0.05) in CC and LC patients compared to controls. Both CC (p < 0.05) and LC patients had higher proportions of Ki67⁺CD8⁺ IELs and LPLs compared to controls.In contrast, decreased proportions of CD4⁺ LPLs were observed in CC and LC as well as CD4⁺ IELs in LC compared to controls. Increased proportions of Ki67⁺CD4⁺ IELs and LPLs (p < 0.05) were observed in CC and LC patients.CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively.ConclusionLC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67⁺ and CD45RO⁺ CD8⁺ and CD4⁺8⁺ mucosal T cells.     

Increased titers of anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients with reduced H-ficolin levels but normal MASP-2 activity

Background and aimsMannan-binding lectin (MBL) and ficolins are microbial pattern recognition molecules that activate the lectin pathway of complement. We previously reported the association of MBL deficiency with anti-Saccharomyces cerevisiae antibodies (ASCA) in patients with Crohn's disease (CD). However, ASCA are also frequently found in MBL-proficient CD patients. Here we addressed expression/function of ficolins and MBL-associated serine protease-2 (MASP-2) regarding potential association with ASCA.MethodsASCA titers and MBL, ficolin and MASP-2 concentrations were determined by ELISA in the serum of patients with CD, ulcerative colitis (UC), and in healthy controls. MASP-2 activity was determined by measuring complement C4b-fixation. Anti-MBL autoantibodies were detected by ELISA.ResultsIn CD and UC patients, L-ficolin concentrations were significantly higher compared to healthy controls (p < 0.001 and p = 0.029). In contrast, H-ficolin concentrations were slightly reduced in CD and UC compared to healthy controls (p = 0.037 for UC vs. hc). CD patients with high ASCA titers had significantly lower H-ficolin concentrations compared to ASCA-low/negative CD patients (p = 0.009). However, MASP-2 activity was not different in ASCA-negative and ASCA-positive CD patients upon both, ficolin- or MBL-mediated MASP-2 activation. Finally, anti-MBL autoantibodies were not over-represented in MBL-proficient ASCA-positive CD patients.ConclusionsOur results suggest that low expression of H-ficolin may promote elevated ASCA titers in the ASCA-positive subgroup of CD patients. However, unlike MBL deficiency, we found no evidence for low expression of serum ficolins or reduced MASP-2 activity that may predispose to ASCA development.     

Proteinase-activated receptor 2 expression on peripheral blood monocytes and T-cells in patients with rheumatoid arthritis

Aim of the workProteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. The aim of this work was to evaluate the expression of PAR2 on peripheral blood monocytes and T-cells in rheumatoid arthritis (RA) patients and its correlation with disease activity.Patients and methodsForty RA patients and 16 healthy controls were enrolled in this study. Flow cytometry was performed to detect PAR2 expression. Disease activity score (DAS28) was assessed.ResultsPAR2 expression was significantly higher on monocytes in RA patients with active disease compared with patients in remission and healthy controls (75.4 ± 7.68; 56 ± 13.93 and 46.5 ± 9.8 respectively; p < 0.001). It was higher in RA patients in remission compared to healthy control (p = 0.01). No significant difference was found between patients with moderate and high disease activity. It significantly correlated with the erythrocyte sedimentation rate (ESR) and DAS28 (p < 0.001). It was significantly higher in patients with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positivity (p = 0.01, p < 0.001, respectively). It was not significantly associated with C-reactive protein (CRP) positivity and was not significantly different between early and long standing RA patients. PAR2 expression on CD3⁺ T-cells was not significantly different between patients with RA disease activity, patients in remission and healthy controls. Also it was not significantly associated with the ESR, DAS28, anti-CCP, RF and CRP positivity.ConclusionPAR2 expression on monocytes is consistent with a pathogenic role for PAR2 in RA and suggests that PAR2 may have utility as a marker for RA disease activity.     

Total soluble and endogenous secretory receptor for advanced glycation endproducts (RAGE) in IBD

Background and aimsRecruitment and activation of neutrophils, with release of specific proteins such as S100 proteins, is a feature of inflammatory bowel disease (IBD). Soluble forms of the receptor for advanced glycation endproducts (sRAGE), and variants such as endogenous secretory (esRAGE), can act as decoy receptors by binding ligands, including S100A12. The aims of this study were to determine total sRAGE and esRAGE concentrations in patients with IBD and correlate these with C-reactive protein (CRP), endoscopic scores and clinical disease activity scores.MethodsEDTA-plasma was collected from patients undergoing colonoscopy including those with Crohn's disease (CD: n = 125), ulcerative colitis (UC: n = 79) and control patients without endoscopic signs of inflammation (non-IBD: n = 156). Concentrations of sRAGE and esRAGE were determined by enzyme-linked immunosorbent assay and plasma CRP concentrations measured. Standard clinical disease activity and endoscopic severity scores were defined for all subjects.ResultsPlasma sRAGE concentrations were lower in UC (but not CD) than non-IBD subjects (p < 0.01). Whilst sRAGE concentrations correlated negatively with endoscopic activity in UC (p < 0.05), this was not seen in CD. In contrast, esRAGE correlated negatively with disease activity in both UC (p = 0.002) and CD (p = 0.0001). Furthermore, sRAGE and esRAGE concentrations correlated inversely with CRP values (p < 0.0001).ConclusionsAlthough total sRAGE varied with activity in UC, esRAGE concentrations correlated inversely with endoscopic disease activity and CRP levels in both UC and CD. Additional studies are required to further define the significance of sRAGE and esRAGE in IBD.     

Crohn's disease and smoking: Is it ever too late to quit?

BackgroundSmoking increases CD risk. The aim was to determine if smoking cessation at, prior to, or following, CD diagnosis affects medication use, disease phenotypic progression and/or surgery.MethodsData on CD patients with disease for ≥ 5 yrs were collected retrospectively including the Montreal classification, smoking history, CD-related abdominal surgeries, family history, medication use and disease behaviour at diagnosis and the time when the disease behaviour changed.Results1115 patients were included across six sites (mean follow-up—16.6 yrs). More non-smokers were male (p = 0.047) with A1 (p < 0.0001), L4 (p = 0.028) and perianal (p = 0.03) disease. Non-smokers more frequently received anti-TNF agents (p = 0.049). (p = 0.017: OR 2.5 95%CI 1.18–5.16) and those who ceased smoking prior to diagnosis (p = 0.045: OR 2.3 95%CI 1.02–5.21) progressed to complicated (B2/B3) disease as compared to those quitting at diagnosis. Patients with uncomplicated terminal ileal disease at diagnosis more frequently developed B2/B3 disease than isolated colonic CD (p < 0.0001). B2/B3 disease was more frequent with perianal disease (p < 0.0001) and if i.v. steroids (p = 0.004) or immunosuppressants (p < 0.0001) were used. 49.3% (558/1115) of patients required at least one intestinal surgery. More smokers had a 2nd surgical resection than patients who quit at, or before, the 1st resection and non-smokers (p = 0.044: HR = 1.39 95%CI 1.01–1.91). Patients smoking > 3 cigarettes/day had an increased risk of developing B2/B3 disease (p = 0.012: OR 3.8 95%CI 1.27–11.17).ConclusionProgression to B2/B3 disease and surgery is reduced by smoking cessation. All CD patients regardless of when they were diagnosed, or how many surgeries, should be strongly encouraged to cease smoking.     

The relationship between coping,health competence and patient participation among patients with inactive inflammatory bowel disease

BackgroundCoping is an integral part of adjustment for patients with Inflammatory Bowel Disease but has not been well described in the literature. This study explored the relationship between coping, perceived health competence, patient preference for involvement in their treatment, depression and quality of life, particularly among patients with inactive disease (in remission).MethodsSubjects (n = 70) with active and inactive IBD completed questionnaires, including the Inflammatory Bowel Disease Quality of Life Questionnaire, Beck Depression Inventory, Perceived Health Competence Scale and the Coping Inventory for Stressful Situations. The Harvey Bradshaw Index measured disease activity.ResultsPatients with inactive IBD demonstrated significantly more interest in participating in their treatment (p < .05), more perceived health competence (p = .001), less depressive symptoms (p < .001), more task oriented coping (p = .02), and better quality of life than those with active disease. Only Task Oriented Coping was significantly negatively associated with the number of flares among inactive patients (p < .001). Patient preference for participation in treatment was inversely associated with Avoidance (p = .005), Distraction (p = .008), and Social Diversion (p = .008) coping among inactive patients.ConclusionAmong patients in remission, those who expressed a greater interest in treatment participation were also less likely to practice maladaptive coping. Our data demonstrate that a more active coping style may be associated with improved health outcome. Compared to patients with active disease, patients in remission are more likely to employ task oriented coping, demonstrate a higher interest in treatment participation, report greater perceived control of their health, and exhibit less depression symptoms. Our findings may increase awareness of the importance of identifying coping strategies for IBD patients, including those in remission.     

CD14++CD16+ monocyte subset expansion in rheumatoid arthritis patients: Relation to disease activity and interleukin-17

Aim of the workMonocytes are divided into three major subsets based on the expression of the cluster of differentiation CD14 and CD16. The aim of this work was to determine which of the CD16⁺ monocyte subpopulations is expanded in rheumatoid arthritis (RA) and its association with disease activity and interleukin-17 (IL17) levels.Patients and methodsFifty-three RA patients and 20 controls were enrolled in this study. Flow cytometry was performed to detect monocyte subsets and IL17 was measured by ELISA. Disease activity score (DAS28) was assessed.ResultsCD14⁺⁺CD16⁺ monocyte percentage was significantly higher in long standing RA patients compared with early patients and controls (p < 0.01, p < 0.001 respectively). It was significantly higher in patients with RA disease activity and remission compared with the controls (p < 0.001, p < 0.01 respectively). It was not significantly associated with resistance to disease modifying antirheumatic drugs (DMARDs), C-reactive protein, rheumatoid factor and anti-CCP positivity (p > 0.05). It significantly correlated with IL17 (p < 0.002). CD14⁺CD16⁺ monocyte percentage was not significantly correlated with any of the above parameters. IL17 level was significantly higher in patients with early and long standing RA compared to controls (p < 0.01, p < 0.001 respectively). IL17 was higher in RA patients with active disease compared to those in remission and controls (p < 0.01, p < 0.001 respectively). It was higher in RA patients resistant to DMARDs than in responding patients (p < 0.017).ConclusionCD14⁺⁺CD16⁺ monocyte subpopulation was expanded in long standing RA and was correlated with IL17 levels indicating its potential pathogenic importance in RA and may represent an attractive target for future therapeutic interventions.     

Low mannose-binding lectin (MBL) is associated with paediatric inflammatory bowel diseases and ileal involvement in patients with Crohn disease

BackgroundMannose-binding lectin (MBL) is a pattern-recognition molecule of the innate immune system and may be involved in the pathogenesis of inflammatory bowel disease (IBD). Our aim was to assess the prevalence of MBL deficiency in a cohort of patients with paediatric-onset IBD and study whether it is associated with the clinical manifestations, serum antibody formation, or genetic factors.MethodsThis prospective study included 159 paediatric patients (mean age: 14.0 years) with IBD [107 patients with Crohn disease (CD) and 52 patients with ulcerative colitis (UC)]. Furthermore, 95 controls were investigated. Serum samples were determined for MBL by enzyme-linked immunosorbent assay (ELISA) and for serologic markers [autoantibodies against Saccharomyces cerevisiae (ASCA) and perinuclear components of neutrophils (pANCA)] by indirect immunofluorescent assay. NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism.ResultsThe MBL serum concentration was significantly lower in IBD patients(both with CD and UC) compared to controls (IBD, p = 0.007, CD, p = 0.04, UC p = 0.004). Prevalence of low MBL level (< 500 ng/mL) was significantly higher in both CD and UC groups compared to controls (p = 0.002 and p = 0.006). Furthermore, low MBL level was associated with isolated ileal involvement (p = 0.01) and MBL deficiency (< 100 ng/mL) with male gender (p = 0.004) in patients with CD. We failed to confirm any correlation between MBL deficiency and serum autoantibodies or NOD2/CARD15 variants.ConclusionsOur results suggest that low MBL associated with paediatric-onset IBD and ileal CD may be considered an additional marker of the IBD pathogenesis.     

Diabetic hands: A study on strength and function

ObjectiveTo study hand strength and function in type 2 DM patients.MethodsWe collected data on hand strength and function, disease duration, glycemic, creatinine and HbA_1C levels, degree of pain and stiffness and physical examination in 100 DM patients comparing than with 100 hand osteoarthritis patients and 100 controls.ResultsDM patients had hand strength and function better than osteoarthritis patients and worse than controls. De Quervain tendonitis associated with hand strength (p = 0.005); hand function associated with carpal tunnel syndrome (p < 0.0001), De Quervain tendinitis (p = 0.006), HbA_1C level (p = 0.005), insulin use (p = 0.030), disease duration (p = 0.0006), pain (p < 0.0001) and stiffness (p < 0.0001) in univariated analysis. In multivariated analysis only disease duration and stiffness remain as significant.ConclusionHand strength and function are impaired in DM patients. Loss of function associated with stiffness and disease duration; loss of strength associates with De Quervain tendinitis.     

Genetic and environmental factors as predictors of disease severity and extent at time of diagnosis in an inception cohort of inflammatory bowel disease,Copenhagen County and City 2003–2005

Background and aimsThe etiology of the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) remains unknown. We aimed to investigate the influence of genetic, serological, and environmental factors on phenotypic presentation of IBD at diagnosis in a population-based Danish inception cohort from 2003–2005.MethodsThree-hundred-forty-seven (62%) of 562 cohort patients were genotyped. ASCA and p/c-ANCA were determined and patients answered a questionnaire concerning environmental factors with possible influence on IBD.ResultsFourteen percent of CD patients vs. 11% of controls were positive for common CARD15 mutation (ns), whereas more CD patients than healthy controls were homozygous for the OCTN-TC haplotype (p = 0.03). ASCA was more common in CD (22%) than UC (14%) (p = 0.045) and was related to age and localization of CD. p-ANCA was more frequent in UC (p = 0.00001) but was related to pure colonic CD (p = 0.0001). Sugar consumption was significantly higher in CD patients than in UC patients (p = 0.0001) and more CD patients than UC patients had undergone appendectomy prior to IBD diagnosis (p = 0.03). A possible relation between tonsillectomy and disease severity in CD, and a relation between use of oral contraception and disease localization of UC to rectum/left-sided colon were found.ConclusionsIn this cohort of unselected IBD patients we found a very low frequency of mutations in IBD susceptibility genes and observed a greater impact of ASCA and ANCA than of genetic factors on disease phenotypes. In addition, several environmental factors seemed to influence disease occurrence and disease presentation in both UC and especially CD.     

Adalimumab monotherapy versus combination therapy with immunomodulators in patients with Crohn's disease: A systematic review and meta-analysis

Background and aimsCombination therapy with infliximab and azathioprine has been shown to be superior to either treatment alone in Crohn's disease (CD). However, the benefit of combining adalimumab with an immunomodulator remains controversial.The aim of this study was to compare the efficacy of adalimumab monotherapy with combination therapy for induction and maintenance of response and remission in CD using a meta-analysis of the current literature.MethodsWe performed a systematic literature search using Medline, Embase, Cochrane and several other databases. Prospective randomized controlled trials, retrospective cohort and case-controlled studies were included. The primary outcomes included induction of response and remission (up to week 12), maintenance of clinical response and remission (1 year) and the need for dose escalation. Several subgroup and sensitivity analyses were performed.ResultsEighteen out of 2743 retrieved studies were included. A meta-analysis of 7 studies assessing induction of remission (n = 1984) showed that ADA monotherapy was inferior to combination therapy [OR = 0.78 (0.64–0.96), p = 0.02]. A meta-analysis of 4 studies revealed that combination therapy was not statistically different from ADA for maintenance of remission [OR = 1.08 (0.79–1.48), p = 0.48]. Combination therapy was also not different from ADA monotherapy in terms of requirement for dose escalation [OR = 1.13 (0.69–1.85), p = 0.62].ConclusionsCombination therapy with ADA and immunomodulator was mildly superior to ADA monotherapy for induction of remission in CD. The rate of remission at 1 year and the need for dose escalation were similar in both groups. These findings should be interpreted with caution in view of possible confounders and should be further validated by randomized controlled trials.     

Low periostin levels in adult patients with Langerhans cell histiocytosis are independently associated with the disease activity

PurposeLangerhans cell histiocytosis (LCH) is a rare proliferative disease of cells of the CD1a +/CD207 + myeloid dendritic cell lineage that may infiltrate one or more organs or systems at all ages. We aimed to evaluate periostin and sclerostin serum levels in adult patients with LCH.ProceduresThis was a cross-sectional study comparing 38 adult patients with LCH with 38 age- and sex-matched healthy controls. Serum periostin and sclerostin levels were measured to compare between LCH patients and controls as well as between patients with active and non-active disease.ResultsSerum periostin levels were significantly lower in LCH patients than controls (457 ± 72 ng/ml vs. 721 ± 79 ng/ml, p = 0.014) but this was not the case for sclerostin levels which did not differ between patients and controls, respectively (29.0 ± 1.8 pmol/L vs. 39.5 ± 3.8 pmol/L, p = 0.12). Patients with active disease had significantly lower periostin levels than those with inactive disease (240 ± 78 ng/ml vs. 558 ± 94 ng/ml, p = 0.008). No effect of specific site involvement, extend of disease, or treatment administered was found on any of the above parameters measured.ConclusionsLower serum periostin levels were observed in adult LCH patients with active disease. The finding warrants further investigation to define whether periostin could serve as a serum biomarker for LCH activity.     

Bile acid malabsorption assessed by 7 alpha-hydroxy-4-cholesten-3-one in pediatric inflammatory bowel disease: Correlation to clinical and laboratory findings

Background and aimsMeasurement of 7 alpha-hydroxy-4-cholesten-3-one (C4) in serum is a semiquantitative test for bile acid malabsorption (BAM). We have previously established pediatric normal values for C4 with an upper limit of normal of 66.5 ng/mL, independent of age and sex. Here we performed the C4 test in 58 pediatric patients with Crohn's disease (CD) and ulcerative colitis (UC).MethodsC4 was measured using high performance liquid chromatography (HPLC) in fasting serum samples of 44 patients with CD (range 7–19 years) and 14 with UC (4–18 years). Disease activity was assessed by the pediatric CD and UC activity indices (PCDAI and PUCAI, respectively) plus serum (CRP, ESR) and fecal inflammatory markers (calprotectin).ResultsC4 concentrations were increased in 10 CD (23%) (range: 70.8–269.3 ng/mL) but only one UC patient (72.9 ng/mL). CD patients with diarrhea (n = 12) had higher C4-values compared to those without (76.9 vs. 30.4 ng/mL; p = 0.0043). Ileal resection in CD patients (n = 10) was associated with increased C4 concentrations (81.2 vs. 24.3 ng/mL, p = 0.0004). No correlation was found between C4 values and inflammatory markers. Six of 7 CD patients with persistent diarrhea but quiescent disease (PCDAI ≤ 12.5) had C4 values indicating BAM.ConclusionElevated C4 concentrations indicating BAM are common in children with CD. They are associated with ileal resection and non-bloody diarrhea in the absence of active disease or elevated inflammatory markers. The C4-test identifies a subgroup of CD patients with persistent diarrhea in spite of clinical remission which may benefit from bile acid binding therapy.