Relationship between autoimmune liver disease and autoimmune thyroid disease: a cross-sectional study

Abstract

Background: A high prevalence of autoimmune thyroid disease (AITD) has been observed in patients with autoimmune liver disease (AILD); however, data on the clinical relationship between AILD and AITD remain scant. We aimed to evaluate the relationship between AILD and AITD.

Methods: We performed a retrospective study using medical records from 324 patients with AILD, 113 of whom had concurrent AITD.

Results: Patients with autoimmune hepatitis (AIH) were more likely to develop AITD (45.8%), followed by autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC OS) (39.5%) and PBC (22.6%). Patients with concurrent AILD and AITD showed higher levels of immunoglobulin G (IgG) (21.5?g/L vs 16.3?g/L, p?<?.0001) and gamma globulin (γ-globulin) (27.1% vs 21.9%, p?<?.0001). IgG was positively correlated with thyroid antibodies [thymoglobulin antibody (TGAb) and thyroperoxidase antibody (TPOAb)] (r?=?0.396, 0.322; p?<?.0001, p?=?.002, respectively). TPOAb positivity was highest in PBC patients with concurrent AITD (83.9%). Patients with concurrent PBC and AITD were significantly older than those with PBC alone (p?=?.0004). Patients with concurrent AIH and AITD had a higher homogenous nuclear pattern of antinuclear antibody positivity compared to those with AIH alone (p?=?.019). Thyroid dysfunction in AILD patients with concurrent AITD was principally characterized by Hashimoto’s thyroiditis (65.5%), and diffuse lesions were mainly found by thyroid ultrasound (53.1%).

Conclusions: The high incidence of AILD concomitant with AITD, the higher levels of serum IgG and γ-globulin, and the strong correlation between thyroid antibodies and IgG suggest that close screening for AITD and accurate physical examinations should be performed for all patients with AILD.     

The add-on effectiveness and safety of iguratimod in patients with rheumatoid arthritis who showed an inadequate response to tocilizumab

Abstract

Objectives: To evaluate the effectiveness of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA) who showed an inadequate response to tocilizumab (TCZ), especially patients who were intolerant of an effective dose of methotrexate (MTX).

Methods: Thirty-one patients with RA (22 women, age 62.4 years, disease duration 13.8 years, prior TCZ duration 35.7 months, 25 intravenous [8?mg/kg/4 weeks] and 6 subcutaneous [162?mg/2 weeks] TCZ treatments, concomitant MTX 8.5?mg/week [35.5%], and prednisolone (PSL) 4.3?mg/day [25.8%]) who showed an inadequate response to TCZ (disease activity score assessing 28 joints with C-reactive protein [DAS28-CRP] 2.9, clinical disease activity index [CDAI] 15.0, 28 secondary inadequate responders) were treated with additional IGU (final dose 41.7?mg/day) and enrolled in this 24-week, multicenter, retrospective study.

Results: Twenty-nine patients (93.5%) continued the treatment for 24 weeks (one dropped out for pneumonia and one for digestive symptoms). The TCZ and the concomitant dose and rate of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) (MTX, salazosulfapyridine [SASP], and tacrolimus [TAC]) were not significantly changed during this period. Outcome measures improved significantly, as follows: DAS28-CRP from 2.9 to 1.7 (p?<?.001); CDAI from 15.0 to 6.0 (p?<?.001); modified Health Assessment Questionnaire (mHAQ) from 0.8 to 0.6 (p?<?.05); and rheumatoid factor (RF) from 382.1 to 240.3?IU/mL (p?<?.001). Using the EULAR criteria, 64.5% achieved a moderate response, and 51.6% achieved ACR 20 at 24 weeks.

Conclusion: Adding IGU to inadequate responders to TCZ may be a promising and safe complementary treatment option.     

Serum levels of proinflammatory,anti-inflammatory cytokines,and RANKL/OPG in synovitis,acne, pustulosis,hyperostosis, and osteitis (SAPHO) syndrome

Abstract

Objective: To measure the expression of proinflammatory, anti-inflammatory cytokines, and receptor activator NK-κB ligand (RANKL)/osteoprotegerin (OPG) in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, and to assess the relationship between those factors and disease activity.

Methods: We studied 30 cases of SAPHO syndrome and 15 healthy controls. According to the Visual Analogue Scale (VAS) pain scores and Bath Ankylosing Spondylitis Activity Index (BASDAI), patients were divided into active group and stable group. The serum levels of IFN-γ, TNF-α, TGF-β1, IL-1β, IL-4, IL-6, IL-8, IL-17A, IL-22, RANKL, and OPG were determined by ELISA.

Results: The active group IL-6 (2.34?±?1.31?pg/ml), IL-8 (36.41?±?12.93?pg/ml), and IL-17A (29.17?±?4.01?pg/ml) levels were significantly higher than those in the stable group (p?<?.01) and healthy controls (p?<?.01). RANKL in active group (73.43?±?57.07?pg/ml) was significantly higher than the ones in other groups (p?<?.0001), with increased RANKL/OPG ratio in the active group compared with other groups (p?<?.05). While the level of TGF-β1 in the active group was significantly lower than that in the stable and control groups (p?<?.0001). There was no significant difference with clinical significance were found in IFN-γ, TNF-α, IL-1β, IL-4, IL-22, and OPG.

Conclusion: In active SAPHO patients, there was an anomaly of proinflammatory and anti-inflammatory cytokines balance in SAPHO syndrome.     

Assessing joint destruction in the knees of patients with rheumatoid arthritis by using a semi-automated software for magnetic resonance imaging: therapeutic effect of methotrexate plus etanercept compared with methotrexate monotherapy

Objectives: To evaluate the prevention of knee joint destruction and clinical efficacy of methotrexate (MTX) plus etanercept (ETN) compared with MTX monotherapy in patients with rheumatoid arthritis (RA) by using semi-automated software for magnetic resonance imaging (MRI) scan analysis.

Materials and methods: This study enrolled patients with active moderate-to-severe RA who displayed an inadequate response to oral MTX at screening. Patients were assigned to receive either MTX plus ETN or MTX monotherapy (≥10?mg/week). The primary endpoint was the quantitative knee cartilage volume using our software developed for MRI scan analysis.

Results: A total of 18 female patients were enrolled in this study and allocated to the MTX?+?ETN group (n?=?9) or the MTX monotherapy group (n?=?9). At 52 weeks, the quantitative knee cartilage volume was significantly reduced compared with baseline in both groups (MTX plus ETN group: 2.3?±?2.3?cm³; MTX monotherapy group: 2.4?±?1.6?cm³); however, the difference was not significant.

Conclusion: The semi-automated software for MRI scan analysis can reveal useful and potentially clinically important information about the characteristics of knee joint destruction in patients with RA.     

Discontinuation of etanercept after achievement of sustained remission in patients with rheumatoid arthritis who initially had moderate disease activity—results from the ENCOURAGE study,a prospective,international, multicenter randomized study

Objectives: To investigate the efficacy and safety of etanercept (ETN) in patients with rheumatoid arthritis (RA) with moderate disease activity and the possibility to discontinue ETN after achieving remission.

Methods: Multicenter, randomized, and open-label study was conducted in Japan and Korea. RA patients (disease duration?<5 years) with moderate disease activity despite methotrexate (MTX) treatment were allocated to either MTX or ETN?+?MTX (Period 1) for 12 months. Patients who achieved sustained remission defined as DAS28?<?2.6 at both 6 and 12 months in the ETN?+?MTX group, were randomized to either continue or discontinue ETN for 12 months (Period 2).

Results: A total of 222 patients were enrolled in Period 1 and clinical remission was achieved in 106/157 (67.5%) and 5/28 (17.9%) patients in the ETN?+?MTX and MTX groups, respectively. In Period 2, sixty-seven patients were randomized and finally 28/32 (87.5%) and 15/28 (53.6%) patients who continued or discontinued ETN maintained clinical remission. Baseline disease activity and the presence of comorbid diseases influenced the maintenance of remission after ETN discontinuation.

Conclusions: ETN?+?MTX was efficient for RA patients with moderate disease activity into remission. After achieving sustained remission, a half of the patients who discontinued ETN could maintain remission for 1 year.     

Interleukin-17 gene expression in patients with rheumatoid arthritis

Abstract

Interleukin-17 is a proinflammatory cytokine. Recent animal studies have shown that IL-17 plays a role in the initiation and progression of arthritis. However, whether IL-17 has a prominent role in human rheumatoid arthritis (RA) or not remains unclear. Here we investigated the role of IL-17 in patients with RA. cDNA was prepared from knee joint synovial tissues of RA (n = 11) and osteoarthritic (OA, n = 10) patients and PBMC of RA (n = 52) and healthy subjects (n = 34). IL-17 gene expression level was measured by real-time PCR, and was compared with various clinical parameters. IL-17 gene expression in synovial tissues of RA was similar to that in OA. IL-17 gene expression level in PBMC of RA patients was significantly higher than in the control. The response (changes in DAS) to two-week treatment with anti-TNF-α blockers (infliximab or etanercept) did not correlate with changes in IL-17 gene expression levels. The IL-17/TNF-α gene expression ratio at baseline (before treatment) tended to be lower in responders to the treatment. Expression of IL-17 gene in PBMC may be associated with the inflammatory process of RA. IL-17/TNF-α expression ratio is a potentially suitable marker of response to anti-TNF-α therapy.     

Ulcerative colitis associated with pemphigus: a population-based large-scale study

Background: The coexistence of pemphigus and ulcerative colitis (UC) has been described, but the association between the two entities was not examined in the past. The primary endpoint of this study was to investigate the association between pemphigus and UC.

Materials and methods: Patients with pemphigus were compared to age-, sex- and ethnicity-matched control subjects regarding the prevalence of UC in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was conducted utilizing the computerized database of Clalit Health Services.

Results: The study enrolled 1985 pemphigus patients and 9874 controls. The prevalence rate of UC was greater in patients with pemphigus than in controls (0.9% vs. 0.4%, respectively; p?=?.004). In a multivariate analysis pemphigus was independently associated with UC (odds ratio 1.9, 95% confidence interval 1.1–3.3, p?=?.034). This association was stronger among younger patients, and persisted after performing a sensitivity-analysis including only patients who were prescribed pemphigus-specific medications.

Conclusions: Pemphigus is significantly associated with UC. Thus, physicians treating patients with pemphigus should be aware of this possible association. Further research is warranted to better understand the mechanism underlying this association.     

Minimum Effective Dosages of Anti-TNF in Rheumatoid Arthritis: A Cross-sectional Study

AimsTo evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR.Patients and methodsCross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. Main variables: dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR.Results195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%).ConclusionsRA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients.     

Anti-tumor necrosis factor therapy does not diminish the immune response to influenza vaccine in Japanese patients with rheumatoid arthritis

Abstract

The superiority of the combination therapy of methotrexate (MTX) and anti-tumor necrosis factor (TNF) biological agents over anti-TNF monotherapy in MTX-naïve patients with rheumatoid arthritis (RA) has been demonstrated. We investigated the efficacy and safety of continuation versus discontinuation of MTX at the commencement of etanercept (ETN) in patients with active RA despite MTX therapy. In total, 151 patients with active RA despite treatment with MTX were randomized to either ETN 25 mg twice a week and MTX 6–8 mg/week (the E + M group) or ETN alone (the E group). Co-primary endpoints included the European League Against Rheumatism (EULAR) good response rate and the American College of Rheumatology (ACR) 50 response rate at week 24. Demographic and clinical features between groups at baseline were similar. The EULAR good response rates were significantly higher in the E + M group (52%) than in the E group (33%) at week 24 (p = 0.0001). Although the ACR50 response rate, one of the co-primary endpoints, and the ACR70 response rate at week 24 were not significantly greater in the E + M group (64 and 38%, respectively) than in the E group (48 and 26%, respectively), the ACR20 response rate was significantly greater in the E + M group (90%) than in the E group (64%; p = 0.0002). Safety profiles were similar for the groups. Thus, MTX should be continued at the commencement of ETN therapy, even in RA patients who show an inappropriate response to MTX.     

Reduction of methotrexate and glucocorticoids use after the introduction of biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis in daily practice based on the IORRA cohort

Objectives: To evaluate usage patterns for methotrexate (MTX) and/or glucocorticoids in rheumatoid arthritis (RA) patients receiving biological disease-modifying antirheumatic drugs (bDMARDs) in daily practice.

Methods: Data from RA patients who commenced treatment with bDMARDs (infliximab [IFX], etanercept [ETN], tocilizumab [TCZ], or adalimumab [ADA]) from 2008 to 2010 were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) database. The proportions of patients taking concomitant MTX and glucocorticoids and doses of these medications were evaluated before and 2 years after initiation of each bDMARD.

Results: A total of 470 RA patients who had initiated a bDMARD (IFX: n?=?98, ETN: n?=?181, TCZ: n?=?90, and ADA: n?=?101) were evaluated. The proportion of patients taking MTX decreased over time among ETN and TCZ users, while it increased among ADA users. The MTX dose decreased over time among IFX, ETN, and TCZ users, but not among ADA users. Although the rate of glucocorticoid use and dose decreased after bDMARD initiation in all four bDMARD groups, approximately 50% of patients continued to receive glucocorticoids 2 years after bDMARD initiation.

Conclusion: MTX and glucocorticoid use and doses in daily practice were commonly reduced after the initiation of bDMARDs, with the dose adjustment varied depending on the bDMARD.     

Hyperplastic polyps arising in autoimmune metaplastic atrophic gastritis patients: is this a distinct clinicopathological entity?

Abstract

Objectives: Gastric hyperplastic polyp (GHP) commonly arises in the abnormal surrounding mucosa, including autoimmune metaplastic atrophic gastritis (AMAG). We aimed to compare clinicopathological features in patients with GHPs associated with AMAG with those in patients with GHPs associated with non-AMAG.

Patients and methods: A total of 1170 patients with GHP(s) were enrolled, and their clinical and pathological data were analyzed, retrospectively.

Results: The GHP patients were divided into 181 A-GHP (type A GHP, AMAG-associated GHP) participants, 312 B-GHP (type B GHP, Helicobacter pylori infection-associated GHP) participants, and 677 other GHP participants (non-A-GHP and non-B-GHP) based on pathological status of the surrounding non-polypoid mucosa. The A-GHP patients were older and predominantly female (p?<?.05). Gastroscopically, A-GHPs showed less distal and more multiple-region distribution in the stomach (p?<?.001). In addition, the A-GHPs were observed to be usually numerous (55.8%), larger (mean maximum diameter 12.3?mm), and more pedunculated or sub-pedunculated (45.3%) (p?<?.001). Histopathologically, the intestinal metaplasia, intraepithelial neoplasia, and carcinomatous transformation within GHPs were present in 24.3%, 9.9%, and 2.8% of AMAG patients, respectively, which were significantly higher than those in the B-GHPs and other GHPs (p?<?.05). However, the differences of intraepithelial neoplasia and adenocarcinoma in surrounding non-polypoid mucosa did not reach statistical significance (p?>?.05).

Conclusions: The GHP(s) arising in AMAG patients is a distinct subgroup of GHP(s) and was an important precancerous lesion. The biopsy from surrounding non-polypoid mucosa was essential to evaluate the underlying etiology of the GHPs, and endoscopists should pay attention to these.     

Evolution of cytokines and inflammatory biomarkers during infliximab induction therapy and the impact of inflammatory burden on primary response in patients with Crohn’s disease

Objective: Primary non-response to infliximab in Crohn’s disease is still incompletely understood. Our aim was to further characterize the role of inflammatory burden during infliximab induction therapy.

Materials and Methods: We studied a well-characterized cohort of 201 anti-TNF naive Crohn’s disease patients treated with infliximab 5mg/kg at week 0, 2, 6 and 14 who had serum samples drawn just before every infusion. All serum samples were analyzed for CRP, albumin, TNF, IFN-γ, IL-6, IL-8, IL-10, infliximab trough concentrations (in-house-developed ELISA) and antibodies to infliximab (HMSA, Prometheus Laboratories Inc., San Diego, CA). Primary non-response was defined as the absence of clinical improvement at week 14.

Results: The incidence of primary non-response to infliximab was 8% (n?=?16). IL-8 concentrations at baseline were higher (p?=?.01) and albumin at week 6 was lower in primary non-responders (p?=?.01) compared to responders. During induction, IFN-γ and IL-6 concentrations decreased significantly at week 2 and week 6 in responders compared to primary non-responders (p?<?.05). Serum TNF increased significantly after each infliximab infusion and this increase from week 0 to week 14 was more pronounced in responders (p?=?.03). Multiple logistic regression identified TNF/CRP ratio at baseline as predictive for primary non-response to infliximab at week 14 (OR 2.8 (95% CI 1.4–5.5; p?=?.003)).

Conclusions: In this intensively sampled cohort of Crohn’s disease patients, we demonstrate that inflammatory burden is more determining for primary non-response than drug exposure or immunogenicity. Our findings furthermore suggest that the contribution of TNF in inflammation might be higher in primary non-response, contradicting the non-TNF-driven concept.     

Add-on iguratimod as a therapeutic strategy to achieve remission in patients with rheumatoid arthritis inadequately responding to biological DMARDs: A retrospective study

Objectives: In this study, iguratimod (IGU) was added to rheumatoid arthritis (RA) patients inadequately responding to 24-week or longer treatment with biological disease-modifying antirheumatic drug (bDMARDs), its effectiveness was assessed, and factors contributing to remission were evaluated.

Methods: RA patients who fulfilled the following criteria were included: (i) ≥?24-week of bDMARDs; (ii) 2.6?Results: DAS assessing 28 joints with ESR (DAS28-ESR) decreased significantly from 3.45?±?0.92 at baseline to 2.85?±?1.13 at 24 weeks (p?p?p =.002). Shorter duration of disease (p =.020) was related to ultrasound remission, in addition to a lower baseline DAS28-ESR (p?Conclusions: IGU add-on therapy can be a therapeutic strategy to achieve remission in RA patients inadequately responding to ≥24-week treatment with bDMARDs.     

A case–control study of rheumatoid arthritis revealed abdominal obesity and environmental risk factor interactions in northern China

Background: The aim of this study was to evaluate new and previously hypothesized environmental risk factors and their interaction with rheumatoid arthritis (RA).

Methods: Four hundred patients recently diagnosed with RA and 400 controls frequency-matched by gender and birth year using Propensity Score Matching (PSM) were selected from northern China. Investigation was performed using self-reported data from interviewer-administered surveys. Associations between exposure variables and risk of RA were evaluated using multifactor non-conditional logistic regression.

Results: It showed that damp localities, draft indoor, abdominal obesity (AO), and family history of RA among first-degree relatives were independent risk factors and drinking of milk was independent protective factors for RA. Besides these risk factors, in women, infrequent delivery times, early age at menopause, and late age at menarche were also independent risk factors for RA. Both the additive model and the multiplication model suggested that there was an interaction relationship between AO and damp localities (p?p?p?p?Conclusions: In northern China, damp localities, draft indoor, AO, family history of RA among first-degree relatives, and no milk drinking may be important risk factors of RA patients.     

Serum interleukin-6 level is associated with response to infliximab in ulcerative colitis

Objectives: Infliximab is effective in patients with ulcerative colitis (UC); however, one-third of patients do not respond and require additional therapies such as other biologic agents. Therefore, the aim of this study was to analyze the association between pro-inflammatory molecules and clinical efficacy to elucidate possible mechanisms for the non-response to infliximab to aid in treatment selection.

Materials and method: Patients with moderate-to-severe active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre-treatment serum samples were available were retrospectively evaluated. We analyzed the association between serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was clinical response at the end of the induction period.

Results: Forty-one patients were included in this study. After induction therapy, 27 patients (65.9%) showed a clinical response. Serum IL-6 levels were significantly lower in responders than in non-responders (p?=?.012), whereas no significant differences were noted in other factors including sMAdCAM-1 and TNF-α. Multivariate analysis identified that serum IL-6 level (odds ratio?=?0.72; 95% confidence interval, 0.54–0.96; p?=?.027) was independently associated with response to infliximab.

Conclusions: Serum IL-6 level is associated with response to infliximab in UC. Elevated concentrations of IL-6 may provide insight to the mechanism of non-response to infliximab.     

Chemotherapy-induced mucositis development in a murine model of colitis-associated colorectal cancer

Abstract

Objectives: Ulcerative colitis is an incurable inflammatory bowel disease that increases the risk of colorectal cancer (CRC). 5-Fluorouracil (5-FU) is the predominant chemotherapy for CRC patients; however, undesirable side-effects, including mucositis, are common. This study utilised 5-FU-treatment in a model of colitis-associated CRC to develop a pre-clinical setting of intestinal mucositis coincident with manifestation of CRC.

Materials/methods: On day 0, female C57BL/6 mice (n?=?10/group); (1) saline control, (2) AOM/DSS control, or (3) AOM/DSS + 5-FU were injected with saline or AOM (i.p; 7.4?mg/kg). Groups 2 and 3 underwent cycles of seven days 2%w/v DSS followed by 14?days plain water. After three cycles, 5-FU was administered weekly (i.p; 75?mg/kg) to group 3 for five weeks. Clinical indicators were measured daily and colonoscopy performed at four time-points. Mice were euthanized at 13?weeks (day 91). Intestinal sections were collected for histological and biochemical analyses. p?<?.05 was considered significant.

Results: AOM/DSS resulted in bodyweight loss, increased disease activity index, colitis-severity and tumour number compared to saline controls (p?<?.05). 5-FU-treatment in AOM/DSS mice decreased bodyweight and disease activity index at selected time-points compared to AOM/DSS controls (p?<?.05). 5-FU did not impact colitis-severity or overall tumour burden; although, resulted in fewer small tumours compared to AOM/DSS controls (<2mm; p?<?.05). AOM/DSS increased histological severity scores in intestinal sections (p?<?.05), however, 5-FU-treatment did not further increase histologically-assessed disease severity (p?>?.05).

Conclusion: Weekly 5-FU administration at a dose of 75?mg/kg was insufficient to reduce overall tumour burden or induce intestinal mucositis in the AOM/DSS mouse model.     

Association of apolipoprotein A-V with mRNA expression of IL-6 and NF-κB genes in type 2 diabetes with hypertriglyceridemia: a possible link with inflammation

Background

Hypertriglyceridemia and inflammation are implicated in cardiovascular complications in type 2 diabetes mellitus (T2DM). While some studies have evaluated apolipoprotein A-V protein (Apo A-V) in diabetes and its effect on triglycerides (TG) levels, only a few have explored its relation with inflammatory markers.

Objectives

To evaluate the expression of mRNA genes involved in inflammatory response (IL-6 and NF-κB) and to study their association with Apo A-V in patients of T2DM, with and without hypertriglyceridemia.

Methods

Two groups of T2DM patients, comprising of 40 participants each, were constituted according to NCEP ATP III criteria for CVD risk: group 1/controls (TG ≤ 1.65 mmol/l) and group 2/cases (TG ≥ 2.2 mmol/l). Serum levels of Apo A-V, free fatty acids (FFA) and IL-6 were estimated. Fold change in mRNA expression of IL-6 and NF-κB (p65) gene in blood was calculated by ΔΔCT method.

Observations

The mRNA expression of IL-6 and p65 was higher in cases. Significant inverse association of Apo A-V levels was observed with expression of p65 gene (p = 0.000) and IL-6 gene (p = 0.003) in all subjects. FFA levels also correlated inversely with the expression of p65 (p = 0.001) and IL-6 (p = 0.005) mRNA. The association of FFA levels and ApoA-V with mRNA expression of IL-6 and p65 genes was independent of each other.

Conclusion

This study highlights that inflammatory pathways are unregulated in hypertriglyceridemia in T2DM. Also, apart from its association with TG levels, Apo A-V may have an anti-inflammatory role as evident from its inverse association with the expression of IL-6 and NF-κB expression. Thus, Apo A-V may provide an important link between TGs, inflammation, and vascular complications in T2DM.

     

A phase 3 randomized,double-blind,multicenter comparative study evaluating the effect of etanercept versus methotrexate on radiographic outcomes,disease activity,and safety in Japanese subjects with active rheumatoid arthritis

Abstract

Objectives The aim of this phase 3, double-blind study was to compare the radiographic and clinical effects of etanercept (ETN) versus methotrexate (MTX) over 52 weeks in Japanese subjects with active rheumatoid arthritis.

Methods The study population comprised 550 subjects with inadequate response to ≥1 disease-modifying anti-rheumatic drugs who were randomized to treatment groups of ETN 25 mg twice weekly (BIW; n = 182), ETN 10 mg BIW (n = 192), or MTX (≤8.0 mg/week; n = 176).

Results Of the 550 subjects initially enrolled in the three treatment groups, 21.6 % discontinued the study; a significantly higher proportion of those who withdrew from the study due to lack of efficacy were in the MTX (21.6 %) group compared with the ETN 25 mg (3.3 %) and ETN 10 mg (6.8 %) groups (P < 0.001). Mean change from baseline in the modified total Sharp score at week 52 (primary endpoint) was significantly lower in the ETN 25 mg [3.33; standard error (SE), 0.73] and ETN 10 mg (5.19; SE 0.93) groups than in the MTX group (9.82; SE 1.16; P < 0.0001 vs. either ETN group). Compared with subjects receiving MTX, significantly higher percentages of subjects treated with ETN 25 and 10 mg achieved American College of Rheumatology (ACR) ACR20 and ACR50 response rates at all time points (P < 0.01). ETN was well-tolerated, with no unexpected safety findings.

Conclusions ETN 25 mg BIW and ETN 10 mg BIW slowed radiographic progression and improved clinical outcomes more effectively than MTX in this Japanese population.     

The diagnostic role and clinical association of serum proteinase 3 anti-neutrophil cytoplasmic antibodies in Chinese patients with inflammatory bowel disease

Abstract

Background and aim: Accurate differentiation of patients with ulcerative colitis (UC) or Crohn’s disease (CD) is important for appropriate therapy and prognosis. This study was designed to explore the utility of proteinase 3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA) in the diagnosis of Chinese patients with inflammatory bowel disease (IBD).

Methods: Blood samples were collected from 216 Chinese patients, including 175 IBD and 41 colorectal polyps (disease control). Clinical characteristics were extracted from electronic medical records.

Results: Serum PR3-ANCA were increased in UC patients compared to those with CD or colorectal polyps (p?<?.0001). PR3-ANCA was negative in colorectal polyps and there was no significant difference between CD and colorectal polyps (p?>?.05). Using the cut-off value of 20 chemiluminescent units (CU) provided by manufacturer, the positive rate of PR3-ANCA was higher in UC than CD (41.7% vs. 1.1%; p?<?.0001). Receiver operating characteristic (ROC) analysis demonstrated an area under the curve (AUC) of 0.89 (95% CI: 0.84–0.95; p?<?.0001) for differentiating UC from CD and suggested an optimized cutoff of 7.3 CU which improved sensitivity from 41.7% to 57.1%, while maintaining a specificity of 98.9%. PR3-ANCA in severe UC patients were higher than those with moderate UC (p?<?.05), no difference was found between those in remission or with mild or moderate activity (p?>?.05).

Conclusions: Serum PR3-ANCA is a potentially useful clinical biomarker in Chinese patients with IBD. A modified cut-off value of 7.3 CU improves the performance for distinguishing UC from CD.     

Haematological response and overall survival in two consecutive Dutch patient cohorts with AL amyloidosis diagnosed between 2008 and 2016

Abstract

Background: Although survival has improved in recent decades, the short-term prognosis of patients with immunoglobulin light chain (AL) amyloidosis remains grim. We aimed to assess overall survival (OS) of AL amyloidosis patients by comparing cohorts in two consecutive time periods.

Methods: Data were collected and compared on 126 patients from two tertiary referral centres in The Netherlands during the time periods 2008–2012 and 2013–2016.

Results: There was a non-significant trend to improved 6-month OS in the last cohort (78% vs. 67%, p?=?.216, crude odds ratio 1.66, 95%CI 0.74–3.70, adjusted odds ratio 2.22, 95%CI 0.88–5.56). Patients in this cohort had higher Mayo risk scores (stage III 40% vs. 24%, p?<?.001 and revised stage IV 14% vs. 11%, p?<?.001), higher use of bortezomib (50% vs. 30%), and better haematological response (complete response/very good partial response in 39% vs. 27%, p?<?.001). Diagnostic delay was similar in both time periods.

Conclusions: In the 2013–2016 cohort there was a trend toward improved 6-month OS, and an improved haematological response. Patients in this cohort had more advanced cardiac disease and received bortezomib more frequently, but diagnostic delay was similar to the 2008–2012 cohort. For further prognostic improvement, practitioners should be more alert, especially for cardiac amyloidosis.