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ID PMID Title PublicationDate abstract
23933487 Tumor necrosis factor inhibition modulates thrombospondin-1 expression in human inflammato 2013 Oct We examined thrombospondin-1 (THBS1, alias TSP-1) expression in human synovial tissue (ST) during the resolution phase of chronic inflammation and elucidated its transcriptional regulation by the orphan receptor 4A2 (NR4A2). In vivo, rheumatoid arthritis (RA) serum and ST revealed altered expression levels and tissue distribution of TSP-1. After anti-tumor necrosis factor therapy, a reciprocal relationship between TSP-1 and NR4A2 expression levels was measured in patients with clinical and ST responses to biological treatment. In vitro, primary RA fibroblast-like synoviocytes (FLSs) expressed minimal TSP-1 mRNA levels with high transcript levels of NR4A2, vascular endothelial growth factor (VEGF), and IL-8 measured. Hypoxic modulation of RA FLSs resulted in inverse expression levels of TSP-1 compared with NR4A2, IL-8, and VEGF. Ectopic NR4A2 expression led to reduced TSP-1 mRNA and protein levels with concomitant increases in proangiogenic mediators. NR4A2 transcriptional activity, independent of DNA binding, repressed the hTSP-1 promoter leading to reduced mRNA and protein release in immortalized K4IM FLSs. Bioinformatic and deletion studies identified a 5' region of the TSP-1 promoter repressed by NR4A2 and proangiogenic transcription factors, including NF-κB and Ets1/2. Stable depletion of NR4A2 levels resulted in a shift in the TSP-1/VEGF expression ratio. Thus, modulation of TSP-1 expression is achieved through anti-tumor necrosis factor therapy effects on specific transcriptional networks, suggesting that enhanced TSP-1 expression may help restore tissue homeostasis during resolution of inflammation.
24816341 Health related quality of life in rheumatoid arthritis, osteoarthritis, diabetes mellitus, 2015 Mar INTRODUCTION: Chronic diseases have a great impact in the morbidity and mortality and in the health-related quality of life (HRQoL) of patients around the world. The impact of rheumatic diseases has not been fully recognized. We conducted a comparative study to evaluate the HRQoL in different chronic diseases. OBJECTIVES: The aim of the present study was to assess the HRQoL and identify specific areas affected in patients with rheumatoid arthritis (RA), osteoarthritis (OA), diabetes mellitus, end-stage renal disease, geriatric subjects and a control group. PATIENTS AND METHODS: We conducted a cross-sectional study, in a General Hospital in Morelia, Mexico. All patients met classification criteria for RA, OA, diabetes mellitus, end-stage renal disease; the geriatric subjects group was≥65 years, and the control group≥30 years. Demographic characteristics were recorded, different instruments were applied: SF-36, visual analogue scale for pain, patient's and physician's global assessments, Beck Depression Inventory and specific instruments (DAS-28, HAQ-Di, WOMAC, Diabetes Quality of Life [DQOL] and Kidney Disease Questionnaire of Life [KDQOL]). Biochemical measures: erythrocyte sedimentation rate, blood count, glucose, HbA1C, serum creatinine and urea. RESULTS: We evaluated 290 subjects (control group: 100; geriatric subjects: 30 and 160 for the rest of groups). Differences were detected in baseline characteristics (P<.0001). The SF-36 scores were different between control group and others groups (P=0.007). The worst HRQoL was in end-stage renal disease group (±SD: 48.06±18.84 x/SD). The general health was the principal affected area in RA. The pain was higher in rheumatic diseases: OA (5.2±2.4) and RA (5.1±3). HAQ was higher in OA compared to RA (1.12±0.76 vs 0.82±0.82, respectively; P=.001). Forty five percent of all subjects had depression. CONCLUSIONS: The HRQoL in RA patients is poor and comparable to other chronic diseases (end-stage renal disease and diabetes mellitus). Rheumatic diseases should be considered high impact diseases and therefore should receive more attention.
25534463 [Sarcoidosis after adalimumab treatment in inflammatory rheumatic diseases: a report of tw 2015 Jan CONTEXT: TNF α antagonists (anti-TNF α) are widely used in inflammatory rheumatic diseases: rheumatoid arthritis (RA) and spondylarthropathy (SpA). The efficacy of the anti-TNF α monoclonal antibodies was also observed in unresponsive sarcoidosis to conventional therapy. In contrast, sarcoidosis in patients with inflammatory rheumatic disease treated with anti-TNF α keep on growing, with a suspected role of anti-TNF α in this pathological process. METHODS: We presented here two cases of sarcoidosis developing while the patient was on adalimumab (ADA) therapy for inflammatory rheumatic disease. In one case, the reintroduction of ADA led to increase in symptomatology. We also analyzed the 16 other cases of sarcoidosis developing under ADA treatment published in literature, mostly in RA patients. RESULTS: These cases show a possible paradoxical effect of ADA in sarcoidosis development in patients treated with anti-TNFα monoclonal antibodies. The iatrogenic mechanism remains unclear. These cases underline the importance of a drug-induced etiology survey facing any symptomatology suggesting the development of sarcoidosis in patients treated with anti-TNF α for an inflammatory rheumatic disease.
23945080 Double-antiangiogenic protein DAAP targeting vascular endothelial growth factor A and angi 2013 Aug 14 INTRODUCTION: Angiogenesis plays a critical role in synovial inflammation and joint destruction in rheumatoid arthritis (RA). Vascular endothelial growth factor A (VEGF-A) and angiopoietins are two important mediators of synovial angiogenesis. We have previously developed a novel chimeric decoy receptor, namely, double-antiangiogenic protein (DAAP), which can both bind VEGF-A and angiopoietins and block their actions. This study was performed to evaluate the antiarthritic effect of DAAP and the combination effect with the tumor necrosis factor α (TNF-α) inhibitor in collagen-induced arthritis (CIA). METHODS: Recombinant DAAP, VEGF-Trap, Tie2-Fc and dimeric Fc proteins were produced and purified from CHO cells in large-scale bioreactors. CIA was induced in DBA/1 mice with type II collagen. The preventive effect of DAAP was determined and compared with other decoy receptors such as VEGF-Trap or Tie2-Fc, which block VEGF-A or angiopoietins, respectively. The clinical, radiographic, pathologic and immunohistochemical analyses were performed in CIA mice. The levels of matrix metalloprotease 3 (MMP-3) and interleukin 1β (IL-1β) were quantified by enzyme-linked immunosorbent assay, and receptor activator of nuclear factor κB ligand (RANKL) mRNA levels were measured by polymerase chain reaction. Finally, we investigated the combination effects of DAAP with a low dose of TNF-α decoy receptor (etanercept 10 mg/kg). RESULTS: On the basis of clinical and radiographic evaluation, DAAP had a much greater inhibitory effect than VEGF-Trap or Tie2-Fc on arthritis severity and bone destruction. These inhibitory effects were accompanied by significantly diminishing pathologic abnormalities, CD31-positive vasculature and synovial infiltration by F4/80-positive macrophages. The levels of MMP-3, IL-1β and RANKL were much lower in the DAAP-injected group than those of the control. Furthermore, DAAP showed a therapeutic effect and a combination effect with etanercept when injected after arthritis onset in established CIA. CONCLUSIONS: DAAP has not only potent prophylactic effects on both inflammation and bone destruction but also therapeutic effects, alone and in combination with a TNF-α inhibitor in CIA mice. These results suggest that DAAP could be used as an effective new therapeutic agent for RA.
23955089 Methotrexate enhances 3T3-L1 adipocytes hypertrophy. 2013 Aug Methotrexate (MTX) is broadly used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA). The prevalence of metabolic syndrome (MeS) in patients with this condition is relatively high. Given the importance of adipose tissue in the development of obesity metabolic complications, this study aimed to investigate the effect of methotrexate on preadipocyte proliferation, adipogenesis, and glucose uptake by adipocytes. 3T3-L1 preadipocytes proliferation was evaluated by sulforhodamine B staining and (3)H-thymidine incorporation, after 24 or 48 h of treatment with MTX (0.1 and 10 μM). Preadipocytes were induced to differentiate with an appropriate adipogenic cocktail in the presence or absence of MTX. Adipogenesis was determined by measuring lipid accumulation after staining with oil red O. (3)H-Deoxyglucose ((3)H-DG) uptake was determined by liquid scintillation counting. MTX treatment reduced culture protein content in a concentration-dependent manner and (3)H-thymidine incorporation (P < 0.05). MTX (0.1 μM) treatment increased lipid accumulation and basal (3)H-DG uptake by adipocytes (P < 0.05). In 0.1 μM MTX-treated adipocytes, insulin stimulation did not result in an increase of (3)H-DG uptake, contrarily to what was observed in control cells. These results demonstrate that methotrexate interferes with adipocyte proliferation and promotes the hypertrophic growth of adipocytes. These molecular effects may have implications on metabolic profile of RA patients treated with MTX.
22562974 Low-dose prednisone chronotherapy for rheumatoid arthritis: a randomised clinical trial (C 2013 Feb OBJECTIVE: To assess the efficacy and safety of low-dose prednisone chronotherapy using a new modified-release (MR) formulation for the treatment of rheumatoid arthritis (RA). METHODS: In this 12-week, double-blind, placebo-controlled study, patients with active RA (n=350) were randomised 2:1 to receive MR prednisone 5 mg or placebo once daily in the evening in addition to their existing RA disease-modifying antirheumatic drug (DMARD) treatment. The primary end point was the percentage of patients achieving a 20% improvement in RA signs and symptoms according to American College of Rheumatology criteria (ie, an ACR20 response) at week 12. Changes in morning pain, duration of morning stiffness, 28-joint Disease Activity Score and health-related quality of life were also assessed. RESULTS: MR prednisone plus DMARD treatment produced higher response rates for ACR20 (48% vs 29%, p<0.001) and ACR50 (22% vs 10%, p<0.006) and a greater median relative reduction from baseline in morning stiffness (55% vs 35%, p<0.002) at week 12 than placebo plus DMARD treatment. Significantly greater reductions in severity of RA (Disease Activity Score 28) (p<0.001) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue score) (p=0.003) as well as a greater improvement in physical function (36-item Short-Form Health Survey score) (p<0.001) were seen at week 12 for MR prednisone versus placebo. The incidence of adverse events was similar for MR prednisone (43%) and placebo (49%). CONCLUSION: Low-dose MR prednisone added to existing DMARD treatment produced rapid and relevant improvements in RA signs and symptoms. CLINICALTRIALS.GOV, NUMBER: NCT00650078.
24644545 Determination of lysosomal exoglycosidases in human saliva. 2014 BACKGROUND: Currently we observe a growing interest in human saliva as a non-invasive material for diagnosis and monitoring of general and oral diseases. METHODS: The aim of our study was adaptation of the Marciniak et al. (Marciniak J, Zalewska A, Popko J, Zwierz K, 2006, Clin Chem Lab Med 44: 933-937) method for determination of HEX and GLU activity in synovial fluid, and for determination of: HEX and GLU, as well as MAN, GAL, and FUC activity in human saliva. RESULTS: Under optimal conditions, 10 μl of saliva for HEX, and 30 μl for GLU, MAN, GAL and FUC, were sufficient for determination of human salivary exoglycosidases activity with variation coefficient ranging from 0.89 for GLU to 0.99 for GAL. CONCLUSION: The adapted method for exoglycosidases activity determination in human saliva is sufficiently sensitive and precise to use in clinical diagnosis.
25540922 Innate immunity alterations in idiopathic interstitial pneumonias and rheumatoid arthritis 2015 Feb BACKGROUND: This is a prospective cohort study elucidating innate immunity in idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), rheumatoid arthritis-associated usual interstitial pneumonia (RA-UIP) and RA-associated non specific interstitial pneumonia (RA-NSIP). METHODS: 23 IPF subjects, 9 COP subjects, 5 RA-UIP subjects, 8 RA-NSIP subjects were enrolled. 10 subjects were excluded. 19 healthy subjects served as controls. Blood and bronchoalveolar lavage (BAL) were obtained. Natural killer (NK) and NKT cells, NK cells apoptosis and the expression of triggering receptor expressed on myeloid cells type 1 (TREM-1) were assessed. Tumor necrosis factor-α (TNF-α) production was measured in cell cultures after stimulation with lipopolysaccharide endotoxin (LPS) and Pam3CysSK3, and in BAL. Surface expression of Toll-like receptors (TLR) 2 and 4 on peripheral blood monocytes (PBMC's) and circulating NK cells was also assessed. RESULTS: RA-NSIP had low blood NKs, marginally insignificant (p=0.07). These NKs poorly produced TNF-α after LPS stimulation. TLR's expression on NK cells was similar throughout disease groups and controls. PBMC's mainly from IPF patients exhibited low TNF-α production after LPS stimulation but not after Pam3CysSK3 stimulation, while TLR4 expression on PBMC's was found normal in all study groups. TLR2 expression on PBMC's was increased in IPF, but mainly in COP, RA-UIP and RA-NSIP (p=0.015). TREM-1 expression was significant on COP monocytes and on COP neutrophils versus controls. RA-NSIP monocytes also exhibited TREM-1 expression (p=0.07). Decreased TNF-α concentration in BAL was finally observed in IPF and RA-UIP. CONCLUSIONS: Innate immunity in the lungs and the peripheral circulation in IPF and RA-UIP are similar and more fibrotic than in RA-NSIP which is characterized by NK cell depletion and dysfunction. TREM-1 and TLR's likely affect patterns of inflammation in various interstitial lung diseases.
23506652 Reducing drug self-injection errors: a randomized trial comparing a "standard" versus "pla 2013 Sep BACKGROUND: Many American adults struggle to use and interpret medical-related instructions. Plain language materials have been shown to improve patient understanding and adherence. OBJECTIVE: The study objective was to compare the effectiveness of a "standard" Patient Instructions for Use (PIFU-standard) with a "plain language" Patient Instructions for Use (PIFU-PL) by testing user comprehension and ability to administer a biologic agent with an auto-injector ("pen"). METHODS: A trained research assistant administered sociodemographic items and the Rapid Estimate of Adult Literacy in Medicine to study participants (n = 50). Next, using a priori random assignment, participants received either PIFU-PL or PIFU-standard. Participants' knowledge of preparation (6 steps) and pre-injection (3 steps) procedures, and demonstrated correctness of self-administration (15 steps) were then evaluated. RESULTS: Participants receiving the PIFU-PL were more likely to correctly describe a greater number of both preparation (4.5 ± 1.3 versus 3.1 ± 1.5, P = 0.01) and pre-injection steps (2.4 ± 0.8 versus 1.6 ± 0.6, P = 0.01), and demonstrated more correct self-injection steps (13.1 ± 2.1 versus 10.8 ± 4.4, P = 0.05) as compared to participants receiving the PIFU-standard. CONCLUSION: Participants given "plain language" instructions had a significantly better understanding of how to prepare for and self-administer medication with a pen and were consistently more accurate in demonstrating how to self-inject.
24252050 Safety and efficacy of combination therapy of iguratimod with methotrexate for patients wi 2014 May OBJECTIVE: To obtain safety and efficacy data on combination treatment with iguratimod and methotrexate (MTX) in an open-label extension study in patients with active rheumatoid arthritis (RA). METHODS: Following a 28-week, randomized, double-blind trial of adding iguratimod or placebo to stable MTX therapy, patients entered a 24-week extension. Patients randomized to the iguratimod + MTX group continued treatment. Patients treated with placebo + MTX switched to iguratimod + MTX [the (placebo/iguratimod) + MTX group]. RESULTS: In the iguratimod + MTX group, the rate of 20% improvement in American College of Rheumatology criteria (ACR20) at week 52 (71.3%) was similar to that at week 24 (69.5%). ACR50, ACR70 and Health Assessment Questionnaire Disability Index at week 52 significantly improved compared with the values at week 24. In the (placebo/iguratimod + MTX) group, the switch to iguratimod treatment significantly improved ACR20 from 30.7% at week 24 to 72.1% at week 52. Frequent adverse events for 52 weeks in the iguratimod + MTX group were nasopharyngitis, upper respiratory tract inflammation, stomatitis, lymphocyte decrease, AST increase, ALT increase and blood iron decrease. These adverse events were predominantly mild or moderate in severity. No deaths occurred. CONCLUSION: Efficacy and tolerance of iguratimod + MTX therapy was maintained to 52 weeks in patients with active RA with inadequate response to MTX.
24743806 Significance of serum peptidylarginine deiminase type 4 in ANCA-associated vasculitis. 2014 Apr 18 OBJECTIVE: To investigate the clinical significance of peptidylarginine deiminase type 4 (PAD4) in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). To make a primary observation on the relationship of chronic bronchitis and bronchiectasis (CB) with the pathogenesis of AAV by PAD4. METHODS: The sera from 13 patients with AAV, 13 patients with CB, 11 patients with rheumatoid arthritis (RA), 11 patients with primary chronic kidney disease (CKD) and 12 normal controls were collected. Serum PAD4 was detected using commercial ELISA kits. The serum levels of PAD4 were compared not only among the different groups but also between the activity and remission stage of the same disease. The associations between serum PAD4 and the Birmingham Vasculitis Activity Score (BVAS) of AAV were further investigated. RESULTS: (1) The serum levels of PAD4 in patients with AAV, RA and CB at activity stage were all higher than that in the normal controls (P<0.001, respectively, α'=0.007). The serum level of PAD4 in patients with CB at remission stage and that in CKD group were not found elevated compared with the normal controls (P=0.02, P=0.085, respectively, α'=0.007). (2) At activity stage, among the groups of simple AAV, AAV with a long history of CB and CB without AAV, no significant difference was detected. While at remission stage among the 3 groups, the serum level of PAD4 was at the lowest level in CB group without AAV. (3) The serum level of PAD4 in some patients with CB without AAV were found still higher at remission stage. (4) The serum level of PAD4 in AAV with renal damage at activity stage was positively correlated with BVAS (the activity score of AAV, r=0.71, P=0.02). CONCLUSION: PAD4 is involved in the pathogenesis of AAV. Whether some patients with CB might progress to AAV by the link with PAD4 still need further investigation.
23053686 Accelerated infusion rates of rituximab are well tolerated and safe in rheumatology practi 2013 Jan Due to the possible risk of infusion reactions of rituximab (RTX), a slow infusion rate (total infusion time, 255 min) is suggested for rheumatological use. However, especially in oncology field, accelerated infusion of RTX is reported to be well tolerated and safe. The aim of our study was to evaluate whether accelerated infusion rates of RTX would similarly be safe and tolerable in rheumatoid arthritis (RA) patients and other off-label rheumatological indications. All patients treated with RTX for RA and other autoimmune diseases between May 2011 and January 2012 were recruited to the study. Each treatment course consisted of two RTX 1,000 mg infusions, 2 weeks apart. Total time of the infusion for the first cycle was 255 min. Second and subsequent infusions were administered over 120 min as follows: 0-30 min, 100 mg; 30-60 min, 200 mg; 60-90 min, 300 mg; and 90-120 min, 400 mg. The Clinical Trials Classification of Adverse Events (CTCAE) version 4.3 was used to categorise side effects. The study population comprised 68 patients [F/M, 59:9; mean age, 52.4 (10.6) years]: 60 with RA, 4 with systemic lupus erythematosus (SLE), 1 with non-Hodgkin's lymphoma with SLE and 3 with vasculitis. A total of 77 fast infusions were administered. Eleven patients (16.2 %) had taken a fast infusion at the first course. A total of nine patients experienced at least one AE. Seven patients had a reaction on the first infusion (infusion-related reaction (IRR)), two patients on the second infusion and one patient on both infusions. When graded from 1 to 5 according to CTCAE v. 4.3, grade 1 IRRs were observed in a total of seven patients and grade 2 IRR in three patients. In this study of fast infusions, adverse events after RTX were mostly mild and seem to be well tolerated. Faster rituximab infusion times seem to be safe and might be incorporated into routine practice.
25369029 Suppression of proteoglycan-induced autoimmune arthritis by myeloid-derived suppressor cel 2014 BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are innate immune cells capable of suppressing T-cell responses. We previously reported the presence of MDSCs with a granulocytic phenotype in the synovial fluid (SF) of mice with proteoglycan (PG)-induced arthritis (PGIA), a T cell-dependent autoimmune model of rheumatoid arthritis (RA). However, the limited amount of SF-MDSCs precluded investigations into their therapeutic potential. The goals of this study were to develop an in vitro method for generating MDSCs similar to those found in SF and to reveal the therapeutic effect of such cells in PGIA. METHODS: Murine bone marrow (BM) cells were cultured for 3 days in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF). The phenotype of cultured cells was analyzed using flow cytometry, microscopy, and biochemical methods. The suppressor activity of BM-MDSCs was tested upon co-culture with activated T cells. To investigate the therapeutic potential of BM-MDSCs, the cells were injected into SCID mice at the early stage of adoptively transferred PGIA, and their effects on the clinical course of arthritis and PG-specific immune responses were determined. RESULTS: BM cells cultured in the presence of GM-CSF, IL-6, and G-CSF became enriched in MDSC-like cells that showed greater phenotypic heterogeneity than MDSCs present in SF. BM-MDSCs profoundly inhibited both antigen-specific and polyclonal T-cell proliferation primarily via production of nitric oxide. Injection of BM-MDSCs into mice with PGIA ameliorated arthritis and reduced PG-specific T-cell responses and serum antibody levels. CONCLUSIONS: Our in vitro enrichment strategy provides a SF-like, but controlled microenvironment for converting BM myeloid precursors into MDSCs that potently suppress both T-cell responses and the progression of arthritis in a mouse model of RA. Our results also suggest that enrichment of BM in MDSCs could improve the therapeutic efficacy of BM transplantation in RA.
23263488 Chromatin marks identify critical cell types for fine mapping complex trait variants. 2013 Feb If trait-associated variants alter regulatory regions, then they should fall within chromatin marks in relevant cell types. However, it is unclear which of the many marks are most useful in defining cell types associated with disease and fine mapping variants. We hypothesized that informative marks are phenotypically cell type specific; that is, SNPs associated with the same trait likely overlap marks in the same cell type. We examined 15 chromatin marks and found that those highlighting active gene regulation were phenotypically cell type specific. Trimethylation of histone H3 at lysine 4 (H3K4me3) was the most phenotypically cell type specific (P < 1 × 10(-6)), driven by colocalization of variants and marks rather than gene proximity (P < 0.001). H3K4me3 peaks overlapped with 37 SNPs for plasma low-density lipoprotein concentration in the liver (P < 7 × 10(-5)), 31 SNPs for rheumatoid arthritis within CD4(+) regulatory T cells (P = 1 × 10(-4)), 67 SNPs for type 2 diabetes in pancreatic islet cells (P = 0.003) and the liver (P = 0.003), and 14 SNPs for neuropsychiatric disease in neuronal tissues (P = 0.007). We show how cell type-specific H3K4me3 peaks can inform the fine mapping of associated SNPs to identify causal variation.
23602891 Pregnancy outcome following in utero exposure to hydroxychloroquine: a prospective compara 2013 Aug OBJECTIVE: To evaluate pregnancy safety of hydroxychloroquine (HCQ) for rheumatologic diseases. DESIGN: Prospective comparative observational study done at the Israeli teratology information service between 1998 and 2006. RESULTS: 114 HCQ-exposed pregnancies (98.2% in the first trimester, T1) were followed-up and compared with 455 pregnancies of women counseled for non-teratogenic exposure. The difference in the rate of congenital anomalies was not statistically significant [7/97 (7.2%) vs. 15/440 (3.4%), p=0.094]. The analysis was repeated among those exposed in T1 excluding genetic or cytogenetic anomalies or congenital infections [5/95 (5.3%) vs. 14/440 (3.2%), p=0.355]. There were no cases of neonatal lupus erythematosus. The gestational age at delivery was earlier, rate of preterm delivery higher, and birth weight lower, in the HCQ group. CONCLUSION: The present study suggests that HCQ treatment in pregnancy is not a major human teratogen. The earlier gestational age and lower birth weight might be associated with maternal disease.
25294371 Hand function in rheumatic diseases: patient and physician evaluations. 2014 Nov AIM: Rheumatic diseases have repercussions in hand function. The m-SACRAH (modified Score for the Assessment and quantification of Chronic Rheumatoid Affections of the Hands) questionnaire evaluates hand function according to the patient's opinion. Our aim was to look for the clinical and para-clinical variables that correlate with m-SACRAH in rheumatic diseases. METHODS: Consecutive patients with diagnoses of rheumatoid arthritis (RA), osteoarthritis (OA), gout, and systemic sclerosis (SS) with hand involvement and who agreed to participate, answered the m-SACRAH and Health Assessment Questionnaire Disability Index (HAQ-DI) and underwent blinded and independent rheumatologist and physiatrist evaluations. Nerve conduction studies (NCS) and hand ultrasonography (USG) were performed. STATISTICAL ANALYSIS: Spearman's correlation and the Mann-Whitney U-test. RESULTS: Forty patients were included. There were 72% women and mean age of 49.25 ± 14.2 years. According to m-SACRAH patients were dived into two groups (mild vs. moderate-severe), only the number limited to motion joints were different among them (median 2 vs. 8 P = 0.036). Patients' perspective variables had a good correlation (HAQ-DI/mSACRAH: r = 0.43, P < 0.05), but only correlated with limited motion joints (r = 0.41, P < 0.05 for m-SACRAH and r = 0.31, P < 0.05 for HAQ-DI). Physician's evaluations had a good correlation. Visual analog scale of hand function with physiatrist evaluations: passive range of motion (r = -0.49, P = 0.001), sum of affected pinches (r = 0.66, P = 0.001), limited to motion joints (r = 0.34, P < 0.05) and palm-finger distance (r = 0.50, P = 0.05). Regarding para-clinical evaluations, only tenosynovitis by ultrasonography correlated with HAQ-Di (r = 0.357, P < 0.05). CONCLUSIONS: Patients' perspectives correlated with the number of limited motion joints but with none of the other physicians' and para-clinical evaluations. The patients' opinion about their function should play a major role in their management.
22874636 Breast reconstruction in the high risk patient with systemic connective tissue disease: a 2013 Jan INTRODUCTION: The presence of severe underlying connective tissue disease may restrict the reconstructive options offered to a woman in the event of mastectomy. Putative concerns about reconstructive surgery include the effects of connective tissue disease and immunosuppression on wound healing and donor site morbidity, and increased risks of deranged clotting and thrombophilia after free tissue transfer. There is also the possibility of an unpredictable tissue reaction after oncological resection surgery and adjuvant radiotherapy. METHODOLOGY: Here we present a review of the current sparse evidence regarding reconstructive breast surgery in this challenging group of patients. In addition we present a series of six consecutive patients with a spectrum of connective tissue disorders including combinations of longstanding Systemic Lupus Erythematosis (SLE), Rheumatoid arthritis and Raynaud's Disease who underwent successful post-mastectomy reconstruction with an extended autologous latissimus dorsi flap, along with subsequent successful correction of asymmetry and/or nipple reconstruction. RESULTS: There is a paucity of literature on this subject perhaps suggesting that surgeons are reluctant to offer reconstruction or that uptake is poor in this group. Complications related to radiotherapy and free tissue transfer in patients with severe CTD is less than may be expected. The most common complications experienced by our patients with CTD after extended ALD breast reconstruction were persistent donor site seroma, wound dehiscence and delayed haematoma formation, reflecting the abnormal inflammatory response and deranged haemostatic cascade common to connective tissue disease. However, all six patients made a full recovery from surgery without residual donor site morbidity and with an acceptable aesthetic breast reconstruction. CONCLUSION: Careful peri-operative management is crucial in this group of patients, but good outcomes are possible using a variety of reconstructive techniques. This is the first reported series of patients with severe connective tissue disease who have been managed with extended ALD breast reconstruction. The majority of complications relate to the donor site but the favourable outcomes demonstrate that the extended ALD flap remains a reliable reconstructive option for this group.
24908630 The PD-1/PD-Ls pathway and autoimmune diseases. 2014 Jul The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, is a new member of the B7/CD28 family, and consists of the PD-1 receptor and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273). Recently, it is reported that PD-1, PD-L1 and PD-L2 also have soluble forms aside from their membrane bound forms. The soluble forms increase the diversity and complexity of PD-1/PD-Ls pathway in both composition and function. The PD-1/PD-Ls pathway is broadly expressed and exerts a wider range of immunoregulatory roles in T-cell activation and tolerance compared with other B7/CD28 family members. Studies show that the PD-1/PD-Ls pathway regulates the induction and maintenance of peripheral tolerance and protects tissues from autoimmune attack in physiological conditions. In addition, it is also involved in various diseases mediated by T cells, such as autoimmunity, tumor immunity, chronic viral infections, and transplantation immunity. In this review, we will summarize the relevance of the soluble forms and the latest researches on the role of PD-1/PD-Ls pathway in autoimmune diseases.
25240110 Wnt5a: a player in the pathogenesis of atherosclerosis and other inflammatory disorders. 2014 Nov OBJECTIVE: The objective of this article is to review the current literature on Wnt5a and its signaling mechanism, along with its role in atherosclerosis. In addition, the significance of Wnt5a as a diagnostic marker and a potential therapeutic target is reviewed. Wnt5a, a secreted glycoprotein, belongs to a family of highly conserved proteins that regulate important processes such as cell fate specification, embryonic development, cell proliferation, migration, and differentiation in a variety of organisms. The complexity of Wnt5a signaling lies in the fact that Wnt5a can bind to different classes of frizzled receptors, receptor tyrosine kinase-like orphan receptor 2, as well as co-receptors such as low density lipoprotein receptor-related protein 5/6. Wnt5a signals primarily through the non-canonical pathway, where it mediates cell proliferation, adhesion, and movement. However, the role of Wnt5a in canonical signaling is still unresolved. Depending on the receptor availability, Wnt5a can serve to activate or inhibit the canonical Wnt signaling pathway. Due to the promiscuous nature of Wnt5a, it has been extremely difficult to fully understand its signaling mechanism. Wnt5a has recently emerged as a macrophage effector molecule that triggers inflammation. Perturbations in Wnt5a signaling have been reported in several inflammatory diseases, particularly in sepsis, rheumatoid arthritis, and atherosclerosis. CONCLUSION: Both existing and emerging evidence suggests that the expression of Wnt5a is always up-regulated in these, and possibly other inflammatory disorders. This knowledge can be useful for targeting Wnt5a and/or its receptor and downstream signaling molecules for therapeutic intervention in inflammatory disorders.
24108504 Methotrexate-induced nausea and vomiting in adolescent and young adult patients. 2014 Mar This study aims to determine the prevalence of methotrexate-induced nausea and vomiting in both adolescent and adult patients with inflammatory arthritis. A survey of methotrexate side effects was conducted on patients with inflammatory arthritis. We provided a brief questionnaire to unselected patients with inflammatory arthritis being treated with methotrexate attending adolescent and adult rheumatology clinics. The questions related to the presence, absence, and severity of nausea and vomiting, the temporal relationship with methotrexate and whether anti-emetics had been prescribed. A total of 106 patients from the age of 13 years and above--57 adults (over 20 years) and 49 adolescents (13-19 years) were included in this study. The median age for those experiencing nausea was 19 years (interquartile range (IQR) 7) and for those with no nausea 55 years (IQR 46) (p < 0.001). Thirty-six out of 49 adolescent patients reported nausea (73%) compared to only 20/57 adults (35%) (p < 0.001). Multiple logistic regression analysis showed that the nausea group had a significantly higher proportion of adolescents (p = 0.0002), patients taking subcutaneous (SC) methotrexate MTX (p = 0.002), and patients with duration of MTX of more than 1 year (p = 0.049). Adolescents were estimated to have over 6 times higher odds of nausea compared to adults (OR 6.31, 95% CI 2.38 to 16.75, p = 0.0002) after adjusting for SC MTX and duration of MTX. Only 22% of adolescents and 10% of adults were prescribed anti-emetics. There is a higher prevalence of MTX-induced nausea and vomiting in adolescents and younger adult patients with inflammatory arthritis compared to older adults. The role of anti-emetics in the treatment of these symptoms is unclear.