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ID PMID Title PublicationDate abstract
21035563 Bone marrow-derived cells: A potential approach for the treatment of xerostomia. 2011 Jan Transplantations of bone marrow-derived cells (BMDCs) are traditionally used for hematologic diseases, but there are increasing numbers of clinical trials using BMDC treatments for non-hematologic disorders, including autoimmune diseases. BMDCs are recently reported to improve organ functions. This paper will review available reports supporting the role of BMDCs in reducing xerostomia (i.e. re-establishing salivary gland functions) due to head and neck irradiation for cancer therapies and in Sjögren's syndrome. There are reports that BMDCs provide a beneficial effect on the saliva production. BMDCs positively affect blood vessels stability and regeneration in irradiated salivary glands. Also, BMDCs provide an immunomodulatory activity in mice with Sjögren's-like disease. While the exact mechanisms by which BMDCs improve organ functions remain controversial, there is preliminary evidence that a combination of them (such as cell transdifferentiation, vasculogenesis, and paracrine effect) occur in salivary glands.
22794096 Improving musculoskeletal health: global issues. 2012 Apr Musculoskeletal (MSK) disorders are among the leading reasons why patients consult a family or primary health practitioner, take time off work and become disabled. Many of the MSK disorders are more common in the elderly. Thus, as the proportion of the elderly increases all over the world, MSK disorders will make a greater contribution to the global burden of disease. Epidemiological studies have shown that the spectrum of MSK disorders in developing countries is similar to that seen in industrialised countries, but the burden of disease tends to be higher due to a delay in diagnosis or lack of access to adequate health-care facilities for effective treatment. Musculoskeletal pain is very common in the community while fibromyalgia is being recognised as part of a continuum of chronic widespread pain rather than a narrowly defined entity. This will allow research to improve our understanding of pain in a variety of diffuse pain syndromes. The availability of newer more effective therapies has resulted in efforts to initiate therapy at an earlier stage of diseases. The new criteria for rheumatoid arthritis, and the diagnosis of axial and peripheral involvement in spondyloarthritis, permit an earlier diagnosis without having to wait for radiological changes. One of the major health challenges is the global shortage of health workers, and based on current training of health workers and traditional models of care for service delivery, the global situation is unlikely to change in the near future. Thus, new models of care and strategies to train community health-care workers and primary health-care practitioners to detect and initiate the management of patients with MSK disorders at an earlier stage are required. There is also a need for prevention strategies with campaigns to educate and raise awareness among the entire population. Lifestyle interventions such as maintaining an ideal body weight to prevent obesity, regular exercises, avoidance of smoking and alcohol abuse, intake of a balanced diet and nutrients to include adequate calcium and vitamin D, modification of the work environment and avoidance of certain repetitive activities will prevent or ameliorate disorders such as osteoarthritis, osteoporosis, rheumatoid arthritis, gout and MSK pain syndromes including low back pain and work-related pain syndromes. These prevention strategies also contribute to reducing the prevalence and outcome of diseases such as hypertension, cardiovascular diseases, diabetes and respiratory diseases. Thus, prevention strategies require urgent attention globally.
22382344 Short-term risk of total malignancy and nonmelanoma skin cancers with certolizumab and gol 2012 Apr OBJECTIVE: To assess the risk of total malignancy and nonmelanoma skin cancers (NMSC) in patients with rheumatoid arthritis (RA) receiving certolizumab and golimumab through a metaanalysis of data from randomized control trials (RCT). METHODS: We systematically reviewed the literature up to May 2011 in Medline databases, as well as abstracts from the 2009 and 2010 annual meetings of the European League Against Rheumatism and the American College of Rheumatology. Mantel-Haenszel method was used to determine a common odds ratio (OR). Statistical heterogeneity was assessed by chi-square Q test. We selected only RCT including more than 30 RA subjects randomly assigned to an anti-tumor necrosis factor (TNF) or a nonbiological disease-modifying antirheumatic drug (DMARD) control group. RESULTS: The literature search identified 793 articles; 6 (2 with certolizumab and 4 with golimumab) were selected for metaanalysis. A total of 2710 patients received at least 1 dose of certolizumab or golimumab. For anti-TNF-treated patients, 18 cancers (excluding NMSC) and 9 NMSC were observed versus 4 cases of total malignancy and 3 NMSC in control groups. Metaanalysis revealed a pooled OR of 1.06 (95% CI 0.39-2.85) for risk of total malignancy and 0.69 (95% CI 0.23-2.11) for risk of NMSC with certolizumab and golimumab versus DMARD. Heterogeneity was not significant. CONCLUSION: Metaanalysis of RCT of golimumab and certolizumab did not find an increased risk of total malignancy and NMSC. These results must be confirmed with longterm extension studies and registry studies, and careful monitoring remains mandatory.
22021751 Non-steroidal anti-inflammatory drug (NSAID) related inhibition of aldosterone glucuronida 2011 May 20 OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular (CV) disease and are also commonly prescribed non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs). New in vitro evidence suggests that this increased CV risk may be mediated through aldosterone glucuronidation inhibition (AGI), which differs between NSAIDs (diclofenac>naproxen>indomethacin>ibuprofen). Our aim was to explore the association between ns-NSAID-related AGI and arterial dysfunction. METHODS: The extent (augmentation index, AIX%) and timing (reflected wave transit time, RWT, ms) of aortic wave reflection (measured using radial applanation pulse wave analysis, PWA, SphygmoCor device) were assessed on a single occasion in 114 consecutive RA patients without overt CV disease aged 40-65 years. A higher AIX% and lower RWT indicate arterial dysfunction. Assessment included a fasting blood sample, patient questionnaire and medical record review. Multivariate analysis was used to adjust for age, sex, mean blood pressure, smoking, cumulative erythrocyte sedimentation rate (ESR-years) and Stanford disability score. RESULTS: We identified 60 patients taking ns-NSAIDs and 25 non-users. Using a ns-NSAID with the highest AGI was associated with a higher AIX% (and lower RWT) versus treatment with a ns-NSAID with the lowest AGI (diclofenac AIX% 32.3, RWT 132.7 ms vs ibuprofen AIX% 23.8, RWT 150.9 ms): adjusted mean differences AIX% 6.5 (95% CI 1.0 to 11.9; p=0.02); RWT -14.2 ms (95% CI -22.2 to -6.3; p=0.001). Indomethacin demonstrated an intermediate level of arterial dysfunction. In relation to arterial dysfunction, both indomethacin and naproxen were more similar to diclofenac than to ibuprofen. CONCLUSIONS: ns-NSAID-related AGI is associated with arterial dysfunction in patients with RA. These findings provide a potentially novel insight into the CV toxicity of commonly used ns-NSAIDs. However, the findings are limited by the small number of patients involved and require further replication in a much larger study.
22015190 [Effects of Tuina and Chinese patent drug Shuxuetong injection on deep venous thrombosis a 2011 Oct OBJECTIVE: To evaluate the efficacy of Tuina and Chinese patent drug Shuxuetong injection in preventing patients undergoing total knee arthroplasty from deep venous thrombosis and in functional rehabilitation. METHODS: A total of 120 patients with diagnosed rheumatoid arthritis in the Department of Orthopaedic Surgery, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine in China were enrolled for this study. The patients underwent total knee arthroplasty and were divided into treatment group (n=60) and control group (n=60) after surgery. Patients in the control group received conventional rehabilitation training, including using a continuous passive motion machine and training of muscle contractions of the lower limb. Patients in the treatment group were administered Shuxuetong injection and Tuina based on the conventional rehabilitation training. The course of treatment lasted for 2 weeks. Hospital for Special Surgery (HSS) knee score, rate of deep venous thrombosis and range of motion of the knee joint were evaluated before and after treatment. RESULTS: There was no significant difference in HSS knee score and range of motion as compared before and after treatment in two group (P>0.05). The rate of deep venous thrombosis of the treatment group was 13.33%, which was lower than 20% of the control group (P<0.05). CONCLUSION: Tuina combined with Shuxuetong injection treatment can prevent deep venous thrombosis in patients with rheumatoid arthritis after total knee arthroplasty.
22161801 Association between systemic antipsoriatic drugs and cardiovascular risk in patients with 2012 Jun OBJECTIVE: Psoriasis is associated with ischemic heart disease (IHD). Results of prior studies have suggested that methotrexate (MTX) may improve vascular disease in patients with psoriasis and rheumatoid arthritis. The aim of this study was to assess the risk of new-onset IHDs in psoriasis patients, comparing those taking MTX with those taking other nonbiologic antipsoriatic drugs. METHODS: In this retrospective cohort study, we utilized claims data from the National Health Insurance Research Database of Taiwan to identify 179,200 subjects who had received a diagnosis of psoriasis, with or without psoriatic arthritis, on at least 3 visits. The risk of hospitalization for new-onset IHD was compared between psoriasis patients taking MTX monotherapy (n = 6,578; MTX case cohort) and psoriasis patients taking other nonbiologic antipsoriatic drugs (n = 5,471; reference control cohort) between January 1996 and December 2008. Additional adjustments were made for cardiovascular risk factors, number of hospital visits, Charlson comorbidity score, and use of other antiinflammatory drugs. RESULTS: The incidence rates of IHD were 666 cases per 100,000 person-years in the MTX case cohort and 830 cases per 100,000 person-years in the reference control cohort (unadjusted P = 0.027). Increasing age, male sex, presence of hypertension, presence of diabetes, Charlson comorbidity score, and use of phototherapies were independent risk factors for hospitalization related to a new IHD in the study cohorts. However, the multivariate-adjusted hazard ratio for IHD-related hospitalizations among patients receiving MTX, in comparison with those receiving other nonbiologic antipsoriatic drugs, was 0.97 (95% confidence interval 0.79-1.19), after adjustment for age, sex, comorbidity score, number of hospital visits, and other antiinflammatory treatments for psoriasis. CONCLUSION: In patients with psoriasis with or without coexisting psoriatic arthritis, the adjusted risk of hospitalization for an IHD among individuals receiving MTX was comparable with that among individuals receiving other nonbiologic antipsoriatic drugs.
23166324 Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor- 2013 Jan 4 The covalent transfer of heavy chains (HCs) from inter-α-inhibitor (IαI) to hyaluronan (HA) via the protein product of tumor necrosis factor-stimulated gene-6 (TSG-6) forms the HC-HA complex, a pathological form of HA that promotes the adhesion of leukocytes to HA matrices. The transfer of HCs to high molecular weight (HMW) HA is a reversible event whereby TSG-6 can shuffle HCs from one HA molecule to another. Therefore, HMW HA can serve as both an HC acceptor and an HC donor. In the present study, we show that transfer of HCs to low molecular weight HA oligosaccharides is an irreversible event where subsequent shuffling does not occur, i.e. HA oligosaccharides from 8 to 21 monosaccharide units in length can serve as HC acceptors, but are unable to function as HC donors. We show that the HC-HA complex is present in the synovial fluid of mice subjected to systemic and monoarticular mouse models of rheumatoid arthritis. Furthermore, we demonstrate that HA oligosaccharides can be used, with TSG-6, to irreversibly shuffle HCs from pathological, HMW HC-HA to HA oligosaccharides, thereby restoring HC-HA matrices from the inflamed joint to their normal state, unmodified with HCs. This process was also effective for HC-HA in the synovial fluid of human rheumatoid arthritis patients (in vitro).
22548187 The risk factors for nosocomial infection in chinese patients with active rheumatoid arthr 2012 Objective. To analyse the potential risk factors of nosocomial infections in patients with active rheumatoid arthritis (RA). Methods. A total of 2452 active RA patients at Hospitals in Shanghai between January 2009 and February 2011 were analyzed. Their demographic and clinical characteristics were compared with those without infection, and the potential risk factors were determined by logistic regression analysis. Results. Multivariate analysis indicated the gender (OR = 0.70, 95% CI 0.53-0.92), duration in hospital (OR = 1.03 , 95%CI 1.01-1.05), number of organs involved (OR = 0.82, 95%CI 0.72-0.92), number of disease-modifying antirheumatic drugs ((DMARDs) (OR = 1.22, 95%CI 1.061-1.40)), corticosteroid therapy (OR = 1.02, 95%CI 1.01-1.03), peripheral white blood cell counts ((WBC) (OR = 1.04, 95%CI 1.00-1.08)), levels of serum albumin (OR = 0.98, 95%CI 0.97-0.99), and C-reactive protein ((CRP) (OR = 1.03 , 95%CI 1.01-1.04)) that were significantly associated with the risk of infections. Conclusion. The female patients, longer hospital stay, more organs involved, more DMARDs, corticosteroid usage, high counts of WBC, lower serum albumin, and higher serum CRP were independent risk factors of infections in active RA patients.
21654058 Hemorheological profile in primary Sjögren's syndrome: a case-control study. 2011 Rheological blood behavior in primary Sjögren's syndrome (SS) has been scarcely investigated. We evaluated the rheological profile (blood viscosity, plasma viscosity, erythrocyte deformability, erythrocyte aggregation, erythrocyte aggregation time and erythrocyte disaggregation threshold) along with fibrinogen, high-sensitive C reactive protein, plasma lipids, immunoglobulins, total proteins and erythrocyte sedimentation rate in 22 patients with primary SS (2 males, 20 females, aged 58 ± 9 years) and in 22 healthy volunteers (3 males, 19 females, aged 57 ± 5 years). Patients showed statistically higher plasma viscosity, erythrocyte sedimentation rate and G immunoglobulin (IgG) levels and lower total cholesterol than controls (p = 0.006, p = 0.023, p = 0.034, p = 0.036, respectively). Three patients with extraglandular involvement showed the highest plasma viscosity values: 1.98 cP, 1.70 cP and 1.65 cP, respectively. No differences were observed for the other rheological parameters analyzed. In a multivariate regression analysis, only fibrinogen, triglycerides and IgG were independent determinants for plasma viscosity values (beta coefficient: 0.335; p = 0.001; beta coefficient: 0.242; p = 0.019; beta coefficient: 0.660; p < 0.001, respectively). Our results indicate that patients with primary SS show increased plasma viscosity, mostly related with IgG levels without other alterations in the rheological profile. Further research with a larger sample size achieved by multicenter studies would be desirable.
21359498 Extremely high serum ferritin levels as a main diagnostic tool of adult-onset Still's dise 2012 Apr Adult-onset Still's disease is a rare systemic inflammatory disease of unknown aetiology characterised by typical symptoms including daily high spiking fever, evanescent salmon-pink rash, sore throat, arthritis/arthralgias and polyserositis. The laboratory findings usually show neutrophilic leucocytosis, seronegativity and raised serum transaminases. We describe six typical cases. All of them had serum ferritin above 5,000 µg/L. Although there are few theories about the origin of the high ferritin level, an extremely high serum ferritin above 5,000 µg/L should be the main diagnostic tool of adult-onset Still's disease.
21280008 MicroRNA expression profiles as biomarkers of minor salivary gland inflammation and dysfun 2011 Feb OBJECTIVE: MicroRNA reflect physiologic and pathologic processes and may be used as biomarkers of concurrent pathophysiologic events in complex settings such as autoimmune diseases. We generated microRNA microarray profiles from the minor salivary glands of control subjects without Sjögren's syndrome (SS) and patients with SS who had low-grade or high-grade inflammation and impaired or normal saliva production, to identify microRNA patterns specific to salivary gland inflammation or dysfunction. METHODS: MicroRNA expression profiles were generated by Agilent microRNA arrays. We developed a novel method for data normalization by identifying housekeeping microRNA. MicroRNA profiles were compared by unsupervised mathematical methods to test how well they distinguish between control subjects and various subsets of patients with SS. Several bioinformatics methods were used to predict the messenger RNA targets of the differentially expressed microRNA. RESULTS: MicroRNA expression patterns accurately distinguished salivary glands from control subjects and patients with SS who had low-degree or high-degree inflammation. Using real-time quantitative polymerase chain reaction, we validated 2 microRNA as markers of inflammation in an independent cohort. Comparing microRNA from patients with preserved or low salivary flow identified a set of differentially expressed microRNA, most of which were up-regulated in the group with decreased salivary gland function, suggesting that the targets of microRNA may have a protective effect on epithelial cells. The predicted biologic targets of microRNA associated with inflammation or salivary gland dysfunction identified both overlapping and distinct biologic pathways and processes. CONCLUSION: Distinct microRNA expression patterns are associated with salivary gland inflammation and dysfunction in patients with SS, and microRNA represent a novel group of potential biomarkers.
20620090 Elderly onset of primary Sjögren's syndrome: clinical manifestations, serological feature 2011 Mar OBJECTIVES: To study and compare the clinical and serological features of patients with elderly versus adult and younger onset of primary Sjögren's syndrome (pSS). METHODS: We analyzed retrospectively 336 consecutive pSS patients followed at our unit. They were subdivided into three groups according to the age at disease onset: elderly (>65 years), adult (>40 and ≤65 years), and young (≤40 years). Clinical and immunological features of the disease, labial salivary glands biopsy, ocular and oral tests were collected at time of diagnosis and then compared among the three groups. RESULTS: In 21 (6%) patients, disease onset occurred after the age of 65 years. At the time of diagnosis, 15 (71.4%) of these patients reported symptoms of dry mouth and 16 (76.1%) of dry eye. The most common extraglandular manifestation were arthralgias in 14 (66.7%), Raynaud's phenomenon in five (23.8%) and purpura in three (14.2%) cases. Ocular diagnostic tests (Schirmer's I and Rose-Bengal staining) were positive respectively in 17 (80%) and nine (44.4%) patients. In eight (38%) cases, unstimulated whole salivary flow showed normal values, while 12 patients (57.1%) showed positivity for salivary sialography. A focus score greater or equal to 1 per 4mm(2) was demonstrated in 11 (53.3%) of the 21 cases. CONCLUSION: Elderly onset of pSS was associated with similar incidence of the diagnostic tests positivity (parotid sialography, ocular tests, minor salivary gland biopsy) in comparison with adult and younger onset. Moreover, no statistical differences were found among the three groups concerning sex, disease duration, as well as ocular and oral symptoms.
23118848 Skewed production of IL-6 and TGFβ by cultured salivary gland epithelial cells from patie 2012 OBJECTIVE: To determine the cytokine production profile of cultured salivary gland epithelial (SGE) cells obtained from patients with Sjögren's syndrome (SS). METHODS: SGE cells obtained from 9 SS patients and 6 normal controls were cultured in the presence of exogenous IFNγ. Cell proliferation and apoptosis in response to IFNγ were determined by WST1 assay and by FACS analysis. The concentrations of IL-6 and TGFβ secreted into culture supernatants were analyzed by ELISA. RESULTS: IFNγ did not significantly affect the proliferation or apoptosis of SGE cells. However, IL-6 concentrations were higher, and TGFβ concentrations were lower, in culture supernatants of SGE cells from SS patients than from normal controls. CONCLUSION: Cytokine production by SGE cells from SS patients showed a skewed balance compared with normal controls, with increased IL-6 and decreased TGFβ secretion. This imbalance may be critical in the regulation of Treg/Th17 cells and may foster a pathogenic milieu that may be causative and predictive in SS.
22374447 [Impaired expression of Act1mRNA in B cells of patients with Sjögren's syndrome]. 2012 Sjögren's syndrome (SS) is a systemic autoimmune disorder characterized by profound lymphocytic infiltration into the lacrimal and salivary glands, thereby diminished secretory function. B cell hyper-activation is a predominant feature of SS related to hypergammaglobulinemia and production of autoantibodies. The adaptor molecule NF-kB activator 1 (Act1) plays an important role in the homeostasis of B cells by attenuating CD40 and B cell-activating factor belonging to the tumor necrosis factor family receptor (BAFFR) signaling. Act1-deficient mice develop autoimmune manifestations similar to SS, which are hypergammaglobulinemia, high levels of anti-SSA and anti-SSB autoantibodies. In this study, to investigate the role of Act1 in the pathogenesis of SS, we examined Act1mRNA expressions in B cells from patients with SS and discussed the association of Act1 with parameters and clinical manifestations of SS. We showed the low level of Act1mRNA expression in patients with SS and reciprocal association of Act1 with serum IgG level. Diminished Act1mRNA expression in SS may be associated with B cell hyperactivity and elevated immunoglobulin production in SS by uncontrolled B cell activation signal through CD40 and BAFFR.
20309693 Hydroxychloroquine improves dry eye symptoms of patients with primary Sjogren's syndrome. 2011 Aug The objective of the study is to investigate the effect of hydroxychloroquine (HCQ) on subjective and objective parameters of dry eye in patients with primary Sjogren's disease and to evaluate the association of tear fluid B-cell activating factor (BAFF) level with the response. Thirty-two patients with primary Sjogren's disease were enrolled in this prospective study. All patients included in the study completed at least a 48-month run-in period of using hydroxychloroquine. Patients were then instructed to drop the treatment for 3 months. Baseline and post cessation of treatment (baseline and 3 months) evaluations included, subjective symptom scoring, fluorescein and lissamine green staining, Schirmer's test, tear break-up time (BUT) and tear fluid BAFF assessments. Significant worsening was observed in, tear break up-time (TBUT) (7.9 ± 3.4 vs. 5.9 ± 2.9, P < 0.001) lissamine green of staining of the ocular surface (1.3 ± 0.9 vs. 1.8 ± 0.8, P < 0.01) and corneal fluorescein staining scores (2.2 ± 2.1 vs. 4.6 ± 3.3, P < 0.003) between on and off HCQ treatment, respectively. Similarly, gritty sensation and burning sensation were significantly changed at week 12 compared to baseline evaluation (1.18 ± 1.02 vs. 1.7 ± 1.05, P < 0.007 and 1.1 ± 1.0 vs. 1.6 ± 1.2, P < 0.0, respectively). Disease duration significantly correlated with baseline OSDI (r = 0.38, P < 0.04) and the average daily use of artificial tears (r = 0.36, P < 0.04). The mean BAFF levels were 0.8 ± 0.5 and 4.0 ± 0.7 ng/ml for baseline and week 12 evaluation, respectively (P < 0.0001). The results of this study suggest that HCQ may alleviate symptoms and signs of dry eye in pSS and decreases tear fluid BAFF levels.
22531553 Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical signi 2012 Apr 24 INTRODUCTION: B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play a crucial role in B cell development, survival, and antibody production. Here we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with an immunoglobulin (Ig) G4-related disease (IgG4-RD). METHODS: We measured serum levels of BAFF and APRIL in patients with IgG4-RD, primary Sjögren's syndrome (pSS), and healthy individuals. Serum BAFF and APRIL levels in IgG4-RD were assessed for correlations with serological parameters, including Ig, particularly IgG4, and the number of affected organs. Serum BAFF and APRIL levels in IgG4-RD were monitored during glucocorticoid (GC) therapy. RESULTS: Serum BAFF and APRIL levels in patients with IgG4-RD were significantly higher (P < 0.01) than in healthy individuals. The BAFF levels of patients with IgG4-RD were comparable to those of patients with pSS. Although clinical parameters, such as serum IgG4 and the number of affected organs, were not correlated with the levels of BAFF, serum APRIL levels were inversely correlated with serum IgG4 levels (r = -0.626, P < 0.05). While serum BAFF levels decreased following GC therapy, serum APRIL levels increased during follow-up. CONCLUSION: These results indicate that BAFF and APRIL might be useful markers for predicting disease activity in IgG4-RD. Further studies are needed to elucidate the role of BAFF and APRIL in the pathogenesis of IgG4-RD.
22253903 Interleukin-1 inhibition and fatigue in primary Sjögren's syndrome--a double blind, rando 2012 OBJECTIVES: Fatigue is a major cause of disability in primary Sjögren's syndrome (pSS). Fatigue has similarities with sickness behaviour in animals; the latter mediated by pro-inflammatory cytokines, in particular interleukin (IL)-1, acting on neuronal brain cells. We hypothesised that IL-1 inhibition might improve fatigue in pSS patients; thus, we examined the effects and safety of an IL-1 receptor antagonist (anakinra) on fatigue. METHODS: Twenty-six pSS patients participated in a double-blind, placebo-controlled parallel group study. Patients were randomised to receive either anakinra or a placebo for four weeks. Fatigue was evaluated by a fatigue visual analogue scale and the Fatigue Severity Scale. The primary outcome measure was a group-wise comparison of the fatigue scores at week 4, adjusted for baseline values. Secondary outcome measures included evaluation of laboratory results and safety. The proportion of patients in each group who experienced a 50% reduction in fatigue was regarded as a post-hoc outcome. All outcomes were measured at week 4. RESULTS: There was no significant difference between the groups in fatigue scores at week 4 compared to baseline after treatment with anakinra. However, six out of 12 patients on anakinra versus one out of 13 patients on the placebo reported a 50% reduction in fatigue VAS (p = 0.03). There were two serious adverse events in each group. CONCLUSIONS: This randomised, double-blind, placebo-controlled trial of IL-1 blockade did not find a significant reduction in fatigue in pSS in its primary endpoint. A 50% reduction in fatigue was analysed post-hoc, and significantly more patients on the active drug than on placebo reached this endpoint. Although not supported by the primary endpoint, this may indicate that IL-1 inhibition influences fatigue in patients with pSS. TRIAL REGISTRATION: ClinicalTrials.gov NCT00683345.
22119104 Biological agents in the management of Felty's syndrome: a systematic review. 2012 Apr OBJECTIVE: To review and summarize the information available on the effectiveness and safety of biological therapies in refractory Felty's syndrome (FS). METHODS: We describe a case of FS with severe neutropenia and recurrent bacterial infections unresponsive to disease-modifying antirheumatic drug treatment and long-term administration with granulocyte colony-stimulating factor, in which treatment with rituximab (RTX) was useful and resulted in a sustained neutrophil response. Current evidence on the use of biological therapies in FS is also analyzed through a systematic review of the English-language literature, based on a PubMed search. RESULTS: Available data on the use of biological therapies in refractory FS are based only on several case reports and are limited to the use of RTX and some anti-tumor necrosis factor α agents (etanercept, infliximab, and adalimumab). Including the case described here, data are available on 8 patients treated with RTX. A sustained increase in the absolute neutrophil count (>1500/mm(3)) was observed in 62.5% (5/8) of these patients after 1 cycle of treatment. In most of them, the hematological response was accompanied by a parallel improvement in biological markers of inflammation and other clinical manifestations of FS (arthritis, recurrent infections, systemic symptoms, etc). After a median follow-up of 9 months (range, 6-14), only 1 of these patients relapsed and neutropenia reappeared; in this patient, retreatment was rapidly effective. No significant adverse events related to RTX therapy were reported. Experience with anti-tumor necrosis factor agents is limited to 6 patients, none of whom presented any sustained increase in neutrophil count. CONCLUSIONS: Although it is not yet possible to make definite recommendations, the global analysis of all cases reported to date only supports the use of RTX as a second-line therapy in patients with refractory FS.
22047044 Correspondence between salivary proteomic pattern and clinical course in primary Sjögren 2011 Nov 2 BACKGROUND: In the last years human proteomic has represented a promising tool to promote the communication between basic and clinical science. METHODS: To explore the correspondence between salivary proteomic profile and clinical response, herein, we used a proteomic approach to analyse the whole saliva of a patient with primary Sjögren's Syndrome (pSS) and non-Hodgkin's-MALT type parotid lymphoma before, during and after a standard treatment with cyclophosphamide (CTX) and rituximab (RTX). To identify any discriminatory therapeutic salivary biomarker patient's whole saliva was collected at the baseline, after the fourth infusion of rituximab, and on remission and analysed combining two-dimensional electrophoresis (2DE) and MALDI-TOF/TOF mass spectrometry. RESULTS: Proteomic results obtained from the comparison of salivary samples indicated several qualitative and quantitative modifications in the salivary expression of putative albumin, immunoglobulin J chain, Ig kappa chain C region, alpha-1-antitrypsin, haptoglobin and Ig alpha-1 chain C region. CONCLUSION: This study suggests that clinical and functional changes of the salivary glands driven by autoimmune and lymphoproliferative processes might be reflected in patients' whole saliva proteins, shedding new light on the potential usefulness of salivary proteomic analysis in the identification of prognostic and therapeutic biomarkers for patients with pSS and non Hodgkin's lymphomas.
21327686 Assessing joint involvement in haemophilia by clinical rheumatologic scores. A pilot study 2011 Jul Because of joint haemorrhages, severe haemophilia subjects often have limitations in their daily activities. Current orthopaedic scores (OJS) in haemophilia miss mild joint impairments and only pick up severe alterations. Twelve young severe haemophiliacs (20.25 ± 1.9 years of age), were evaluated for OJS as well as for indices employed in rheumatoid arthritis [28-joint Disease Activity Score (DAS-28), Ritchie index, Health Assessment Questionnaire (HAQ), visual analogue scale (VAS)], spondyloarthritis [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), HAQ, VAS] and osteoarthritis [Knee injury and Osteoarthritis Outcome Score (KOOS), VAS]. Twenty-four matched apparently healthy subjects and 29 subjects with psoriatic arthritis (PsA) with oligoarticular involvement (one to three swollen joints) served as controls. In addition to the impairment of target joints (elbow, in five of five in those on-demand treatment; three, elbows; four, knee in those on secondary prophylaxis), HAQ (mean 0.71 ± 0.95) and VAS (3.12 ± 2.36) documented a quality of life and a perception of pain in haemophiliacs similar to that of PsA subjects (p = 0.061 and p = 0.063, respectively). Their Ritchie index did not differ from that of subjects with psoriatic arthritis (5.75 ± 8.1 vs 7.73 ± 9.22; p = 0.408), nor did the BASDAI score with respect to psoriatic arthritis patients (p = 0.105). Six of 12 haemophiliacs (50%) had KOOS values from 70 to 50 (significant function joint impairment); 3 of 12 (25%) showed DAS-28 values >3.2 (moderate disease activity), 2 of 12 (16.6%) severe disease activity (>5.1). All these indices significantly correlated with VAS and HAQ in haemophilia subjects. A rheumatologic assessment may help identify early polyarticular disease and subclinical abnormalities involving joints not usually studied (not target joint) in haemophiliacs. These pilot data provide the rationale for testing a systemic involvement in haemophiliacs by means of high-tech imaging and to start early-onset prophylaxis/treatment in this setting.