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1.  Comparisons of Body Image Perceptions of a Sample of Black and White Women with Rheumatoid Arthritis and Fibromyalgia in the US 
Objective :
To explore the disease-related, body image (BI) perceptions of women diagnosed with, rheumatoid arthritis (RA) and fibromyalgia (FM).
Methods :
A purposive sample of twenty-seven females participated in individual semi-structured phone interviews to elicit BI perceptions relative to pain, activity limitations and coping measures. Sessions were digitally recorded, transcribed verbatim, and content analyzed.
Results :
Body image perceptions relative to 5 major themes emerged in the analysis. They focused on Pain, Disease Impact on Physical and Mental Function, Weight, Diseased-Induced Fears and, Coping measures. Pain was a common experience of all participants. Other troubling factors verbalized by participants included dislike and shame of visibly affected body parts, and disease-induced social, psychological and physical limitations. RA participants thought that manifested joint changes, such as swelling and redness, undergirded their prompt diagnosis and receipt of health care. Contrarily, women with fibromyalgia perceived that the lack of visible, disease-related, physical signs led to a discounting of their disease, which led to delayed health care and subsequent frustrations and anger. All but one participant used prayer and meditation as a coping measure.
Conclusion :
The body image perceptions evidenced by the majority of participants were generally negative and included specific focus on their disease-affected body parts (e.g. joints), mental function, self-identity, health care experiences, activity limitations and overall quality of life. Given the global effect of RA and FM, assessment and integration of findings about the BI perceptions of individuals with FM and RA may help define suitable interdisciplinary strategies for managing these conditions and improving participants’ quality of life.
PMCID: PMC4319189
Black women; body image; fibromyalgia; perceptions; rheumatoid arthritis; white women.
2.  Comparing Five Year Out-Come in Two Cohorts of Patients with Early Rheumatoid Arthritis – A BARFOT Study 
The objective of the study was to compare disease characteristics over the first 5 years of disease in patients with RA, with disease onset in 1990s and 2000s, respectively.
Methods :
All 2235 patients with early RA (disease duration ≤12 months) were recruited from the BARFOT prospective observational study. These patients were divided into group 1 included 1992 to 1999 (N=1084, 66% women) and group 2 included 2000 to 2006 (N=1151, 69% women). Disease Activity Score (DAS28), VAS pain and Health Assessment Questionnaire (HAQ) were assessed during 5 years. Remission was defined as DAS28 <2.6.
Results :
At inclusion, both women and men in group 2 had higher mean DAS28 (SD) than group 1, 5.42 (1.22) vs 5.26 (1.19), p=0.004 and 5.28 (1.22) vs 5.00 (1.27), p=0.004, respectively, mainly dependant on pain and not on inflammatory related measures. Over time DAS28 decreased and was in both genders, from 6 months to the 5-year follow-up, significantly lower in group 2. At 5-year, both women and men in group 2 had higher rate of remission than women and men in group 1. However, despite reduction of VAS pain and HAQ there were no differences in pain and HAQ between groups at any time point.
Conclusion :
Patients included in the 2000s achieved higher frequency of remission at the 5 year follow-up compared with those included in the 1990s, suggested to reflect the more active medical treatment. Interestingly, however, improvement in pain and HAQ did not differ between the two patient cohorts.
PMCID: PMC4319195
Disease activity; early RA; HAQ; pain; “cohort compare”; rheumatoid arthritis.
3.  Resilience and Treatment Adhesion in Patients with Systemic Lupus Erythematosus 
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune, rheumatic inflammatory disease that can cause significant morbidity with evident psychological impacts and obvious harm to quality-of-life that require the patient to adapt treatment.
Assessment of resilience and the self-reported treatment adhesion behaviors of patients with SLE, investigating which of these factors are associated to resilience.
Cross-sectional study of 40 women with SLE. A questionnaire with social demographic data, health history and the Wagnild Young Resilience Scale were used.
62.5% followed the medical treatment properly but 55% found it difficult. 27.5% of the patients presented low resilience, 57.5% medium and 15% high resilience. Resilience was associated in the chi-square test (p-value < 0.05) with the variables work, understanding SLE, trying to find out about SLE, following the treatment correctly, difficulty in following the treatment and stopping some activity because of the disease. In the correlation analysis, resilience was associated with age (-0.3960), number of working hours (0.5533), specialized treatment duration (-0.8103) and disease duration from diagnosis (-0.8014).
Patients with high resilience tended to follow treatment correctly, tried to understand the disease and adhered more to the treatment to avoid risks and promote protection factors. Therefore knowledge of resilience in patients with SLE is necessary. It is important that the state takes necessary actions to facilitate access to treatment, to educational programs and to medical support. Awareness and counselling sessions must be initiated to develop and promote individual capacities to learn how to tackle with the disease for which psychological support of family and doctors can play a significant role.
PMCID: PMC3963129  PMID: 24665352
Resilience; treatment adhesion; systemic lupus erythematosus.
4.  Adult-Onset Still’s Disease Associated with Thyroid Dysfunction: Case Report and Review of the Literature 
To our knowledge, the possible unveiled interaction between adult-onset Still’s disease (AOSD) with autoimmune thyroid disease (AITD) has never been reported although it is well established that systemic autoimmune disease may usually occur in relation to AITD. As increasingly clear links of AITD with other autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS) have been reported, and the incidence of AOSD concurrent AITD draws our attention rapidly. In this study, we searched relevant literatures published in the past 30 years to explore that condition.
PMCID: PMC4110384  PMID: 25067964
Adult-onset Still’s disease; autoimmune thyroid disease.
5.  Prevalence of Group A Beta-Hemolytic Streptococcus Oropharyngeal Colonization in Children and Therapeutic Regimen Based on Antistreptolysin Levels: Data from a City From Southern Brazil 
The aim of this study is to determinate the prevalence of oropharyngeal colonization by group A beta-hemolytic Streptococcus (GABHS) in pediatric population of Ponta Grossa, a midsize city of southern Brazil; estimate the effectiveness of antistreptolysin-O (ASO), compared to culture, in presence of infection; and design an unpublished investigative algorithm of rheumatic fever's suspicion, based on needs identified in worldwide consensus. It is an epidemiologic, observational and transversal study, involving 180 children younger than 12 years. Secretion of posterior oropharynx was collected for culture; and peripheral blood for determination of ASO. Student-t and chi-square tests, with Yates correction, were performed for statistical analysis. The ASO cutoff was determined by Receiver Operating Characteristic (ROC) curve. The prevalence encountered was 3.9%, and 25.5% of the children showed reagent ASO. This serological test demonstrated quantitatively and qualitatively significant associations to the GABHS presence (p=0.0001 for both associations) throughout the ROC curve, 200 U Todd was the value that resulted in the best accuracy, demonstrating 100% of sensibility and 80% of specificity in the GAS infection documentation. Also, it was found that the value of 1.200 U represents a specificity of 100%. The results emphasize the need for similar studies in other populations, to provide better targeting of the diagnosis and treatment of oropharyngitis by GABHS, which in turn can prevent up to 80% the cases of rheumatic fever, and consequently, the chronic rheumatic heart disease.
PMCID: PMC4136371  PMID: 25136388
Antistreptolysin-O; group A Streptococcus; oropharynx; rheumatic fever.
7.  A Case with Atypical Clinical Course Diagnosed as Osteoarthritis, Osteonecrosis, Subchondral Insufficiency Fracture, or Rapidly Destructive Coxopathy 
Osteonecrosis (ON), subchondral insufficiency fracture (SIF), and rapidly destructive coxopathy (RDC) are considered to be clinically different disorders despite exhibiting several overlapping features. We encountered an elderly female patient with an atypical clinical course who was radiographically diagnosed as having osteoarthritis (OA), ON, SIF, and/or RDC over a long-term follow-up. In this case, radiographic diagnosis was apparently affected by the timing of imaging evaluation and was challenging because of radiographic overlap and atypical disease progression. The disorders of OA, SIF, ON, and RDC might share a similar pathophysiology.
PMCID: PMC4166791  PMID: 25250098
8.  Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters in Patients with Rheumatoid Arthritis 
Serum adenosine deaminase (ADA) has been previously proposed to predict disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the level of serum ADA, and the relationship between ADA and disease activity markers, in a group of patients with RA.
A hundred and 10 patients with a diagnosis of RA were recruited from outpatient clinic of Rheumatology Unit. Demographic properties comprising age, gender, disease duration and drugs were recorded. Disease activity based on disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28- C reactive protein (CRP,) ESR, CRP levels, as well as pain by visual analog scale and rheumatoid factor (RF) were recorded. Serum ADA levels (IU/L) were determined in all RA patients and in 55 age and sex similar healthy control subjects.
Ninety-six female and 14 male RA patients with a mean age of 54.32±11.51, and with a mean disease duration of 11.5±9.13 years were included to the study. The control group comprised of 48 female and 7 male healthy subjects. 35.5% of the patients were on methotrexate (MTX) and 64.5% of patients were on combined DMARDs or combined MTX and anti-TNF therapies. The mean serum ADA level was statistically higher in RA patients than in control subjects (27.01±10.6 IU/L vs 21.8 ±9.9 IU/L). The mean values of ESR (23.2±14.8 mm/h), CRP (1.71±1.11mg/dL), pain by VAS (37.2±27.1), DAS28-ESR (2.72±0.77), DAS28 CRP (1.37±0.5) were not correlated with ADA levels (p>0.05).
Our results have shown that serum ADA levels are higher in RA patients than in controls but were not related with any of the disease activity markers. We conclude that ADA in the serum may not be a reliable biochemical marker to predict disease activity in patients with RA.
PMCID: PMC4166793  PMID: 25279018
Adenosine deaminase; disease activity; rheumatoid arthritis; serum.
9.  Lack of Association of the CD247 SNP rs2056626 with Systemic Sclerosis in Han Chinese 
Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors. A recent genome-wide association study (GWAS) indicated that CD247 was strongly associated with SSc, which was subsequently confirmed in a SSc cohort of European population. However, genetic heterogeneity in different ethnic populations may significantly impact the complex trait of SSc. The studies herein aimed to examine whether the SSc-associated SNP rs2056626 of CD247 identified in Caucasian is also associated with Han Chinese SSc. A Han Chinese cohort consisting of 387 SSc patients and 523 healthy controls were examined in the studies. TaqMan assays were performed to examine the SNP. Exact p-values were obtained (Fisher’s test) from 2x2 tables of allele counts and disease status. The results showed that there was no association between rs2056626 of CD247 and SSc or any SSc subtypes of Han Chinese. The negative results are important in understanding genetics of SSc in different ethnic populations, which further suggest complex nature of genetics of SSc.
PMCID: PMC4192828  PMID: 25317213
CD247; Chinese population; genetics; polymorphism/SNP; scleroderma systemic sclerosis/SSc.
10.  The Pathophysiology and Progression of Hip Osteoarthritis Accompanied with Joint Pain are Potentially Due to Bone Alterations - Follow-up Study of Hip OA Patients 
Objectives :
This study examined hip osteoarthritis (OA) patients with joint pain and accompanying signal changes detected by magnetic resonance imaging (MRI).
Methods :
A total of 19 hip OA patients with suddenly occurring or worsening pain regardless of Kellgren-Lawrence grading were enrolled. The patients were monitored using MRI, plain radiographs, and the Denis pain scale for a minimum of 6 months. The patients were classified into 2 groups: those whose pain improved during conservative treatment (Group A) and those whose pain persisted (Group B).
Results :
Joint pain disappeared or was markedly improved in all 10 cases in Group A. Radiographic OA progression occurred in 7 of 8 cases with available radiographs. Hip MRI was performed on 7 of 10 patients, among whom bone signal changes disappeared in 6 patients. One patient exhibited persisting bone signal alterations although joint pain had completely disappeared. In Group B, joint pain remained in all 9 cases. Radiographic OA progression occurred in 8 of 9 cases, and local (4 cases) or broad (5 cases) bone signal alterations were present in end-point MRI examinations. Two patients exhibited different regional MRI bone signal changes (local or broad) at the end of follow-up. The mean age of Group B was significantly higher than that of Group A.
Conclusion :
This study uncovered the following observations: 1) hip OA with joint pain had bone alterations that were detectable by MRI, 2) these bone alterations disappeared when joint pain improved, 3) bone alterations remained when joint pain continued, and 4) radiographic OA progressed to a more advanced stage over a short time period. These findings indicate that the pathophysiology of OA, joint pain, and OA progression may primarily be due to bone changes.
PMCID: PMC4192849  PMID: 25317214
Bone alteration; hip; joint pain; MRI; OA.
11.  Long-Term (1-Year) Safety and Efficacy of a Single 6-mL Injection of Hylan G-F 20 in Indian Patients with Symptomatic Knee Osteoarthritis 
The prevalence of symptomatic knee osteoarthritis (OA) among Asians ≥65 years is estimated to double by 2040. This study was designed to evaluate the safety and efficacy of a single, 6-mL intra-articular injection of hylan G-F 20 in Indian patients with knee OA at 26 weeks through to 52 weeks.
This study was an open-label, multicentre, phase 4 clinical trial. Enrolled patients (N=394) were ≥30 years old with Kellgren-Lawrence grade 1–3 OA; all patients received hylan G-F 20. WOMAC, SF-12, PTGA, and COGA scores, and OA medication use were evaluated at weeks 1, 4, 12, 26, 39, and 52 (initial treatment phase). At 26, 39, or 52 weeks, eligible patients could participate in a repeat treatment phase. McNemar-Bowkers, paired t-tests and ANOVA analyses were performed (alpha=0.05).
At 26 weeks, statistically significant changes from baseline were observed in all efficacy parameters, including the primary efficacy endpoint of WOMAC A1 (p<0.0001). Improvements continued for 52 weeks. No significant changes occurred in concomitant medication use. Eleven patients (2.8%) were re-injected at week 26 or 52. After repeat injection, statistically significant decreases were observed in WOMAC A1, WOMAC C and PTGA scores (p≤0.028). Twenty-three (5.8%) patients reported 26 local target knee AEs.
Among Indian patients within this study, a 6-mL hylan G-F 20 injection was well tolerated and effective in treating symptomatic knee OA with significant long-term (1 year) improvement of outcomes. When needed, repeat treatment was safe and efficacious for 4 weeks.
Trial Registration:
Clinical Trial Registry of India (CTRI/2010/091/000052)
PMCID: PMC4196249  PMID: 25328555
Hyaluronan; hylan G-F 20; osteoarthritis; Western Ontario and McMaster Universities Osteoarthritis Index.
12.  Temporal and Spatial Expression Patterns of Bone Morphogenetic Protein 3 in Developing Zebrafish 
Bone morphogenetic proteins (BMPs) are important elements in bone biology. We herein report the expression profiles of zebrafish bmp3 (zbmp3) as demonstrated by real-time PCR and in situ hybridization. The expression of zbmp3 was highly detectable by real-time PCR from 1 day post-fertilization (1 dpf) to 2 weeks post-fertilization (2 wpf) and peaked at 1 wpf. For in situ hybridization experiments, zbmp3 was expressed in the otic vesicle at 1 dpf, 2 dpf, 3 dpf, and 5 dpf. It was also expressed in the pharyngeal arches, including the opercle, branchiostegal ray, and pectoral fins, at 2 dpf. Our results suggest that zbmp3 may play an important role in the skeletal biology of developing zebrafish.
PMCID: PMC4196250  PMID: 25328556
Bmp3; Expression patterns; Zebrafish.
13.  Systemic Sclerosis is a Complex Disease Associated Mainly with Immune Regulatory and Inflammatory Genes 
Systemic sclerosis (SSc) is a fibrotic and autoimmune disease characterized clinically by skin and internal organ fibrosis and vascular damage, and serologically by the presence of circulating autoantibodies. Although etiopathogenesis is not yet well understood, the results of numerous genetic association studies support genetic contributions as an important factor to SSc. In this paper, the major genes of SSc are reviewed. The most recent genome-wide association studies (GWAS) are taken into account along with robust candidate gene studies. The literature search was performed on genetic association studies of SSc in PubMed between January 2000 and March 2014 while eligible studies generally had over 600 total participants with replication. A few genetic association studies with related functional changes in SSc patients were also included. A total of forty seven genes or specific genetic regions were reported to be associated with SSc, although some are controversial. These genes include HLA genes, STAT4, CD247, TBX21, PTPN22, TNFSF4, IL23R, IL2RA, IL-21, SCHIP1/IL12A, CD226, BANK1, C8orf13-BLK, PLD4, TLR-2, NLRP1, ATG5, IRF5, IRF8, TNFAIP3, IRAK1, NFKB1, TNIP1, FAS, MIF, HGF, OPN, IL-6, CXCL8, CCR6, CTGF, ITGAM, CAV1, MECP2, SOX5, JAZF1, DNASEIL3, XRCC1, XRCC4, PXK, CSK, GRB10, NOTCH4, RHOB, KIAA0319, PSD3 and PSOR1C1. These genes encode proteins mainly involved in immune regulation and inflammation, and some of them function in transcription, kinase activity, DNA cleavage and repair. The discovery of various SSc-associated genes is important in understanding the genetics of SSc and potential pathogenesis that contribute to the development of this disease.
PMCID: PMC4200700  PMID: 25328554
CD247; genetics; genome-wide association studies; HLA class genes; IRF5; scleroderma; STAT4; Systemic sclerosis.
14.  Response to Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis for Function and Pain is Affected by Rheumatoid Factor 
Objectives :
To investigate differences in response to tumor necrosis factor inhibitor treatment (TNFi) in seropositive (rheumatoid factor positive; RF+) versus seronegative (RF-) patients with established RA as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI) and pain.
Methods :
RA patients from an established RA cohort were studied according to rheumatoid factor (RF) status for change in HAQ-DI and pain (0-3 VAS) one year after starting treatment with a TNFi.
Results :
There were 238 patients treated with TNFi who had follow-up data (178 RF+ and 60 RF-). Disease duration was longer in RF+ vs RF- (12+8 vs 8+8 years) but the proportion of females (82% vs 72%, P=0.7), baseline HAQ-DI (1.44+0.63 vs 1.41+0.63, P=0.8) and pain (1.92+0.67 vs 1.93+0.67, P=0.9) were not different. The mean duration of treatment of first TNFi was 2.8 vs 2.3 years, P=0.1 and 68% of RF+ vs 62% of RF- were still receiving first TNFi at last visit (P=0.5). For patients with data at baseline and one year, the one-year HAQ-DI change was significantly greater in 90 RF+ patients (-0.356) versus 38 RF- patients (-0.126; P=0.04). The mean pain improvement was also greater in 77 RF+ vs 32 RF- patients (-0.725 vs -0.332 respectively; P=0.03). Numbers are small, data are missing and comorbidities, DAS28 and anti-CCP were not collected.
Conclusion :
Despite limitations in the data, in established RA after failure of DMARDs, RF+ patients may be more responsive to TNFi therapy as measured by changes in HAQ-DI and pain.
Innovation :
There may be a better response to TNFi in RA if RF positive for function and pain.
PMCID: PMC4209495  PMID: 25352925
Adalimumab; etanercept; health assessment questionnaire disability index (HAQ-DI); infliximab; pain; response; rheumatoid arthritis (RA); rheumatoid factor (RF); tumour necrosis factor inhibitor (TNFi).
15.  A New Curcuma Extract (Flexofytol®) in Osteoarthritis: Results from a Belgian Real-Life Experience 
This retrospective observational study summarizes the experiences of 820 patients treated with a new Curcuma extract (Flexofytol®, 4-6 capsules per day), for more than 6 months for various forms of painful osteoarthritis. These experiences were reported by 110 Belgian general practitioners via a questionnaire that included quality-of-life parameters for assessing patient experience. Data were submitted to an independent statistician for analysis. Within the first 6 weeks, Flexofytol® improved patient pain, articular mobility, and quality of life. Excellent tolerance was reported, and more than half of these patients were able to discontinue analgaesic and anti-inflammatory drugs. Patient satisfaction was confirmed by their decision to maintain Flexofytol® therapy for more than 6 months. These data must be confirmed with randomized controlled studies. We currently conclude that Flexofytol® which is based on a new preparation of curcumin, is as a potential neutraceutical for the care of patients complaining of joint problems, with excellent tolerance and rapid benefits for articular mobility, pain, and quality of life.
PMCID: PMC4209497  PMID: 25352926
Curcumin; osteoarthritis; real life experience.
16.  Cervical Spine Involvement: A Rare Manifestation of Reiter's Syndrome 
Spine involvement is less common in Reiter's syndrome than in other seronegative spondyloarthropathies. Also, cervical spine involvement rarely occurs in Reiter's syndrome and other spondyloarthropathies. This paper reports a rare case of Reiter's syndrome in which there was cervical spine involvement that presented clinically as an atlanto-axial rotatory subluxation. Reiter's Syndrome (RS) is one of the most common types of seronegative spondyloarthropathies (SSAs) that presents clinically with a triad of symptoms, i.e., conjunctivitis, urethritis, and arthritis. This case highlighted the importance of radiographs of the lateral cervical spine and dynamic cervical imaging for all patients who have Reiter's syndrome with cervical spine symptoms to ensure that this dangerous abnormality is not overlooked.
PMCID: PMC4212507  PMID: 25360183
Atlanto-axial rotatory subluxation; Reiter’s syndrome; spondyloarthropathy.
17.  Physical Exercise and Weight Loss for Hip and Knee Osteoarthritis in Very Old Patients: A Systematic Review of the Literature 
Background :
Rheumatologic and geriatric scholarly organisations recommendations for the management of hip and knee osteoarthritis, which emphasise the usefulness of non-pharmacological therapies, are not scaled according to patient’s age and physical condition. We conducted a systematic review of clinical trials on exercise and weight loss in hip and knee osteoarthritis in very old patients.
Methods :
Electronic search in MEDLINE, EMBASE, PASCAL database, systematic search of the Cochrane Reviews, manual search in guidelines, meta-analyses and identified relevant articles.
Results :
We identified 83 trials, with only 2 on patients aged ≥ 75 years; we therefore lowered the mean age threshold to 70 years and found 15 trials, mainly performed in knee osteoarthritis and outpatients.
Physical exercise (8 trials):
was effective on pain and function (4 controlled trials), with a persistent effect only in case of self-rehabilitation.
Aquatic exercise (5 trials):
was as effective as land-based exercise.
Weight loss (2 trials):
only patients under diet + exercise had significant improvement on symptoms.
Conclusion :
Our systematic review confirms that international recommendations on exercise for knee osteoarthritis also apply to subjects aged 70-80 years. Long-term effectiveness requires a maintenance strategy. Specific trials on very old patients with various comorbidities are mandatory, given that these subjects are more exposed to drug-related iatrogenesis.
PMCID: PMC4258698  PMID: 25489352
Hip osteoarthritis; knee; physical exercise; systematic review; very old; weight loss.
18.  A Positive Association Between Foot Posture Index and Medial Compartment Knee Osteoarthritis in Moroccan People 
Objectives :
To compare foot posture in people with and without medial compartment knee osteoarthritis (OA), and to assess association between its abnormalities and medial compartment knee OA.
Methods :
We compared the foot posture of patients with clinically and radiographically-confirmed medial compartment knee OA and asymptomatic healthy controls using the foot posture index (FPI), navicular height, and the medial arch.
Results :
We included 100 patients and 80 asymptomatic controls. The mean age of patients was 59 ± 7 (44-76) years and 48 ± 9 (28-60) years in the control (p=0.06). Patients group have more pronated foot for FPI (1.50 ± 2.68 vs 0.72 ± 2.63; p=0.05), more flat foot (42% vs 22%; p=0.03), and less pes cavus than the control group (58% vs 77%; p=0.004). However, there was no significant difference between the groups in the navicular height (3.90 ± 0.85 cm vs 4.00 ± 0.76 cm; p=0.41).
In multivariate statistical analysis, after adjusting for age and body mass index, pronated foot in FPI (OR=1.22, 95%IC= [1.06-1.40], p=0.005), and pes cavus (OR=0.32, 95%IC= [0.11-0.93], p=0.03) had a significant correlation with the knee osteoarthritis.
Conclusion :
Pronated foot posture and flat foot are significantly associated with medial compartment knee osteoarthritis.
PMCID: PMC4279032  PMID: 25553141
Foot posture; foot posture index; knee osteoarthritis; medial arch; medial compartment; navicular height.
19.  Sjögren’s, Renal Tubular Acidosis And Osteomalacia - An Asian Indian Series 
To study the profile of Renal Tubular Acidosis (RTA) in Asian Indian patients with Primary Sjögren's Syndrome (pSS).
The Electronic medical records of patients with a diagnosis of pSS seen between 2003 and 2010 at our tertiary care teaching hospital were screened for RTA. Clinical features, immunological profile, acid-base balance and electrolyte status, 25-hydroxyvitamin D (25(OH) D3) levels, histopathological changes in minor salivary gland biopsy samples and radiological findings were retrieved. RTA was diagnosed in cases of hyperchloremic metabolic acidosis with urinary pH values higher than 5.5. Those with known features suggestive of RTA including hypokalemic paralysis, hyperchloremia and nephrocalcinosis without acidosis were defined as incomplete RTA.
Of the 380 patients with clinically suspected pSS, 25 had RTA. The median age was 32 (18-60) years. Nineteen patients had complete RTA. Six had incomplete RTA. Only 10 patients (40%) had symptoms related to RTA at presentation. Sixteen patients (64%) had present or past history of hypokalemic paralysis. Pseudofractures were seen in 7 patients and an additional 2 had subclinical radiological osteomalacia. Majority of the patients (61.2%) had a normal 25(OH) D3 level. Those with osteomalacia had significantly lower serum phosphate, blood ph and higher alkaline phosphatase. Serum calcium and 25(OH) D3 levels were not significantly different between patients with osteomalacia and those without.
Most patients were asymptomatic for RTA inspite of clinically overt and elicitable features. Skeletal manifestation was a common finding in patients with Sjögren and RTA, despite normal levels of 25 (OH) D3 in a majority.
PMCID: PMC4286932  PMID: 25584094
Osteomalacia; Pseudofractures; Renal Tubular Acidosis; Sj gren s syndrome; Vitamin D.
20.  Comparative Efficacy and Safety Study of Two Chondroitin Sulfate Preparations from Different Origin (Avian and Bovine) in Symptomatic Osteoarthritis of the Knee 
Some argued that clinical efficacy of Chondroitin Sulfate (CS) could vary upon the product origin. The objective of this trial is to compare the effect of 2 CS medicinal products from different origin: Structum® (avian, 1000mg/day) and Chondrosulf® (bovine, 1200mg/day).
This was a randomized, double-blind, double placebo, active-controlled, parallel-group study using a non-inferiority design. Symptomatic osteoarthritis of the knee patients, according to American College of Rheumatology criteria, aged 50-80 years received either Structum® (500mg BID) or Chondrosulf® (400mg TID) during 24 weeks. Inclusion criteria were: global pain in the target knee ≥ 40mm on a Visual Analog Scale (VAS 0-100), a Lequesne’s Algofunctional Index (LFI) score ≥ 7 (range: 0-24) and a radiological Kellgren-Lawrence grade 2 or 3. Primary outcome was the mean change over 24 weeks of pain VAS and LFI score. Secondary outcomes were patient’s and physician’s global assessments, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responders rate, analgesics intake and Medical Outcomes Survey Short-Form 12 (SF-12). Safety was assessed by recording adverse events. A non-inferiority test was performed on the Structum®-Chondrosulf® difference for VAS and LFI score changes. Predefined non inferiority limit was settled as the lower limit of the 95% CI above -5mm and -1pt for pain VAS and LFI score respectively.
837 patients were randomized: 817 available for the full analysis dataset (FAS), 692 for the per protocol (PP) analysis. No statistical and clinical differences were observed for demographics and disease characteristics between the 2 groups. PP analysis showed no difference between groups on mean variations of pain VAS or LFI scores over 24 weeks. Mean Pain VAS decreased by 23.9mm (17.5) in Structum® group and 23.8mm (17.2) in Chondrosulf® group (difference: 0.012 [CI95%: -2.6 ; 2.6]). Mean LFI score decreased by 3.2 (2.4) and 3.1 (2.4) respectively (difference: 0.139 [CI95%: -0.2 ; 0.5]). The lower limits of the 2 CI were above predefined non inferiority margin, which demonstrated the non inferiority of Structum® in comparison with Chondrosulf®. FAS analysis gave similar results. Secondary efficacy outcomes analysis showed the same trends. Responders rate were 76.3% and 73.8% respectively (PP, W24). Treatments were well tolerated: 2.4% in Structum® group and 4.5% in Chondrosulf® group withdrew from the study for safety reasons.
Structum® and Chondrosulf® were equally effective in reducing functional impairment and relieving pain over 6 months in knee osteoarthritis patients, without any safety concerns.
Trial Registration: Number: ISRCTN04305346.
PMCID: PMC3594706  PMID: 23493263
Knee osteoarthritis; chondroitin sulfate; randomised clinical trial; noninferiority.
21.  Human Endogenous Retroviruses (HERVs) and Autoimmune Rheumatic Disease: Is There a Link? 
Autoimmune rheumatic diseases, such as RA and SLE, are caused by genetic, hormonal and environmental factors. Human Endogenous Retroviruses (HERVs) may be triggers of autoimmune rheumatic disease. HERVs are fossil viruses that began to be integrated into the human genome some 30-40 million years ago and now make up 8% of the genome. Evidence suggests HERVs may cause RA and SLE, among other rheumatic diseases. The key mechanisms by which HERVS are postulated to cause disease include molecular mimicry and immune dysregulation. Identification of HERVs in RA and SLE could lead to novel treatments for these chronic conditions. This review summarises the evidence for HERVs as contributors to autoimmune rheumatic disease and the clinical implications and mechanisms of pathogenesis are discussed.
PMCID: PMC3636489  PMID: 23750183
Human endogenous retrovirus; HERV; rheumatoid arthritis; molecular mimicry; bioinformatics.
22.  Inflammatory Cells in Tissues of Gout Patients and Their Correlations with Comorbidities 
The major pathological finding of gout is the deposition of monosodium urate monohydrate (MSU) crystals with inflammatory infiltrate in the tissue. There have been many reports of in vitro analysis of inflammatory mechanism and comorbidities in gout. However, the associations of immune response cells and comorbidities of gout have not been well documented. Our studies aimed to examine the immune cell types and quantity in gout tissues, and to define the association of individual cell type with comorbidities.
Surgically resected or biopsied tissues from 48 patients diagnosed as gout were used for this study. Cell count was performed on Hemotoxylin and Eosin stained sections for macrophages, plasma cells, neutrophils and on immunostained slides for T and B lymphocytes.
Hyperlipidemia, hypertension and diabetes mellitus were seen in 70.8%, 87.5% and 37.5% of patients, respectively. There were 35.6% and 37.8% of patients who admitted history of smoking and alcohol intake, respectively. Mean serum uric acid level was 8.5 mg/dl. The average body mass index was 30.1 kg/m2. H&E stained tissue sections demonstrated the crystalline deposits rimmed by palisading multinucleated giant cells, macrophages, neutrophils, plasma cells, T and B cells. Significant correlations between the clinical features and tissue inflammatory cells were observed in hyperlipidemia with number of T cells (p = 0.0363), hypertension with number of T cells and B cells (p = 0.0138 and 0.0033, respectively), diabetes mellitus with macrophages (p = 0.0016), and uric acid level with giant cells (p = 0.0088).
Comorbidity factors including hyperlipidemia, hypertension and diabetes are significantly associated with the inflammatory cells in the tissues.
PMCID: PMC3681035  PMID: 23802027
Gout; mononucleated macrophages; multinucleated giant cells; T-cells; B-cells; uric acid; comorbidities.
23.  MEFV Variants in Patients with PFAPA Syndrome in Japan 
The pathogenesis of PFAPA (periodic fever, aphthous stomatitis, pharyngitis, adenitis) syndrome is unknown as yet. In order to understand whether genes implicated in other auto-inflammatory diseases might be involved in the pathogenesis of PFAPA, all variants in the genes causing familial Mediterranean fever (FMF), tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS), and Hyper IgD syndrome were analyzed in children with PFAPA.
Patients and Methods:
All variants in MEFV, TNFRSF1A, and MVK were analyzed in 20 patients with PFAPA. PFAPA were diagnosed by previous published criteria. The findings of all analyses in PFAPA patients were compared with those of unaffected normal subjects (n=62).
In the 13 children of 20 with PFAPA, the heterozygous variants of MEFV (5 patients: E148Q-L110P, 2 patients: E148Q, 1 patient: E148Q-L110P/E148Q, 1 patient: E148Q-P369S-R408Q-E84K, 1 patient: E148Q-L110P-P369S-A408G, 1 patient: R202Q, 1 patient: P115R) were found. No variants belonging to TNFRSF1A or MVK were detected in children with PFAPA. The frequency of the E148Q-L110P variants in children with PFAPA was significantly higher than that observed in unaffected normal subjects (7/20 versus 8/62). The duration of the episodes of illness in PFAPA children with MEFV variants was shorter than that of patients without variants.
Genes involved in the development and progression of MEFV may affect the incidence and the phenotype of PFAPA in children.
PMCID: PMC3681033  PMID: 23847694
PFAPA; MEFV; FMF; Variant; Japanese.
24.  The Efficacy of Continuous Versus Intermittent Celecoxib Treatment in Osteoarthritis Patients with Body Mass Index ≥30 and <30 kg/m2 
Characterize the effect of body mass index (BMI) on the efficacy of continuous daily celecoxib treatment compared with intermittent celecoxib treatment.
Prespecified exploratory analysis of a 24-week, double-blind, parallel-group, randomized, multicenter international study. 858 patients with knee or hip osteoarthritis (OA) were randomized to receive celecoxib 200 mg daily either as continuous or intermittent treatment. Efficacy was measured by Western Ontario and McMaster Universities Arthritis Index (WOMAC) total and subscale scores and the number of flare events.
Least squares mean increases (worsening) in WOMAC total scores were significantly less in the continuous treatment group than in the intermittent treatment group in patients with a BMI <30 kg/m2 (1.33 vs 4.85; p=0.016) and in patients with a BMI ≥30 kg/m2 (1.84 vs 5.12; p=0.019). There was a greater worsening in patients with a BMI ≥30 kg/m2 than in those with a BMI <30 kg/m2 in both the continuous and intermittent groups. Fewer flares were reported in the continuous treatment group than in the intermittent group in patients with a BMI <30 kg/m2 (0.55 vs 0.88; p<0.0001) and ≥30 kg/m2 (0.54 vs 0.97; p<0.0001). There were no differences in adverse events in the two BMI groups.
Continuous celecoxib treatment was significantly more efficacious than intermittent use in patients with a BMI <30 kg/m2 compared with obese patients (≥30 kg/m2) as assessed by WOMAC total scores and the number of flares. These data suggest that including weight loss as part of a treatment regimen for obese OA patients could be important.
PMCID: PMC3731795  PMID: 23919092
NSAIDs; osteoarthritis; BMI; flare; WOMAC; continuous; intermittent.
25.  Intra-Articular Hyaluronic Acid as Treatment in Elderly and Middle-Aged Patients with Knee Osteoarthritis 
Osteoarthritis is the most common age-related degenerative joint disease. It affects all the joints containing hyaline cartilage. Knee osteoarthritis is the most cumbersome in terms of prevalence and disability. The aim of this study to evaluate the efficacy of intra-articular hyaluronic acid in patients with knee osteoarthritis with regard to joint pain and function, as well as patient satisfaction, assessed at one month and at one year, and by age group.
In this prospective randomised study, 172 patients who were diagnosed knee OA and who received three consecutive intra-articular injections of HA weekly were included. Patients 65 years of age or older were accepted as the “elderly group”, and those under 65 were accepted as the “middle-aged group”. Clinical evaluations of efficacy and safety were conducted at the beginning of the study, one month after the third injection, and one year after the third injection.
In the two groups, the intragroup analysis revealed significant improvements following injection when compared with preinjection values. According to the last followup controls (after 12 months) in the middle-aged group, VAS activity pain, VAS rest pain, WOMAC physical function, and WOMAC pain values were found to be statistically lower when compared with pre-injection values. In the elderly group, no statistically significant differences were found between pre-injection and after 12 months.
We can conclude that intra-articular joint HA injections are effective in both young and old patients with OA with regard to pain and functional status over a short-term period. Further, HA injections in patients younger than 65 years can be planned for a one-year period.
PMCID: PMC3731797  PMID: 23919093
Knee osteoarthritis; hyaluronic acid; knee pain.

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